Pejman Ghanouni, MD, PhD

All Publications

• "Quality over quantity:" smaller, targeted lesions optimize quality of life outcomes after MR-guided focused ultrasound thalamotomy for essential tremor. Frontiers in neurology Buch, V. P., Purger, D., Datta, A., Wang, A., Barbosa, D., Chodakiewitz, Y., Lev-Tov, L., Li, C., Halpern, C., Henderson, J., McNab, J. A., Bitton, R. R., Ghanouni, P. 2024; 15: 1450699

  Abstract

  MRI-guided focused ultrasound (MRgFUS) thalamotomy of the nucleus ventralis intermedius (VIM) has emerged as a powerful and safe treatment modality for refractory essential tremor. While the efficacy of this technique has been extensively described, much remains unclear about how to optimize MRgFUS for patient quality of life (QoL), which may depend as much on a patient's adverse effect profile as on the magnitude of tremor suppression. Diffusion tensor imaging (DTI) has been used to help guide targeting strategies but can pose certain challenges for scalability.In this study, we propose the use of a simplified patient-reported change in QoL assessment to create an unbiased representation of a patient's perception of overall benefit. Further, we propose a large-sample-size, high-resolution, 7 T DTI database from the Human Connectome Project to create a normative tractographic atlas (NTA) with representations of ventral intermediate nucleus subregions most likely to be structurally connected to the motor cortex. The NTA network-based hotspots are then nonlinearly fitted to each patient's T1-weighted MRI.We found that smaller lesion size and higher extent to which the lesion is within the NTA hotspot predicted patients' change in QoL at last follow-up. Though long-term change in clinical rating scale for tremor (CRST) impacted QoL, neither intraoperative tremor suppression nor the patient's long-term perception of tremor suppression correlated with QoL. We provide an intraoperative threshold for accumulated dose volume (<0.06 cc), which along with the network-based hotspot in the NTA, may facilitate an easily scalable approach to help limit treatment to small, safe yet effective lesions that optimize change in QoL after MRgFUS.

  View details for DOI 10.3389/fneur.2024.1450699

  View details for PubMedID 39610701

  View details for PubMedCentralID PMC11603361

• Reply to Letter to the Editor: "What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multi-center trial in 8 academic centers". European radiology Bitton, R. R., Ghanouni, P. 2024

  View details for DOI 10.1007/s00330-024-11104-9

  View details for PubMedID 39422722

• Nested Semi-Transparent Isosurface Simulated Volume-Rendering (NESTIS-VR) - An efficient on-device rendering approach for Augmented Reality headsets increasing surgeon confidence of kidney donor arterial anatomy. Computers in biology and medicine Necker, F. N., Melcher, M. L., Busque, S., Leuze, C. W., Ghanouni, P., Le Castillo, C., Nguyen, E., Daniel, B. L. 2024; 183: 109267

  Abstract

  Volume-renderings of computed tomography or magnetic resonance angiograms (MRAs) are routinely used by surgeons in the preoperative assessment of vascular anatomy in kidney donors. Stereoscopic headsets (OST-HMD) like Microsoft HoloLens allow intuitive interaction with three-dimensional content for more intuitive comprehension, but do not allow real-time ray-casting volume-rendering of medical volume datasets on-device due to computational limitations.We introduce NEsted Semi-Transparent Isosurface Simulated Volume-Rendering (NESTIS-VR), as an on-device alternative to ray-casting volume-rendering and developed an application for HoloLens to render kidney donor MRAs with interactive control of fundamental rendering parameters. We compared NESTIS-VR with current standard pre-calculated 2D ray-cast volume-renderings in an observational study with 2 expert kidney transplant surgeons, measuring their confidence in pre-operatively assessing the kidney pedicle arterial anatomy in 20 potential donors. We also compared it against other 3D rendering techniques to understand which features contributed most to any improvements.Real-time stereoscopic three-dimensional (3D) NESTIS-VR in Augmented Reality significantly improves surgeons' confidence compared with pre-calculated conventional two-dimensional (2D) ray-casting volume-rendered images (p = 0.0415/p = 0.00003). 2D non-stereoscopic NESTIS-VR was significantly superior to pre-calculated 2D ray-casting volume-rendered images for both surgeons (p = 0.044/p = 0.0003). Single isosurface 2D rendering was significantly superior than pre-calculated 2D volume-rendered images for one surgeon. There was no significant difference between binocular 3D display over 2D views with NESTIS-VR or between constrained and unconstrained vantage points for 2D viewing.NESTIS-VR provides a new approach to rendering medical datasets in computationally limited OST-HMD headsets and significantly increases surgeons' confidence of kidney donor arterial anatomy. The principal confidence benefit arises from providing surgeons interactive control over rendering parameters compared to pre-calculated renderings at preset parameters whilst rendering on-device and keeping the OST-HMD untethered from a workstation.

  View details for DOI 10.1016/j.compbiomed.2024.109267

  View details for PubMedID 39405728

• Intraprocedural Diffusion-weighted Imaging for Predicting Ablation Zone during MRI-guided Focused Ultrasound of Prostate Cancer. Radiology. Imaging cancer Bitton, R. R., Shao, W., Chodakeiwitz, Y., Brunsing, R. L., Sonn, G., Rusu, M., Ghanouni, P. 2024; 6 (5): e240009

  Abstract

  Purpose To compare diffusion-weighted imaging (DWI) with thermal dosimetry as a noncontrast method to predict ablation margins in individuals with prostate cancer treated with MRI-guided focused ultrasound (MRgFUS) ablation. Materials and Methods This secondary analysis of a prospective trial (ClinicalTrials.gov no. NCT01657942) included 17 participants (mean age, 64 years ± 6 [SD]; all male) who were treated for prostate cancer using MRgFUS in whom DWI was performed immediately after treatment. Ablation contours from computed thermal dosimetry and DWI as drawn by two blinded radiologists were compared against the reference standard of ablation assessment, posttreatment contrast-enhanced nonperfused volume (NPV) contours. The ability of each method to predict the ablation zone was analyzed quantitively using Dice similarity coefficients (DSCs) and mean Hausdorff distances (mHDs). Results DWI revealed a hyperintense rim at the margin of the ablation zone. While DWI accurately helped predict treatment margins, thermal dose contours underestimated the extent of the ablation zone compared with the T1-weighted NPV imaging reference standard. Quantitatively, contour assessment between methods showed that DWI-drawn contours matched postcontrast NPV contours (mean DSC = 0.84 ± 0.05 for DWI, mHD = 0.27 mm ± 0.13) better than the thermal dose contours did (mean DSC = 0.64 ± 0.12, mHD = 1.53 mm ± 1.20) (P < .001). Conclusion This study demonstrates that DWI, which can visualize the ablation zone directly, is a promising noncontrast method that is robust to treatment-related bulk motion compared with thermal dosimetry and correlates better than thermal dosimetry with the reference standard T1-weighted NPV. Keywords: Interventional-Body, Ultrasound-High-Intensity Focused (HIFU), Genital/Reproductive, Prostate, Oncology, Imaging Sequences, MRI-guided Focused Ultrasound, MR Thermometry, Diffusionweighted Imaging, Prostate Cancer ClinicalTrials.gov Identifier no. NCT01657942 Supplemental material is available for this article. © RSNA, 2024.

  View details for DOI 10.1148/rycan.240009

  View details for PubMedID 39212524

• Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor: An Open-Label Clinical Trial. JAMA neurology Kaplitt, M. G., Krishna, V., Eisenberg, H. M., Elias, W. J., Ghanouni, P., Baltuch, G. H., Rezai, A., Halpern, C. H., Dalm, B., Fishman, P. S., Buch, V. P., Moosa, S., Sarva, H., Murray, A. M. 2024

  Abstract

  Unilateral magnetic resonance-guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option.To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy.This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category).A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation.Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months.The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient.Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient.ClinicalTrials.gov Identifier NCT04112381.

  View details for DOI 10.1001/jamaneurol.2024.2295

  View details for PubMedID 39073822

• RAPHIA: A deep learning pipeline for the registration of MRI and whole-mount histopathology images of the prostate. Computers in biology and medicine Shao, W., Vesal, S., Soerensen, S. J., Bhattacharya, I., Golestani, N., Yamashita, R., Kunder, C. A., Fan, R. E., Ghanouni, P., Brooks, J. D., Sonn, G. A., Rusu, M. 2024; 173: 108318

  Abstract

  Image registration can map the ground truth extent of prostate cancer from histopathology images onto MRI, facilitating the development of machine learning methods for early prostate cancer detection. Here, we present RAdiology PatHology Image Alignment (RAPHIA), an end-to-end pipeline for efficient and accurate registration of MRI and histopathology images. RAPHIA automates several time-consuming manual steps in existing approaches including prostate segmentation, estimation of the rotation angle and horizontal flipping in histopathology images, and estimation of MRI-histopathology slice correspondences. By utilizing deep learning registration networks, RAPHIA substantially reduces computational time. Furthermore, RAPHIA obviates the need for a multimodal image similarity metric by transferring histopathology image representations to MRI image representations and vice versa. With the assistance of RAPHIA, novice users achieved expert-level performance, and their mean error in estimating histopathology rotation angle was reduced by 51% (12 degrees vs 8 degrees), their mean accuracy of estimating histopathology flipping was increased by 5% (95.3% vs 100%), and their mean error in estimating MRI-histopathology slice correspondences was reduced by 45% (1.12 slices vs 0.62 slices). When compared to a recent conventional registration approach and a deep learning registration approach, RAPHIA achieved better mapping of histopathology cancer labels, with an improved mean Dice coefficient of cancer regions outlined on MRI and the deformed histopathology (0.44 vs 0.48 vs 0.50), and a reduced mean per-case processing time (51 vs 11 vs 4.5 min). The improved performance by RAPHIA allows efficient processing of large datasets for the development of machine learning models for prostate cancer detection on MRI. Our code is publicly available at: https://github.com/pimed/RAPHIA.

  View details for DOI 10.1016/j.compbiomed.2024.108318

  View details for PubMedID 38522253

• MR Imaging-Guided Prostate Cancer Therapies. Radiologic clinics of North America Adamo, D. A., Greenwood, B. M., Ghanouni, P., Arora, S. 2024; 62 (1): 121-133

  Abstract

  Prostate cancer is the most common malignancy diagnosed in men. MR imaging-guided therapies for prostate cancer have become an increasingly common treatment alternative to traditional whole-gland therapies, such as radical prostatectomy or radiation therapy. This is especially true in men with localized, low- to intermediate-risk prostate cancer. Although long-term oncologic data remain limited, the authors describe several MR imaging-guided therapeutic options for the treatment of prostate cancer, including cryoablation, laser ablation, transrectal high-intensity focused ultrasound, and transurethral ultrasound ablation.

  View details for DOI 10.1016/j.rcl.2023.06.012

  View details for PubMedID 37973238

• ArtHiFy: Artificial Histopathology-style Features for Improving MRI-Based Prostate Cancer Detection Bhattacharya, I., Shao, W., Li, X., Soerensen, S. C., Fan, R. E., Ghanouni, P., Brooks, J. D., Sonn, G. A., Rusu, M., Chen, W., Astley, S. M. SPIE-INT SOC OPTICAL ENGINEERING. 2024

  View details for DOI 10.1117/12.3006879

  View details for Web of Science ID 001208134600061

• High-Intensity Focused Ultrasound Surgery for Tumor Ablation: A Review of Current Applications. Radiology. Imaging cancer De Maio, A., Alfieri, G., Mattone, M., Ghanouni, P., Napoli, A. 2024; 6 (1): e230074

  Abstract

  The management of cancer with alternative approaches is a matter of clinical interest worldwide. High-intensity focused ultrasound (HIFU) surgery is a noninvasive technique performed under US or MRI guidance. The most studied therapeutic uses of HIFU involve thermal tissue ablation, demonstrating both palliative and curative potential. However, concurrent mechanical bioeffects also provide opportunities in terms of augmented drug delivery and immunosensitization. The safety and efficacy of HIFU integration with current cancer treatment strategies are being actively investigated in managing primary and secondary tumors, including cancers of the breast, prostate, pancreas, liver, kidney, and bone. Current primary HIFU indications are pain palliation, complete ablation of localized earlystage tumors, or debulking of unresectable late-stage cancers. This review presents the latest HIFU applications, from investigational to clinically approved, in the field of tumor ablation. Keywords: Ultrasound, Ultrasound-High Intensity Focused (HIFU), Interventional-MSK, Interventional-Body, Oncology, Technology Assessment, Tumor Response, MR Imaging © RSNA, 2023.

  View details for DOI 10.1148/rycan.230074

  View details for PubMedID 38099828

• MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients. European radiology Düx, D. M., Baal, J. D., Bitton, R., Chen, J., Brunsing, R. L., Sheth, V. R., Rosenberg, J., Kim, K., Ozhinsky, E., Avedian, R., Ganjoo, K., Bucknor, M., Dobrotwir, A., Ghanouni, P. 2023

  Abstract

  To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids.A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded.The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns.MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis.Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely.• Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

  View details for DOI 10.1007/s00330-023-10073-9

  View details for PubMedID 37615768

• What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers. European radiology Bitton, R. R., Fast, A., Vu, K. N., Lum, D. A., Chen, B., Hesley, G. K., Raman, S. S., Matsumoto, A. H., Price, T. M., Tempany, C., Dhawan, N., Dolen, E., Kohi, M., Fennessey, F. M., Ghanouni, P. 2023

  Abstract

  To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids.In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36 months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes.Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01).Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother.Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid.Clinical trial ID: NCT01285960.• Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment.

  View details for DOI 10.1007/s00330-023-09984-4

  View details for PubMedID 37553488

  View details for PubMedCentralID 4561549

• Immunoglobulin G4-Seronegative Autoimmune Cholangiopathy With Pancreatic and Hepatic Involvement Mimicking as Primary Sclerosing Cholangitis. ACG case reports journal Achalu, S., Berry, R., Wei, M. T., Banerjee, S., Ghanouni, P., Kambham, N., Kwo, P. Y. 2023; 10 (4): e01044

  Abstract

  Immunoglobulin G4-seronegative autoimmune cholangiopathy is a rare cause of biliary strictures. We describe a 27-year-old man presenting with elevated liver enzymes, recurrent cholangitis/bacteremia, biliary strictures, and normal immunoglobulin G4 levels, who was initially diagnosed with primary sclerosing cholangitis, and later listed for transplantation for recurrent bacteremia. Subsequent surveillance imaging demonstrated morphologic changes consistent with biliary strictures and autoimmune pancreatitis. Initiating corticosteroids resulted in liver enzyme normalization and stricture improvement. Diagnosing seronegative autoimmune cholangiopathy remains challenging given similar presentation to primary sclerosing cholangitis. This case highlights importance of a wide differential for biliary strictures, with increased suspicion in those developing pancreatic changes in this setting.

  View details for DOI 10.14309/crj.0000000000001044

  View details for PubMedID 37091206

  View details for PubMedCentralID PMC10118323

• CT-guided Pulsed Radiofrequency Combined with Steroid Injection for Sciatica from Herniated Disk: A Randomized Trial. Radiology Napoli, A., Alfieri, G., De Maio, A., Panella, E., Scipione, R., Facchini, G., Albisinni, U., Spinnato, P., Nardis, P. G., Tramutoli, R., Lenzi, J., Ghanouni, P., Bazzocchi, A., Perotti, S., Schoenfeld, A. J., Catalano, C. 2023: 221478

  Abstract

  Background Evidence regarding effective nonsurgical management of sciatica remains limited. Purpose To determine a difference in effectiveness between combined pulsed radiofrequency (PRF) and transforaminal epidural steroid injection (TFESI) treatment versus TFESI alone for sciatic pain due to lumbar disk herniation. Materials and Methods This prospective multicenter double-blind randomized clinical trial was conducted between February 2017 and September 2019 in participants with sciatica due to lumbar disk herniation lasting 12 weeks or longer that was not responsive to conservative treatment. Study participants were randomly assigned to undergo one CT-guided treatment with combined PRF and TFESI (n = 174) or TFESI alone (n = 177). The primary outcome was leg pain severity, as assessed with the numeric rating scale (NRS) (range, 0-10) at weeks 1 and 52 after treatment. Secondary outcomes included Roland-Morris Disability Questionnaire (RMDQ) score (range, 0-24) and Oswestry Disability Index (ODI) score (range, 0-100). Outcomes were analyzed according to the intention-to-treat principle via linear regression. Results Mean age of the 351 participants (223 men) was 55 years ± 16 (SD). At baseline, NRS was 8.1 ± 1.1 in the PRF and TFESI group and 7.9 ± 1.1 in the TFESI group. NRS was 3.2 ± 0.2 in the PRF and TFESI group and 5.4 ± 0.2 in the TFESI group (average treatment effect, 2.3; 95% CI: 1.9, 2.8; P < .001) at week 1 and 1.0 ± 0.2 and 3.9 ± 0.2 (average treatment effect, 3.0; 95% CI: 2.4, 3.5; P < .001), respectively, at week 52. At week 52, the average treatment effect was 11.0 (95% CI: 6.4, 15.6; P < .001) for ODI and 2.9 (95% CI: 1.6, 4.3; P < .001) for RMDQ, favoring the combined PRF and TFSEI group. Adverse events were reported in 6% (10 of 167) of participants in the PRF and TFESI group and in 3% (six of 176) of participants in the TFESI group (eight participants did not complete follow-up questionnaires). No severe adverse events occurred. Conclusion In the treatment of sciatica caused by lumbar disk herniation, pulsed radiofrequency combined with transforaminal epidural steroid injection is more effective for pain relief and disability improvement than steroid injection alone. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Jennings in this issue.

  View details for DOI 10.1148/radiol.221478

  View details for PubMedID 36975815

• Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease. The New England journal of medicine Krishna, V., Fishman, P. S., Eisenberg, H. M., Kaplitt, M., Baltuch, G., Chang, J. W., Chang, W., Martinez Fernandez, R., Del Alamo, M., Halpern, C. H., Ghanouni, P., Eleopra, R., Cosgrove, R., Guridi, J., Gwinn, R., Khemani, P., Lozano, A. M., McDannold, N., Fasano, A., Constantinescu, M., Schlesinger, I., Dalvi, A., Elias, W. J. 2023; 388 (8): 683-693

  Abstract

  BACKGROUND: Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies.METHODS: We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months.RESULTS: Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P=0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness.CONCLUSIONS: Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).

  View details for DOI 10.1056/NEJMoa2202721

  View details for PubMedID 36812432

• Focused Ultrasound and External Beam Radiation Therapy for Painful Bone Metastases: A Phase II Clinical Trial. Radiology Napoli, A., De Maio, A., Alfieri, G., Gasperini, C., Scipione, R., Campanacci, L., Siepe, G., De Felice, F., Siniscalchi, B., Chiurchioni, L., Tombolini, V., Donati, D. M., Morganti, A. G., Ghanouni, P., Catalano, C., Bazzocchi, A. 2023: 211857

  Abstract

  Background Recent consensus statements and clinical trials have assessed the value of MRI-guided focused ultrasound surgery for pain palliation of bone metastases; however, a comparison with external beam radiation therapy (EBRT) has not been performed. Purpose To compare safety and effectiveness data of MRI-guided focused ultrasound and EBRT in the treatment of bone metastases. Materials and Methods Participants with painful bone metastases, excluding skull and vertebral bodies, were enrolled in a prospective open-label nonrandomized phase II study between January 2017 and May 2019 and underwent either MRI-guided focused ultrasound or EBRT. The primary end point was the overall response rate at 1-month following treatment, assessed via the numeric rating scale (NRS) for pain (0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"). Secondary end points were improvements at 12-month follow-up in NRS and quality of life (QoL) measures, including the Brief Pain Inventory (BPI), QoL-Questionnaire Cancer-15 Palliative Care (QLQ-C15-PAL), and QoL-Questionnaire Bone Metastases-22 (QLQ-BM22) and analysis of adverse events. Statistical analyses, including linear regression, chi2 test, and Student t test followed the per-protocol principle. Results Among 198 participants, 100 underwent MRI-guided focused ultrasound (mean age, 63 years ± 13 [SD]; 51 women), and 98 underwent EBRT (mean age, 65 years ± 14; 52 women). The overall response rates at 1-month follow-up were 91% (91 of 100) and 67% (66 of 98), respectively, in the focused ultrasound and EBRT arms (P < .001), and complete response rates were 43% (43 of 100) and 16% (16 of 98) (P < .001). The mean baseline NRS score was 7.0 ± 2.1 for focused ultrasound and 6.6 ± 2.4 for EBRT (P = .16); at 1-month follow-up, they were reduced to 3.2 ± 0.3 and 5.1 ± 0.3 (P < .001), respectively. QLQ-C15-PAL for physical function (P = .002), appetite (P < .001), nausea and vomiting (P < .001), dyspnea (P < .001), and QoL (P < .001) scores were lower in the focused ultrasound group. The overall adverse event rates were 15% (15 of 100) after focused ultrasound and 24% (24 of 98) after EBRT. Conclusion MRI-guided focused ultrasound surgery and external beam radiation therapy showed similar improvements in pain palliation and quality of life, with low adverse event rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kelekis in this issue.

  View details for DOI 10.1148/radiol.211857

  View details for PubMedID 36594834

• A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Thong, A., Kunder, C., Mari Aparici, C., Davidzon, G. A., Moradi, F., Sonn, G. A., Iagaru, A. 2022

  Abstract

  Purpose: Targeting of lesions seen on multiparametric MRI (mpMRI) improves prostate cancer (PC) detection at biopsy. However, 20-65% of highly suspicious lesions on mpMRI (PI-RADS 4 or 5) are false positives (FP), while 5-10% of clinically significant PC (csPC) are missed. Prostate specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) are both overexpressed in PC. We therefore aimed to evaluate the potential of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for biopsy guidance in patients with suspected PC. Methods: A highly selective cohort of 13 men, aged 58.0±7.1 years, with suspected PC (persistently high prostate-specific antigen [PSA] and PSA density) but negative or equivocal mpMRI and/or negative biopsy were prospectively enrolled to undergo 68Ga-PSMA11 and 68Ga-RM2 PET/MRI. PET/MRI included whole-body and dedicated pelvic imaging after a delay of 20 minutes. All patients had targeted biopsy of any lesions seen on PET followed by standard 12-core biopsy. Maximum standardized uptake values (SUVmax) of suspected PC lesions were collected and compared to gold standard biopsy. Results: PSA and PSA density at enrollment were 9.8±6.0 (1.5-25.5) ng/mL and 0.20±0.18 (0.06-0.68) ng/mL2, respectively. Standardized systematic biopsy revealed a total of 14 PC in 8 participants: 7 were csPC and 7 were non-clinically significant PC (ncsPC). 68Ga-PSMA11 identified 25 lesions, of which 11 (44%) were true positive (TP) (5 csPC). 68Ga-RM2 showed 27 lesions, of which 14 (52%) were TP, identifying all 7 csPC and also 7 ncsPC. There were 17 concordant lesions in 11 patients vs. 14 discordant lesions in 7 patients between 68Ga-PSMA11 and 68Ga-RM2 PET. Incongruent lesions had the highest rate of FP (12 FP vs. 2 TP). SUVmax was significantly higher for TP than FP lesions in delayed pelvic imaging for 68Ga-PSMA11 (6.49±4.14 vs. 4.05±1.55, P = 0.023) but not for whole-body images, nor for 68Ga-RM2. Conclusion: Our results show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI are feasible for biopsy guidance in suspected PC. Both radiopharmaceuticals detected additional clinically significant cancers not seen on mpMRI in this selective cohort. 68Ga-RM2 PET/MRI identified all csPC confirmed at biopsy.

  View details for DOI 10.2967/jnumed.122.264448

  View details for PubMedID 36396456

• The Association of Tissue Change and Treatment Success During High-intensity Focused Ultrasound Focal Therapy for Prostate Cancer. European urology focus Khandwala, Y. S., Soerensen, S. J., Morisetty, S., Ghanouni, P., Fan, R. E., Vesal, S., Rusu, M., Sonn, G. A. 2022

  Abstract

  BACKGROUND: Tissue preservation strategies have been increasingly used for the management of localized prostate cancer. Focal ablation using ultrasound-guided high-intensity focused ultrasound (HIFU) has demonstrated promising short and medium-term oncological outcomes. Advancements in HIFU therapy such as the introduction of tissue change monitoring (TCM) aim to further improve treatment efficacy.OBJECTIVE: To evaluate the association between intraoperative TCM during HIFU focal therapy for localized prostate cancer and oncological outcomes 12 mo afterward.DESIGN, SETTING, AND PARTICIPANTS: Seventy consecutive men at a single institution with prostate cancer were prospectively enrolled. Men with prior treatment, metastases, or pelvic radiation were excluded to obtain a final cohort of 55 men.INTERVENTION: All men underwent HIFU focal therapy followed by magnetic resonance (MR)-fusion biopsy 12 mo later. Tissue change was quantified intraoperatively by measuring the backscatter of ultrasound waves during ablation.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Gleason grade group (GG) ≥2 cancer on postablation biopsy was the primary outcome. Secondary outcomes included GG ≥1 cancer, Prostate Imaging Reporting and Data System (PI-RADS) scores ≥3, and evidence of tissue destruction on post-treatment magnetic resonance imaging (MRI). A Student's t - test analysis was performed to evaluate the mean TCM scores and efficacy of ablation measured by histopathology. Multivariate logistic regression was also performed to identify the odds of residual cancer for each unit increase in the TCM score.RESULTS AND LIMITATIONS: A lower mean TCM score within the region of the tumor (0.70 vs 0.97, p=0.02) was associated with the presence of persistent GG ≥2 cancer after HIFU treatment. Adjusting for initial prostate-specific antigen, PI-RADS score, Gleason GG, positive cores, and age, each incremental increase of TCM was associated with an 89% reduction in the odds (odds ratio: 0.11, confidence interval: 0.01-0.97) of having residual GG ≥2 cancer on postablation biopsy. Men with higher mean TCM scores (0.99 vs 0.72, p=0.02) at the time of treatment were less likely to have abnormal MRI (PI-RADS ≥3) at 12 mo postoperatively. Cases with high TCM scores also had greater tissue destruction measured on MRI and fewer visible lesions on postablation MRI.CONCLUSIONS: Tissue change measured using TCM values during focal HIFU of the prostate was associated with histopathology and radiological outcomes 12 mo after the procedure.PATIENT SUMMARY: In this report, we looked at how well ultrasound changes of the prostate during focal high-intensity focused ultrasound (HIFU) therapy for the treatment of prostate cancer predict patient outcomes. We found that greater tissue change measured by the HIFU device was associated with less residual cancer at 1 yr. This tool should be used to ensure optimal ablation of the cancer and may improve focal therapy outcomes in the future.

  View details for DOI 10.1016/j.euf.2022.10.010

  View details for PubMedID 36372735

• A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Davidzon, G. A., Mari Aparici, C., Kunder, C., Sonn, G., Iagaru, A. 2022

  Abstract

  Rationale: Focal therapy for localized prostate cancer (PC) using high intensity focused ultrasound (HIFU) is gaining in popularity as it is non-invasive and associated with fewer side effects than standard whole-gland treatments. However, better methods to evaluate response to HIFU ablation are an unmet need. Prostate specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) are both overexpressed in PC. In this study, we evaluated a novel approach of using both 68Ga-RM2 and 68Ga-PSMA11 PET/MRI in each patient before and after HIFU to assess accuracy of target tumor localization and response to treatment. Methods: Fourteen men, 64.5 ± 8.0 (range 48-78) years-old, with newly diagnosed PC were prospectively enrolled. Pre-HIFU, patients underwent prostate biopsy, multiparametric MRI (mpMRI), 68Ga-PSMA11, and 68Ga-RM2 PET/MRI. Response to treatment was assessed at a minimum of 6 months after HIFU with prostate biopsy (n = 13), as well as 68Ga-PSMA11 and 68Ga-RM2 PET/MRI (n = 14). Maximum and peak standardized uptake values (SUVmax and SUVpeak) of known or suspected PC lesions were collected. Results: Pre-HIFU biopsy revealed 18 cancers of which 14 were clinically significant (Gleason score ≥3+4). mpMRI identified 18 lesions; 14 of them were ≥PI-RADS 4. 68Ga-PSMA11 and 68Ga-RM2 PET/MRI each showed 23 positive intraprostatic lesions; 21 were congruent in 13 patients and five were incongruent in 5 patients. Pre-HIFU, 68Ga-PSMA11 identified all target tumors while 68Ga-RM2 PET/MRI missed two tumors. Post-HIFU, 68Ga-RM2 and 68Ga-PSMA11 PET/MRI both identified clinically significant residual disease in one patient. Three significant ipsilateral recurrent lesions were identified, whereas one was missed by 68Ga-PSMA11. Pre-treatment prostate specific antigen (PSA) decreased significantly after HIFU by 66%. Concordantly, pre-treatment SUVmax decreased significantly after HIFU for 68Ga-PSMA11 (P = 0.001) and 68Ga-RM2 (P = 0.005). Conclusion: The results of this pilot study show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI identified the target tumor for HIFU in 100% and 86%, respectively, and accurately verified response to treatment. PET might be a useful tool in the guidance and monitoring of treatment success in patients receiving focal therapy for PC. These preliminary findings warrant larger studies for validation.

  View details for DOI 10.2967/jnumed.122.264783

  View details for PubMedID 36328488

• A review of artificial intelligence in prostate cancer detection on imaging. Therapeutic advances in urology Bhattacharya, I., Khandwala, Y. S., Vesal, S., Shao, W., Yang, Q., Soerensen, S. J., Fan, R. E., Ghanouni, P., Kunder, C. A., Brooks, J. D., Hu, Y., Rusu, M., Sonn, G. A. 2022; 14: 17562872221128791

  Abstract

  A multitude of studies have explored the role of artificial intelligence (AI) in providing diagnostic support to radiologists, pathologists, and urologists in prostate cancer detection, risk-stratification, and management. This review provides a comprehensive overview of relevant literature regarding the use of AI models in (1) detecting prostate cancer on radiology images (magnetic resonance and ultrasound imaging), (2) detecting prostate cancer on histopathology images of prostate biopsy tissue, and (3) assisting in supporting tasks for prostate cancer detection (prostate gland segmentation, MRI-histopathology registration, MRI-ultrasound registration). We discuss both the potential of these AI models to assist in the clinical workflow of prostate cancer diagnosis, as well as the current limitations including variability in training data sets, algorithms, and evaluation criteria. We also discuss ongoing challenges and what is needed to bridge the gap between academic research on AI for prostate cancer and commercial solutions that improve routine clinical care.

  View details for DOI 10.1177/17562872221128791

  View details for PubMedID 36249889

  View details for PubMedCentralID PMC9554123

• Tempering optimism for MRI-guided focused ultrasound therapy Reply LANCET ONCOLOGY Ehdaie, B., Sonn, G. A., Ghanouni, P. 2022; 23 (10): E439

  View details for DOI 10.1016/S1470-2045(22)00519-8

  View details for Web of Science ID 000878568900006

• IgG4-Seronegative Autoimmune Cholangiopathy With Pancreatic and Hepatic Involvement Mimicking as Primary Sclerosing Cholangitis Achalu, S., Wei, M., Berry, R., Banerjee, S., Ghanouni, P., Kwo, P. LIPPINCOTT WILLIAMS & WILKINS. 2022: S1231

  View details for Web of Science ID 000897916004174

• Therapeutic US Applications for the Abdomen and Pelvis. Radiographics : a review publication of the Radiological Society of North America, Inc Sailer, A., Ghanouni, P., Schade, G. R., Napoli, A., Vidal-Jove, J., Raman, S. S., Mendiratta-Lala, M., Ghai, S., Abreu, A., Sundaram, K. M., Westphalen, A., Arora, S. 2022; 42 (6): E182-E183

  View details for DOI 10.1148/rg.220044

  View details for PubMedID 36190852

• Tempering optimism for MRI-guided focused ultrasound therapy - Authors' reply. The Lancet. Oncology Ehdaie, B., Sonn, G. A., Ghanouni, P. 2022; 23 (10): e439

  View details for DOI 10.1016/S1470-2045(22)00557-5

  View details for PubMedID 36174620

• A Pilot Study of Ga-68-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Thong, A., Sonn, G. A., Kunder, C., Davidzon, G. A., Aparici, C., Moradi, F., Iagaru, A. SPRINGER. 2022: S484

  View details for Web of Science ID 000857046602091

• Evaluation of post-ablation mpMRI as a predictor of residual prostate cancer after focal high intensity focused ultrasound (HIFU) ablation. Urologic oncology Khandwala, Y. S., Morisetty, S., Ghanouni, P., Fan, R. E., Soerensen, S. J., Rusu, M., Sonn, G. A. 2022

  Abstract

  PURPOSE: To evaluate the performance of multiparametric magnetic resonance imaging (mpMRI) and PSA testing in follow-up after high intensity focused ultrasound (HIFU) focal therapy for localized prostate cancer.METHODS: A total of 73 men with localized prostate cancer were prospectively enrolled and underwent focal HIFU followed by per-protocol PSA and mpMRI with systematic plus targeted biopsies at 12 months after treatment. We evaluated the association between post-treatment mpMRI and PSA with disease persistence on the post-ablation biopsy. We also assessed post-treatment functional and oncological outcomes.RESULTS: Median age was 69 years (Interquartile Range (IQR): 66-74) and median PSA was 6.9 ng/dL (IQR: 5.3-9.9). Of 19 men with persistent GG ≥ 2 disease, 58% (11 men) had no visible lesions on MRI. In the 14 men with PIRADS 4 or 5 lesions, 7 (50%) had either no cancer or GG 1 cancer at biopsy. Men with false negative mpMRI findings had higher PSA density (0.16 vs. 0.07 ng/mL2, P = 0.01). No change occurred in the mean Sexual Health Inventory for Men (SHIM) survey scores (17.0 at baseline vs. 17.7 post-treatment, P = 0.75) or International Prostate Symptom Score (IPSS) (8.1 at baseline vs. 7.7 at 24 months, P = 0.81) after treatment.CONCLUSIONS: Persistent GG ≥ 2 cancer may occur after focal HIFU. mpMRI alone without confirmatory biopsy may be insufficient to rule out residual cancer, especially in patients with higher PSA density. Our study also validates previously published studies demonstrating preservation of urinary and sexual function after HIFU treatment.

  View details for DOI 10.1016/j.urolonc.2022.07.017

  View details for PubMedID 36058811

• A Pilot Study of Ga-68-PSMA11 and Ga-68-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Kunder, C., Iagaru, A. SPRINGER. 2022: S497-S498

  View details for Web of Science ID 000857046602123

• Management of Patients with Newly Diagnosed Desmoid Tumors in a First-Line Setting. Cancers Testa, S., Bui, N. Q., Charville, G. W., Avedian, R. S., Steffner, R., Ghanouni, P., Mohler, D. G., Ganjoo, K. N. 2022; 14 (16)

  Abstract

  The initial management of desmoid tumors (DTs) is shifting from surgery towards active surveillance, with systemic and locally ablative treatments reserved for enlarging and/or symptomatic disease. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed adult and pediatric patients with DTs treated at a tertiary academic cancer center between 1992 and 2022. Outcomes measured were progression-free survival (PFS) and time to next treatment (TTNT) after first-line therapy. A total of 262 treatment-naïve patients were eligible for analysis with a median age of 36.5 years (range, 0-87 years). The 5-year PFS and the median TTNT (months) after first-line treatment were, respectively: 50.6% and 69.1 mo for surgery; 64.9% and 149.5 mo for surgery plus adjuvant radiotherapy; 57.1% and 44.7 mo for surgery plus adjuvant systemic therapy; 24.9% and 4.4 mo for chemotherapy; 26.7% and 5.3 mo for hormonal therapy; 41.3% and 29.6 mo for tyrosine kinase inhibitors (TKIs); 44.4% and 8.9 mo for cryoablation and high intensity focused ultrasound; and 43.1% and 32.7 mo for active surveillance. Age ≤ 40 years (p < 0.001), DTs involving the extremities (p < 0.001), a maximum tumor diameter > 60 mm (p = 0.04), and hormonal therapy (p = 0.03) predicted a higher risk of progression. Overall, our results suggest that active surveillance should be considered initially for patients with smaller asymptomatic DTs, while upfront TKIs, local ablation, and surgery achieve similar outcomes in those with more aggressive disease.

  View details for DOI 10.3390/cancers14163907

  View details for PubMedID 36010900

• Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results. Journal of neurosurgery Cosgrove, G. R., Lipsman, N., Lozano, A. M., Chang, J. W., Halpern, C., Ghanouni, P., Eisenberg, H., Fishman, P., Taira, T., Schwartz, M. L., McDannold, N., Hayes, M., Ro, S., Shah, B., Gwinn, R., Santini, V. E., Hynynen, K., Elias, W. J. 2022: 1-6

  Abstract

  OBJECTIVE: The objective of this study was to evaluate, at 4 and 5 years posttreatment, the long-term safety and efficacy of unilateral MRI-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor in a cohort of patients from a prospective, controlled, multicenter clinical trial.METHODS: Outcomes per the Clinical Rating Scale for Tremor (CRST), including postural tremor scores (CRST Part A), combined hand tremor/motor scores (CRST Parts A and B), and functional disability scores (CRST Part C), were measured by a qualified neurologist. The Quality of Life in Essential Tremor Questionnaire (QUEST) was used to assess quality of life. CRST and QUEST scores at 48 and 60 months post-MRgFUS were compared to those at baseline to assess treatment efficacy and durability. All adverse events (AEs) were reported.RESULTS: Forty-five and 40 patients completed the 4- and 5-year follow-ups, respectively. CRST scores for postural tremor (Part A) for the treated hand remained significantly improved by 73.3% and 73.1% from baseline at both 48 and 60 months posttreatment, respectively (both p < 0.0001). Combined hand tremor/motor scores (Parts A and B) also improved by 49.5% and 40.4% (p < 0.0001) at each respective time point. Functional disability scores (Part C) increased slightly over time but remained significantly improved through the 5 years (p < 0.0001). Similarly, QUEST scores remained significantly improved from baseline at year 4 (p < 0.0001) and year 5 (p < 0.0003). All previously reported AEs remained mild or moderate, and no new AEs were reported.CONCLUSIONS: Unilateral MRgFUS thalamotomy demonstrates sustained and significant tremor improvement at 5 years with an overall improvement in quality-of-life measures and without any progressive or delayed complications. Clinical trial registration no.: NCT01827904 (ClinicalTrials.gov).

  View details for DOI 10.3171/2022.6.JNS212483

  View details for PubMedID 35932269

• Comparison between MR and CT imaging used to correct for skull-induced phase aberrations during transcranial focused ultrasound. Scientific reports Leung, S. A., Moore, D., Gilbo, Y., Snell, J., Webb, T. D., Meyer, C. H., Miller, G. W., Ghanouni, P., Butts Pauly, K. 2022; 12 (1): 13407

  Abstract

  Transcranial focused ultrasound with the InSightec Exablate system uses thermal ablation for the treatment of movement and mood disorders and blood brain barrier disruption for tumor therapy. The system uses computed tomography (CT) images to calculate phase corrections that account for aberrations caused by the human skull. This work investigates whether magnetic resonance (MR) images can be used as an alternative to CT images to calculate phase corrections. Phase corrections were calculated using the gold standard hydrophone method and the standard of care InSightec ray tracing method. MR binary image mask, MR-simulated-CT (MRsimCT), and CT images of three ex vivo human skulls were supplied as inputs to the InSightec ray tracing method. The degassed ex vivo human skulls were sonicated with a 670kHz hemispherical phased array transducer (InSightec Exablate 4000). 3D raster scans of the beam profiles were acquired using a hydrophone mounted on a 3-axis positioner system. Focal spots were evaluated using six metrics: pressure at the target, peak pressure, intensity at the target, peak intensity, positioning error, and focal spot volume. Targets at the geometric focus and 5mm lateral to the geometric focus were investigated. There was no statistical difference between any of the metrics at either target using either MRsimCT or CT for phase aberration correction. As opposed to the MRsimCT, the use of CT images for aberration correction requires registration to the treatment day MR images; CT misregistration within a range of±2 degrees of rotation error along three dimensions was shown to reduce focal spot intensity by up to 9.4%. MRsimCT images used for phase aberration correction for the skull produce similar results as CT-based correction, while avoiding both CT to MR registration errors and unnecessary patient exposure to ionizing radiation.

  View details for DOI 10.1038/s41598-022-17319-4

  View details for PubMedID 35927449

• Improving Transcranial Acoustic Targeting: The Limits of CT Based Velocity Estimates and The Role of MR. IEEE transactions on ultrasonics, ferroelectrics, and frequency control Webb, T. D., Fu, F., Leung, S. A., Ghanouni, P., Dahl, J., Does, M. D., Pauly, K. B. 2022; PP

  Abstract

  Transcranial magnetic resonance (MR) guided focused ultrasound (tcMRgFUS) enables the non-invasive treatment of the deep brain. This capacity relies on the ability to focus acoustic energy through the in-tact skull, a feat that requires accurate estimates of the acoustic velocity in individual patient skulls. In current practice, these estimates are generated using a pre-treatment CT scan and then registered to an MR dataset on the day of the treatment. Treatment safety and efficacy can be improved by eliminating the need to register the CT data to the MR images and by improving the accuracy of acoustic velocity measurements. In this study we examine the capacity of MR to supplement or replace CT as a means of estimating velocity in the skull. We find that MR can predict velocity with less but comparable accuracy to CT. We then use micro CT imaging to better understand the limitations of Hounsfield Unit (HU) based estimates of velocity, demonstrating that the macrostructure of pores in the skull contributes to the acoustic velocity of the bone. We find evidence that detailed T2 measurements provide information about pore macrostructure similar to the information obtained with micro CT, offering a potential clinical mechanism for improving patient specific estimates of acoustic velocity in the human skull.

  View details for DOI 10.1109/TUFFC.2022.3192224

  View details for PubMedID 35853046

• MRI-guided focused ultrasound focal therapy for patients with intermediate-risk prostate cancer: a phase 2b, multicentre study. The Lancet. Oncology Ehdaie, B., Tempany, C. M., Holland, F., Sjoberg, D. D., Kibel, A. S., Trinh, Q., Durack, J. C., Akin, O., Vickers, A. J., Scardino, P. T., Sperling, D., Wong, J. Y., Yuh, B., Woodrum, D. A., Mynderse, L. A., Raman, S. S., Pantuck, A. J., Schiffman, M. H., McClure, T. D., Sonn, G. A., Ghanouni, P. 2022

  Abstract

  BACKGROUND: Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer.METHODS: In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting.FINDINGS: Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths.INTERPRETATION: 24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term.FUNDING: Insightec and the National Cancer Institute.

  View details for DOI 10.1016/S1470-2045(22)00251-0

  View details for PubMedID 35714666

• Changes In The Cerebello-thalamo-cortical Network After MR-guided Focused Ultrasound Thalamotomy. Brain connectivity Thaler, C., Tian, Q., WIntermark, M., Ghanouni, P., Halpern, C., Henderson, J., Airan, R., Zeineh, M., Goubran, M., Leuze, C., Fiehler, J., Butts Pauly, K., McNab, J. A. 2022

  Abstract

  Object In recent years, transcranial MR-guided focused ultrasound (tcMRgFUS) has been established as a potential treatment option for movement disorders, including essential tremor. So far, however, little is known about the impact of tcMRgFUS on structural connectivity. The objective of this study was to detect microstructural changes in tremor- and motor-related white matter tracts in essential tremor patients treated with tcMRgFUS thalamotomy. Methods Eleven patients diagnosed with essential tremor were enrolled in this tcMRgFUS thalamotomy study. For each patient, 3T MRI including structural and diffusion MRI were acquired and the Clinical Rating Scale for Tremor was assessed prior to the procedure as well as one year after the treatment. Diffusion MRI tractography was performed to identify the cerebello-thalamo-cortical tract (CTCT), the medial lemniscus (ML) and the corticospinal tract (CST) in both hemispheres on pre-treatment data. Pre-treatment tractography results were co-registered to post-treatment diffusion data. Diffusion tensor imaging (DTI) metrics, including fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD), were averaged across the tracts in the pre- and post-treatment data. Results The mean value of tract-specific DTI metrics changed significantly within the thalamic lesion and in the CTCT on the treated side (p<0.05). Changes of DTI-derived indices within the CTCT correlated well with lesion overlap (FA: r=-0.54, p=0.04; MD: r=0.57, p=0.04); RD: r=0.67, p=0.036). Furthermore, a trend was seen for the correlation between changes of DTI-derived indices within the CTCT and clinical improvement (FA: r=0.58; p=0.062; MD: r=-0.52, p=0.64; RD: r=-0.61 p=0.090). Conclusions Microstructural changes were detected within the CTCT after tcMRgFUS and these changes correlated well with lesion-tract overlap. Our results show that diffusion MRI is able to detect the microstructural effects of tcMRgFUS, thereby further elucidating the treatment mechanism and ultimately to improve targeting prospectively.

  View details for DOI 10.1089/brain.2021.0157

  View details for PubMedID 35678063

• Computational Detection of Extraprostatic Extension of Prostate Cancer on Multiparametric MRI Using Deep Learning. Cancers Moroianu, S. L., Bhattacharya, I., Seetharaman, A., Shao, W., Kunder, C. A., Sharma, A., Ghanouni, P., Fan, R. E., Sonn, G. A., Rusu, M. 2022; 14 (12)

  Abstract

  The localization of extraprostatic extension (EPE), i.e., local spread of prostate cancer beyond the prostate capsular boundary, is important for risk stratification and surgical planning. However, the sensitivity of EPE detection by radiologists on MRI is low (57% on average). In this paper, we propose a method for computational detection of EPE on multiparametric MRI using deep learning. Ground truth labels of cancers and EPE were obtained in 123 patients (38 with EPE) by registering pre-surgical MRI with whole-mount digital histopathology images from radical prostatectomy. Our approach has two stages. First, we trained deep learning models using the MRI as input to generate cancer probability maps both inside and outside the prostate. Second, we built an image post-processing pipeline that generates predictions for EPE location based on the cancer probability maps and clinical knowledge. We used five-fold cross-validation to train our approach using data from 74 patients and tested it using data from an independent set of 49 patients. We compared two deep learning models for cancer detection: (i) UNet and (ii) the Correlated Signature Network for Indolent and Aggressive prostate cancer detection (CorrSigNIA). The best end-to-end model for EPE detection, which we call EPENet, was based on the CorrSigNIA cancer detection model. EPENet was successful at detecting cancers with extraprostatic extension, achieving a mean area under the receiver operator characteristic curve of 0.72 at the patient-level. On the test set, EPENet had 80.0% sensitivity and 28.2% specificity at the patient-level compared to 50.0% sensitivity and 76.9% specificity for the radiologists. To account for spatial location of predictions during evaluation, we also computed results at the sextant-level, where the prostate was divided into sextants according to standard systematic 12-core biopsy procedure. At the sextant-level, EPENet achieved mean sensitivity 61.1% and mean specificity 58.3%. Our approach has the potential to provide the location of extraprostatic extension using MRI alone, thus serving as an independent diagnostic aid to radiologists and facilitating treatment planning.

  View details for DOI 10.3390/cancers14122821

  View details for PubMedID 35740487

• Bridging the gap between prostate radiology and pathology through machine learning. Medical physics Bhattacharya, I., Lim, D. S., Aung, H. L., Liu, X., Seetharaman, A., Kunder, C. A., Shao, W., Soerensen, S. J., Fan, R. E., Ghanouni, P., To'o, K. J., Brooks, J. D., Sonn, G. A., Rusu, M. 2022

  Abstract

  Prostate cancer remains the second deadliest cancer for American men despite clinical advancements. Currently, Magnetic Resonance Imaging (MRI) is considered the most sensitive non-invasive imaging modality that enables visualization, detection and localization of prostate cancer, and is increasingly used to guide targeted biopsies for prostate cancer diagnosis. However, its utility remains limited due to high rates of false positives and false negatives as well as low inter-reader agreements.Machine learning methods to detect and localize cancer on prostate MRI can help standardize radiologist interpretations. However, existing machine learning methods vary not only in model architecture, but also in the ground truth labeling strategies used for model training. We compare different labeling strategies and the effects they have on the performance of different machine learning models for prostate cancer detection on MRI.Four different deep learning models (SPCNet, U-Net, branched U-Net, and DeepLabv3+) were trained to detect prostate cancer on MRI using 75 patients with radical prostatectomy, and evaluated using 40 patients with radical prostatectomy and 275 patients with targeted biopsy. Each deep learning model was trained with four different label types: pathology-confirmed radiologist labels, pathologist labels on whole-mount histopathology images, and lesion-level and pixel-level digital pathologist labels (previously validated deep learning algorithm on histopathology images to predict pixel-level Gleason patterns) on whole-mount histopathology images. The pathologist and digital pathologist labels (collectively referred to as pathology labels) were mapped onto pre-operative MRI using an automated MRI-histopathology registration platform.Radiologist labels missed cancers (ROC-AUC: 0.75 - 0.84), had lower lesion volumes (~68% of pathology lesions), and lower Dice overlaps (0.24 - 0.28) when compared with pathology labels. Consequently, machine learning models trained with radiologist labels also showed inferior performance compared to models trained with pathology labels. Digital pathologist labels showed high concordance with pathologist labels of cancer (lesion ROC-AUC: 0.97 - 1, lesion Dice: 0.75 - 0.93). Machine learning models trained with digital pathologist labels had the highest lesion detection rates in the radical prostatectomy cohort (aggressive lesion ROC-AUC: 0.91 - 0.94), and had generalizable and comparable performance to pathologist label trained-models in the targeted biopsy cohort (aggressive lesion ROC-AUC: 0.87 - 0.88), irrespective of the deep learning architecture. Moreover, machine learning models trained with pixel-level digital pathologist labels were able to selectively identify aggressive and indolent cancer components in mixed lesions on MRI, which is not possible with any human-annotated label type.Machine learning models for prostate MRI interpretation that are trained with digital pathologist labels showed higher or comparable performance with pathologist label-trained models in both radical prostatectomy and targeted biopsy cohort. Digital pathologist labels can reduce challenges associated with human annotations, including labor, time, inter- and intra-reader variability, and can help bridge the gap between prostate radiology and pathology by enabling the training of reliable machine learning models to detect and localize prostate cancer on MRI. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/mp.15777

  View details for PubMedID 35633505

• Correlation of 68Ga-RM2 PET with Post-Surgery Histopathology Findings in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Baratto, L., Fan, R. E., Soerensen, S. J., Liang, T., Chung, B. I., Thong, A. E., Gill, H., Kunder, C., Stoyanova, T., Rusu, M., Loening, A. M., Ghanouni, P., Davidzon, G. A., Moradi, F., Sonn, G. A., Iagaru, A. 2022

  Abstract

  Rationale: 68Ga-RM2 targets gastrin-releasing peptide receptors (GRPR), which are overexpressed in prostate cancer (PC). Here, we compared pre-operative 68Ga-RM2 PET to post-surgery histopathology in patients with newly diagnosed intermediate- or high-risk PC. Methods: Forty-one men, 64.0+/-6.7-year-old, were prospectively enrolled. PET images were acquired 42 - 72 (median+/-SD 52.5+/-6.5) minutes after injection of 118.4 - 247.9 (median+/-SD 138.0+/-22.2)MBq of 68Ga-RM2. PET findings were compared to pre-operative mpMRI (n = 36) and 68Ga-PSMA11 PET (n = 17) and correlated to post-prostatectomy whole-mount histopathology (n = 32) and time to biochemical recurrence. Nine participants decided to undergo radiation therapy after study enrollment. Results: All participants had intermediate (n = 17) or high-risk (n = 24) PC and were scheduled for prostatectomy. Prostate specific antigen (PSA) was 8.8+/-77.4 (range 2.5 - 504) ng/mL, and 7.6+/-5.3 (range 2.5 - 28.0) ng/mL when excluding participants who ultimately underwent radiation treatment. Pre-operative 68Ga-RM2 PET identified 70 intraprostatic foci of uptake in 40/41 patients. Post-prostatectomy histopathology was available in 32 patients in which 68Ga-RM2 PET identified 50/54 intraprostatic lesions (detection rate = 93%). 68Ga-RM2 uptake was recorded in 19 non-enlarged pelvic lymph nodes in 6 patients. Pathology confirmed lymph node metastases in 16 lesions, and follow-up imaging confirmed nodal metastases in 2 lesions. 68Ga-PSMA11 and 68Ga-RM2 PET identified 27 and 26 intraprostatic lesions, respectively, and 5 pelvic lymph nodes each in 17 patients. Concordance between 68Ga-RM2 and 68Ga-PSMA11 PET was found in 18 prostatic lesions in 11 patients, and 4 lymph nodes in 2 patients. Non-congruent findings were observed in 6 patients (intraprostatic lesions in 4 patients and nodal lesions in 2 patients). Both 68Ga-RM2 and 68Ga-PSMA11 had higher sensitivity and accuracy rates with 98%, 89%, and 95%, 89%, respectively, compared to mpMRI at 77% and 77%. Specificity was highest for mpMRI with 75% followed by 68Ga-PSMA11 (67%), and 68Ga-RM2 (65%). Conclusion: 68Ga-RM2 PET accurately detects intermediate- and high-risk primary PC with a detection rate of 93%. In addition, it showed significantly higher specificity and accuracy compared to mpMRI and similar performance to 68Ga-PSMA11 PET. These findings need to be confirmed in larger studies to identify which patients will benefit from one or the other or both radiopharmaceuticals.

  View details for DOI 10.2967/jnumed.122.263971

  View details for PubMedID 35552245

• 68Ga-PSMA-11 PET/MRI in patients with newly diagnosed intermediate or high-risk prostate adenocarcinoma: PET findings correlate with outcomes after definitive treatment. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Moradi, F., Duan, H., Song, H., Davidzon, G. A., Chung, B. I., Thong, A. E., Loening, A. M., Ghanouni, P., Sonn, G., Iagaru, A. 2022

  Abstract

  Prostate-specific membrane antigen (PSMA) PET offers superior accuracy to other imaging modalities in initial staging of prostate cancer and is more likely to affect management. We examined the prognostic value of 68Ga-PSMA-11 uptake in primary lesion and presence of metastatic disease on PET in newly diagnosed prostate cancer patients prior to initial therapy. Methods: In a prospective study from April 2016 to December 2020, 68Ga-PSMA-11 PET/MRI was done in men with new diagnosis of intermediate or high-grade prostate cancer who were candidates for prostatectomy. Patients were followed up after initial therapy for up to 5 years. We examined the Kendall correlation between PET (intense uptake in primary lesion and presence of metastatic disease) and clinical and pathologic findings (grade group, extraprostatic extension, nodal involvement) relevant for risk stratification, and examined the relationship between PET findings and outcome using Kaplan-Meier analysis. Results: Seventy-three men, 64.0±6.3 years of age were imaged. Seventy-two had focal uptake in prostate and in 20 (27%), PSMA-avid metastatic disease was identified. Uptake correlated with grade group and prostate-specific antigen (PSA). Presence of PSMA metastasis correlated with grade group and pathologic nodal stage. PSMA PET had higher per-patients positivity than nodal dissection in patients with only 5-15 nodes removed (8/41 vs. 3/41) but lower positivity if more than 15 nodes were removed (13/21 vs. 10/21). High uptake in primary (SUVmax>12.5, P = .008) and presence of PSMA metastasis (P = .013) were associated with biochemical failure, and corresponding hazard ratios for recurrence within 2-years (4.93 and 3.95, respectively) were similar or higher than other clinicopathologic prognostic factors. Conclusions: 68Ga-PSMA-11 PET can risk stratify patients with intermediate or high-grade prostate cancer prior to prostatectomy based on degree of uptake in prostate and presence of metastatic disease.

  View details for DOI 10.2967/jnumed.122.263897

  View details for PubMedID 35512996

• A Review of Imaging Methods to Assess Ultrasound-Mediated Ablation. BME frontiers Fite, B. Z., Wang, J., Ghanouni, P., Ferrara, K. W. 2022; 2022

  Abstract

  Ultrasound ablation techniques are minimally invasive alternatives to surgical resection and have rapidly increased in use. The response of tissue to HIFU ablation differs based on the relative contributions of thermal and mechanical effects, which can be varied to achieve optimal ablation parameters for a given tissue type and location. In tumor ablation, similar to surgical resection, it is desirable to include a safety margin of ablated tissue around the entirety of the tumor. A factor in optimizing ablative techniques is minimizing the recurrence rate, which can be due to incomplete ablation of the target tissue. Further, combining focal ablation with immunotherapy is likely to be key for effective treatment of metastatic cancer, and therefore characterizing the impact of ablation on the tumor microenvironment will be important. Thus, visualization and quantification of the extent of ablation is an integral component of ablative procedures. The aim of this review article is to describe the radiological findings after ultrasound ablation across multiple imaging modalities. This review presents readers with a general overview of the current and emerging imaging methods to assess the efficacy of ultrasound ablative treatments.

  View details for DOI 10.34133/2022/9758652

  View details for PubMedID 35957844

  View details for PubMedCentralID PMC9364780

• Current management and recent progress in desmoid tumors. Cancer treatment and research communications Zhou, M. Y., Bui, N. Q., Charville, G. W., Ghanouni, P., Ganjoo, K. N. 2022; 31: 100562

  Abstract

  Desmoid tumors are rare soft tissue tumors that can have aggressive infiltrative growth and relapse locally. Desmoid tumors can impact functionality and cause treatment-related morbidity and mortality. Here, the authors review current management strategies and avenues for further investigation. As part of the evolution of therapy away from primary surgical approaches to less invasive options, image-guided ablation has been accepted as less morbid and include cryoablation and high-intensity focused ultrasound. Systemic therapy options currently include hormonal agents, nonsteroidal anti-inflammatory drugs, tyrosine kinase inhibitors, and anthracycline-based regimens. Hormonal agents and nonsteroidal anti-inflammatory drugs have benign side effect profiles but generally limited efficacy. Anthracycline-based therapies are limited by the risk of secondary malignancies and cardiomyopathy. Tyrosine kinase inhibitors are well studied, and sorafenib is now one of the most utilized therapies, though limited by its side effect profile. Nirogacestat (PF-0308401) is an investigational small molecule gamma-secretase (GS) inhibitor that has demonstrated efficacy in phase 1 and II trials. A phase III trial investigating patients with desmoid tumors or aggressive fibromatosis is estimated to be completed December 2021 (NCT03785964). In addition to nirogacestat, the gamma-secretase inhibitor AL102 is being investigated for the treatment of patients with progressing desmoid tumors in the phase II/III RINGSIDE trial. Finally, the beta-catenin inhibitor Tegavivint (BC2059) is being investigated in a phase 1 open-label trial in patients with a proven primary or recurrent desmoid tumor that is unresectable and symptomatic or progressive.

  View details for DOI 10.1016/j.ctarc.2022.100562

  View details for PubMedID 35460976

• Real-Time MRI-Guided Prostate Interventions. Cancers Masoom, S. N., Sundaram, K. M., Ghanouni, P., Futterer, J., Oto, A., Ayyagari, R., Sprenkle, P., Weinreb, J., Arora, S. 2022; 14 (8)

  Abstract

  Prostate cancer (PCa) is the second most common cause of cancer death in males. Targeting MRI-visible lesions has led to an overall increase in the detection of clinically significant PCa compared to the prior practice of random ultrasound-guided biopsy of the prostate. Additionally, advances in MRI-guided minimally invasive focal treatments are providing new options for patients with PCa. This review summarizes the currently utilized real-time MRI-guided interventions for PCa diagnosis and treatment.

  View details for DOI 10.3390/cancers14081860

  View details for PubMedID 35454773

• Confirmation of Ectopic Pancreatic Tissue: A Novel Use for 18F-Fluciclovine PET. Clinical nuclear medicine Keller, E. J., de Castro, C. M., Ghanouni, P., Shah, J. 2022

  Abstract

  ABSTRACT: This case features a 21-year-old woman with a history of ulcerative colitis who was incidentally found to have a para-jejunal mass when she presented with an ulcerative colitis flare. The mass was further characterized on MR enterography as most likely representing ectopic pancreatic tissue. Given the normal intense pancreatic uptake of 18F-fluciclovine, PET/CT was subsequently used to confirm that the mass represented ectopic pancreatic tissue.

  View details for DOI 10.1097/RLU.0000000000004134

  View details for PubMedID 35261353

• Increasing the transmission efficiency of transcranial ultrasound using a dual-mode conversion technique based on Lamb waves. The Journal of the Acoustical Society of America Kang, K. C., Kim, Y. H., Kim, J. N., Kabir, M., Zhang, Y., Ghanouni, P., Park, K. K., Firouzi, K., Khuri-Yakub, B. T. 2022; 151 (3): 2159

  Abstract

  Transcranial focused ultrasound (FUS) is a noninvasive treatment for brain tumors and neuromodulation. Based on normal incidence, conventional FUS techniques use a focused or an array of ultrasonic transducers to overcome the attenuation and absorption of ultrasound in the skull; however, this remains the main limitation of using FUS. A dual-mode conversion technique based on Lamb waves is proposed to achieve high transmission efficiency. This concept was validated using the finite element analysis (FEA) and experiments based on changes in the incident angle. Aluminum, plexiglass, and a human skull were used as materials with different attenuations. The transmission loss was calculated for each material, and the results were compared with the reflectance function of the Lamb waves. Oblique incidence based on dual-mode conversion exhibited a better transmission efficiency than that of a normal incidence for all of the specimens. The total transmission losses for the materials were 13.7, 15.46, and 3.91dB less than those associated with the normal incidence. A wedge transducer was designed and fabricated to implement the proposed method. The results demonstrated the potential applicability of the dual-mode conversion technique for the human skull.

  View details for DOI 10.1121/10.0009849

  View details for PubMedID 35364946

• Focused Ultrasound for Pediatric Diseases. Pediatrics Janwadkar, R., Leblang, S., Ghanouni, P., Brenner, J., Ragheb, J., Hennekens, C. H., Kim, A., Sharma, K. 2022; 149 (3)

  Abstract

  Focused ultrasound (FUS) is a noninvasive therapeutic technology with multiple pediatric clinical applications. The ability of focused ultrasound to target tissues deep in the body without exposing children to the morbidities associated with conventional surgery, interventional procedures, or radiation offers significant advantages. In 2021, there are 10 clinical pediatric focused ultrasound studies evaluating various musculoskeletal, oncologic, neurologic, and vascular diseases of which 8 are actively recruiting and 2 are completed. Pediatric musculoskeletal applications of FUS include treatment of osteoid osteoma and bone metastases using thermal ablation and high-intensity FUS. Pediatric oncologic applications of FUS include treatment of soft tissue tumors including desmoid tumors, malignant sarcomas, and neuroblastoma with high-intensity FUS ablation alone, or in combination with targeted chemotherapy delivery. Pediatric neurologic applications include treatment of benign tumors such as hypothalamic hamartomas with thermal ablation and malignant diffuse intrinsic pontine glioma with low-intensity FUS for blood brain barrier opening and targeted drug delivery. Additionally, low-intensity FUS can be used to treat seizures. Pediatric vascular applications of FUS include treatment of arteriovenous malformations and twin-twin transfusion syndrome using ablation and vascular occlusion. FUS treatment appears safe and efficacious in pediatric populations across many subspecialties. Although there are 7 Food and Drug Administration-approved indications for adult applications of FUS, the first Food and Drug Administration approval for pediatric patients with osteoid osteoma was obtained in 2020. This review summarizes the preclinical and clinical research on focused ultrasound of potential benefit to pediatric populations.

  View details for DOI 10.1542/peds.2021-052714

  View details for PubMedID 35229123

• A Review of Imaging Methods to Assess Ultrasound-Mediated Ablation BMEF: A Science Partner Journal Fite, B. Z., Wang, J., Ghanouni, P., Ferrara, K. W. 2022

  View details for DOI 10.34133/2022/9758652

• Integrating zonal priors and pathomic MRI biomarkers for improved aggressive prostate cancer detection on MRI Bhattacharya, I., Shao, W., Soerensen, S. C., Fan, R. E., Wang, J. B., Kunder, C., Ghanouni, P., Sonn, G. A., Rusu, M., Drukker, K., Iftekharuddin, K. M. SPIE-INT SOC OPTICAL ENGINEERING. 2022

  View details for DOI 10.1117/12.2612433

  View details for Web of Science ID 000838048600024

• Patterned Interference Radiation Force for Transcranial Neuromodulation. Ultrasound in medicine & biology Kim, Y. H., Kang, K. C., Kim, J. N., Pai, C. N., Zhang, Y., Ghanouni, P., Park, K. K., Firouzi, K., Khuri-Yakub, B. T. 1800

  Abstract

  Compared with the conventional method of transcranial focused ultrasound stimulation using a single transducer or a focused beam, the compression and tensile forces are generated from the high-pressure gradient of a standing wave that can generate increased stimulation. We experimentally verified a neuromodulation system using patterned interference radiation force (PIRF) and propose a method for obtaining the magnitude of the radiation force, which is considered the main factor influencing ultrasound neuromodulation. The radiation forces generated using a single focused transducer and a standing wave created via two focused transducers were compared using simulations. Radiation force was calculated based on the relationship between the acoustic pressure, radiation force and time-averaged second-order pressure obtained using an acoustic streaming simulation. The presence of the radiation force was verified by measuring the time-averaged second-order pressure generated due to the radiation force, by using a glass tube.

  View details for DOI 10.1016/j.ultrasmedbio.2021.11.006

  View details for PubMedID 34955292

• The stanford prostate cancer calculator: Development and external validation of online nomograms incorporating PIRADS scores to predict clinically significant prostate cancer. Urologic oncology Wang, N. N., Zhou, S. R., Chen, L., Tibshirani, R., Fan, R. E., Ghanouni, P., Thong, A. E., To'o, K. J., Amirkhiz, K., Nix, J. W., Gordetsky, J. B., Sprenkle, P., Rais-Bahrami, S., Sonn, G. A. 2021

  Abstract

  BACKGROUND: While multiparametric MRI (mpMRI) has high sensitivity for detection of clinically significant prostate cancer (CSC), false positives and negatives remain common. Calculators that combine mpMRI with clinical variables can improve cancer risk assessment, while providing more accurate predictions for individual patients. We sought to create and externally validate nomograms incorporating Prostate Imaging Reporting and Data System (PIRADS) scores and clinical data to predict the presence of CSC in men of all biopsy backgrounds.METHODS: Data from 2125 men undergoing mpMRI and MR fusion biopsy from 2014 to 2018 at Stanford, Yale, and UAB were prospectively collected. Clinical data included age, race, PSA, biopsy status, PIRADS scores, and prostate volume. A nomogram predicting detection of CSC on targeted or systematic biopsy was created.RESULTS: Biopsy history, Prostate Specific Antigen (PSA) density, PIRADS score of 4 or 5, Caucasian race, and age were significant independent predictors. Our nomogram-the Stanford Prostate Cancer Calculator (SPCC)-combined these factors in a logistic regression to provide stronger predictive accuracy than PSA density or PIRADS alone. Validation of the SPCC using data from Yale and UAB yielded robust AUC values.CONCLUSIONS: The SPCC combines pre-biopsy mpMRI with clinical data to more accurately predict the probability of CSC in men of all biopsy backgrounds. The SPCC demonstrates strong external generalizability with successful validation in two separate institutions. The calculator is available as a free web-based tool that can direct real-time clinical decision-making.

  View details for DOI 10.1016/j.urolonc.2021.06.004

  View details for PubMedID 34247909

• AAPM Task Group 241: A Medical Physicist's Guide to MRI-guided Focused Ultrasound Body Systems. Medical physics Payne, A., Chopra, R., Ellens, N., Chen, L., Ghanouni, P., Sammet, S., Diederich, C., Ter Haar, G., Parker, D., Moonen, C., Stafford, J., Moros, E., Schlesinger, D., Benedict, S., Wear, K., Partanen, A., Farahani, K. 2021

  Abstract

  Magnetic resonance-guided focused ultrasound (MRgFUS) is a completely non-invasive technology that has been FDA approved to treat several diseases. This report, prepared by the American Association of Physicist in Medicine (AAPM) Task Group 241, provides a background on MRgFUS technology with a focus on clinical body MRgFUS systems. The report addresses the issues of interest to the medical physics community, specific to the body MRgFUS system configuration, and provides recommendations on how to successfully implement and maintain a clinical MRgFUS program. The following sections describe the key features of typical MRgFUS systems and clinical workflow and provide key points and best practices for the medical physicist. Commonly used terms, metrics and physics are defined and sources of uncertainty that affect MRgFUS procedures are described. Finally, safety and quality assurance procedures are explained, the recommended role of the medical physicist in MRgFUS procedures is described, and regulatory requirements for planning clinical trials are detailed. Although this report is limited in scope to clinical body MRgFUS systems that are approved or currently undergoing clinical trials in the United States, much of the material presented is also applicable to systems designed for other applications.

  View details for DOI 10.1002/mp.15076

  View details for PubMedID 34224149

• A Pilot Study of68Ga-PSMA11 PET/MRI and68GaRM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ferri, V., Ghanouni, P., Daniel, B., Hatami, N., Davidzon, G., Aparici, C., Moradi, F., Thong, A., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600481

• Automated Detection of Aggressive and Indolent Prostate Cancer on Magnetic Resonance Imaging. Medical physics Seetharaman, A., Bhattacharya, I., Chen, L. C., Kunder, C. A., Shao, W., Soerensen, S. J., Wang, J. B., Teslovich, N. C., Fan, R. E., Ghanouni, P., Brooks, J. D., To'o, K. J., Sonn, G. A., Rusu, M. 2021

  Abstract

  PURPOSE: While multi-parametric Magnetic Resonance Imaging (MRI) shows great promise in assisting with prostate cancer diagnosis and localization, subtle differences in appearance between cancer and normal tissue lead to many false positive and false negative interpretations by radiologists. We sought to automatically detect aggressive cancer (Gleason pattern ≥ 4) and indolent cancer (Gleason pattern 3) on a per-pixel basis on MRI to facilitate the targeting of aggressive cancer during biopsy.METHODS: We created the Stanford Prostate Cancer Network (SPCNet), a convolutional neural network model, trained to distinguish between aggressive cancer, indolent cancer, and normal tissue on MRI. Ground truth cancer labels were obtainedby registering MRI with whole-mount digital histopathology images from patients that underwent radical prostatectomy. Before registration, these histopathology images were automatically annotated to show Gleason patterns on a per-pixel basis. The model was trained on data from 78 patients that underwent radical prostatectomy and 24 patients without prostate cancer. The model was evaluated on a pixel and lesion level in 322 patients, including: 6 patients with normal MRI and no cancer, 23 patients that underwent radical prostatectomy, and 293 patients that underwent biopsy. Moreover, we assessed the ability of our model to detect clinically significant cancer (lesions with an aggressive component) and compared it to the performance of radiologists.RESULTS: Our model detected clinically significant lesions with an Area Under the Receiver Operator Characteristics Curve of 0.75 for radical prostatectomy patients and 0.80 for biopsy patients. Moreover, the model detected up to 18% of lesions missed by radiologists, and overall had a sensitivity and specificity that approached that of radiologists in detecting clinically significant cancer.CONCLUSIONS: Our SPCNet model accurately detected aggressive prostate cancer. Its performance approached that of radiologists, and it helped identify lesions otherwise missed by radiologists. Our model has the potential to assist physicians in specifically targeting the aggressive component of prostate cancers during biopsy or focal treatment.

  View details for DOI 10.1002/mp.14855

  View details for PubMedID 33760269

• Transcranial focused ultrasound phase correction using the hybrid angular spectrum method. Scientific reports Leung, S. A., Moore, D., Webb, T. D., Snell, J., Ghanouni, P., Butts Pauly, K. 2021; 11 (1): 6532

  Abstract

  The InSightec Exablate system is the standard of care used for transcranial focused ultrasound ablation treatments in the United States. The system calculates phase corrections that account for aberrations caused by the human skull. This work investigates whether skull aberration correction can be improved by comparing the standard of care InSightec ray tracing method with the hybrid angular spectrum (HAS) method and the gold standard hydrophone method. Three degassed ex vivo human skulls were sonicated with a 670kHz hemispherical phased array transducer (InSightec Exablate 4000). Phase corrections were calculated using four different methods (straight ray tracing, InSightec ray tracing, HAS, and hydrophone) and were used to drive the transducer. 3D raster scans of the beam profiles were acquired using a hydrophone mounted on a 3-axis positioner system. Focal spots were evaluated using six metrics: pressure at the target, peak pressure, intensity at the target, peak intensity, positioning error, and focal spot volume. For three skulls, the InSightec ray tracing method achieved 52±21% normalized target intensity (normalized to hydrophone), 76±17% normalized peak intensity, and 0.72±0.47mm positioning error. The HAS method achieved 74±9% normalized target intensity, 81±9% normalized peak intensity, and 0.35±0.09mm positioning error. The InSightec-to-HAS improvement in focal spot targeting provides promise in improving treatment outcomes. These improvements to skull aberration correction are also highly relevant for the applications of focused ultrasound neuromodulation and blood brain barrier opening, which are currently being translated for human use.

  View details for DOI 10.1038/s41598-021-85535-5

  View details for PubMedID 33753771

• 3D Registration of pre-surgical prostate MRI and histopathology images via super-resolution volume reconstruction. Medical image analysis Sood, R. R., Shao, W. n., Kunder, C. n., Teslovich, N. C., Wang, J. B., Soerensen, S. J., Madhuripan, N. n., Jawahar, A. n., Brooks, J. D., Ghanouni, P. n., Fan, R. E., Sonn, G. A., Rusu, M. n. 2021; 69: 101957

  Abstract

  The use of MRI for prostate cancer diagnosis and treatment is increasing rapidly. However, identifying the presence and extent of cancer on MRI remains challenging, leading to high variability in detection even among expert radiologists. Improvement in cancer detection on MRI is essential to reducing this variability and maximizing the clinical utility of MRI. To date, such improvement has been limited by the lack of accurately labeled MRI datasets. Data from patients who underwent radical prostatectomy enables the spatial alignment of digitized histopathology images of the resected prostate with corresponding pre-surgical MRI. This alignment facilitates the delineation of detailed cancer labels on MRI via the projection of cancer from histopathology images onto MRI. We introduce a framework that performs 3D registration of whole-mount histopathology images to pre-surgical MRI in three steps. First, we developed a novel multi-image super-resolution generative adversarial network (miSRGAN), which learns information useful for 3D registration by producing a reconstructed 3D MRI. Second, we trained the network to learn information between histopathology slices to facilitate the application of 3D registration methods. Third, we registered the reconstructed 3D histopathology volumes to the reconstructed 3D MRI, mapping the extent of cancer from histopathology images onto MRI without the need for slice-to-slice correspondence. When compared to interpolation methods, our super-resolution reconstruction resulted in the highest PSNR relative to clinical 3D MRI (32.15 dB vs 30.16 dB for BSpline interpolation). Moreover, the registration of 3D volumes reconstructed via super-resolution for both MRI and histopathology images showed the best alignment of cancer regions when compared to (1) the state-of-the-art RAPSODI approach, (2) volumes that were not reconstructed, or (3) volumes that were reconstructed using nearest neighbor, linear, or BSpline interpolations. The improved 3D alignment of histopathology images and MRI facilitates the projection of accurate cancer labels on MRI, allowing for the development of improved MRI interpretation schemes and machine learning models to automatically detect cancer on MRI.

  View details for DOI 10.1016/j.media.2021.101957

  View details for PubMedID 33550008

• Selective identification and localization of indolent and aggressive prostate cancers via CorrSigNIA: an MRI-pathology correlation and deep learning framework. Medical image analysis Bhattacharya, I., Seetharaman, A., Kunder, C., Shao, W., Chen, L. C., Soerensen, S. J., Wang, J. B., Teslovich, N. C., Fan, R. E., Ghanouni, P., Brooks, J. D., Sonn, G. A., Rusu, M. 2021; 75: 102288

  Abstract

  Automated methods for detecting prostate cancer and distinguishing indolent from aggressive disease on Magnetic Resonance Imaging (MRI) could assist in early diagnosis and treatment planning. Existing automated methods of prostate cancer detection mostly rely on ground truth labels with limited accuracy, ignore disease pathology characteristics observed on resected tissue, and cannot selectively identify aggressive (Gleason Pattern≥4) and indolent (Gleason Pattern=3) cancers when they co-exist in mixed lesions. In this paper, we present a radiology-pathology fusion approach, CorrSigNIA, for the selective identification and localization of indolent and aggressive prostate cancer on MRI. CorrSigNIA uses registered MRI and whole-mount histopathology images from radical prostatectomy patients to derive accurate ground truth labels and learn correlated features between radiology and pathology images. These correlated features are then used in a convolutional neural network architecture to detect and localize normal tissue, indolent cancer, and aggressive cancer on prostate MRI. CorrSigNIA was trained and validated on a dataset of 98 men, including 74 men that underwent radical prostatectomy and 24 men with normal prostate MRI. CorrSigNIA was tested on three independent test sets including 55 men that underwent radical prostatectomy, 275 men that underwent targeted biopsies, and 15 men with normal prostate MRI. CorrSigNIA achieved an accuracy of 80% in distinguishing between men with and without cancer, a lesion-level ROC-AUC of 0.81±0.31 in detecting cancers in both radical prostatectomy and biopsy cohort patients, and lesion-levels ROC-AUCs of 0.82±0.31 and 0.86±0.26 in detecting clinically significant cancers in radical prostatectomy and biopsy cohort patients respectively. CorrSigNIA consistently outperformed other methods across different evaluation metrics and cohorts. In clinical settings, CorrSigNIA may be used in prostate cancer detection as well as in selective identification of indolent and aggressive components of prostate cancer, thereby improving prostate cancer care by helping guide targeted biopsies, reducing unnecessary biopsies, and selecting and planning treatment.

  View details for DOI 10.1016/j.media.2021.102288

  View details for PubMedID 34784540

• Weakly Supervised Registration of Prostate MRI and Histopathology Images Shao, W., Bhattacharya, I., Soerensen, S. C., Kunder, C. A., Wang, J. B., Fan, R. E., Ghanouni, P., Brooks, J. D., Sonn, G. A., Rusu, M., DeBruijne, M., Cattin, P. C., Cotin, S., Padoy, N., Speidel, S., Zheng, Y., Essert, C. SPRINGER INTERNATIONAL PUBLISHING AG. 2021: 98-107

  View details for DOI 10.1007/978-3-030-87202-1_10

  View details for Web of Science ID 000712021400010

• Focused ultrasound for functional neurosurgery. Journal of neuro-oncology Lev-Tov, L., Barbosa, D. A., Ghanouni, P., Halpern, C. H., Buch, V. P. 2021

  Abstract

  Brain lesioning is a fundamental technique in the functional neurosurgery world. It has been investigated for decades and presented promising results long before novel pharmacological agents were introduced to treat movement disorders, psychiatric disorders, pain, and epilepsy. Ablative procedures were replaced by effective drugs during the 1950s and by Deep Brain Stimulation (DBS) in the 1990s as a reversible neuromodulation technique. In the last decade, however, the popularity of brain lesioning has increased again with the introduction of magnetic resonance-guided focused ultrasound (MRgFUS).In this review, we will cover the current and emerging role of MRgFUS in functional neurosurgery.Literature review from PubMed and compilation.Investigated since 1930, MRgFUS is a technology enabling targeted energy delivery at the convergence of mechanical sound waves. Based on technological advancements in phased array ultrasound transducers, algorithms accounting for skull penetration by sound waves, and MR imaging for targeting and thermometry, MRgFUS is capable of brain lesioning with sub-millimeter precision and can be used in a variety of clinical indications.MRgFUS is a promising technology evolving as a dominant tool in different functional neurosurgery procedures in movement disorders, psychiatric disorders, epilepsy, among others.

  View details for DOI 10.1007/s11060-021-03818-3

  View details for PubMedID 34383232

• Clinically significant prostate cancer detection on MRI with self-supervised learning using image context restoration Bolous, A., Seetharaman, A., Bhattacharya, I., Fan, R. E., Soerensen, S., Chen, L., Ghanouni, P., Sonn, G. A., Rusu, M., Mazurowski, M. A., Drukker, K. SPIE-INT SOC OPTICAL ENGINEERING. 2021

  View details for DOI 10.1117/12.2581557

  View details for Web of Science ID 000672800100052

• Design and evaluation of an open-source, conformable skin-cooling system for body magnetic resonance guided focused ultrasound treatments. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group Merrill, R., Odeen, H., Dillon, C., Bitton, R., Ghanouni, P., Payne, A. 2021; 38 (1): 679–90

  Abstract

  PURPOSE: Magnetic resonance guided focused ultrasound (MRgFUS) treatment of tumors uses inter-sonication delays to allow heat to dissipate from the skin and other near-field tissues. Despite inter-sonication delays, treatment of tumors close to the skin risks skin burns. This work has designed and evaluated an open-source, conformable, skin-cooling system for body MRgFUS treatments to reduce skin burns and enable ablation closer to the skin.METHODS: A MR-compatible skin cooling system is described that features a conformable skin-cooling pad assembly with feedback control allowing continuous flow and pressure maintenance during the procedure. System performance was evaluated with hydrophone, phantom and invivo porcine studies. Sonications were performed 10 and 5mm from the skin surface under both control and forced convective skin-cooling conditions. 3D MR temperature imaging was acquired in real time and the accumulated thermal dose volume was measured. Gross analysis of the skin post-sonication was further performed. Device conformability was demonstrated at several body locations.RESULTS: Hydrophone studies demonstrated no beam aberration, but a 5-12% reduction of the peak pressure due to the presence of the skin-cooling pad assembly in the acoustic near field. Phantom evaluation demonstrated there is no MR temperature imaging precision reduction or any other artifacts present due to the coolant flow during MRgFUS sonication. The porcine studies demonstrated skin burns were reduced in size or eliminated when compared to the control condition.CONCLUSION: An open-source design of an MRgFUS active skin cooling system demonstrates device conformability with a reduction of skin burns while ablating superficial tissues.

  View details for DOI 10.1080/02656736.2021.1914872

  View details for PubMedID 33899653

• Evaluation of an MRI receive head coil for use in transcranial MR guided focused ultrasound for functional neurosurgery. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group Bitton, R. R., Sheingaouz, E., Assif, B., Kelm, N., Dayan, M., Butts Pauly, K., Ghanouni, P. 2021; 38 (1): 22–29

  Abstract

  BACKGROUND: Trans-cranial MR guided focused ultrasound (tcMRgFUS) ablation targets are <5mm from critical neurological structures, creating a need for improved MR imaging and thermometry. The purpose of this study was to evaluate the performance of a dual-channel radiofrequency receive-only head coil designed specifically for integrated use in tcMRgFUS.METHODS: Imaging used a 3T MRI and the ExAblate Neuro System (INSIGHTEC Inc., Israel). Sensitivity maps determined receive-only coil uniformity. The head coil was compared to the volume body coil at the level of the thalamus using 1) T2-weighted imaging and 2) multi-echo MR thermometry of volunteers in the transducer helmet. Thermal sonications (40W, 24s) were acquired in a heating phantom. Thermal maps in were constructed to evaluate temperature uncertainty, focal heating, and temperature evolution.RESULTS: The normalized signal intensity showed up to a 35% variation. On T2wFSE images the SNR with the head coil is improved by 4x in the axial plane, and 3x in sagittal and coronal planes. The head coil provided better visualization of the thalamus and globus pallidus (axial), and of the anterior/posterior commissure, and brain stem/cerebellum (sagittal) compared to the body coil. MR thermometry showed a 4x gain in SNR in the thalamus. Thermometry showed a preserved focal spot with 20°C temperature rise. The average temperature uncertainty (mean±std) was reduced from sigma T = 0.96°C±0.55°C for the body coil to sigma T = 0.41°C±0.24°C for the head coil.CONCLUSIONS: Greater SNR from the dual-channel head coil provides access to better treatment day visualization for treatment planning and higher precision intra-operative thermometry.

  View details for DOI 10.1080/02656736.2020.1867242

  View details for PubMedID 33459092

• Registration of pre-surgical MRI and histopathology images from radical prostatectomy via RAPSODI. Medical physics Rusu, M., Shao, W., Kunder, C. A., Wang, J. B., Soerensen, S. J., Teslovich, N. C., Sood, R. R., Chen, L. C., Fan, R. E., Ghanouni, P., Brooks, J. D., Sonn, G. A. 2020

  Abstract

  PURPOSE: Magnetic resonance imaging (MRI) has great potential to improve prostate cancer diagnosis, however, subtle differences between cancer and confounding conditions render prostate MRI interpretation challenging. The tissue collected from patients who undergo radical prostatectomy provides a unique opportunity to correlate histopathology images of the prostate with pre-operative MRI to accurately map the extent of cancer from histopathology images onto MRI. We seek to develop an open-source, easy-to-use platform to align pre-surgical MRI and histopathology images of resected prostates in patients who underwent radical prostatectomy to create accurate cancer labels on MRI.METHODS: Here, we introduce RAdiology Pathology Spatial Open-Source multi-Dimensional Integration (RAPSODI), the first open-source framework for the registration of radiology and pathology images. RAPSODI relies on three steps. First, it creates a 3D reconstruction of the histopathology specimen as a digital representation of the tissue before gross sectioning. Second, RAPSODI registers corresponding histopathology and MRI slices. Third, the optimized transforms are applied to the cancer regions outlined on the histopathology images to project those labels onto the pre-operative MRI.RESULTS: We tested RAPSODI in a phantom study where we simulated various conditions, e.g., tissue shrinkage during fixation. Our experiments showed that RAPSODI can reliably correct multiple artifacts. We also evaluated RAPSODI in 157 patients from three institutions that underwent radical prostatectomy and have very different pathology processing and scanning. RAPSODI was evaluated in 907 corresponding histpathology-MRI slices and achieved a Dice coefficient of 0.97±0.01 for the prostate, a Hausdorff distance of 1.99±0.70 mm for the prostate boundary, a urethra deviation of 3.09±1.45 mm, and a landmark deviation of 2.80±0.59 mm between registered histopathology images and MRI.CONCLUSION: Our robust framework successfully mapped the extent of cancer from histopathology slices onto MRI providing labels from training machine learning methods to detect cancer on MRI.

  View details for DOI 10.1002/mp.14337

  View details for PubMedID 32564359

• Impact of skull density ratio on efficacy and safety of magnetic resonance-guided focused ultrasound treatment of essential tremor JOURNAL OF NEUROSURGERY D'Souza, M., Chen, K. S., Rosenberg, J., Elias, W., Eisenberg, H. M., Gwinn, R., Taira, T., Chang, J., Lipsman, N., Krishna, V., Igase, K., Yamada, K., Kishima, H., Cosgrove, R., Rumia, J., Kaplitt, M. G., Hirabayashi, H., Nandi, D., Henderson, J. M., Pauly, K., Dayan, M., Halpern, C. H., Ghanouni, P. 2020; 132 (5): 1392–97

  View details for DOI 10.3171/2019.2.JNS183517

  View details for Web of Science ID 000530830500009

• Does Fibroid Size and Bulk Affect Uterine Fibroid Symptom (UFS) Scores in Asian Compared to Caucasian Women? Dhanani, Z., Ramirez, N., Ghanouni, P., Chen, B. LIPPINCOTT WILLIAMS & WILKINS. 2020: 21S

  View details for Web of Science ID 000554572900069

• Does Fibroid Size and Bulk Affect Uterine Fibroid Symptom (UFS) Scores in Asian Compared to Caucasian Women? Ramirez, N., Dhanani, Z., Ghanouni, P., Chen, B. SPRINGER HEIDELBERG. 2020: 134A

  View details for Web of Science ID 000525432600201

• MRI-Guided Focused Ultrasound of Osseous Metastases: Treatment Parameters Associated With Successful Pain Reduction. Investigative radiology Bitton, R. R., Rosenberg, J. n., LeBlang, S. n., Napoli, A. n., Meyer, J. n., Butts Pauly, K. n., Hurwitz, M. n., Ghanouni, P. n. 2020

  Abstract

  A phase 3 multicenter trial demonstrated that magnetic resonance imaging (MRI)-guided focused ultrasound (US) is a safe, noninvasive treatment that alleviated pain from bone metastases. However, outcomes varied among institutions (from 0%-100% treatment success).The aim of this study was to identify patient selection, technical treatment, and imaging parameters that predict successful pain relief of osseous metastases after MRI-guided focused US.This was a secondary analysis of a phase 3 clinical study that included participants who received MRI-guided focused US treatment for painful osseous metastases. Noncontrast CT was obtained before treatment. T2-weighted and T1-weighted postcontrast MRIs at 1.5 T or 3 T were obtained before, at the time of, and at 3 months after treatment. Numerical Rating Scale pain scores and morphine equivalent daily dose data were obtained over a 3-month follow-up period. At the 3-month endpoint, participants were categorized as pain relief responders or nonresponders based on Numerical Rating Scale and morphine equivalent daily dose data. Demographics, technical parameters, and imaging features associated with pain relief were determined using stepwise univariable and multivariable models. Responder rates between the subgroup of participants with all predictive parameters and that with none of the parameters were compared using Fisher exact test.The analysis included 99 participants (mean age, 59 ± 14 years; 56 women). The 3 variables that predicted successful pain relief were energy density on the bone surface (EDBS) (P = 0.001), the presence of postprocedural periosteal devascularization (black band, BB+) (P = 0.005), and female sex (P = 0.02). The subgroup of participants with BB+ and EDBS greater than 5 J/mm had a larger decrease in mean pain score (5.2; 95% confidence interval, 4.6-5.8) compared with those without (BB-, EDBS ≤ 5 J/mm) (1.1; 95% confidence interval, 0.8-3.0; P < 0.001). Participants with all 3 predictive variables had a pain relief responder rate of 93% compared with 0% in participants having none of the predictive variables (P < 0.001).High EDBS during treatment, postprocedural periosteal devascularization around the tumor site (BB+), and female sex increased the likelihood of pain relief after MRI-guided focused US of osseous metastasis.

  View details for DOI 10.1097/RLI.0000000000000721

  View details for PubMedID 32858582

• Acoustic Attenuation: Multifrequency Measurement and Relationship To CT and MR Imaging. IEEE transactions on ultrasonics, ferroelectrics, and frequency control Webb, T. D., Leung, S. A., Ghanouni, P. n., Dahl, J. J., Pelc, N. J., Pauly, K. B. 2020; PP

  Abstract

  Transcranial magnetic resonance guided focused ultrasound (tcMRgFUS) is gaining significant acceptance as a non-invasive treatment for motion disorders and shows promise for novel applications such as blood brain barrier opening for tumor treatment. A typical procedure relies on CT derived acoustic property maps to simulate the transfer of ultrasound through the skull. Accurate estimates of the acoustic attenuation in the skull are essential to accurate simulations, but there is no consensus about how attenuation should be estimated from CT images and there is interest in exploring MR as a predictor of attenuation in the skull. In this study we measure the acoustic attenuation at 0.5, 1, and 2.25 MHz in 89 samples taken from two ex-vivo human skulls. CT scans acquired with a variety of x-ray energies, reconstruction kernels, and reconstruction algorithms and MR images acquired with ultra short and zero echo time sequences are used to estimate the average Hounsfield unit value, MR magnitude, and T2* value in each sample. The measurements are used to develop a model of attenuation as a function of frequency and each individual imaging parameter.

  View details for DOI 10.1109/TUFFC.2020.3039743

  View details for PubMedID 33226938

• Improved Vim targeting for focused ultrasound ablation treatment of essential tremor: A probabilistic and patient-specific approach. Human brain mapping Su, J. H., Choi, E. Y., Tourdias, T. n., Saranathan, M. n., Halpern, C. H., Henderson, J. M., Pauly, K. B., Ghanouni, P. n., Rutt, B. K. 2020

  Abstract

  Magnetic resonance-guided focused ultrasound (MRgFUS) ablation of the ventral intermediate (Vim) thalamic nucleus is an incisionless treatment for essential tremor (ET). The standard initial targeting method uses an approximate, atlas-based stereotactic approach. We developed a new patient-specific targeting method to identify an individual's Vim and the optimal MRgFUS target region therein for suppression of tremor. In this retrospective study of 14 ET patients treated with MRgFUS, we investigated the ability of WMnMPRAGE, a highly sensitive and robust sequence for imaging gray matter-white matter contrast, to identify the Vim, FUS ablation, and a clinically efficacious region within the Vim in individual patients. We found that WMnMPRAGE can directly visualize the Vim in ET patients, segmenting this nucleus using manual or automated segmentation capabilities developed by our group. WMnMPRAGE also delineated the ablation's core and penumbra, and showed that all patients' ablation cores lay primarily within their Vim segmentations. We found no significant correlations between standard ablation features (e.g., ablation volume, Vim-ablation overlap) and 1-month post-treatment clinical outcome. We then defined a group-based probabilistic target, which was nonlinearly warped to individual brains; this target was located within the Vim for all patients. The overlaps between this target and patient ablation cores correlated significantly with 1-month clinical outcome (r = -.57, p = .03), in contrast to the standard target (r = -.23, p = .44). We conclude that WMnMPRAGE is a highly sensitive sequence for segmenting Vim and ablation boundaries in individual patients, allowing us to find a novel tremor-associated center within Vim and potentially improving MRgFUS treatment for ET.

  View details for DOI 10.1002/hbm.25157

  View details for PubMedID 32762005

• Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation. Frontiers in human neuroscience Saluja, S. n., Barbosa, D. A., Parker, J. J., Huang, Y. n., Jensen, M. R., Ngo, V. n., Santini, V. E., Pauly, K. B., Ghanouni, P. n., McNab, J. A., Halpern, C. H. 2020; 14: 191

  Abstract

  Essential tremor (ET) is the most prevalent movement disorder in adults, and can often be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound (MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for treating ET, optimal targeting during MRgFUS is essential for efficacy and durability. Various studies have reported cases of tremor recurrence following MRgFUS and long-term outcome data is limited to 3-4 years. We present a tractography-based investigation on a case of DBS rescue for medically refractory ET that was treated with MRgFUS that was interrupted due to the development of dysarthria during the procedure. After initial improvement, her hand tremor started to recur within 6 months after treatment, and bilateral DBS was performed targeting the VIM 24 months after MRgFUS. DBS induced long-term tremor control with monopolar stimulation. Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT) and corticothalmic (CTT) tracts being modulated by the procedures to understand the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines, it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for further investigation of targeting the CTT when using neuromodulatory procedures to treat refractory ET for more permanent tremor relief.

  View details for DOI 10.3389/fnhum.2020.00191

  View details for PubMedID 32676015

  View details for PubMedCentralID PMC7333679

• ProsRegNet: A deep learning framework for registration of MRI and histopathology images of the prostate. Medical image analysis Shao, W. n., Banh, L. n., Kunder, C. A., Fan, R. E., Soerensen, S. J., Wang, J. B., Teslovich, N. C., Madhuripan, N. n., Jawahar, A. n., Ghanouni, P. n., Brooks, J. D., Sonn, G. A., Rusu, M. n. 2020; 68: 101919

  Abstract

  Magnetic resonance imaging (MRI) is an increasingly important tool for the diagnosis and treatment of prostate cancer. However, interpretation of MRI suffers from high inter-observer variability across radiologists, thereby contributing to missed clinically significant cancers, overdiagnosed low-risk cancers, and frequent false positives. Interpretation of MRI could be greatly improved by providing radiologists with an answer key that clearly shows cancer locations on MRI. Registration of histopathology images from patients who had radical prostatectomy to pre-operative MRI allows such mapping of ground truth cancer labels onto MRI. However, traditional MRI-histopathology registration approaches are computationally expensive and require careful choices of the cost function and registration hyperparameters. This paper presents ProsRegNet, a deep learning-based pipeline to accelerate and simplify MRI-histopathology image registration in prostate cancer. Our pipeline consists of image preprocessing, estimation of affine and deformable transformations by deep neural networks, and mapping cancer labels from histopathology images onto MRI using estimated transformations. We trained our neural network using MR and histopathology images of 99 patients from our internal cohort (Cohort 1) and evaluated its performance using 53 patients from three different cohorts (an additional 12 from Cohort 1 and 41 from two public cohorts). Results show that our deep learning pipeline has achieved more accurate registration results and is at least 20 times faster than a state-of-the-art registration algorithm. This important advance will provide radiologists with highly accurate prostate MRI answer keys, thereby facilitating improvements in the detection of prostate cancer on MRI. Our code is freely available at https://github.com/pimed//ProsRegNet.

  View details for DOI 10.1016/j.media.2020.101919

  View details for PubMedID 33385701

• Bilateral Deep Brain Stimulation is the Procedure to Beat for Advanced Parkinson Disease: A Meta-Analytic, Cost-Effective Threshold Analysis for Focused Ultrasound. Neurosurgery Mahajan, U. V., Ravikumar, V. K., Kumar, K. K., Ku, S. n., Ojukwu, D. I., Kilbane, C. n., Ghanouni, P. n., Rosenow, J. M., Stein, S. C., Halpern, C. H. 2020

  Abstract

  Parkinson disease (PD) impairs daily functioning for an increasing number of patients and has a growing national economic burden. Deep brain stimulation (DBS) may be the most broadly accepted procedural intervention for PD, but cost-effectiveness has not been established. Moreover, magnetic resonance image-guided focused ultrasound (FUS) is an emerging incisionless, ablative treatment that could potentially be safer and even more cost-effective.To (1) quantify the utility (functional disability metric) imparted by DBS and radiofrequency ablation (RF), (2) compare cost-effectiveness of DBS and RF, and (3) establish a preliminary success threshold at which FUS would be cost-effective compared to these procedures.We performed a meta-analysis of articles (1998-2018) of DBS and RF targeting the globus pallidus or subthalamic nucleus in PD patients and calculated utility using pooled Unified Parkinson Disease Rating Scale motor (UPDRS-3) scores and adverse events incidences. We calculated Medicare reimbursements for each treatment as a proxy for societal cost.Over a 22-mo mean follow-up period, bilateral DBS imparted the most utility (0.423 quality-adjusted life-years added) compared to (in order of best to worst) bilateral RF, unilateral DBS, and unilateral RF, and was the most cost-effective (expected cost: $32 095 ± $594) over a 22-mo mean follow-up. Based on this benchmark, FUS would need to impart UPDRS-3 reductions of ∼16% and ∼33% to be the most cost-effective treatment over 2- and 5-yr periods, respectively.Bilateral DBS imparts the most utility and cost-effectiveness for PD. If our established success threshold is met, FUS ablation could dominate bilateral DBS's cost-effectiveness from a societal cost perspective.

  View details for DOI 10.1093/neuros/nyaa485

  View details for PubMedID 33295629

• Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor. Neurology Halpern, C. H., Santini, V., Lipsman, N., Lozano, A. M., Schwartz, M. L., Shah, B. B., Elias, W. J., Cosgrove, G. R., Hayes, M. T., McDannold, N., Aldrich, C., Eisenberg, H. M., Gandhi, D., Taira, T., Gwinn, R., Ro, S., Witt, J., Jung, N. Y., Chang, J. W., Rosenberg, J., Ghanouni, P. 2019

  Abstract

  OBJECTIVE: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial.METHODS: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported.RESULTS: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred.CONCLUSIONS: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant.CLINICALTRIALSGOV IDENTIFIER: NCT01827904.CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

  View details for DOI 10.1212/WNL.0000000000008561

  View details for PubMedID 31748250

• Predictors of Outcomes After Focused Ultrasound Thalamotomy. Neurosurgery Krishna, V., Sammartino, F., Cosgrove, R., Ghanouni, P., Schwartz, M., Gwinn, R., Eisenberg, H., Fishman, P., Chang, J. W., Taira, T., Kaplitt, M., Rezai, A., Rumia, J., Gedroyc, W., Igase, K., Kishima, H., Yamada, K., Ohnishi, H., Halpern, C. 2019

  Abstract

  BACKGROUND: Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET).OBJECTIVE: To determine the predictors of outcomes after FUS-T.METHODS: Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables.RESULTS: A total of 179 patients completed the 12-mo evaluation. The significant predictors of tremor outcomes were patient age, disease duration, peak temperature, and number of sonications. A greater improvement in hand tremor scores was observed in the postpivotal group at all time points, including 12 mo (61.9%±24.9% vs 52.1%±24.9%, P=.009). In the postpivotal group, higher energy was used, resulting in higher peak temperatures (56.7±2.5 vs 55.6±2.8°C, P=.004). After adjusting for age, years of disease, number of sonications, and maximum temperature, the treatment group was a significant predictor of outcomes (F=7.9 [1,165], P=.005).CONCLUSION: We observed an improvement in outcomes in the postpivotal group compared to the pivotal group potentially reflecting a learning curve with FUS-T.

  View details for DOI 10.1093/neuros/nyz417

  View details for PubMedID 31690945

• Prolonged heating in nontargeted tissue during MR-guided focused ultrasound of bone tumors JOURNAL OF MAGNETIC RESONANCE IMAGING Bitton, R. R., Webb, T. D., Pauly, K., Ghanouni, P. 2019; 50 (5): 1526–33

  View details for DOI 10.1002/jmri.26726

  View details for Web of Science ID 000490258000017

• Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists EUROPEAN UROLOGY FOCUS Sonn, G. A., Fan, R. E., Ghanouni, P., Wang, N. N., Brooks, J. D., Loening, A. M., Daniel, B. L., To'o, K. J., Thong, A. E., Leppert, J. T. 2019; 5 (4): 592–99

  View details for DOI 10.1016/j.euf.2017.11.010

  View details for Web of Science ID 000486156800014

• Evaluation of the routine use of pelvic MRI in women presenting with symptomatic uterine fibroids: When is pelvic MRI useful? JOURNAL OF MAGNETIC RESONANCE IMAGING Kim-Nhien Vu, Fast, A. M., Shaffer, R. K., Rosenberg, J., Dababou, S., Marrocchio, C., Vasanawala, S. S., Lum, D. A., Chen, B., Hovsepian, D. M., Ghanouni, P. 2019; 49 (7): E271–E281

  View details for DOI 10.1002/jmri.26620

  View details for Web of Science ID 000474612300028

• Magnetic-resonance-guided focused ultrasound treatment of non-spinal osteoid osteoma in children: multicentre experience. Pediatric radiology Arrigoni, F., Napoli, A., Bazzocchi, A., Zugaro, L., Scipione, R., Bruno, F., Palumbo, P., Anzidei, M., Mercatelli, D., Gravina, G. L., Zoccali, C., Ghanouni, P., Barile, A., Catalano, C., Masciocchi, C. 2019

  Abstract

  BACKGROUND: Osteoid osteoma is a benign and painful musculoskeletal tumour that usually affects children. Current standard treatment is CT-guided radiofrequency ablation, a minimally invasive percutaneous procedure, with clinical success rates ranging between 85% and 98%. Though minimally invasive, however, this type of procedure is not free from complications.OBJECTIVE: To investigate the efficacy and safety of magnetic resonance (MR)-guided focused ultrasound (MRgFUS), a needleless procedure of thermal ablation employed in the treatment of non-spinal osteoid osteoma in paediatric patients.MATERIALS AND METHODS: We report the results of 33 procedures of ablation of osteoid osteoma performed with MRgFUS in three university hospitals. To ablate a lesion on the bone surface, MRgFUS employs the ultrasound energy transduced along the soft tissue. The follow-up studies lasted 24months and were performed combining clinical and imaging data.RESULTS: Mean age of the children was 13.8years. The clinical outcome showed a primary success of 97%. One case alone was submitted to repeat treatment because the first one failed (secondary success). No major or minor complications were recorded. During the investigation time, no relapse of symptomatology or delayed complications were observed.CONCLUSION: Although our study is preliminary and limited by a low number of patients, our data show that MRgFUS is effective. This suggests that it might be useful as the first-line treatment in paediatric patients with osteoid osteoma.

  View details for DOI 10.1007/s00247-019-04426-0

  View details for PubMedID 31129699

• How Often is the Dynamic Contrast Enhanced Score Needed in PI-RADS Version 2? Current problems in diagnostic radiology Roh, A. T., Fan, R. E., Sonn, G. A., Vasanawala, S. S., Ghanouni, P., Loening, A. M. 2019

  Abstract

  BACKGROUND: Prostate imaging reporting and data system version 2 (PI-RADS v2) relegates dynamic contrast enhanced (DCE) imaging to a minor role. We sought to determine how often DCE is used in PI-RADS v2 scoring.MATERIALS AND METHODS: We retrospectively reviewed data from 388 patients who underwent prostate magnetic resonance imaging and subsequent biopsy from January 2016 through December 2017. In accordance with PI-RADS v2, DCE was deemed necessary if a peripheral-zone lesion had a diffusion-weighted imaging score of 3, or if a transition-zone lesion had a T2 score of 3 and diffusion-weighted imaging experienced technical failure. Receiver operating characteristic curve analysis assessed the accuracy of prostate-specific antigen density (PSAD) at different threshold values for differentiating lesions that would be equivocal with noncontrast technique. Accuracy of PSAD was compared to DCE using McNemar's test.RESULTS: Sixty-nine lesions in 62 patients (16%) required DCE for PI-RADS scoring. Biopsy of 10 (14%) of these lesions showed clinically significant cancer (Gleason score ≥7). In the subgroup of patients with equivocal lesions, those with clinically significant cancer had significantly higher PSADs than those with clinically insignificant lesions (means of 0.18 and 0.13 ng/mL/mL, respectively; P= 0.038). In this subgroup, there was no statistical difference in accuracy in determining clinically significant cancer between a PSAD threshold value of 0.13 and DCE (P= 0.25).CONCLUSIONS: Only 16% of our patients needed DCE to generate the PI-RADS version 2 score, raising the possibility of limiting the initial screening prostate MRI to a noncontrast exam. PSAD may also be used to further decrease the need for or to replace DCE altogether.

  View details for DOI 10.1067/j.cpradiol.2019.05.008

  View details for PubMedID 31126664

• Are fibroid and bony pelvis characteristics associated with urinary and pelvic symptom severity? Shaffer, R. K., Dobberfuhl, A. D., Vu, K., Fast, A. M., Dababou, S., Marrocchio, C., Lum, D. A., Hovsepian, D. M., Ghanouni, P., Chen, B. MOSBY-ELSEVIER. 2019

  View details for DOI 10.1016/j.ajog.2019.01.230

  View details for Web of Science ID 000467043800011

• Prolonged Heating in Nontargeted Tissue During MR-guided Focused Ultrasound of Bone Tumors. Journal of magnetic resonance imaging : JMRI Bitton, R. R., Webb, T. D., Pauly, K. B., Ghanouni, P. 2019

  Abstract

  BACKGROUND: Thermal dosimetry during MR-guided focused ultrasound (MRgFUS) of bone tumors underpredicts ablation zone. Intraprocedural understanding of heat accumulation near bone is needed to prevent undesired treatment of nontargeted tissue.HYPOTHESIS: Temperature decay rates predict prolonged, spatially varying heating during MRgFUS bone treatments.STUDY TYPE: Prospective case series.PATIENTS: Nine patients with localized painful bone tumors (five bone metastasis, four osteoid osteomas), were compared with five patients with uterine fibroid tumors treated using MRgFUS.FIELD STRENGTH/SEQUENCE: Proton resonance frequency shift thermometry using 2D-GRE with echo-planar imaging at 3T.ASSESSMENT: Tissue response was derived by fitting data from extended thermometry acquisitions to a decay model. Decay rates and time to peak temperature (TTP) were analyzed in segmented zones between the bone target and skin. Decay rates were used to calculate intersonication cooling times required to return to body temperature; these were compared against conventional system-mandated cooling times.STATISTICAL TESTS: Kolmogorov-Smirnov tests for normality, and Student's t-test was used to compare decay rates. Spatial TTP delay and predicted cooling times used Wilcoxon signed rank tests. P<0.05 was significant.RESULTS: Tissue decay rates in bone tumor patients were 3.5 times slower than those in patients with fibroids (taubone =0.037±0.012 vs. taufibroid =0.131±0.010, P<0.05). Spatial analysis showed slow decay rates effecting baseline temperature as far as 12mm away from the bone surface, tau4 =0.015±0.026 (median±interquartile range [IQR]). Tissue within 9mm of bone experienced delayed TTP (P<0.01). In the majority of bone tumor treatments, system-predicted intersonication cooling times were insufficient for nearby tissue to return to body temperature (P=0.03 in zone 4).DATA CONCLUSION: MRgFUS near bone is susceptible to long tissue decay rates, and unwanted cumulative heating up to 1.2cm from the surface of the bone. Knowledge of decay rates may be used to alter treatment planning and intraprocedural thermal monitoring protocols to account for prolonged heating by bone.LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019.

  View details for PubMedID 30950554

• MR-Guided Focused Ultrasound Versus Radiofrequency Capsulotomy for Treatment-Refractory Obsessive-Compulsive Disorder: A Cost-Effectiveness Threshold Analysis FRONTIERS IN NEUROSCIENCE Kumar, K. K., Bhati, M. T., Ravikumar, V. K., Ghanouni, P., Stein, S. C., Halpern, C. H. 2019; 13

  View details for DOI 10.3389/fnins.2019.00066

  View details for Web of Science ID 000458081000001

• MR-Guided Focused Ultrasound Versus Radiofrequency Capsulotomy for Treatment-Refractory Obsessive-Compulsive Disorder: A Cost-Effectiveness Threshold Analysis. Frontiers in neuroscience Kumar, K. K., Bhati, M. T., Ravikumar, V. K., Ghanouni, P., Stein, S. C., Halpern, C. H. 2019; 13: 66

  Abstract

  Meta-analytic techniques support neuroablation as a promising therapy for treatment-refractory obsessive-compulsive disorder (OCD). This technique appears to offer a more favorable complication rate and higher utility than deep brain stimulation. Moreover, these pooled findings suggest that bilateral radiofrequency (RF) capsulotomy has marginally greater efficacy than stereotactic radiosurgery or cingulotomy. MR-guided focused ultrasound (MRgFUS) capsulotomy is an emerging approach with a potentially more favorable profile than RF ablation and radiosurgery, with preliminary data suggesting safety and efficacy. As a clinical trial is being developed, our study examined the cost and clinical parameters necessary for MRgFUS capsulotomy to be a more cost-effective alternative to RF capsulotomy. A decision analytical model of MRgFUS with RF capsulotomy for OCD was performed using outcome parameters of percent surgical improvement in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score, complications, and side effects. The analysis compared measured societal costs, derived from Medicare reimbursement rates, and effectiveness, based on published RF data. Effectiveness was defined as the degree to which MRgFUS lowered Y-BOCS score. Given that MRgFUS is a new therapy for OCD with scant published data, theoretical risks of MRgFUS capsulotomy were derived from published essential tremor outcomes. Sensitivity analysis yielded cost, effectiveness, and complication rates as critical MRgFUS parameters defining the cost-effectiveness threshold. Literature search identified eight publications (162 subjects). The average reduction of preoperative Y-BOCS score was 56.6% after RF capsulotomy with a 22.6% improvement in utility, a measure of quality of life. Complications occurred in 16.2% of RF cases. In 1.42% of cases, complications were considered acute-perioperative and incurred additional hospitalization cost. The adverse events, including neurological and neurobehavioral changes, in the other 14.8% of cases did not incur further costs, although they impacted utility. Rollback analysis of RF capsulotomy yielded an expected effectiveness of 0.212 quality-adjusted life years/year at an average cost of $24,099. Compared to RF capsulotomy, MRgFUS was more cost-effective under a range of possible cost and complication rates. While further study will be required, MRgFUS lacks many of the inherent risks associated with more invasive modalities and has potential as a safe and cost-effective treatment for OCD.

  View details for DOI 10.3389/fnins.2019.00066

  View details for PubMedID 30792625

  View details for PubMedCentralID PMC6374333

• Are Fibroid and Bony Pelvis Characteristics Associated with Urinary and Pelvic Symptom Severity? American journal of obstetrics and gynecology Shaffer, R. K., Dobberfuhl, A. D., Vu, K., Fast, A. M., Dababou, S., Marrocchio, C., Lum, D. A., Hovsepian, D. M., Ghanouni, P., Chen, B. 2019

  Abstract

  BACKGROUND: Urinary and pelvic floor symptoms are often attributed to size and location of uterine fibroids. However, direct supporting evidence linking increased size to worsening symptoms is scant and limited to ultrasound evaluation of fibroids. Because management of fibroids is targeted towards symptomatic relief, identification of fibroid and pelvic characteristics associated with worse symptoms is vital to optimizing therapies and preventing needless interventions.OBJECTIVES: We examined the correlation between urinary, pelvic floor and fibroid symptoms, and fibroid size and location using precise uterine fibroid and bony pelvis characteristics obtained from magnetic resonance imaging (MRI).STUDY DESIGN: A retrospective review (2013-2017) of a multidisciplinary fibroid clinic identified 338 women examined via pelvic MRI, Pelvic Floor Distress Inventory questionnaire (PFDI; score 0-300), and a Uterine Fibroid Symptoms questionnaire (UFS; score 1-100). Multiple linear regression analysis was used to assess the influence of clinical factors and MRI findings on scaled PFDI and UFS scores. Data were analyzed in STATA.RESULTS: Our cohort of 338 women had a median PFDI of 72.7 (IQR 41-112.3). Increased PFDI score was associated with clinical factors of higher BMI (p<0.001), non-commercial insurance (p<0.001), increased parity (p=0.001) and history of incontinence surgery (p=0.003). Uterine volume, dominant fibroid volume, dimension and location, and fibroid location relative to the bony pelvis structure did not reach significance when compared with pelvic floor symptom severity. The mean UFS score was 52.0 (SD 23.5). Increased UFS score was associated with dominant submucosal fibroid (p=0.011) as well as BMI (p<0.0016), and a clinical history of anemia (p<0.001) or any hormonal treatment for fibroids (p=0.009).CONCLUSION: Contrary to common belief, in this cohort of women presenting for fibroid care, size and position of fibroids or uterus were not associated with pelvic floor symptom severity. Whereas, bleeding symptom severity was associated with dominant submucosal fibroid and prior hormonal treatment. Careful attention to clinical factors such as BMI and medical history is recommended when evaluating pelvic floor symptoms in women with uterine fibroids.

  View details for PubMedID 30711512

• Evaluation of the routine use of pelvic MRI in women presenting with symptomatic uterine fibroids: When is pelvic MRI useful? Journal of magnetic resonance imaging : JMRI Vu, K., Fast, A. M., Shaffer, R. K., Rosenberg, J., Dababou, S., Marrocchio, C., Vasanawala, S. S., Lum, D. A., Chen, B., Hovsepian, D. M., Ghanouni, P. 2019

  Abstract

  BACKGROUND: Pelvic ultrasound (US) diagnosis of uterine fibroids may overlook coexisting gynecological conditions that contribute to women's symptoms.PURPOSE: To determine the added value of pelvic MRI for women diagnosed with symptomatic fibroids by US, and to identify clinical factors associated with additional MRI findings.STUDY TYPE: Retrospective observational study.POPULATION: In all, 367 consecutive women with fibroids diagnosed by US and referred to our multidisciplinary fibroid center between 2013-2017.FIELD STRENGTH/SEQUENCE: All patients had both pelvic US and MRI prior to their consultations. MRIs were performed at 1.5 T or 3 T and included multiplanar T2 -weighted sequences, and precontrast and postcontrast T1 -weighted imaging.ASSESSMENT: Demographics, symptoms, uterine fibroid symptom severity scores, and health-related quality of life scores, as well as imaging findings were evaluated.STATISTICAL TESTS: Patients were separated into two subgroups according to whether MRI provided additional findings to the initial US. Univariate and multivariate regression analyses were performed.RESULTS: Pelvic MRI provided additional information in 162 patients (44%; 95% confidence interval [CI] 39-49%). The most common significant findings were adenomyosis (22%), endometriosis (17%), and partially endocavitary fibroids (15%). Women with pelvic pain, health-related quality of life scores less than 30 out of 100, or multiple fibroids visualized on US had greater odds of additional MRI findings (odds ratio [OR] 1.68, 2.26, 1.63; P = 0.02, 0.004, 0.03, respectively), while nulliparous women had reduced odds (OR 0.55, P = 0.01). Patients with additional MRI findings were treated less often with uterine fibroid embolization (14% vs. 36%, P < 0.001) or MR-guided focused US (1% vs. 5%, P = 0.04), and more often with medical management (17% vs. 8%, P = 0.01).DATA CONCLUSION: Pelvic MRI revealed additional findings in more than 40% of women presenting with symptoms initially ascribed to fibroids by US. Further evaluation using MRI is particularly useful for parous women with pelvic pain, poor quality of life scores, and/or multiple fibroids.LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019.

  View details for PubMedID 30614145

• Applying the PRECISION approach in biopsy naïve and previously negative prostate biopsy patients. Urologic oncology Wang, N. N., Teslovich, N. C., Fan, R. E., Ghanouni, P. n., Leppert, J. T., Brooks, J. D., Ahmadi, S. n., Sonn, G. A. 2019

  Abstract

  The PRECISION trial provides level 1 evidence supporting prebiopsy multiparametric magnetic resonance imaging (mpMRI) followed by targeted biopsy only when mpMRI is abnormal [1]. This approach reduced over-detection of low-grade cancer while increasing detection of clinically significant cancer (CSC). Still, important questions remain regarding the reproducibility of these findings outside of a clinical trial and quantifying missed CSC diagnoses using this approach. To address these issues, we retrospectively applied the PRECISION strategy in men who each underwent prebiopsy mpMRI followed by systematic and targeted biopsy.Clinical, imaging, and pathology data were prospectively collected from 358 biopsy naïve men and 202 men with previous negative biopsies. To apply the PRECISION approach, a retrospective analysis was done comparing the cancer yield from 2 diagnostic strategies: (1) mpMRI followed by targeted biopsy alone for men with Prostate Imaging Reporting and Data System ≥ 3 lesions and (2) systematic biopsy alone for all men. Primary outcomes were biopsies avoided and the proportion of CSC cancer (Grade Group 2-5) and non-CSC (Grade Group 1).In biopsy naïve patients, the mpMRI diagnostic strategy would have avoided 19% of biopsies while detecting 2.5% more CSC (P= 0.480) and 12% less non-CSC (P< 0.001). Thirteen percent (n= 9) of men with normal mpMRI had CSC on systematic biopsy. For previous negative biopsy patients, the mpMRI diagnostic strategy avoided 21% of biopsies, while detecting 1.5% more CSC (P= 0.737) and 13% less non-CSC (P< 0.001). Seven percent (n= 3) of men with normal mpMRI had CSC on systematic biopsy.Our results provide external validation of the PRECISION finding that mpMRI followed by targeted biopsy of suspicious lesions reduces biopsies and over-diagnosis of low-grade cancer. Unlike PRECISION, we did not find increased diagnosis of CSC. This was true in both biopsy naïve and previously negative biopsy cohorts. We have incorporated this information into shared decision making, which has led some men to choose to avoid biopsy. However, we continue to recommend targeted and systematic biopsy in men with abnormal MRI.

  View details for DOI 10.1016/j.urolonc.2019.05.002

  View details for PubMedID 31151788

• Framework for the co-registration of MRI and Histology Images in Prostate Cancer Patients with Radical Prostatectomy Rusu, M., Kunder, C., Fan, R., Ghanouni, P., West, R., Sonn, G., Brooks, J., Angelini, E. D., Landman, B. A. SPIE-INT SOC OPTICAL ENGINEERING. 2019

  View details for DOI 10.1117/12.2513099

  View details for Web of Science ID 000483012700057

• Impact of skull density ratio on efficacy and safety of magnetic resonance-guided focused ultrasound treatment of essential tremor. Journal of neurosurgery D'Souza, M. n., Chen, K. S., Rosenberg, J. n., Elias, W. J., Eisenberg, H. M., Gwinn, R. n., Taira, T. n., Chang, J. W., Lipsman, N. n., Krishna, V. n., Igase, K. n., Yamada, K. n., Kishima, H. n., Cosgrove, R. n., Rumià, J. n., Kaplitt, M. G., Hirabayashi, H. n., Nandi, D. n., Henderson, J. M., Butts Pauly, K. n., Dayan, M. n., Halpern, C. H., Ghanouni, P. n. 2019: 1–6

  Abstract

  OBJECTIVESkull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs.METHODSIn 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria.RESULTSOf 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups.CONCLUSIONSMRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

  View details for PubMedID 31026836

• A rapid beam simulation framework for transcranial focused ultrasound. Scientific reports Leung, S. A., Webb, T. D., Bitton, R. R., Ghanouni, P. n., Butts Pauly, K. n. 2019; 9 (1): 7965

  Abstract

  Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.

  View details for DOI 10.1038/s41598-019-43775-6

  View details for PubMedID 31138821

• Teaching Urologists "How to Read Multi-Parametric Prostate MRIs Using PIRADSv2": Results of an iBook Pilot Study. Urology Wang, N. N., Fan, R. E., Ghanouni, P. n., Sonn, G. A. 2019

  Abstract

  To create an online resource that teaches urologists how to interpret prostate multi-parametric MRIs (mpMRI). As prostate mpMRI becomes widely adopted for cancer diagnosis and targeted biopsy, it is increasingly important that urologists are comfortable and experienced in assessing the images. The purpose of this study was to create an online mpMRI ibook and measure its effect on instilling proficiency amongst urology residents.We created a case-based ibook aimed at teaching clinicians how to identify and score prostate lesions on mpMRI using the Prostate Imaging and Reporting Data System (PIRADS) v2. Residents completed a 43-question pre-test before gaining access to the ibook for one month. The test asks participants to identify and score visible lesions using interactive mpMRI images. After a formal review of the material, they completed a post-test. Participants also rated their diagnostic confidence on a scale of 1 to 10 before and after reviewing the ibook. The change in performance and confidence scores for each resident was compared using Wilcoxon Signed-Rank test.Eleven urology residents completed the pre-test, review session and post-test. The mean test score rose from 37% (median 40%) to 57% (median 58%) after reviewing the ibook. Improvement was significant (p=0.0039). Confidence scores also improved (p=0.001).We created an interactive ibook that teaches urologists how to evaluate prostate mpMRIs and demonstrated improved performance in interpretation amongst urology residents. This effective module can be incorporated into resident education on a national level and offered as a self-teaching resource for practicing urologists.

  View details for DOI 10.1016/j.urology.2019.04.040

  View details for PubMedID 31150691

• Performance of multiparametric MRI appears better when measured in patients who undergo radical prostatectomy. Research and reports in urology Wang, N. N., Fan, R. E., Leppert, J. T., Ghanouni, P., Kunder, C. A., Brooks, J. D., Chung, B. I., Sonn, G. A. 2018; 10: 233-235

  Abstract

  Utilization of pre-biopsy multiparametric MRI (mpMRI) is increasing. To optimize the usefulness of mpMRI, physicians should accurately quote patients a numerical risk of cancer based on their MRI. The Prostate Imaging Reporting and Data System (PIRADS) standardizes interpretation of mpMRI; however, reported rates of clinically significant prostate cancer (CSC) stratified by PIRADS score vary widely. While some publications use radical prostatectomy (RP) specimens as gold standard, others use biopsy. We hypothesized that much of the variation in CSC stems from differences in cancer prevalence in RP cohorts (100% prevalence) vs biopsy cohorts. To quantify the impact of this selection bias on cancer yield according to PIRADS score, we analyzed data from 614 men with 854 lesions who underwent targeted biopsy from 2014 to 2018. Of these, 125 men underwent RP. We compared the PIRADS detection rates of CSC (Gleason ≥7) on targeted biopsy between the biopsy-only and RP cohorts. For all PIRADS scores, CSC yield was much greater in patients who underwent RP. For example, CSC was found in 30% of PIRADS 3 lesions in men who underwent RP vs 7.6% in men who underwent biopsy. Our results show that mpMRI performance appears to be better in men who undergo RP compared with those who only receive biopsy. Physicians should understand the effect of this selection bias and its magnitude when discussing mpMRI results with patients considering biopsy, and take great caution in quoting CSC yields from publications using RP as gold standard.

  View details for DOI 10.2147/RRU.S178064

  View details for PubMedID 30538970

  View details for PubMedCentralID PMC6254536

• Measurements of the Relationship Between CT Hounsfield Units and Acoustic Velocity and How It Changes With Photon Energy and Reconstruction Method IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Webb, T. D., Leung, S. A., Rosenberg, J., Ghanouni, P., Dahl, J. J., Pelc, N. J., Pauly, K. 2018; 65 (7): 1111–24

  Abstract

  Transcranial magnetic resonance-guided focused ultrasound continues to gain traction as a noninvasive treatment option for a variety of pathologies. Focusing ultrasound through the skull can be accomplished by adding a phase correction to each element of a hemispherical transducer array. The phase corrections are determined with acoustic simulations that rely on speed of sound estimates derived from CT scans. While several studies have investigated the relationship between acoustic velocity and CT Hounsfield units (HUs), these studies have largely ignored the impact of X-ray energy, reconstruction method, and reconstruction kernel on the measured HU, and therefore the estimated velocity, and none have measured the relationship directly. In this paper, 91 ex vivo human skull fragments from two skulls are imaged by 80 CT scans with a variety of energies and reconstruction methods. The average HU from each fragment is found for each scan and correlated with the speed of sound measured using a through transmission technique in that fragment. As measured by the -squared value, the results show that CT is able to account for 23%-53% of the variation in velocity in the human skull. Both the X-ray energy and the reconstruction technique significantly alter the -squared value and the linear relationship between HU and speed of sound in bone. Accounting for these variations will lead to more accurate phase corrections and more efficient transmission of acoustic energy through the skull.

  View details for DOI 10.1109/TUFFC.2018.2827899

  View details for Web of Science ID 000436933000004

  View details for PubMedID 29993366

• Bowel endometriosis: diagnosis and management AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Nezhat, C., Li, A., Falik, R., Copeland, D., Razavi, G., Shakib, A., Mihailide, C., Bamford, H., DiFrancesco, L., Tazuke, S., Ghanouni, P., Rivas, H., Nezhat, A., Nezhat, C., Nezhat, F. 2018; 218 (6): 549–62

  Abstract

  The most common location of extragenital endometriosis is the bowel. Medical treatment may not provide long-term improvement in patients who are symptomatic, and consequently most of these patients may require surgical intervention. Over the past century, surgeons have continued to debate the optimal surgical approach to treating bowel endometriosis, weighing the risks against the benefits. In this expert review we will describe how the recommended surgical approach depends largely on the location of disease, in addition to size and depth of the lesion. For lesions approximately 5-8 cm from the anal verge, we encourage conservative surgical management over resection to decrease the risk of short- and long-term complications.

  View details for PubMedID 29032051

• Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer. Radiology Park, S. Y., Zacharias, C., Harrison, C., Fan, R. E., Kunder, C., Hatami, N., Giesel, F., Ghanouni, P., Daniel, B., Loening, A. M., Sonn, G. A., Iagaru, A. 2018: 172232

  Abstract

  Purpose To report the results of dual-time-point gallium 68 (68Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUVmax]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68Ga-PSMA-11 increased at later acquisition times, with higher mean SUVmax (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection.

  View details for PubMedID 29786490

• Neurological adverse event profile of magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor MOVEMENT DISORDERS Fishman, P. S., Elias, W., Ghanouni, P., Gwinn, R., Lipsman, N., Schwartz, M., Chang, J. W., Taira, T., Krishna, V., Rezai, A., Yamada, K., Igase, K., Cosgrove, R., Kishima, H., Kaplitt, M. G., Tierney, T. S., Eisenberg, H. M. 2018; 33 (5): 843–47

  Abstract

  Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery.To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events.Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies).Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events.The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society.

  View details for PubMedID 29701263

• Neurologic Adverse Event Profile of MRI-Guided Focused Ultrasound Thalamotomy for Essential Tremor Fishman, P. S., Elias, W., Ghanouni, P., Gwinn, R., Lipsman, N., Schwartz, M., Chang, J., Taira, T., Krishna, V., Yamada, K., Igase, K., Cosgrove, G., Kishima, H., Kaplitt, M., Tierney, T., Eisenberg, H. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000453090804336

• Tumor characterization by ultrasound-release of multiple protein and microRNA biomarkers, preclinical and clinical evidence PLOS ONE D'Souza, A. L., Chevillet, J. R., Ghanouni, P., Yan, X., Tewari, M., Gambhir, S. S. 2018; 13 (3): e0194268

  Abstract

  We have previously shown that low frequency ultrasound can release biomarkers from cells into the murine circulation enabling an amplification and localization of the released biomarker that could be used as a blood-based method to detect cancer earlier and monitor therapy. In this study, we further demonstrate that this technique could be used for characterization of tumors and/or identification of cellular masses of unknown origin due to the release of multiple protein and nucleic acid biomarkers in cells in culture, mice and patients. We sonicated colon (LS174T) and prostate (LNCaP) cancer cell lines in culture at a low frequency of 1 MHz and show that there were several-fold changes in multiple protein and microRNA (miRNA) abundance with treatment at various intensities and time. This release was dependent on the duration and intensity of the sonication for both cell lines. Significant increased release in biomarkers was also observed following tumor sonication in living mice bearing subcutaneous LS174T cell line xenografts (for proteins and nucleic acids) and in an experimental LS174T liver tumor model (for proteins only). Finally, we demonstrated this methodology of multiple biomarker release in patients undergoing ablation of uterine fibroids using MR guided high intensity focused ultrasound. Two protein biomarkers significantly increased in the plasma after the ultrasound treatment in 21 samples tested. This proof that ultrasound-amplification method works in soft tissue tumor models together with biomarker multiplexing, could allow for an effective non-invasive method for identification, characterization and localization of incidental lesions, cancer and other disease. Pre-treatment quantification of the biomarkers, allows for individualization of quantitative comparisons. This individualization of normal marker levels in this method allows for specificity of the biomarker-increase to each patient, tumor or organ being studied.

  View details for PubMedID 29547636

• High-Intensity Focused Ultrasound for Pain Management in Patients with Cancer RADIOGRAPHICS Dababou, S., Marrocchio, C., Scipione, R., Erasmus, H., Ghanouni, P., Anzidei, M., Catalano, C., Napoli, A. 2018; 38 (2): 603–23

  Abstract

  Cancer-related pain affects up to 80% of patients with malignancies. Pain is an important distressing symptom that diminishes the quality of life and negatively affects the survival of patients. Opioid analgesics are generally the primary therapy for cancer-related pain, with surgery, radiation therapy, chemotherapy, and other interventions used in cases of treatment-resistant pain. These treatments, which can be associated with substantial side effects and systemic toxicity, may not be effective. High-intensity focused ultrasound is an entirely noninvasive technique that is approved for treatment of uterine fibroids, bone metastases, and essential tremors. With magnetic resonance imaging or ultrasonographic guidance, high-intensity ultrasound waves are focused on a small well-demarcated region to result in precise localized ablation. This treatment may represent a multimodality approach to treating patients with malignant diseases-facilitating pain palliation, enhanced local drug delivery and radiation therapy effects, and stimulation of anticancer specific immune responses, and potentially facilitating local tumor control. Focused ultrasound can be used to achieve pain palliation by producing several effects, including tissue denervation, tumor mass reduction, and neuromodulation, that can influence different pathways at the origin of the pain. This technology has several key advantages compared with other analgesic therapies: It is completely noninvasive, might be used to achieve rapid pain control, can be safely repeated, and can be used in combination with chemotherapy and radiation therapy to enhance their effects. Online supplemental material is available for this article. ©RSNA, 2018.

  View details for PubMedID 29394144

• Thermal diffusivity and perfusion constants from in vivo MR-guided focussed ultrasound treatments: a feasibility study INTERNATIONAL JOURNAL OF HYPERTHERMIA Dillon, C. R., Rieke, V., Ghanouni, P., Payne, A. 2018; 34 (4): 352–62

  Abstract

  This study investigates the feasibility of non-invasively determining thermal diffusivity (α) and the Pennes perfusion parameter (w) from pre-clinical and clinical magnetic resonance-guided focussed ultrasound (MRgFUS) temperature data.Pre-clinical MRgFUS experiments were performed in rabbit muscle (N = 3, 28 sonications) using three-dimensional MR thermometry. Eight sonications were made in a clinical QA phantom with two-dimensional thermometry. Retrospective property determination was performed on clinical uterine fibroid (N = 8, 9 sonications) and desmoid tumour (N = 4, 7 sonications) data. The property determination method fits an analytical solution to MRgFUS temperatures in the coronal MR plane, including all temperatures acquired during heating and one cooling image. When possible, additional cooling data were acquired for property determination.Rabbit α and w from Heating Data (α = 0.164 mm2s-1, w = 7.9 kg m-3 s-1) and Heating and Cooling Data (α = 0.146 mm2s-1, w = 3.3 kg m-3 s-1) were within the range of gold-standard invasive measurements, with >50% reduction in variability by including cooling data. QA phantom property determination with cooling data yielded properties within 3% of expected values (α = 0.144 mm2s-1, w = 0.0 kg m-3 s-1), a difference that was not statistically significant (p = 0.053). Uterine fibroid (Heating Data: α = 0.212 mm2s-1, w = 11.0 kg m-3 s-1) and desmoid tumour (Heating & Cooling Data: α = 0.245 mm2s-1, w = 4.7 kg m-3 s-1) properties are feasible but lack independent verification.Thermal diffusivity and the Pennes perfusion parameter can be obtained from in vivo data and with clinical MRgFUS protocols. Property values are consistently improved by including cooling data. The utility of this property determination method will increase as clinical protocols implement improved temperature imaging.

  View details for PubMedID 28595499

• Performance of multiparametric MRI appears better when measured in patients who undergo radical prostatectomy RESEARCH AND REPORTS IN UROLOGY Wang, N. N., Fan, R. E., Leppert, J. T., Ghanouni, P., Kunder, C. A., Brooks, J. D., Chung, B., Sonn, G. A. 2018; 10: 233–35

  View details for DOI 10.2147/RRU.S178064

  View details for Web of Science ID 000451113100001

• Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor. NeuroImage. Clinical Tian, Q., Wintermark, M., Jeffrey Elias, W., Ghanouni, P., Halpern, C. H., Henderson, J. M., Huss, D. S., Goubran, M., Thaler, C., Airan, R., Zeineh, M., Pauly, K. B., McNab, J. A. 2018; 19: 572–80

  Abstract

  Purpose: To evaluate the use of diffusion magnetic resonance imaging (MRI) tractography for neurosurgical guidance of transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy for essential tremor (ET).Materials and methods: Eight patients with medication-refractory ET were treated with tcMRgFUS targeting the ventral intermediate nucleus (Vim) of the thalamus contralateral to their dominant hand. Diffusion and structural MRI data and clinical evaluations were acquired pre-treatment and post-treatment. To identify the optimal target location, tractography was performed on pre-treatment diffusion MRI data between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus. The tractography-identified locations were compared to the lesion location delineated on 1 year post-treatment T2-weighted MR image. Their overlap was correlated with the clinical outcomes measured by the percentage change of the Clinical Rating Scale for Tremor scores acquired pre-treatment, as well as 1 month, 3 months, 6 months and 1 year post-treatment.Results: The probabilistic tractography was consistent from subject-to-subject and followed the expected anatomy of the thalamocortical radiation and the dentatothalamic tract. Higher overlap between the tractography-identified location and the tcMRgFUS treatment-induced lesion highly correlated with better treatment outcome (r = -0.929, -0.75, -0.643, p = 0.00675, 0.0663, 0.139 for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus, respectively, at 1 year post-treatment). The correlation for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex is the highest for all time points (r = -0.719, -0.976, -0.707, -0.929, p = 0.0519, 0.000397, 0.0595, 0.00675 at 1 month, 3 months, 6 months and 1 year post-treatment, respectively).Conclusion: Our data support the use of diffusion tractography as a complementary approach to current targeting methods for tcMRgFUS thalamotomy.

  View details for PubMedID 29984165

• Use of High-intensity Focused Ultrasound in the Management of Extra-abdominal Desmoid Tumors CURRENT MEDICAL IMAGING REVIEWS Bartocci, M., Bazzocchi, A., Napoli, A., Ghanouni, P., Spinnato, P., Facchini, G., Bonomo, L., Albisinni, U. 2018; 14 (1): 47–52

  View details for DOI 10.2174/1573405613666170616122812

  View details for Web of Science ID 000418919000004

• A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up. Annals of neurology Chang, J. W., Park, C. K., Lipsman, N. n., Schwartz, M. L., Ghanouni, P. n., Henderson, J. M., Gwinn, R. n., Witt, J. n., Tierney, T. S., Cosgrove, G. R., Shah, B. B., Abe, K. n., Taira, T. n., Lozano, A. M., Eisenberg, H. M., Fishman, P. S., Elias, W. J. 2018; 83 (1): 107–14

  Abstract

  Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET.A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed.Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years.Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.

  View details for PubMedID 29265546

• The impact of computed high b-value images on the diagnostic accuracy of DWI for prostate cancer: A receiver operating characteristics analysis. Scientific reports Ning, P. n., Shi, D. n., Sonn, G. A., Vasanawala, S. S., Loening, A. M., Ghanouni, P. n., Obara, P. n., Shin, L. K., Fan, R. E., Hargreaves, B. A., Daniel, B. L. 2018; 8 (1): 3409

  Abstract

  To evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b = 1200 s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value images (contrast equivalent to b = 2000 s/mm2) to compare their diagnostic accuracy. Receiver operating characteristic (ROC) analysis and McNemar's test were performed to assess the relative performance of computed high b value DWI, native high b-value DWI and ADC maps. No significant difference existed in the area under the curve (AUC) for ROCs comparing B1200 (b = 1200 s/mm2) to computed B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly increased sensitivity and/or decreased specificity compared to B1200 (McNemar's p < 0.05), at selected thresholds of interpretation. ADC maps were less accurate than B1200 or c-B2000 for 2 of 5 readers (P < 0.05). This study detected no consistent improvement in overall diagnostic accuracy using c-B2000, compared with B1200 images. Readers detected more cancer with c-B2000 images (increased sensitivity) but also more false positive findings (decreased specificity).

  View details for PubMedID 29467370

• MRI monitoring of focused ultrasound sonications near metallic hardware. Magnetic resonance in medicine Weber, H. n., Ghanouni, P. n., Pascal-Tenorio, A. n., Pauly, K. B., Hargreaves, B. A. 2018; 80 (1): 259–71

  Abstract

  To explore the temperature-induced signal change in two-dimensional multi-spectral imaging (2DMSI) for fast thermometry near metallic hardware to enable MR-guided focused ultrasound surgery (MRgFUS) in patients with implanted metallic hardware.2DMSI was optimized for temperature sensitivity and applied to monitor focus ultrasound surgery (FUS) sonications near metallic hardware in phantoms and ex vivo porcine muscle tissue. Further, we evaluated its temperature sensitivity for in vivo muscle in patients without metallic hardware. In addition, we performed a comparison of temperature sensitivity between 2DMSI and conventional proton-resonance-frequency-shift (PRFS) thermometry at different distances from metal devices and different signal-to-noise ratios (SNR).2DMSI thermometry enabled visualization of short ultrasound sonications near metallic hardware. Calibration using in vivo muscle yielded a constant temperature sensitivity for temperatures below 43 °C. For an off-resonance coverage of ± 6 kHz, we achieved a temperature sensitivity of 1.45%/K, resulting in a minimum detectable temperature change of ∼2.5 K for an SNR of 100 with a temporal resolution of 6 s per frame.The proposed 2DMSI thermometry has the potential to allow MR-guided FUS treatments of patients with metallic hardware and therefore expand its reach to a larger patient population. Magn Reson Med 80:259-271, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for PubMedID 29215150

  View details for PubMedCentralID PMC5876098

• Treatment of Low-Flow Vascular Malformations of the Extremities Using MR-Guided High Intensity Focused Ultrasound: Preliminary Experience JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Ghanouni, P., Kishore, S., Lungren, M. P., Bitton, R., Chan, L., Avedian, R., Bazzocchi, A., Pauly, K., Napoli, A., Hovsepian, D. M. 2017; 28 (12): 1739–44

  Abstract

  Five patients with painful vascular malformations of the extremities that were refractory to standard treatment and were confirmed as low-flow malformations on dynamic contrast-enhanced magnetic resonance (MR) imaging were treated with MR imaging-guided high intensity focused ultrasound. Daily maximum numeric rating scale scores for pain improved from 8.4 ± 1.5 to 1.6 ± 2.2 (P = .004) at a median follow-up of 9 months (range, 4-36 mo). The size of the vascular malformations decreased on follow-up MR imaging (median enhancing volume, 8.2 mL [0.7-10.1 mL] before treatment; 0 mL [0-2.3 mL] after treatment; P = .018) at a median follow-up of 5 months (range, 3-36 mo). No complications occurred.

  View details for PubMedID 29157478

  View details for PubMedCentralID PMC5726422

• Noninvasive Therapy for Osteoid Osteoma: A Prospective Developmental Study with MR Imaging-guided High-Intensity Focused Ultrasound. Radiology Napoli, A., Bazzocchi, A., Scipione, R., Anzidei, M., Saba, L., Ghanouni, P., Cozzi, D. A., Catalano, C. 2017: 162680-?

  Abstract

  Purpose To demonstrate that magnetic resonance (MR) imaging-guided high-intensity focused ultrasound (HIFU) is a safe, effective, and durable treatment option for the management of osteoid osteoma in children and young adults. Materials and Methods This prospective study was institutional review board approved and is registered with clinicaltrials.gov (identification number NCT02302651). Written informed consent was obtained from patients or their parents. Patients who had both clinical and radiologic findings that were diagnostic for nonvertebral osteoid osteoma and no contraindications to MR imaging-guided HIFU were enrolled between June 2010 and June 2013. The feasibility, safety, and clinical effectiveness of MR imaging-guided HIFU were considered primary outcomes; tumor control at imaging was considered a secondary outcome. Analyses were conducted on a per-protocol basis. Results Forty-five of the 50 recruited patients underwent MR imaging-guided HIFU. All patients were discharged without treatment-related complications. The median visual analog scale (VAS) pain score (scale, 0-10) decreased from 8 before treatment to 0 at 1-week and 1- , 6- , 12- , 24- , and 36-month follow-up. Similarly, median VAS scores for the degree to which pain interfered with sleep and physical and daily activities decreased to 0 within the 1st month after treatment and remained stable at subsequent follow-up. Overall, 39 (87%) of the 45 patients achieved and maintained a VAS score of 0 during the 3-year observation period. Quality of life, as assessed by using Functional Assessment of Cancer Therapy-Bone Pain (FACT-BP) scores (scale, 0-60 points), improved, with the median FACT-BP score of 28 (points) before treatment increasing to a median score of 55 at 1-week follow-up and 60 at 6-month and subsequent follow-ups. At (final) 36-month follow-up, MR imaging depicted an absence of residual nidus vascularity in 32 (76%) of the 42 patients who were treated with MR imaging-guided HIFU only. Conclusion The durable clinical efficacy and safety of MR imaging-guided HIFU were demonstrated. These features are evidence of the potential of MR imaging-guided HIFU to be part of a routine strategy for the treatment of osteoid osteoma. (©) RSNA, 2017.

  View details for DOI 10.1148/radiol.2017162680

  View details for PubMedID 28590796

• Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor. Movement disorders Ravikumar, V. K., Parker, J. J., Hornbeck, T. S., Santini, V. E., Pauly, K. B., Wintermark, M., Ghanouni, P., Stein, S. C., Halpern, C. H. 2017

  Abstract

  Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options.Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques.Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery.Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society.

  View details for DOI 10.1002/mds.26997

  View details for PubMedID 28370272

• MR Thermometry Near Metallic Devices Using Multispectral Imaging MAGNETIC RESONANCE IN MEDICINE Weber, H., Taviani, V., Yoon, D., Ghanouni, P., Pauly, K. B., Hargreaves, B. A. 2017; 77 (3): 1162-1169

  Abstract

  The lack of a technique for MR thermometry near metal excludes a growing patient population from promising treatments such as MR-guided focused ultrasound therapy. Here we explore the feasibility of multispectral imaging (MSI) for noninvasive temperature measurement in the presence of strong field inhomogeneities by exploiting the temperature dependency of the T1 relaxation time.A two-dimensional inversion-recovery-prepared MSI pulse sequence (2DMSI) was implemented for artifact-reduced T1 mapping near metal. A series of T1 maps was acquired in a metallic implant phantom while increasing the phantom temperature. The measured change in T1 was analyzed with respect to the phantom temperature. For comparison, proton resonance frequency shift (PRFS) thermometry was performed.2DMSI achieved artifact-reduced, single-slice T1 mapping in the presence of strong off-resonance with a spatial resolution of 1.9 mm in-plane and a temporal resolution of 5 min. The maps enabled temperature measurements over a range of 30°C with an uncertainty below 1.4°C. The quality of the resulting temperature maps was independent of the distance from the metal, whereas the PRFS-based temperature measurements were increasingly impaired with increasing off-resonance.We demonstrated the ability to noninvasively measure temperature near metal using MSI and the T1 temperature sensitivity. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26203

  View details for Web of Science ID 000397407800025

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study EUROPEAN RADIOLOGY Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2017; 27 (2): 732-740

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.• Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for DOI 10.1007/s00330-016-4376-5

  View details for Web of Science ID 000392142000034

• Improved cortical bone specificity in UTE MR Imaging MAGNETIC RESONANCE IN MEDICINE Johnson, E. M., Vyas, U., Ghanouni, P., Pauly, K. B., Pauly, J. M. 2017; 77 (2): 684-695

  Abstract

  Methods for direct visualization of compact bone using MRI have application in several "MR-informed" technologies, such as MR-guided focused ultrasound, MR-PET reconstruction and MR-guided radiation therapy. The specificity of bone imaging can be improved by manipulating image sensitivity to Bloch relaxation phenomena, facilitating distinction of bone from other tissues detected by MRI.From Bloch equation dynamics, excitation pulses suitable for creating specific sensitivity to short-T2 magnetization from cortical bone are identified. These pulses are used with UTE subtraction demonstrate feasibility of MR imaging of compact bone with positive contrast.MR images of bone structures are acquired with contrast similar to that observed in x-ray CT images. Through comparison of MR signal intensities with CT Hounsfield units of the skull, the similarity of contrast is quantified. The MR technique is also demonstrated in other regions of the body that are relevant for interventional procedures, such as the shoulder, pelvis and leg.Matching RF excitation pulses to relaxation rates improves the specificity to bone of short-T2 contrast. It is demonstrated with a UTE sequence to acquire images of cortical bone with positive contrast, and the contrast is verified by comparison with x-ray CT. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26160

  View details for Web of Science ID 000394544700025

  View details for PubMedCentralID PMC5040625

• Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors. Sarcoma Moding, E. J., Million, L., Avedian, R., Ghanouni, P., Kunder, C., Ganjoo, K. N. 2017; 2017: 2316839

  Abstract

  Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function.

  View details for PubMedID 28761389

• Efficient Transcranial Ultrasound Delivery via Excitation of Lamb Waves: Concept and Preliminary Results Firouzi, K., Ghanouni, P., Khuri-Yakub, B. T., IEEE IEEE. 2017

  View details for Web of Science ID 000416948402016

• Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists. European urology focus Sonn, G. A., Fan, R. E., Ghanouni, P. n., Wang, N. N., Brooks, J. D., Loening, A. M., Daniel, B. L., To'o, K. J., Thong, A. E., Leppert, J. T. 2017

  Abstract

  Multiparametric magnetic resonance imaging (mpMRI) interpreted by experts is a powerful tool for diagnosing prostate cancer. However, the generalizability of published results across radiologists of varying expertise has not been verified.To assess variability in mpMRI reporting and diagnostic accuracy across radiologists of varying experience in routine clinical care.Men who underwent mpMRI and MR-fusion biopsy between 2014-2016. Each MRI scan was read by one of nine radiologists using the Prostate Imaging Reporting and Data System (PIRADS) and was not re-read before biopsy. Biopsy histopathology was the reference standard.Outcomes were the PIRADS score distribution and diagnostic accuracy across nine radiologists. We evaluated the association between age, prostate-specific antigen, PIRADS score, and radiologist in predicting clinically significant cancer (Gleason ≥7) using multivariable logistic regression. We conducted sensitivity analyses for case volume and changes in accuracy over time.We analyzed data for 409 subjects with 503 MRI lesions. While the number of lesions (mean 1.2 lesions/patient) did not differ across radiologists, substantial variation existed in PIRADS distribution and cancer yield. The significant cancer detection rate was 3-27% for PIRADS 3 lesions, 23-65% for PIRADS 4, and 40-80% for PIRADS 5 across radiologists. Some 13-60% of men with a PIRADS score of <3 on MRI harbored clinically significant cancer. The area under the receiver operating characteristic curve varied from 0.69 to 0.81 for detection of clinically significant cancer. PIRADS score (p<0.0001) and radiologist (p=0.042) were independently associated with cancer in multivariable analysis. Neither individual radiologist volume nor study period impacted the results. MRI scans were not retrospectively re-read by all radiologists, precluding measurement of inter-observer agreement.We observed considerable variability in PIRADS score assignment and significant cancer yield across radiologists. We advise internal evaluation of mpMRI accuracy before widespread adoption.We evaluated the interpretation of multiparametric magnetic resonance imaging of the prostate in routine clinical care. Diagnostic accuracy depends on the Prostate Imaging Reporting and Data System score and the radiologist.

  View details for PubMedID 29226826

• Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: A pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome. Journal of magnetic resonance imaging : JMRI Federau, C. n., Goubran, M. n., Rosenberg, J. n., Henderson, J. n., Halpern, C. H., Santini, V. n., Wintermark, M. n., Butts Pauly, K. n., Ghanouni, P. n. 2017

  Abstract

  Transcranial MR-guided high-intensity focused ultrasound (tcMRgFUS) is a promising noninvasive method to treat medication-refractory essential tremor.To define the correlation between lesion size after ablation, thermal dose, and clinical outcome in tcMRgFUS treatment of essential tremor.Retrospective.Eight patients with medication-refractory essential tremor were treated using a tcMRgFUS system at 3T.T2 -weighted images were acquired immediately and at 1 year posttreatment at 3T.An atlas of the thalamic nuclei and dose maps were warped to the posttreatment images. The thermal dose, the immediate posttreatment lesion volume and 1-year final lesion volume, and the volumes confined inside the ventral division of the ventral lateral posterior thalamic nucleus (VLpv) were correlated to clinical outcome at 1 month and 1 year using Pearson's coefficient. The spatial region of treatment correlating with maximal clinical outcome was derived in a normalized space from average maps of clinical tremor score improvement at 1 year.Statistical significance was assessed using the Wilcoxon two-tailed rank test.The correlations between thermal dose, lesion volume posttreatment and at 1 year, and outcome at 1 year were good (r = 0.73, 0.65, 0.73, respectively), and were slightly better than at 1 month (r = 0.57, 0.49, 0.65). Reducing the measurement to include only the portion within the VLpv did not significantly modify the correlations (P = 0.09). The center of the spatial region of treatment was found in the anterior commissure - posterior commissure plane, 14.3 mm lateral from the midline, and 8.3 mm rostral to the posterior commissure.In this pilot study a good correlation was found between the size of the lesion, the thermal dose, and the clinical outcome in patients treated for essential tremor with ablation of the VLpv with tcMRgFUS.1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017.

  View details for PubMedID 29076274

• A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound. Journal of therapeutic ultrasound Dababou, S., Marrocchio, C., Rosenberg, J., Bitton, R., Pauly, K. B., Napoli, A., Hwang, J. H., Ghanouni, P. 2017; 5: 9-?

  Abstract

  Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60-90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma.An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ(2), and Cochran's Q test for heterogeneity among studies. The I(2) was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias.The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ(2) (variance among studies) was 0.195, and I(2) (percentage of variation among studies) was 40% (95% CI: 1-64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76-86).HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.

  View details for DOI 10.1186/s40349-017-0080-4

  View details for PubMedID 28373906

• Clinically Approved Nanoparticle Imaging Agents. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Thakor, A. S., Jokerst, J. V., Ghanouni, P., Campbell, J., Mittra, E., Gambhir, S. S. 2016

  Abstract

  Nanoparticles are a new class of imaging agent used for both anatomic and molecular imaging. Nanoparticle-based imaging exploits the signal intensity, stability, and biodistribution behavior of submicron-diameter molecular imaging agents. This review focuses on nanoparticles used in human medical imaging, with an emphasis on radionuclide imaging and MRI. Newer nanoparticle platforms are also discussed in relation to theranostic and multimodal uses.

  View details for PubMedID 27738007

• Specialized volumetric thermometry for improved guidance of MRgFUS in brain. Magnetic resonance in medicine Marx, M., Ghanouni, P., Butts Pauly, K. 2016

  Abstract

  MR thermometry is critical for safe and effective transcranial focused ultrasound. The current single-slice MR thermometry sequence cannot achieve all desired treatment monitoring requirements. We propose an approach in which the imaging requirements of different aspects of treatment monitoring are met by optimizing multiple sequences.Imaging requirements were determined for three stages of MR-guided focused ultrasound brain treatment: 1) focal spot localization, 2) focal spot monitoring, and 3) background monitoring. Multiple-echo spiral thermometry sequences were optimized for each set of requirements and then validated with in vivo signal-to-noise ratio measurements and with phantom heating experiments.Each of the proposed sequences obtained better precision than the current two-dimensional Fourier transform (2DFT) thermometry sequence. Five-slice focal spot localization achieved two-fold better resolution with 1.9-fold better precision but two-fold longer acquisition compared to 2DFT. Five-slice focal monitoring achieved 2.1-fold better precision with similar speed but 12% larger voxels than 2DFT. Full-brain background monitoring was demonstrated in both axial (7.1 s) and sagittal (11.4 s) orientations. Phantom heating time curves were consistent across all sequences after correcting for resolution.Multiple-echo spiral imaging significantly improves MR thermometry efficiency, enabling multiple-slice monitoring. Optimizing multiple specialized sequences provides better performance than can be achieved by any single sequence. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26385

  View details for PubMedID 27699844

• Predicting variation in subject thermal response during transcranial magnetic resonance guided focused ultrasound surgery: Comparison in seventeen subject datasets. Medical physics Vyas, U., Ghanouni, P., Halpern, C. H., Elias, J., Pauly, K. B. 2016; 43 (9): 5170-?

  Abstract

  In transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) treatments, the acoustic and spatial heterogeneity of the skull cause reflection, absorption, and scattering of the acoustic beams. These effects depend on skull-specific parameters and can lead to patient-specific thermal responses to the same transducer power. In this work, the authors develop a simulation tool to help predict these different experimental responses using 3D heterogeneous tissue models based on the subject CT images. The authors then validate and compare the predicted skull efficiencies to an experimental metric based on the subject thermal responses during tcMRgFUS treatments in a dataset of seventeen human subjects.Seventeen human head CT scans were used to create tissue acoustic models, simulating the effects of reflection, absorption, and scattering of the acoustic beam as it propagates through a heterogeneous skull. The hybrid angular spectrum technique was used to model the acoustic beam propagation of the InSightec ExAblate 4000 head transducer for each subject, yielding maps of the specific absorption rate (SAR). The simulation assumed the transducer was geometrically focused to the thalamus of each subject, and the focal SAR at the target was used as a measure of the simulated skull efficiency. Experimental skull efficiency for each subject was calculated using the thermal temperature maps from the tcMRgFUS treatments. Axial temperature images (with no artifacts) were reconstructed with a single baseline, corrected using a referenceless algorithm. The experimental skull efficiency was calculated by dividing the reconstructed temperature rise 8.8 s after sonication by the applied acoustic power.The simulated skull efficiency using individual-specific heterogeneous models predicts well (R(2) = 0.84) the experimental energy efficiency.This paper presents a simulation model to predict the variation in thermal responses measured in clinical ctMRGFYS treatments while being computationally feasible.

  View details for DOI 10.1118/1.4955436

  View details for PubMedID 27587047

• A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. New England journal of medicine Elias, W. J., Lipsman, N., Ondo, W. G., Ghanouni, P., Kim, Y. G., Lee, W., Schwartz, M., Hynynen, K., Lozano, A. M., Shah, B. B., Huss, D., Dallapiazza, R. F., Gwinn, R., Witt, J., Ro, S., Eisenberg, H. M., Fishman, P. S., Gandhi, D., Halpern, C. H., Chuang, R., Butts Pauly, K., Tierney, T. S., Hayes, M. T., Cosgrove, G. R., Yamaguchi, T., Abe, K., Taira, T., Chang, J. W. 2016; 375 (8): 730-739

  Abstract

  Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor.We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort).Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively.MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

  View details for DOI 10.1056/NEJMoa1600159

  View details for PubMedID 27557301

• Correcting Heat-Induced Chemical Shift Distortions in Proton Resonance Frequency-Shift Thermometry MAGNETIC RESONANCE IN MEDICINE Gaur, P., Partanen, A., Werner, B., Ghanouni, P., Bitton, R., Pauly, K. B., Grissom, W. A. 2016; 76 (1): 172-182

  Abstract

  To reconstruct proton resonance frequency-shift temperature maps free of chemical shift distortions.Tissue heating created by thermal therapies such as focused ultrasound surgery results in a change in proton resonance frequency that causes geometric distortions in the image and calculated temperature maps, in the same manner as other chemical shift and off-resonance distortions if left uncorrected. We propose an online-compatible algorithm to correct these distortions in 2DFT and echo-planar imaging acquisitions, which is based on a k-space signal model that accounts for proton resonance frequency change-induced phase shifts both up to and during the readout. The method was evaluated with simulations, gel phantoms, and in vivo temperature maps from brain, soft tissue tumor, and uterine fibroid focused ultrasound surgery treatments.Without chemical shift correction, peak temperature and thermal dose measurements were spatially offset by approximately 1 mm in vivo. Spatial shifts increased as readout bandwidth decreased, as shown by up to 4-fold greater temperature hot spot asymmetry in uncorrected temperature maps. In most cases, the computation times to correct maps at peak heat were less than 10 ms, without parallelization.Heat-induced proton resonance frequency changes create chemical shift distortions in temperature maps resulting from MR-guided focused ultrasound surgery ablations, but the distortions can be corrected using an online-compatible algorithm. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.25899

  View details for Web of Science ID 000384996900016

  View details for PubMedCentralID PMC4766074

• Correcting heat-induced chemical shift distortions in proton resonance frequency-shift thermometry. Magnetic resonance in medicine Gaur, P., Partanen, A., Werner, B., Ghanouni, P., Bitton, R., Butts Pauly, K., Grissom, W. A. 2016; 76 (1): 172-182

  Abstract

  To reconstruct proton resonance frequency-shift temperature maps free of chemical shift distortions.Tissue heating created by thermal therapies such as focused ultrasound surgery results in a change in proton resonance frequency that causes geometric distortions in the image and calculated temperature maps, in the same manner as other chemical shift and off-resonance distortions if left uncorrected. We propose an online-compatible algorithm to correct these distortions in 2DFT and echo-planar imaging acquisitions, which is based on a k-space signal model that accounts for proton resonance frequency change-induced phase shifts both up to and during the readout. The method was evaluated with simulations, gel phantoms, and in vivo temperature maps from brain, soft tissue tumor, and uterine fibroid focused ultrasound surgery treatments.Without chemical shift correction, peak temperature and thermal dose measurements were spatially offset by approximately 1 mm in vivo. Spatial shifts increased as readout bandwidth decreased, as shown by up to 4-fold greater temperature hot spot asymmetry in uncorrected temperature maps. In most cases, the computation times to correct maps at peak heat were less than 10 ms, without parallelization.Heat-induced proton resonance frequency changes create chemical shift distortions in temperature maps resulting from MR-guided focused ultrasound surgery ablations, but the distortions can be corrected using an online-compatible algorithm. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.25899

  View details for PubMedID 26301458

  View details for PubMedCentralID PMC4766074

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study. European radiology Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2016: -?

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.• Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for PubMedID 27147222

• MR thermometry near metallic devices using multispectral imaging. Magnetic resonance in medicine Weber, H., Taviani, V., Yoon, D., Ghanouni, P., Pauly, K. B., Hargreaves, B. A. 2016

  Abstract

  The lack of a technique for MR thermometry near metal excludes a growing patient population from promising treatments such as MR-guided focused ultrasound therapy. Here we explore the feasibility of multispectral imaging (MSI) for noninvasive temperature measurement in the presence of strong field inhomogeneities by exploiting the temperature dependency of the T1 relaxation time.A two-dimensional inversion-recovery-prepared MSI pulse sequence (2DMSI) was implemented for artifact-reduced T1 mapping near metal. A series of T1 maps was acquired in a metallic implant phantom while increasing the phantom temperature. The measured change in T1 was analyzed with respect to the phantom temperature. For comparison, proton resonance frequency shift (PRFS) thermometry was performed.2DMSI achieved artifact-reduced, single-slice T1 mapping in the presence of strong off-resonance with a spatial resolution of 1.9 mm in-plane and a temporal resolution of 5 min. The maps enabled temperature measurements over a range of 30°C with an uncertainty below 1.4°C. The quality of the resulting temperature maps was independent of the distance from the metal, whereas the PRFS-based temperature measurements were increasingly impaired with increasing off-resonance.We demonstrated the ability to noninvasively measure temperature near metal using MSI and the T1 temperature sensitivity. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26203

  View details for PubMedID 26991803

• Improved cortical bone specificity in UTE MR Imaging. Magnetic resonance in medicine Johnson, E. M., Vyas, U., Ghanouni, P., Pauly, K. B., Pauly, J. M. 2016

  Abstract

  Methods for direct visualization of compact bone using MRI have application in several "MR-informed" technologies, such as MR-guided focused ultrasound, MR-PET reconstruction and MR-guided radiation therapy. The specificity of bone imaging can be improved by manipulating image sensitivity to Bloch relaxation phenomena, facilitating distinction of bone from other tissues detected by MRI.From Bloch equation dynamics, excitation pulses suitable for creating specific sensitivity to short-T2 magnetization from cortical bone are identified. These pulses are used with UTE subtraction demonstrate feasibility of MR imaging of compact bone with positive contrast.MR images of bone structures are acquired with contrast similar to that observed in x-ray CT images. Through comparison of MR signal intensities with CT Hounsfield units of the skull, the similarity of contrast is quantified. The MR technique is also demonstrated in other regions of the body that are relevant for interventional procedures, such as the shoulder, pelvis and leg.Matching RF excitation pulses to relaxation rates improves the specificity to bone of short-T2 contrast. It is demonstrated with a UTE sequence to acquire images of cortical bone with positive contrast, and the contrast is verified by comparison with x-ray CT. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26160

  View details for PubMedID 26972442

  View details for PubMedCentralID PMC5040625

• Is MR-guided High-intensity Focused Ultrasound a Feasible Treatment Modality for Desmoid Tumors? CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Avedian, R. S., Bitton, R., Gold, G., Butts-Pauly, K., Ghanouni, P. 2016; 474 (3): 697-704

  Abstract

  MR-guided high-intensity focused ultrasound is a noninvasive treatment modality that uses focused ultrasound waves to thermally ablate tumors within the human body while minimizing side effects to surrounding healthy tissues. This technology is FDA-approved for certain tumors and has potential to be a noninvasive treatment option for extremity soft tissue tumors. Development of treatment modalities that achieve tumor control, decrease morbidity, or both might be of great benefit for patients. We wanted to assess the potential use of this technology in the treatment of extremity desmoid tumors.(1) Can we use MR-guided high-intensity focused ultrasound to accurately ablate a predetermined target volume within a human cadaver extremity? (2) Does MR-guided high-intensity focused ultrasound treatment stop progression and/or cause regression of extremity desmoid tumors?Simulated tumor volumes in four human cadavers, created by using plastic markers, were ablated using a commercially available focused ultrasound system. Accuracy was determined in accordance with the International Organization of Standards location error by measuring the farthest distance between the ablated tissue and the plane corresponding to the target. Between 2012 and 2014, we treated nine patients with desmoid tumors using focused ultrasound ablation. Indications for this were tumor-related symptoms or failure of conventional treatment. Of those, five of them were available for MRI followup at 12 months or longer (mean, 18.2 months; range, 12-23 months). The radiographic and clinical outcomes of five patients who had desmoid tumors treated with focused ultrasound were prospectively recorded. Patients were assessed preoperatively with MRI and followed at routine intervals after treatment with MRI scans and clinical examination.The ablation accuracy for the four cadaver extremities was 5 mm, 3 mm, 8 mm, and 8 mm. Four patients' tumors became smaller after treatment and one patient has slight progression at the time of last followup. The mean decrease in tumor size determined by MRI measurements was 36% (95% confidence interval, 7%-66%). No patient has received additional adjuvant systemic or local treatment. Treatment-related adverse events included first- and second-degree skin burns occurring in four patients, which were managed successfully without further surgery.This preliminary investigation provides some evidence that MR-guided high-intensity focused ultrasound may be a feasible treatment for desmoid tumors. It may also be of use for other soft tissue neoplasms in situations in which there are limited traditional treatment options such as recurrent sarcomas. Further investigation is necessary to better define the indications, efficacy, role, and long-term oncologic outcomes of focused ultrasound treatment.Level IV, therapeutic study.

  View details for DOI 10.1007/s11999-015-4364-0

  View details for Web of Science ID 000370150000018

  View details for PubMedID 26040967

  View details for PubMedCentralID PMC4746191

• Improving thermal dose accuracy in magnetic resonance-guided focused ultrasound surgery: Long-term thermometry using a prior baseline as a reference. Journal of magnetic resonance imaging Bitton, R. R., Webb, T. D., Pauly, K. B., Ghanouni, P. 2016; 43 (1): 181-189

  Abstract

  To investigate thermal dose volume (TDV) and non-perfused volume (NPV) of magnetic resonance-guided focused ultrasound (MRgFUS) treatments in patients with soft tissue tumors, and describe a method for MR thermal dosimetry using a baseline reference.Agreement between TDV and immediate post treatment NPV was evaluated from MRgFUS treatments of five patients with biopsy-proven desmoid tumors. Thermometry data (gradient echo, 3T) were analyzed over the entire course of the treatments to discern temperature errors in the standard approach. The technique searches previously acquired baseline images for a match using 2D normalized cross-correlation and a weighted mean of phase difference images. Thermal dose maps and TDVs were recalculated using the matched baseline and compared to NPV.TDV and NPV showed between 47%-91% disagreement, using the standard immediate baseline method for calculating TDV. Long-term thermometry showed a nonlinear local temperature accrual, where peak additional temperature varied between 4-13°C (mean = 7.8°C) across patients. The prior baseline method could be implemented by finding a previously acquired matching baseline 61% ± 8% (mean ± SD) of the time. We found 7%-42% of the disagreement between TDV and NPV was due to errors in thermometry caused by heat accrual. For all patients, the prior baseline method increased the estimated treatment volume and reduced the discrepancies between TDV and NPV (P = 0.023).This study presents a mismatch between in-treatment and post treatment efficacy measures. The prior baseline approach accounts for local heating and improves the accuracy of thermal dose-predicted volume. J. MAGN. RESON. IMAGING 2016;43:181-189.

  View details for DOI 10.1002/jmri.24978

  View details for PubMedID 26119129

  View details for PubMedCentralID PMC4691444

• Establishing a clinical service for the treatment of osteoid osteoma using magnetic resonance-guided focused ultrasound: overview and guidelines. Journal of therapeutic ultrasound Temple, M. J., Waspe, A. C., Amaral, J. G., Napoli, A., LeBlang, S., Ghanouni, P., Bucknor, M. D., Campbell, F., Drake, J. M. 2016; 4: 16-?

  Abstract

  Recent studies have demonstrated the effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of osteoid osteoma (OO), a painful, benign bone tumor. As MRgFUS is a noninvasive and radiation-free treatment, it stands to replace the current standard of care, percutaneous radiofrequency, or laser thermal ablation. Within an institution, creation of a clinical OO MRgFUS treatment program would not only provide cutting edge medical treatment at the current time but would also establish the foundation for an MRgFUS clinical service to introduce treatments currently under development into clinical practice in the future. The purpose of this document is to provide information to facilitate creation of a clinical service for MRgFUS treatment of OO by providing (1) recommendations for the multi-disciplinary management of patients and (2) guidelines regarding current best practices for MRgFUS treatment. This paper will discuss establishment of a multi-disciplinary clinic, patient accrual, inclusion/exclusion criteria, diagnosis, preoperative imaging, patient preparation, anesthesia, treatment planning, targeting and treatment execution, complication avoidance, and patient follow-up to assure safety and effectiveness.

  View details for DOI 10.1186/s40349-016-0059-6

  View details for PubMedID 27213043

  View details for PubMedCentralID PMC4873984

• Transcranial MRI-Guided Focused Ultrasound: A Review of the Technologic and Neurologic Applications AMERICAN JOURNAL OF ROENTGENOLOGY Ghanouni, P., Pauly, K. B., Elias, W. J., Henderson, J., Sheehan, J., Monteith, S., Wintermark, M. 2015; 205 (1): 150-159

  Abstract

  This article reviews the physical principles of MRI-guided focused ultra-sound and discusses current and potential applications of this exciting technology.MRI-guided focused ultrasound is a new minimally invasive method of targeted tissue thermal ablation that may be of use to treat central neuropathic pain, essential tremor, Parkinson tremor, and brain tumors. The system has also been used to temporarily disrupt the blood-brain barrier to allow targeted drug delivery to brain tumors.

  View details for DOI 10.2214/AJR.14.13632

  View details for PubMedID 26102394

• TU-B-210-01: MRg HIFU - Bone and Soft Tissue Tumor Ablation. Medical physics Ghanouni, P. 2015; 42 (6): 3598-?

  Abstract

  MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advanced techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, "MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue", will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, "MRI guided High Intensity Focused Ultrasound - Advanced Approaches for Ablation and Hyperthermia", will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs.1.Learn background on devices and techniques for MR guided HIFU for cancer therapy2.Understand issues and current status of clinical MRg HIFU3.Understand strategies for compensating for organ movement during MRgHIFU4.Understand strategies for strategies for delivering hyperthermia with MRgHIFUCM - research collaboration with Philips.

  View details for DOI 10.1118/1.4925563

  View details for PubMedID 26128866

• Optimization of White-Matter-Nulled Magnetization Prepared Rapid Gradient Echo (MP-RAGE) Imaging MAGNETIC RESONANCE IN MEDICINE Saranathan, M., Tourdias, T., Bayram, E., Ghanouni, P., Rutt, B. K. 2015; 73 (5): 1786-1794

  Abstract

  To optimize the white-matter-nulled (WMn) Magnetization Prepared Rapid Gradient Echo (MP-RAGE) sequence at 7 Tesla (T), with comparisons to 3T.Optimal parameters for maximizing signal-to-noise ratio (SNR) efficiency were derived. The effect of flip angle and repetition time (TR) on image blurring was modeled using simulations and validated in vivo. A novel two-dimensional (2D) -centric radial fan beam (RFB) k-space segmentation scheme was used to shorten scan times and improve parallel imaging. Healthy subjects as well as patients with multiple sclerosis and tremor were scanned using the optimized protocols.Inversion repetition times (TS) of 4.5 s and 6 s were found to yield the highest SNR efficiency for WMn MP-RAGE at 3T and 7T, respectively. Blurring was more sensitive to flip in WMn than in CSFn MP-RAGE and relatively insensitive to TR for both regimes. The 2D RFB scheme had 19% and 47% higher thalamic SNR and SNR efficiency than the 1D centric scheme for WMn MP-RAGE. Compared with 3T, SNR and SNR efficiency were higher for the 7T WMn regime by 56% and 41%, respectively. MS lesions in the cortex and thalamus as well as thalamic subnuclei in tremor patients were clearly delineated using WMn MP-RAGE.Optimization and new view ordering enabled MP-RAGE imaging with 0.8-1 mm(3) isotropic spatial resolution in scan times of 5 min with whole brain coverage.

  View details for DOI 10.1002/mrm.25298

  View details for Web of Science ID 000353240600010

  View details for PubMedID 24889754

  View details for PubMedCentralID PMC4247820

• International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions INTERNATIONAL JOURNAL OF HYPERTHERMIA Huisman, M., Ter Haar, G., Napoli, A., Hananel, A., Ghanouni, P., Loevey, G., Nijenhuis, R. J., Van den Bosch, M. A., Rieke, V., Majumdar, S., Marchetti, L., Pfeffer, R. M., Hurwitz, M. D. 2015; 31 (3): 251-259

  Abstract

  Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), is an emerging non-invasive thermal treatment modality in oncology that has recently proven to be effective for the palliation of metastatic bone pain. A consensus panel of internationally recognised experts in focused ultrasound critically reviewed all available data and developed consensus statements to increase awareness, accelerate the development, acceptance and adoption of FUS as a treatment for painful bone metastases and provide guidance towards broader application in oncology. In this review, evidence-based consensus statements are provided for (1) current treatment goals, (2) current indications, (3) technical considerations, (4) future directions including research priorities, and (5) economic and logistical considerations.

  View details for DOI 10.3109/02656736.2014.995237

  View details for Web of Science ID 000355926300005

  View details for PubMedID 25677840

• T2-based temperature monitoring in abdominal fat during MR-guided focused ultrasound treatment of patients with uterine fibroids. Journal of therapeutic ultrasound Ozhinsky, E., Kohi, M. P., Ghanouni, P., Rieke, V. 2015; 3: 15-?

  Abstract

  Near-field heating is a potential problem in focused ultrasound treatments, as it can result in thermal injury to skin, subcutaneous fat, and other tissues. Our goals were to determine if T2-based temperature mapping could be used reliably to measure near-field heating in adipose tissue and whether it is practical to perform such mapping during focused ultrasound treatments.We investigated the dependence of T2 on temperature in ex vivo adipose tissue at 3T using a double-echo fast spin echo (FSE) sequence. We implemented and evaluated the T2-based temperature mapping technique in the adipose tissue of two healthy volunteers. Finally, we applied the technique during magnetic resonance-guided focused ultrasound (MRgFUS) treatments to measure near-field heating in eight patients with uterine fibroids.Calibration experiments in porcine adipose tissue determined a temperature coefficient of 6.16 ms/°C during heating and 5.37 ms/°C during cooling. The volunteer experiments demonstrated a strong correlation between the skin temperature and T2-based temperature measurements in the fat layer. During the treatments of patients with uterine fibroids, we observed a measurable change in the T2 of fat tissue within the path of the ultrasound beam and a temperature increase of up to 15 °C with sustained heating of more than 10 °C.Our results demonstrate the feasibility and importance of monitoring near-field heating in fatty tissues. The implementation of near-field monitoring between sonications can shorten treatments by reducing the cooling time. It can help improve safety by avoiding excessive heating in the near field.

  View details for DOI 10.1186/s40349-015-0036-5

  View details for PubMedID 26366288

  View details for PubMedCentralID PMC4567827

• Magnetic resonance-guided focused ultrasound for patients with painful bone metastases: phase III trial results. Journal of the National Cancer Institute Hurwitz, M. D., Ghanouni, P., Kanaev, S. V., Iozeffi, D., Gianfelice, D., Fennessy, F. M., Kuten, A., Meyer, J. E., Leblang, S. D., Roberts, A., Choi, J., Larner, J. M., Napoli, A., Turkevich, V. G., Inbar, Y., Tempany, C. M., Pfeffer, R. M. 2014; 106 (5)

  Abstract

  Pain due to bone metastases is a common cause of cancer-related morbidity, with few options available for patients refractory to medical therapies and who do not respond to radiation therapy. This study assessed the safety and efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS), a noninvasive method of thermal tissue ablation for palliation of pain due to bone metastases.Patients with painful bone metastases were randomly assigned 3:1 to receive MRgFUS sonication or placebo. The primary endpoint was improvement in self-reported pain score without increase of pain medication 3 months after treatment and was analyzed by Fisher's exact test. Components of the response composite, Numerical Rating Scale for pain (NRS) and morphine equivalent daily dose intake, were analyzed by t test and Wilcoxon rank-sum test, respectively. Brief Pain Inventory (BPI-QoL), a measure of functional interference of pain on quality of life, was compared between MRgFUS and placebo by t test. Statistical tests were two-sided.One hundred forty-seven subjects were enrolled, with 112 and 35 randomly assigned to MRgFUS and placebo treatments, respectively. Response rate for the primary endpoint was 64.3% in the MRgFUS arm and 20.0% in the placebo arm (P < .001). MRgFUS was also superior to placebo at 3 months on the secondary endpoints assessing worst score NRS (P < .001) and the BPI-QoL (P < .001). The most common treatment-related adverse event (AE) was sonication pain, which occurred in 32.1% of MRgFUS patients. Two patients had pathological fractures, one patient had third-degree skin burn, and one patient suffered from neuropathy. Overall 60.3% of all AEs resolved on the treatment day.This multicenter phase III trial demonstrated that MRgFUS is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments.

  View details for DOI 10.1093/jnci/dju082

  View details for PubMedID 24760791

• Respiration Based Steering for High Intensity Focused Ultrasound Liver Ablation MAGNETIC RESONANCE IN MEDICINE Holbrook, A. B., Ghanouni, P., Santos, J. M., Dumoulin, C., Medan, Y., Pauly, K. B. 2014; 71 (2): 797-806

  Abstract

  PURPOSE: Respiratory motion makes hepatic ablation using high intensity focused ultrasound (HIFO) challenging. Previous HIFU liver treatment had required apnea induced during general anesthesia. We describe and test a system that allows treatment of the liver in the presence of breathing motion. METHODS: Mapping a signal from an external respiratory bellow to treatment locations within the liver allows the ultrasound transducer to be steered in real time to the target location. Using a moving phantom, three metrics were used to compare static, steered, and unsteered sonications: the area of sonications once a temperature rise of 15°C was achieved, the energy deposition required to reach that temperature, and the average rate of temperature rise during the first 10 s of sonication. Steered HIFU in vivo ablations of the porcine liver were also performed and compared to breath-hold ablations. RESULTS: For the last phantom metric, all groups were found to be statistically significantly different (P ≤ 0.003). However, in the other two metrics, the static and unsteered sonications were not statistically different (P > 0.9999). Steered in vivo HIFU ablations were not statistically significantly different from ablations during breath-holding. CONCLUSIONS: A system for performing HIFU steering during ablation of the liver with breathing motion is presented and shown to achieve results equivalent to ablation performed with breath-holding. Magn Reson Med 000:000-000, 2012. © 2012 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.24695

  View details for Web of Science ID 000330769700036

• Respiration based steering for high intensity focused ultrasound liver ablation. Magnetic resonance in medicine Holbrook, A. B., Ghanouni, P., Santos, J. M., Dumoulin, C., Medan, Y., Pauly, K. B. 2014; 71 (2): 797-806

  Abstract

  PURPOSE: Respiratory motion makes hepatic ablation using high intensity focused ultrasound (HIFO) challenging. Previous HIFU liver treatment had required apnea induced during general anesthesia. We describe and test a system that allows treatment of the liver in the presence of breathing motion. METHODS: Mapping a signal from an external respiratory bellow to treatment locations within the liver allows the ultrasound transducer to be steered in real time to the target location. Using a moving phantom, three metrics were used to compare static, steered, and unsteered sonications: the area of sonications once a temperature rise of 15°C was achieved, the energy deposition required to reach that temperature, and the average rate of temperature rise during the first 10 s of sonication. Steered HIFU in vivo ablations of the porcine liver were also performed and compared to breath-hold ablations. RESULTS: For the last phantom metric, all groups were found to be statistically significantly different (P ≤ 0.003). However, in the other two metrics, the static and unsteered sonications were not statistically different (P > 0.9999). Steered in vivo HIFU ablations were not statistically significantly different from ablations during breath-holding. CONCLUSIONS: A system for performing HIFU steering during ablation of the liver with breathing motion is presented and shown to achieve results equivalent to ablation performed with breath-holding. Magn Reson Med 000:000-000, 2012. © 2012 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.24695

  View details for PubMedID 23460510

• Magnetic Resonance-Guided Focused Ultrasound for Patients With Painful Bone Metastases: Phase III Trial Results. Journal of the National Cancer Institute Hurwitz, M. D., Ghanouni, P., Kanaev, S. V., Iozeffi, D., Gianfelice, D., Fennessy, F. M., Kuten, A., Meyer, J. E., Leblang, S. D., Roberts, A., Choi, J., Larner, J. M., Napoli, A., Turkevich, V. G., Inbar, Y., Tempany, C. M., Pfeffer, R. M. 2014; 106 (5)

  View details for DOI 10.1093/jnci/dju082

  View details for PubMedID 24760791

• In vivo USPIO magnetic resonance imaging shows that minocycline mitigates macrophage recruitment to a peripheral nerve injury MOLECULAR PAIN Ghanouni, P., Behera, D., Xie, J., Chen, X., Moseley, M., Biswal, S. 2012; 8

  Abstract

  Minocycline has proven anti-nociceptive effects, but the mechanism by which minocycline delays the development of allodynia and hyperalgesia after peripheral nerve injury remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI) to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline modulates macrophage trafficking to the site of nerve injury in vivo and, in turn, results in altered pain thresholds.Animal experiments were approved by Stanford IACUC. A model of neuropathic pain was created using the Spared Nerve Injury (SNI) model that involves ligation of the left sciatic nerve in the left thigh of adult Sprague-Dawley rats. Animals with SNI and uninjured animals were then injected with/without USPIOs (300 μmol/kg i.v.) and with/without minocycline (50 mg/kg i.p.). Bilateral sciatic nerves were scanned with a volume coil in a 7 T magnet 7 days after USPIO administration. Fluid-sensitive MR images were obtained, and ROIs were placed on bilateral sciatic nerves to quantify signal intensity. Pain behavior modulation by minocycline was measured using the Von Frey filament test. Sciatic nerves were ultimately harvested at day 7, fixed in 10% buffered formalin and stained for the presence of iron oxide-laden macrophages. Behavioral measurements confirmed the presence of allodynia in the neuropathic pain model while the uninjured and minocycline-treated injured group had significantly higher paw withdrawal thresholds (p < 0.011). Decreased MR signal is observed in the SNI group that received USPIOs (3.3+/-0.5%) compared to the minocycline-treated SNI group that received USPIOs (15.2+/-4.5%) and minocycline-treated group that did not receive USPIOs (41.2+/-2.3%) (p < 0.04). Histology of harvested sciatic nerve specimens confirmed the presence USPIOs at the nerve injury site in the SNI group without minocycline treatment.Animals with neuropathic pain in the left hindpaw show increased trafficking of USPIO-laden macrophages to the site of sciatic nerve injury. Minocycline to retards the migration of macrophages to the nerve injury site, which may partly explain its anti-nociceptive effects. USPIO-MRI is an effective in vivo imaging tool to study the role of macrophages in the development of neuropathic pain.

  View details for DOI 10.1186/1744-8069-8-49

  View details for Web of Science ID 000309839300001

  View details for PubMedID 22742763

  View details for PubMedCentralID PMC3472277

• Rapid MR venography in children using a blood pool contrast agent and multi-station fat-water-separated volumetric imaging PEDIATRIC RADIOLOGY Ghanouni, P., Walters, S. G., Vasanawala, S. S. 2012; 42 (2): 242-248

  Abstract

  A rapid, reliable radiation-free method of pediatric body venography might complement US by evaluating veins in the abdomen and pelvis and by providing a global depiction of venous anatomy. We describe a MR venography technique utilizing gadofosveset, a blood pool contrast agent, in children. The technique allows high-spatial-resolution imaging of the veins from the diaphragm to the knees in less than 15 min of total exam time.

  View details for DOI 10.1007/s00247-011-2254-5

  View details for Web of Science ID 000301664100015

  View details for PubMedID 21989981

  View details for PubMedCentralID PMC3288576

• MR Imaging-guided Cryoablation for the Treatment of Benign Prostatic Hyperplasia JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Ghanouni, P., Gill, H., Kaye, E., Pauly, K. B., Daniel, B. 2011; 22 (10): 1427-1430

  Abstract

  A patient with benign prostatic hyperplasia presented with chronic lower urinary tract symptoms despite prior surgery and continued medical therapy. Using a magnetic resonance imaging-guided transperineal approach, two cryoprobes were placed into the transition zone of the prostate gland, and two cryoablation freeze-thaw cycles were performed. At 10 weeks after treatment, the frequency of nocturia had decreased from once every 1.5 hours to once per night, urinary peak flow rates had increased from 5.1 mL/s to 10.3 mL/s, and postvoid residual urinary bladder volume had decreased from 187 mL to 58 mL. Improved flow rates and symptoms remained stable 16 weeks after treatment.

  View details for DOI 10.1016/j.jvir.2011.08.010

  View details for PubMedID 21961982

• In vivo MR acoustic radiation force imaging in the porcine liver MEDICAL PHYSICS Holbrook, A. B., Ghanouni, P., Santos, J. M., Medan, Y., Pauly, K. B. 2011; 38 (9): 5081-5089

  Abstract

  High intensity focused ultrasound (HIFU) in the abdomen can be sensitive to acoustic aberrations that can exist in the beam path of a single sonication. Having an accurate method to quickly visualize the transducer focus without damaging tissue could assist with executing the treatment plan accurately and predicting these changes and obstacles. By identifying these obstacles, MR acoustic radiation force imaging (MR-ARFI) provides a reliable method for visualizing the transducer focus quickly without damaging tissue and allows accurate execution of the treatment plan.MR-ARFI was used to view the HIFU focus, using a gated spin echo flyback readout-segmented echo-planar imaging sequence. HIFU spots in a phantom and in the livers of five live pigs under general anesthesia were created with a 550 kHz extracorporeal phased array transducer initially localized with a phase-dithered MR-tracking sequence to locate microcoils embedded in the transducer. MR-ARFI spots were visualized, observing the change of focal displacement and ease of steering. Finally, MR-ARFI was implemented as the principle liver HIFU calibration system, and MR-ARFI measurements of the focal location relative to the thermal ablation location in breath-hold and breathing experiments were performed.Measuring focal displacement with MR-ARFI was achieved in the phantom and in vivo liver. In one in vivo experiment, where MR-ARFI images were acquired repeatedly at the same location with different powers, the displacement had a linear relationship with power [y = 0.04x + 0.83 μm (R(2) = 0.96)]. In another experiment, the displacement images depicted the electronic steering of the focus inside the liver. With the new calibration system, the target focal location before thermal ablation was successfully verified. The entire calibration protocol delivered 20.2 J of energy to the animal (compared to greater than 800 J for a test thermal ablation). ARFI displacement maps were compared with thermal ablations during seven breath-hold ablations. The error was 0.83 ± 0.38 mm in the S/I direction and 0.99 ± 0.45 mm in the L/R direction. For six spots in breathing ablations, the mean error in the nonrespiration direction was 1.02 ± 0.89 mm.MR-ARFI has the potential to improve free-breathing plan execution accuracy compared to current calibration and acoustic beam adjustment practices. Gating the acquisition allows for visualization of the focal spot over the course of respiratory motion, while also being insensitive to motion effects that can complicate a thermal test spot. That MR-ARFI measures a mechanical property at the focus also makes it insensitive to high perfusion, of particular importance to highly perfused organs such as the liver.

  View details for DOI 10.1118/1.3622610

  View details for Web of Science ID 000294482900019

  View details for PubMedID 21978053

  View details for PubMedCentralID PMC3170397

• Magnetic resonance guided high-intensity focused ultrasound ablation of musculoskeletal tumors. Current orthopaedic practice Avedian, R. S., Gold, G., Ghanouni, P., Pauly, K. B. 2011; 22 (4): 303-308

  Abstract

  This article reviews the fundamental principles and clinical experimental uses of magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) ablation of musculoskeletal tumors. MRgHIFU is a noninvasive treatment modality that takes advantage of the ability of magnetic resonance to measure tissue temperature and uses this technology to guide high-intensity focused ultrasound waves to a specific focus within the human body that results in heat generation and complete thermal necrosis of the targeted tissue. Adjacent normal tissues are spared because of the accurate delivery of thermal energy, as well as, local blood perfusion that provides a cooling effect. MRgHIFU is approved by the Food and Drug Administration for the treatment of uterine fibroids and is used on an experimental basis to treat breast, prostate, liver, bone, and brain tumors.

  View details for PubMedID 26120376

• Computed Tomographic Diagnosis of Appendicitis Within a Spigelian Hernia JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Deshmukh, S., Ghanouni, P., Mindelzun, R., Roos, J. 2010; 34 (2): 199-200

  Abstract

  A Spigelian hernia is a rare abdominal wall hernia diagnosed with ultrasonography or computed tomography. We report the first case of acute appendicitis within a Spigelian hernia diagnosed by computed tomography.

  View details for DOI 10.1097/RCT.0b013e3181b766d9

  View details for Web of Science ID 000276496600007

  View details for PubMedID 20351503

• An Interdisciplinary Initiative to Reduce Radiation Exposure: Evaluation of Appendicitis in a Pediatric Emergency Department With Clinical Assessment Supported by a Staged Ultrasound and Computed Tomography Pathway 10th Annual Academic Emergency Medicine Consensus Conference/Annual Meeting of the Society-for-Academic-Emergency-Medicine Ramarajan, N., Krishnamoorthi, R., Barth, R., Ghanouni, P., Mueller, C., Dannenburg, B., Wang, N. E. WILEY-BLACKWELL PUBLISHING, INC. 2009: 1258–65

  Abstract

  In the emergency department (ED), a significant amount of radiation exposure is due to computed tomography (CT) scans performed for the diagnosis of appendicitis. Children are at increased risk of developing cancer from low-dose radiation and it is therefore desirable to utilize CT only when appropriate. Ultrasonography (US) eliminates radiation but has sensitivity inferior to that of CT. We describe an interdisciplinary initiative to use a staged US and CT pathway to maximize diagnostic accuracy while minimizing radiation exposure.This was a retrospective outcomes analysis of patients presenting after hours for suspected appendicitis at an academic children's hospital ED over a 6-year period. The pathway established US as the initial imaging modality. CT was recommended only if US was equivocal. Clinical and pathologic outcomes from ED diagnosis and disposition, histopathology and return visits, were correlated with the US and CT. ED diagnosis and disposition, pathology, and return visits were used to determine outcome.A total of 680 patients met the study criteria. A total of 407 patients (60%) followed the pathway. Two-hundred of these (49%) were managed definitively without CT. A total of 106 patients (26%) had a positive US for appendicitis; 94 (23%) had a negative US. A total of 207 patients had equivocal US with follow-up CT. A total of 144 patients went to the operating room (OR); 10 patients (7%) had negative appendectomies. One case of appendicitis was missed (<0.5%). The sensitivity, specificity, negative predictive value, and positive predictive values of our staged US-CT pathway were 99%, 91%, 99%, and 85%, respectively. A total of 228 of 680 patients (34%) had an equivocal US with no follow-up CT. Of these patients, 10 (4%) went to the OR with one negative appendectomy. A total of 218 patients (32%) were observed clinically without complications.Half of the patients who were treated using this pathway were managed with definitive US alone with an acceptable negative appendectomy rate (7%) and a missed appendicitis rate of less than 0.5%. Visualization of a normal appendix (negative US) was sufficient to obviate the need for a CT in the authors' experience. Emergency physicians (EPs) used an equivocal US in conjunction with clinical assessment to care for one-third of study patients without a CT and with no known cases of missed appendicitis. These data suggest that by employing US first on all children needing diagnostic imaging for diagnosis of acute appendicitis, radiation exposure may be substantially decreased without a decrease in safety or efficacy.

  View details for DOI 10.1111/j.1553-2712.2009.00511.x

  View details for Web of Science ID 000271465000031

  View details for PubMedID 20053244

• Early Sonographic Diagnosis of Intrauterine Device Migration to the Adnexa JOURNAL OF CLINICAL ULTRASOUND Deshmukh, S., Ghanouni, P., Jeffrey, R. B. 2009; 37 (7): 414-419

  Abstract

  Uterine perforation is an uncommon complication of intrauterine devices (IUDs). Perforating IUDs can migrate to various locations but paradoxically are rarely found in ovaries or broad ligament. We describe an unusual case of a 23-year-old woman 1-month postpartum with an IUD translocation to the right adnexa. The IUD was inserted only 1 week prior to presentation, and she experienced pain on insertion. After visualization by ultrasound, the IUD was laparoscopically removed. We suggest early use of ultrasound in cases of potential IUD migration, particularly in high-risk patients and when IUD insertion causes pain.

  View details for DOI 10.1002/jcu.20591

  View details for Web of Science ID 000269365100011

  View details for PubMedID 19484740

• Ductal pattern enhancement on magnetic resonance imaging of the breast due to ductal lavage BREAST JOURNAL Ghanouni, P., Kurian, A. W., Margolis, D., Hartman, A., Mills, M. A., Plevritis, S. K., Ford, J. M., Daniel, B. L. 2007; 13 (3): 281-286

  Abstract

  Our purpose is to describe the appearance of breast ductal enhancement found on magnetic resonance imaging (MRI) after breast ductal lavage (DL). We describe a novel etiology of enhancement in a ductal pattern on postcontrast MRI of the breast. Knowledge of the potential for breast MRI enhancement subsequent to DL, which can mimic the appearance of a pathologic lesion, is critical to the care of patients who undergo breast MRI and DL or other intraductal cannulation procedures.

  View details for PubMedID 17461903

• General purpose, field-portable cell-based biosensor platform BIOSENSORS & BIOELECTRONICS Gilchrist, K. H., Barker, V. N., Fletcher, L. E., DeBusschere, B. D., Ghanouni, P., Giovangrandi, L., Kovacs, G. T. 2001; 16 (7-8): 557-564

  Abstract

  There are several groups of researchers developing cell-based biosensors for chemical and biological warfare agents based on electrophysiologic monitoring of cells. In order to transition such sensors from the laboratory to the field, a general-purpose hardware and software platform is required. This paper describes the design, implementation, and field-testing of such a system, consisting of cell-transport and data acquisition instruments. The cell-transport module is a self-contained, battery-powered instrument that allows various types of cell-based modules to be maintained at a preset temperature and ambient CO(2) level while in transit or in the field. The data acquisition module provides 32 channels of action potential amplification, filtering, and real-time data streaming to a laptop computer. At present, detailed analysis of the data acquired is carried out off-line, but sufficient computing power is available in the data acquisition module to enable the most useful algorithms to eventually be run real-time in the field. Both modules have sufficient internal power to permit realistic field-testing, such as the example presented in this paper.

  View details for Web of Science ID 000171257900015

  View details for PubMedID 11544049

• Single-molecule spectroscopy of the beta(2) adrenergic receptor: Observation of conformational substates in a membrane protein PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Peleg, G., Ghanouni, P., Kobilka, B. K., Zare, R. N. 2001; 98 (15): 8469-8474

  Abstract

  Single-molecule studies of the conformations of the intact beta(2) adrenergic receptor were performed in solution. Photon bursts from the fluorescently tagged adrenergic receptor in a micelle were recorded. A photon-burst algorithm and a Poisson time filter were implemented to characterize single molecules diffusing across the probe volume of a confocal microscope. The effects of molecular diffusion and photon number fluctuations were deconvoluted by assuming that Poisson distributions characterize the molecular occupation and photon numbers. Photon-burst size histograms were constructed, from which the source intensity distributions were extracted. Different conformations of the beta(2) adrenergic receptor cause quenching of the bound fluorophore to different extents and hence produce different photon-burst sizes. An analysis of the photon-burst histograms shows that there are at least two distinct substates for the native adrenergic membrane receptor. This behavior is in contrast to one peak observed for the dye molecule, rhodamine 6G. We test the reliability and robustness of the substate number determination by investigating the application of different binning criteria. Conformational changes associated with agonist binding result in a marked change in the distribution of photon-burst sizes. These studies provide insight into the conformational heterogeneity of G protein-coupled receptors in the presence and absence of a bound agonist.

  View details for Web of Science ID 000169967000049

  View details for PubMedID 11438704

  View details for PubMedCentralID PMC37459

• Functionally different agonists induce distinct conformations in the G protein coupling domain of the beta(2) adrenergic receptor JOURNAL OF BIOLOGICAL CHEMISTRY Ghanouni, P., Gryczynski, Z., Steenhuis, J. J., LEE, T. W., Farrens, D. L., Lakowicz, J. R., Kobilka, B. K. 2001; 276 (27): 24433-24436

  Abstract

  G protein-coupled receptors represent the largest class of drug discovery targets. Drugs that activate G protein-coupled receptors are classified as either agonists or partial agonists. To study the mechanism whereby these different classes of activating ligands modulate receptor function, we directly monitored ligand-induced conformational changes in the G protein-coupling domain of the beta(2) adrenergic receptor. Fluorescence lifetime analysis of a reporter fluorophore covalently attached to this domain revealed that, in the absence of ligands, this domain oscillates around a single detectable conformation. Binding to an antagonist does not change this conformation but does reduce the flexibility of the domain. However, when the beta(2) adrenergic receptor is bound to a full agonist, the G protein coupling domain exists in two distinct conformations. Moreover, the conformations induced by a full agonist can be distinguished from those induced by partial agonists. These results provide new insight into the structural consequence of antagonist binding and the basis of agonism and partial agonism.

  View details for Web of Science ID 000169800700001

  View details for PubMedID 11320077

• Agonist-induced conformational changes in the G-protein-coupling domain of the beta(2) adrenergic receptor PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ghanouni, P., Steenhuis, J. J., Farrens, D. L., Kobilka, B. K. 2001; 98 (11): 5997-6002

  Abstract

  The majority of extracellular physiologic signaling molecules act by stimulating GTP-binding protein (G-protein)-coupled receptors (GPCRs). To monitor directly the formation of the active state of a prototypical GPCR, we devised a method to site specifically attach fluorescein to an endogenous cysteine (Cys-265) at the cytoplasmic end of transmembrane 6 (TM6) of the beta(2) adrenergic receptor (beta(2)AR), adjacent to the G-protein-coupling domain. We demonstrate that this tag reports agonist-induced conformational changes in the receptor, with agonists causing a decline in the fluorescence intensity of fluorescein-beta(2)AR that is proportional to the biological efficacy of the agonist. We also find that agonists alter the interaction between the fluorescein at Cys-265 and fluorescence-quenching reagents localized to different molecular environments of the receptor. These observations are consistent with a rotation and/or tilting of TM6 on agonist activation. Our studies, when compared with studies of activation in rhodopsin, indicate a general mechanism for GPCR activation; however, a notable difference is the relatively slow kinetics of the conformational changes in the beta(2)AR, which may reflect the different energetics of activation by diffusible ligands.

  View details for PubMedID 11353823

• The effect of pH on beta(2) adrenoceptor function - Evidence for protonation-dependent activation JOURNAL OF BIOLOGICAL CHEMISTRY Ghanouni, P., Schambye, H., Seifert, R., LEE, T. W., Rasmussen, S. G., Gether, U., Kobilka, B. K. 2000; 275 (5): 3121-3127

  Abstract

  The transition of rhodopsin from the inactive to the active state is associated with proton uptake at Glu(134) (1), and recent mutagenesis studies suggest that protonation of the homologous amino acid in the alpha(1B) adrenergic receptor (Asp(142)) may be involved in its mechanism of activation (2). To further explore the role of protonation in G protein-coupled receptor activation, we examined the effects of pH on the rate of ligand-induced conformational change and on receptor-mediated G protein activation for the beta(2) adrenergic receptor (beta(2)AR). The rate of agonist-induced change in the fluorescence of NBD-labeled, purified beta(2)AR was 2-fold greater at pH 6.5 than at pH 8, even though agonist affinity was lower at pH 6.5. This biophysical analysis was corroborated by functional studies; basal (agonist-independent) activation of Galpha(s) by the beta(2)AR was greater at pH 6.5 compared with pH 8.0. Taken together, these results provide evidence that protonation increases basal activity by destabilizing the inactive state of the receptor. In addition, we found that the pH sensitivity of beta(2)AR activation is not abrogated by mutation of Asp(130), which is homologous to the highly conserved acidic amino acids that link protonation to activation of rhodopsin (Glu(134)) and the alpha(1B) adrenergic receptor (Asp(142)).

  View details for Web of Science ID 000085146500017

  View details for PubMedID 10652295

• Characterization of ligand-induced conformational states in the beta(2) adrenergic receptor 8th Swiss Workshop of Methodology in Receptor Research Kobilka, B., Gether, U., Seifert, R., Lin, S., Ghanouni, P. MARCEL DEKKER INC. 1999: 293–300

  Abstract

  Drugs acting at G protein coupled receptors can be classified in biological assays as either agonists, partial agonists, neutral antagonists, or as inverse agonists. Very little is known about the actual molecular events and structural changes that occur in the receptor following ligand binding and during transmission of a signal across the membrane. Therefore, the structural basis for the biological classification of drug action remains unknown. To date, the conformational state of G protein coupled receptors has been inferred from the activity of the effector enzyme modulated by the G protein. We have used two different approaches to monitor conformational changes in beta 2 adrenergic receptor. Fluorescence spectroscopy can be used to directly monitor structural changes in purified beta 2 adrenergic receptor in real-time. The emission from many fluorescent molecules is strongly dependent on the polarity of the environment in which they are located. Thus, fluorescent probes covalently bound to proteins can be used as sensitive indicators of conformational changes and protein-protein interactions. In addition, we examined functional differences between agonists and partial agonists using fusion proteins between wild-type beta 2 receptor or a constitutively active beta 2 receptor mutant and Gs alpha. These receptor-G protein fusion proteins guarantee highly efficient coupling with a defined stoichiometry. The results of these experiments will be discussed in the context of current models of G protein coupled receptor activation.

  View details for Web of Science ID 000078825900021

  View details for PubMedID 10071765

• Examination of ligand-induced conformational changes in the beta(2) adrenergic receptor 2nd International Symposium on Membrane Receptors Signal Transduction and Drug Action / 19th Symposium on Biomembrane-Drug Interaction Kobilka, B., Gether, U., Seifert, R., Lin, S. S., Ghanouni, P. PERGAMON-ELSEVIER SCIENCE LTD. 1998: 1509–12

  Abstract

  The environmentally sensitive and cysteine reactive fluorescent probe, IANBD, was used to monitor ligand-induced structural changes in the beta2 adrenergic receptor (beta2AR) by fluorescent spectroscopy. We found that agonists caused a dose-dependent and reversible decrease in fluorescence from the purified IANBD-labeled beta2AR. This suggested that agonists promote a conformational change in the receptor that leads to an increase in the polarity of the environment around one or more IANBD labeled cysteines. The wildtype receptor contains eight free cysteines and mutagenesis and peptide mapping experiments have indicated that several of these sites are accessible for chemical derivatization. Thus, to identify the cysteine(s) involved in the agonist-induced change in fluorescence and thereby map agonist-induced conformational changes in the beta2AR, we generated a series of mutant receptors having limited numbers of cysteines available for fluorescent labeling. Fluorescence spectroscopy analysis of the purified and site-selectively IANBD-labeled mutants showed that IANBD labeled 125Cys and 285Cys are responsible for the observed changes in fluorescence consistent with movements of TM III and VI in response to agonist binding.

  View details for Web of Science ID 000072850800013

  View details for PubMedID 9585127

• Agonists induce conformational changes in transmembrane domains III and VI of the beta(2) adrenoceptor EMBO JOURNAL Gether, U., Lin, S., Ghanouni, P., Ballesteros, J. A., Weinstein, H., Kobilka, B. K. 1997; 16 (22): 6737-6747

  Abstract

  Agonist binding to G protein-coupled receptors is believed to promote a conformational change that leads to the formation of the active receptor state. However, the character of this conformational change which provides the important link between agonist binding and G protein coupling is not known. Here we report evidence that agonist binding to the beta2 adrenoceptor induces a conformational change around 125Cys in transmembrane domain (TM) III and around 285Cys in TM VI. A series of mutant beta2 adrenoceptors with a limited number of cysteines available for chemical derivatization were purified, site-selectively labeled with the conformationally sensitive, cysteine-reactive fluorophore IANBD and analyzed by fluorescence spectroscopy. Like the wild-type receptor, mutant receptors containing 125Cys and/or 285Cys showed an agonist-induced decrease in fluorescence, while no agonist-induced response was observed in a receptor where these two cysteines were mutated. These data suggest that IANBD bound to 125Cys and 285Cys are exposed to a more polar environment upon agonist binding, and indicate that movements of transmembrane segments III and VI are involved in activation of G protein-coupled receptors.

  View details for Web of Science ID A1997YJ20700013

  View details for PubMedID 9362488

  View details for PubMedCentralID PMC1170278