Academic Appointments


  • Clinical Assistant Professor, Radiology

Honors & Awards


  • Featured Cover Article, Journal of Magnetic Resonance in Imaging (2016)
  • NIH LRP Award for Clinical Research, National Institutes of Health (2014)
  • Magna Cum Laude Merit Award, International Society of Magnetic Resonance in Medicine - 20th Annual Symposium (2012)
  • Postdoctoral Fellowship Award, California Breast Cancer Research Program (2010-2012)
  • Member, Tau Beta Pi Engineering Honor Society (2000)

Boards, Advisory Committees, Professional Organizations


  • Director, RSL Trainee Council (2012 - 2014)
  • Member, International Society of Magnetic Resonance in Medicine (2009 - Present)

Professional Education


  • Ph.D., University of Southern California, Biomedical Engineering (2008)
  • M.S., University of Southern California, Biomedical Engineering (2005)
  • B.S., University of South Florida, Electrical Engineering (2002)

Current Research and Scholarly Interests


Developing interventional techniques and patient specific models in MR image guided High Intensity Focused Ultrasound (HIFU). PRF thermometry monitoring for ablative applications in cancer trans-cranial functional neurosurgery to treat essential tremor and Parkinson's disease.

Treatment efficacy and clinical outcomes analysis in multi-center trials of MR guided interventions to treat desmoid tumors, uterine leiomyomas, and osseous metastasis.
Photoacoustic imaging of microvasculature.

All Publications


  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo swine brain. Journal of magnetic resonance imaging Bitton, R. R., Pauly, K. R. 2014; 39 (5): 1294-1300

    Abstract

    To present the use of MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo brain tissue as a planning indicator for MR-guided focused ultrasound (MRgFUS).Calcifications were implanted in ex vivo swine brain and imaged using SWI, MR-ARFI, and computed tomography (CT). SWI-filtered phase images used 3D gradient recalled echo (GRE) images with a Fourier-based unwrapping algorithm. The MR-ARFI pulse sequence used a 2DFT spin-echo with repeated bipolar encoding gradients in the direction of the longitudinal ultrasound beam. MR-ARFI interrogations scanned a subregion (14 × 10 × 12 mm) of the brain surrounding the calcification. They were combined into a single displacement weighted map, using the sum of squares method. Calcification size estimates were based on image profiles plotted along the ±x and ±z direction, at the full-width half-maximum.Both MR-ARFI and SWI were able to visualize the calcifications. The contrast ratio was 150 for CT, 12 for SWI, and 12 for MR-ARFI. Profile measures were 1.35 × 1.28 mm on CT, 1.24 × 1.73 mm on SWI, and 2.45 × 3.02 mm on MR-ARFI. MR-ARFI displacement showed a linear increase with acoustic power (20-80W), and also increased with calcification size.The use of SWI-filtered phase and MR-ARFI have the potential to provide a clinical indicator of calcification relevance in the planning of a transcranial MRgFUS treatment.J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jmri.24255

    View details for PubMedID 24123504

  • Toward MR-guided high intensity focused ultrasound for presurgical localization: Focused ultrasound lesions in cadaveric breast tissue JOURNAL OF MAGNETIC RESONANCE IMAGING Bitton, R. R., Kaye, E., Dirbas, F. M., Daniel, B. L., Pauly, K. B. 2012; 35 (5): 1089-1097

    Abstract

    To investigate magnetic resonance image-guided high intensity focused ultrasound (MR-HIFU) as a surgical guide for nonpalpable breast tumors by assessing the palpability of MR-HIFU-created lesions in ex vivo cadaveric breast tissue.MR-HIFU ablations spaced 5 mm apart were made in 18 locations using the ExAblate2000 system. Ablations formed a square perimeter in mixed adipose and fibroglandular tissue. Ablation was monitored using T1-weighted fast spin echo images. MR-acoustic radiation force impulse (MR-ARFI) was used to remotely palpate each ablation location, measuring tissue displacement before and after thermal sonications. Displacement profiles centered at each ablation spot were plotted for comparison. The cadaveric breast was manually palpated to assess stiffness of ablated lesions and dissected for gross examination. This study was repeated on three cadaveric breasts.MR-ARFI showed a collective postablation reduction in peak displacement of 54.8% ([4.41 ± 1.48] μm pre, [1.99 ± 0.82] μm post), and shear wave velocity increase of 65.5% ([10.69 ± 1.60] mm pre, [16.33 ± 3.10] mm post), suggesting tissue became stiffer after the ablation. Manual palpation and dissection of the breast showed increased palpability, a darkening of ablation perimeter, and individual ablations were visible in mixed adipose/fibroglandular tissue.The results of this preliminary study show MR-HIFU has the ability to create palpable lesions in ex vivo cadaveric breast tissue, and may potentially be used to preoperatively localize nonpalpable breast tumors.

    View details for DOI 10.1002/jmri.23529

    View details for PubMedID 22170814

  • A 3-D High-Frequency Array Based 16 Channel Photoacoustic Microscopy System for In Vivo Micro- Vascular Imaging IEEE TRANSACTIONS ON MEDICAL IMAGING Bitton, R., Zemp, R., Yen, J., Wang, L. V., Shung, K. K. 2009; 28 (8): 1190-1197

    Abstract

    This paper discusses the design of a novel photoacoustic microscopy imaging system with promise for studying the structure of tissue microvasculature for applications in visualizing angiogenesis. A new 16 channel analog and digital high-frequency array based photoacoustic microscopy system (PAM) was developed using an Nd:YLF pumped tunable dye laser, a 30 MHz piezo composite linear array transducer, and a custom multichannel receiver electronics system. Using offline delay and sum beamforming and beamsteering, phantom images were obtained from a 6 mum carbon fiber in water at a depth of 8 mm. The measured -6 dB lateral and axial spatial resolution of the system was 100+/-5 microm and 45+/-5 microm, respectively. The dynamic focusing capability of the system was demonstrated by imaging a composite carbon fiber matrix through a 12.5 mm imaging depth. Next, 2-D in vivo images were formed of vessels around 100 mum in diameter in the human hand. Three-dimensional in vivo images were also formed of micro-vessels 3 mm below the surface of the skin in two Sprague Dawley rats.

    View details for DOI 10.1109/TMI.2008.2011899

    View details for Web of Science ID 000268525500005

    View details for PubMedID 19131292

    View details for PubMedCentralID PMC2757099

  • Realtime Photoacoustic Microscopy of Murine Cardiovascular Dynamics OPTICS EXPRESS Zemp, R. J., Song, L., Bitton, R., Shung, K. K., Wang, L. V. 2008; 16 (22): 18551-18556

    Abstract

    Non-invasive visualization of cardiovascular dynamics in small animals is challenging due to their rapid heart-rates. We present a realtime photoacoustic imaging system consisting of a 30-MHz ultrasound array transducer, receive electronics, a high-repetition-rate laser, and a multicore-computer, and demonstrate its ability to image optically-absorbing structures of the beating hearts of young athymic nude mice at rates of approximately 50 frames per second with 100 microm x 25 microm spatial resolution. To our knowledge this is the first report of realtime photoacoustic imaging of physiological dynamics.

    View details for Web of Science ID 000260865900140

    View details for PubMedID 18958134

  • Realtime photoacoustic microscopy in vivo with a 30-MHz ultrasound array transducer OPTICS EXPRESS Zemp, R. J., Song, L., Bitton, R., Shung, K. K., Wang, L. V. 2008; 16 (11): 7915-7928

    Abstract

    We present a novel high-frequency photoacoustic microscopy system capable of imaging the microvasculature of living subjects in realtime to depths of a few mm. The system consists of a high-repetition-rate Q-switched pump laser, a tunable dye laser, a 30-MHz linear ultrasound array transducer, a multichannel high-frequency data acquisition system, and a shared-RAM multi-core-processor computer. Data acquisition, beamforming, scan conversion, and display are implemented in realtime at 50 frames per second. Clearly resolvable images of 6-microm-diameter carbon fibers are experimentally demonstrated at 80 microm separation distances. Realtime imaging performance is demonstrated on phantoms and in vivo with absorbing structures identified to depths of 2.5-3 mm. This work represents the first high-frequency realtime photoacoustic imaging system to our knowledge.

    View details for Web of Science ID 000256469900038

    View details for PubMedID 18545502

  • Design of a high frequency array based photoacoustic Microscopy system for micro-vascular Imaging 29th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Bitton, R., Zerrip, R., Yen, J., Wang, L. H., Shung, K. K. IEEE. 2007: 2175–2178

    Abstract

    The rapidly expanding field of photoacoustic imaging includes a technique called photoacoustic microscopy. Photoacoustic microscopy is a hybrid imaging modality with sub-millimeter resolution that possesses the contrast benefit of optical imaging and the resolution benefit of ultrasonic imaging. This technique can be used to image the structure and dynamics of microvessels involved in angiogenesis within biological tissue. In this paper we present results of a new high frequency array based photoacoustic microscopy system (PAM) using an Nd:YLF pumped tunable dye laser, a 30MHz piezo composite linear array and a custom multi-channel receiver system. Using offline delay and sum beamforming and beamsteering, phantom images were obtained from a 6microm carbon fiber in water at a depth of 8mm. The measured axial and lateral spatial resolution of the system was 103+/-5microm and 45+/-5microm, respectively. In vivo B-scans were obtained from vessels within a human hand as well as 3D photoacoustic images of vessels 3mm below the skin surface in a Sprague Dawley Rat.

    View details for Web of Science ID 000253467001228

    View details for PubMedID 18002420

  • Photoacoustic imaging of the microvasculature with a high-frequency ultrasound array transducer JOURNAL OF BIOMEDICAL OPTICS Zemp, R. J., Bitton, R., Li, M., Shung, K. K., Stoica, G., Wang, L. V. 2007; 12 (1)

    Abstract

    Visualization of microvascular networks could provide new information about function and disease. We demonstrate the capabilities of a 30-MHz ultrasound array system for photoacoustic microscopy of small (< or = 300 microm) vessels in a rat. 3D images obtained by translating the array in the elevation direction are compared with photographs of excised skin. The system is shown to have 100-microm lateral resolution, 25-microm axial resolution, and 3-mm imaging depth. To our knowledge this is the first report on photoacoustic microscopy of the microvasculature with a high-frequency array transducer. It is anticipated that the system can be used for studying and diagnosing a number of diseases including cancer, atherosclerosis, dermatological disorders, and peripheral microvascular complications in diabetes.

    View details for DOI 10.1117/1.2709850

    View details for Web of Science ID 000245505400001

    View details for PubMedID 17343475

  • Photoacoustic Microscopy with a 30MHz Array and Receive System Proc IEEE Ultrasonics Symposium 2006 Bitton R, Zemp R, Li M.L., Yen J., Wang L.H., Shung K.K. 2006: 389-392