All Publications

  • Segmenting Cervical Arteries in Phase Contrast Magnetic Resonance Imaging Using Convolutional Encoder-Decoder Networks APPLIED SCIENCES-BASEL Campbell, B., Yadav, D., Hussein, R., Jovin, M., Hoover, S., Halbert, K., Holley, D., Khalighi, M., Davidzon, G. A., Tong, E., Steinberg, G. K., Moseley, M., Zhao, M. Y., Zaharchuk, G. 2023; 13 (21)
  • Reductions in synaptic marker SV2A in early-course Schizophrenia. Journal of psychiatric research Yoon, J. H., Zhang, Z., Mormino, E., Davidzon, G., Minzenberg, M. J., Ballon, J., Kalinowski, A., Hardy, K., Naganawa, M., Carson, R. E., Khalighi, M., Park, J. H., Levinson, D. F., Chin, F. T. 2023; 161: 213-217


    Excess synaptic pruning during neurodevelopment has emerged as one of the leading hypotheses on the causal mechanism for schizophrenia. It proposes that excess synaptic elimination occurs during development before the formal onset of illness. Accordingly, synaptic deficits may be observable at all stages of illnesses, including in the early phases. The availability of [11C]UCB-J, the first-in-human in vivo synaptic marker, represents an opportunity for testing this hypothesis with a relatively high level of precision. The first two published [11C]UCB-J schizophrenia studies have documented significant, widespread reductions in binding in chronic patients. The present study tested the hypothesis that reductions are present in early-course patients. 18 subjects completed [11C]UCB-J PET scans, (nine with schizophrenia, average duration of illness of 3.36 years, and nine demographically-matched healthy individuals). We compared binding levels, quantified as non-displaceable specific binding (BPND), in a set of a priori-specified brain regions of interest (ROIs). Eight ROIs (left and right hippocampus, right superior temporal and Heschl's gyrus, left and right putamen, and right caudal and rostral middle frontal gyrus) showed large reductions meeting Bonferroni corrected significant levels, p<0.0036. Exploratory, atlas-wide analyses confirmed widespread reductions in schizophrenia. We also observed significant positive correlations between binding levels and cognitive performance and a negative correlation with the severity of delusions. These results largely replicate findings from chronic patients, indicating that extensive [11C]UCB-J binding deficits are reliable and reproducible. Moreover, these results add to the growing evidence that excess synaptic pruning is a major disease mechanism for schizophrenia.

    View details for DOI 10.1016/j.jpsychires.2023.02.026

    View details for PubMedID 36934603

  • Harmonization of PET image reconstruction parameters in simultaneous PET/MRI. EJNMMI physics Laforest, R., Khalighi, M., Natsuaki, Y., Rajagopal, A., Chandramohan, D., Byrd, D., An, H., Larson, P., James, S. S., Sunderland, J. J., Kinahan, P. E., Hope, T. A. 2021; 8 (1): 75


    OBJECTIVE: Simultaneous PET/MRIs vary in their quantitative PET performance due to inherent differences in the physical systems and differences in the image reconstruction implementation. This variability in quantitative accuracy confounds the ability to meaningfully combine and compare data across scanners. In this work, we define image reconstruction parameters that lead to comparable contrast recovery curves across simultaneous PET/MRI systems.METHOD: The NEMA NU-2 image quality phantom was imaged on one GE Signa and on one Siemens mMR PET/MRI scanner. The phantom was imaged at 9.7:1 contrast with standard spheres (diameter 10, 13, 17, 22, 28, 37mm) and with custom spheres (diameter: 8.5, 11.5, 15, 25, 32.5, 44mm) using a standardized methodology. Analysis was performed on a 30min listmode data acquisition and on 6 realizations of 5min from the listmode data. Images were reconstructed with the manufacturer provided iterative image reconstruction algorithms with and without point spread function (PSF) modeling. For both scanners, a post-reconstruction Gaussian filter of 3-7mm in steps of 1mm was applied. Attenuation correction was provided from a scaled computed tomography (CT) image of the phantom registered to the MR-based attenuation images and verified to align on the non-attenuation corrected PET images. For each of these image reconstruction parameter sets, contrast recovery coefficients (CRCs) were determined for the SUVmean, SUVmax and SUVpeak for each sphere. A hybrid metric combining the root-mean-squared discrepancy (RMSD) and the absolute CRC values was used to simultaneously optimize for best match in CRC between the two scanners while simultaneously weighting toward higher resolution reconstructions. The image reconstruction parameter set was identified as the best candidate reconstruction for each vendor for harmonized PET image reconstruction.RESULTS: The range of clinically relevant image reconstruction parameters demonstrated widely different quantitative performance across cameras. The best match of CRC curves was obtained at the lowest RMSD values with: for CRCmean, 2 iterations-7mm filter on the GE Signa and 4 iterations-6mm filter on the Siemens mMR, for CRCmax, 4 iterations-6mm filter on the GE Signa, 4 iterations-5mm filter on the Siemens mMR and for CRCpeak, 4 iterations-7mm filter with PSF on the GE Signa and 4 iterations-7mm filter on the Siemens mMR. Over all reconstructions, the RMSD between CRCs was 1.8%, 3.6% and 2.9% for CRC mean, max and peak, respectively. The solution of 2 iterations-3mm on the GE Signa and 4 iterations-3mm on Siemens mMR, both with PSF, led to simultaneous harmonization and with high CRC and low RMSD for CRC mean, max and peak with RMSD values of 2.8%, 5.8% and 3.2%, respectively.CONCLUSIONS: For two commercially available PET/MRI scanners, user-selectable parameters that control iterative updates, image smoothing and PSF modeling provide a range of contrast recovery curves that allow harmonization in harmonization strategies of optimal match in CRC or high CRC values. This work demonstrates that nearly identical CRC curves can be obtained on different commercially available scanners by selecting appropriate image reconstruction parameters.

    View details for DOI 10.1186/s40658-021-00416-0

    View details for PubMedID 34739621

  • A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2 Induced Glycolytic Reprogramming in Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research Beinat, C., Patel, C. B., Haywood, T., Murty, S., Naya, L., Castillo, J. B., Reyes, S. T., Phillips, M., Buccino, P., Shen, B., Park, J. H., Koran, M. E., Alam, I. S., James, M. L., Holley, D., Halbert, K., Gandhi, H., He, J. Q., Granucci, M., Johnson, E., Liu, D. D., Uchida, N., Sinha, R., Chu, P., Born, D. E., Warnock, G. I., Weissman, I., Hayden Gephart, M., Khalighi, M. M., Massoud, T. F., Iagaru, A., Davidzon, G., Thomas, R., Nagpal, S., Recht, L. D., Gambhir, S. S. 2021


    PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel positron emission tomography (PET) tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and GBM patients.EXPERIMENTAL DESIGN: [18F]DASA-23 was synthesized with a molar activity of 100.47 {plus minus} 29.58 GBq/mol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers, and a pilot cohort of glioma patients.RESULTS: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio (TBR) of 3.6 {plus minus} 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In GBM patients, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced magnetic resonance imaging (MRI). The uptake of [18F]DASA-23 was markedly elevated in GBMs compared to normal brain, and it identified a metabolic non-responder within 1-week of treatment initiation.CONCLUSIONS: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

    View details for DOI 10.1158/1078-0432.CCR-21-0544

    View details for PubMedID 34475101

  • Dual tracer brain PET simulation from two separate exams Khalighi, M., Chen, K., Deller, T., Jansen, F., Mormino, E., Zaharchuk, G. SOC NUCLEAR MEDICINE INC. 2021
  • True ultra-low-dose amyloid PET/MRI enhanced with deep learning for clinical interpretation. European journal of nuclear medicine and molecular imaging Chen, K. T., Toueg, T. N., Koran, M. E., Davidzon, G. n., Zeineh, M. n., Holley, D. n., Gandhi, H. n., Halbert, K. n., Boumis, A. n., Kennedy, G. n., Mormino, E. n., Khalighi, M. n., Zaharchuk, G. n. 2021


    While sampled or short-frame realizations have shown the potential power of deep learning to reduce radiation dose for PET images, evidence in true injected ultra-low-dose cases is lacking. Therefore, we evaluated deep learning enhancement using a significantly reduced injected radiotracer protocol for amyloid PET/MRI.Eighteen participants underwent two separate 18F-florbetaben PET/MRI studies in which an ultra-low-dose (6.64 ± 3.57 MBq, 2.2 ± 1.3% of standard) or a standard-dose (300 ± 14 MBq) was injected. The PET counts from the standard-dose list-mode data were also undersampled to approximate an ultra-low-dose session. A pre-trained convolutional neural network was fine-tuned using MR images and either the injected or sampled ultra-low-dose PET as inputs. Image quality of the enhanced images was evaluated using three metrics (peak signal-to-noise ratio, structural similarity, and root mean square error), as well as the coefficient of variation (CV) for regional standard uptake value ratios (SUVRs). Mean cerebral uptake was correlated across image types to assess the validity of the sampled realizations. To judge clinical performance, four trained readers scored image quality on a five-point scale (using 15% non-inferiority limits for proportion of studies rated 3 or better) and classified cases into amyloid-positive and negative studies.The deep learning-enhanced PET images showed marked improvement on all quality metrics compared with the low-dose images as well as having generally similar regional CVs as the standard-dose. All enhanced images were non-inferior to their standard-dose counterparts. Accuracy for amyloid status was high (97.2% and 91.7% for images enhanced from injected and sampled ultra-low-dose data, respectively) which was similar to intra-reader reproducibility of standard-dose images (98.6%).Deep learning methods can synthesize diagnostic-quality PET images from ultra-low injected dose simultaneous PET/MRI data, demonstrating the general validity of sampled realizations and the potential to reduce dose significantly for amyloid imaging.

    View details for DOI 10.1007/s00259-020-05151-9

    View details for PubMedID 33416955

  • Hippocampal subfield imaging and fractional anisotropy show parallel changes in Alzheimer's disease tau progression using simultaneous tau-PET/MRI at 3T. Alzheimer's & dementia (Amsterdam, Netherlands) Carlson, M. L., Toueg, T. N., Khalighi, M. M., Castillo, J., Shen, B., Azevedo, E. C., DiGiacomo, P., Mouchawar, N., Chau, G., Zaharchuk, G., James, M. L., Mormino, E. C., Zeineh, M. M. 2021; 13 (1): e12218


    Introduction: Alzheimer's disease (AD) is the most common form of dementia, characterized primarily by abnormal aggregation of two proteins, tau and amyloid beta. We assessed tau pathology and white matter connectivity changes in subfields of the hippocampus simultaneously in vivo in AD.Methods: Twenty-four subjects were scanned using simultaneous time-of-flight 18F-PI-2620 tau positron emission tomography/3-Tesla magnetic resonance imaging and automated segmentation.Results: We observed extensive tau elevation in the entorhinal/perirhinal regions, intermediate tau elevation in cornu ammonis 1/subiculum, and an absence of tau elevation in the dentate gyrus, relative to controls. Diffusion tensor imaging showed parahippocampal gyral fractional anisotropy was lower in AD and mild cognitive impairment compared to controls and strongly correlated with early tau accumulation in the entorhinal and perirhinal cortices.Discussion: This study demonstrates the potential for quantifiable patterns of 18F-PI2620 binding in hippocampus subfields, accompanied by diffusion and volume metrics, to be valuable markers of AD.

    View details for DOI 10.1002/dad2.12218

    View details for PubMedID 34337132

  • Quantitative Assessment of Deep Learning-enhanced Actual Ultra-low-dose Amyloid PET/MR Imaging Chen, K., Holley, D., Halbert, K., Toueg, T., Boumis, A., Kennedy, G., Mormino, E., Khalighi, M., Zaharchuk, G. SOC NUCLEAR MEDICINE INC. 2020
  • Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases. European journal of nuclear medicine and molecular imaging Mormino, E. C., Toueg, T. N., Azevedo, C. n., Castillo, J. B., Guo, W. n., Nadiadwala, A. n., Corso, N. K., Hall, J. N., Fan, A. n., Trelle, A. N., Harrison, M. B., Hunt, M. P., Sha, S. J., Deutsch, G. n., James, M. n., Fredericks, C. A., Koran, M. E., Zeineh, M. n., Poston, K. n., Greicius, M. D., Khalighi, M. n., Davidzon, G. A., Shen, B. n., Zaharchuk, G. n., Wagner, A. D., Chin, F. T. 2020


    In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD).Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum.SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient.Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

    View details for DOI 10.1007/s00259-020-04923-7

    View details for PubMedID 32572562

  • The Effect of Various β Values on Image Quality and Semiquantitative Measurements in 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI Images Reconstructed With a Block Sequential Regularized Expectation Maximization Algorithm. Clinical nuclear medicine Baratto, L. n., Duan, H. n., Ferri, V. n., Khalighi, M. n., Iagaru, A. n. 2020


    To compare the block sequential regularized expectation maximization (BSREM) algorithm with the ordered subsets expectation maximization (OSEM) algorithm and to evaluate how different penalty factors (b values) influence image quality and SUV measurements.We analyzed data from 78 prostate cancer patients who underwent Ga-RM2 (n = 42) or Ga-prostate-specific membrane antigen (PSMA)-11 (n = 36) PET/MRI. The raw PET data were retrospectively reconstructed using both time-of-flight (TOF)-BSREM with b values of 250, 350, 500, 750, and 1000 and TOF-OSEM. Each reconstruction was reviewed independently by 3 nuclear medicine physicians and scored qualitatively using a Likert scale (1 = poor, 5 = excellent quality). SUV measurements were analyzed as well.Fifty-seven lesions were detected (21 on Ga-RM2 and 36 on Ga-PSMA-11 PET/MRI); SUVmax decreased with the increase of β values for both tracers. Background noise (SUVsd) decreased with increasing of β values for both tracers. The mean ± SD scores for Ga-RM2 PET images were 2.4 ± 0.5 for b = 250 reconstructions, 3.2 ± 0.6 for b = 350, 4 ± 0.6 for b = 500, 4.5 ± 0.5 for b = 750, 4.4 ± 0.7 for b = 1000, and 3.4 ± 0.6 for TOF-OSEM. The mean ± SD scores for Ga-PSMA-11 PET images were 3.2 ± 0.8 for b = 250 reconstructions, 4.1 ± 0.8 for b = 350, 4.7 ± 0.6 for b = 500, 4.8 ± 0.4 for b = 750, 4.7 ± 0.6 for b = 1000, and 3.8 ± 0.5 for TOF-OSEM.Time-of-flight-BSREM algorithm improves image quality. Different b values should be used for different Ga-labeled radiopharmaceuticals such as those targeting GRPR and PSMA receptors. Once selected, the same b value should be consistently used because SUVmax measurements differ with different b values.

    View details for DOI 10.1097/RLU.0000000000003075

    View details for PubMedID 32433170

  • Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2. European journal of nuclear medicine and molecular imaging Beinat, C. n., Patel, C. B., Haywood, T. n., Shen, B. n., Naya, L. n., Gandhi, H. n., Holley, D. n., Khalighi, M. n., Iagaru, A. n., Davidzon, G. n., Gambhir, S. S. 2020


    To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers.We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software.All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 μSv/MBq.We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies,, NCT03539731 (registered 28 May 2018).

    View details for DOI 10.1007/s00259-020-04687-0

    View details for PubMedID 31938892

  • Ultra-Low-Dose 18F-Florbetaben Amyloid PET Imaging Using Deep Learning with Multi-Contrast MRI Inputs. Radiology Chen, K. T., Gong, E., de Carvalho Macruz, F. B., Xu, J., Boumis, A., Khalighi, M., Poston, K. L., Sha, S. J., Greicius, M. D., Mormino, E., Pauly, J. M., Srinivas, S., Zaharchuk, G. 2018: 180940


    Purpose To reduce radiotracer requirements for amyloid PET/MRI without sacrificing diagnostic quality by using deep learning methods. Materials and Methods Forty data sets from 39 patients (mean age ± standard deviation [SD], 67 years ± 8), including 16 male patients and 23 female patients (mean age, 66 years ± 6 and 68 years ± 9, respectively), who underwent simultaneous amyloid (fluorine 18 [18F]-florbetaben) PET/MRI examinations were acquired from March 2016 through October 2017 and retrospectively analyzed. One hundredth of the raw list-mode PET data were randomly chosen to simulate a low-dose (1%) acquisition. Convolutional neural networks were implemented with low-dose PET and multiple MR images (PET-plus-MR model) or with low-dose PET alone (PET-only) as inputs to predict full-dose PET images. Quality of the synthesized images was evaluated while Bland-Altman plots assessed the agreement of regional standard uptake value ratios (SUVRs) between image types. Two readers scored image quality on a five-point scale (5 = excellent) and determined amyloid status (positive or negative). Statistical analyses were carried out to assess the difference of image quality metrics and reader agreement and to determine confidence intervals (CIs) for reading results. Results The synthesized images (especially from the PET-plus-MR model) showed marked improvement on all quality metrics compared with the low-dose image. All PET-plus-MR images scored 3 or higher, with proportions of images rated greater than 3 similar to those for the full-dose images (-10% difference [eight of 80 readings], 95% CI: -15%, -5%). Accuracy for amyloid status was high (71 of 80 readings [89%]) and similar to intrareader reproducibility of full-dose images (73 of 80 [91%]). The PET-plus-MR model also had the smallest mean and variance for SUVR difference to full-dose images. Conclusion Simultaneously acquired MRI and ultra-low-dose PET data can be used to synthesize full-dose-like amyloid PET images. © RSNA, 2018 Online supplemental material is available for this article.

    View details for PubMedID 30526350

  • Clinical Evaluation of Ga-68-PSMA-Iota Iota and Ga-68-RM2 PET Images Reconstructed With an Improved Scatter Correction Algorithm AMERICAN JOURNAL OF ROENTGENOLOGY Wangerin, K. A., Baratto, L., Khalighi, M., Hope, T. A., Gulaka, P. K., Deller, T. W., Iagaru, A. H. 2018; 211 (3): 655–60


    Gallium-68-labeled radiopharmaceuticals pose a challenge for scatter estimation because their targeted nature can produce high contrast in these regions of the kidneys and bladder. Even small errors in the scatter estimate can result in washout artifacts. Administration of diuretics can reduce these artifacts, but they may result in adverse events. Here, we investigated the ability of algorithmic modifications to mitigate washout artifacts and eliminate the need for diuretics or other interventions.The model-based scatter algorithm was modified to account for PET/MRI scanner geometry and challenges of non-FDG tracers. Fifty-three clinical 68Ga-RM2 and 68Ga-PSMA-11 whole-body images were reconstructed using the baseline scatter algorithm. For comparison, reconstruction was also processed with modified sampling in the single-scatter estimation and with an offset in the scatter tail-scaling process. None of the patients received furosemide to attempt to decrease the accumulation of radiopharmaceuticals in the bladder. The images were scored independently by three blinded reviewers using the 5-point Likert scale.The scatter algorithm improvements significantly decreased or completely eliminated the washout artifacts. When comparing the baseline and most improved algorithm, the image quality increased and image artifacts were reduced for both 68Ga-RM2 and for 68Ga-PSMA-11 in the kidneys and bladder regions.Image reconstruction with the improved scatter correction algorithm mitigated washout artifacts and recovered diagnostic image quality in 68Ga PET, indicating that the use of diuretics may be avoided.

    View details for PubMedID 29873506

  • PET Imaging Stability Measurements During Simultaneous Pulsing of Aggressive MR Sequences on the SIGNA PET/MR System JOURNAL OF NUCLEAR MEDICINE Deller, T. W., Khalighi, M., Jansen, F. P., Glover, G. H. 2018; 59 (1): 167–72


    The recent introduction of simultaneous whole-body PET/MR scanners has enabled new research taking advantage of the complementary information obtainable with PET and MRI. One such application is kinetic modeling, which requires high levels of PET quantitative stability. To accomplish the required PET stability levels, the PET subsystem must be sufficiently isolated from the effects of MR activity. Performance measurements have previously been published, demonstrating sufficient PET stability in the presence of MR pulsing for typical clinical use; however, PET stability during radiofrequency (RF)-intensive and gradient-intensive sequences has not previously been evaluated for a clinical whole-body scanner. In this work, PET stability of the GE SIGNA PET/MR was examined during simultaneous scanning of aggressive MR pulse sequences. Methods: PET performance tests were acquired with MR idle and during simultaneous MR pulsing. Recent system improvements mitigating RF interference and gain variation were used. A fast recovery fast spin echo MR sequence was selected for high RF power, and an echo planar imaging sequence was selected for its high heat-inducing gradients. Measurements were performed to determine PET stability under varying MR conditions using the following metrics: sensitivity, scatter fraction, contrast recovery, uniformity, count rate performance, and image quantitation. A final PET quantitative stability assessment for simultaneous PET scanning during functional MRI studies was performed with a spiral in-and-out gradient echo sequence. Results: Quantitation stability of a 68Ge flood phantom was demonstrated within 0.34%. Normalized sensitivity was stable during simultaneous scanning within 0.3%. Scatter fraction measured with a 68Ge line source in the scatter phantom was stable within the range of 40.4%-40.6%. Contrast recovery and uniformity were comparable for PET images acquired simultaneously with multiple MR conditions. Peak noise equivalent count rate was 224 kcps at an effective activity concentration of 18.6 kBq/mL, and the count rate curves and scatter fraction curve were consistent for the alternating MR pulsing states. A final test demonstrated quantitative stability during a spiral functional MRI sequence. Conclusion: PET stability metrics demonstrated that PET quantitation was not affected during simultaneous aggressive MRI. This stability enables demanding applications such as kinetic modeling.

    View details for PubMedID 28747522

  • Clinical evaluation of TOF versus non-TOF on PET artifacts in simultaneous PET/MR: a dual centre experience. European journal of nuclear medicine and molecular imaging Ter Voert, E. E., Veit-Haibach, P., Ahn, S., Wiesinger, F., Khalighi, M. M., Levin, C. S., Iagaru, A. H., Zaharchuk, G., Huellner, M., Delso, G. 2017; 44 (7): 1223-1233


    Our objective was to determine clinically the value of time-of-flight (TOF) information in reducing PET artifacts and improving PET image quality and accuracy in simultaneous TOF PET/MR scanning.A total 65 patients who underwent a comparative scan in a simultaneous TOF PET/MR scanner were included. TOF and non-TOF PET images were reconstructed, clinically examined, compared and scored. PET imaging artifacts were categorized as large or small implant-related artifacts, as dental implant-related artifacts, and as implant-unrelated artifacts. Differences in image quality, especially those related to (implant) artifacts, were assessed using a scale ranging from 0 (no artifact) to 4 (severe artifact).A total of 87 image artifacts were found and evaluated. Four patients had large and eight patients small implant-related artifacts, 27 patients had dental implants/fillings, and 48 patients had implant-unrelated artifacts. The average score was 1.14 ± 0.82 for non-TOF PET images and 0.53 ± 0.66 for TOF images (p < 0.01) indicating that artifacts were less noticeable when TOF information was included.Our study indicates that PET image artifacts are significantly mitigated with integration of TOF information in simultaneous PET/MR. The impact is predominantly seen in patients with significant artifacts due to metal implants.

    View details for DOI 10.1007/s00259-017-3619-2

    View details for PubMedID 28124091

  • Validation of an image derived input function estimation method on PET/MR Khalighi, M., Engstrom, M., Fan, A., Gulaka, P., Appell, L., Lubberink, M., Zaharchuk, G. SOC NUCLEAR MEDICINE INC. 2017
  • Image-derived input function estimation on a TOF-enabled PET/MR for cerebral blood flow mapping. Journal of cerebral blood flow and metabolism Khalighi, M. M., Deller, T. W., Fan, A. P., Gulaka, P. K., Shen, B., Singh, P., Park, J., Chin, F. T., Zaharchuk, G. 2017: 271678X17691784-?


    (15)O-H2O PET imaging is an accurate method to measure cerebral blood flow (CBF) but it requires an arterial input function (AIF). Historically, image-derived AIF estimation suffers from low temporal resolution, spill-in, and spill-over problems. Here, we optimized tracer dose on a time-of-flight PET/MR according to the acquisition-specific noise-equivalent count rate curve. An optimized dose of 850 MBq of (15)O-H2O was determined, which allowed sufficient counts to reconstruct a short time-frame PET angiogram (PETA) during the arterial phase. This PETA enabled the measurement of the extent of spill-over, while an MR angiogram was used to measure the true arterial volume for AIF estimation. A segment of the high cervical arteries outside the brain was chosen, where the measured spill-in effects were minimal. CBF studies were performed twice with separate [15O]-H2O injections in 10 healthy subjects, yielding values of 88 ± 16, 44 ± 9, and 58 ± 11 mL/min/100 g for gray matter, white matter, and whole brain, with intra-subject CBF differences of 5.0 ± 4.0%, 4.1 ± 3.3%, and 4.5 ± 3.7%, respectively. A third CBF measurement after the administration of 1 g of acetazolamide showed 35 ± 23%, 29 ± 20%, and 33 ± 22% increase in gray matter, white matter, and whole brain, respectively. Based on these findings, the proposed noninvasive AIF method provides robust CBF measurement with (15)O-H2O PET.

    View details for DOI 10.1177/0271678X17691784

    View details for PubMedID 28155582

  • MR Performance Comparison of a PET/MR System Before and After SiPM-Based Time-of-Flight PET Detector Insertion IEEE TRANSACTIONS ON NUCLEAR SCIENCE Khalighi, M. M., Delso, G., Maramraju, S. H., Deller, T. W., Levin, C. S., Glover, G. H. 2016; 63 (5): 2419-2423
  • Design Features and Mutual Compatibility Studies of the Time-of-Flight PET Capable GE SIGNA PET/MR System. IEEE transactions on medical imaging Levin, C. S., Maramraju, S. H., Khalighi, M. M., Deller, T. W., Delso, G., Jansen, F. 2016; 35 (8): 1907-1914


    A recent entry into the rapidly evolving field of integrated PET/MR scanners is presented in this paper: a whole body hybrid PET/MR system (SIGNA PET/MR, GE Healthcare) capable of simultaneous acquisition of both time-of-flight (TOF) PET and high resolution MR data. The PET ring was integrated into an existing 3T MR system resulting in a (patient) bore opening of 60 cm diameter, with a 25 cm axial FOV. PET performance was evaluated both on the standalone PET ring and on the same detector integrated into the MR system, to assess the level of mutual interference between both subsystems. In both configurations we obtained detector performance data. PET detector performance was not significantly affected by integration into the MR system. The global energy resolution was within 2% (10.3% versus 10.5%), and the system coincidence time resolution showed a maximum change of < 3% (385 ps versus 394 ps) when measured outside MR and during simultaneous PET/MRI acquisitions, respectively. To evaluate PET image quality and resolution, the NEMA IQ phantom was acquired with MR idle and with MR active. Impact of PET on MR IQ was assessed by comparing SNR with PET acquisition on and off. B0 and B1 homogeneities were acquired before and after the integration of the PET ring inside the magnet. In vivo brain and whole body head-to-thighs data were acquired to demonstrate clinical image quality.

    View details for DOI 10.1109/TMI.2016.2537811

    View details for PubMedID 26978664

  • NEMA NU 2-2012 performance studies for the SiPM-based ToF-PET component of the GE SIGNA PET/MR system MEDICAL PHYSICS Grant, A. M., Deller, T. W., Khalighi, M. M., Maramraju, S. H., Delso, G., Levin, C. S. 2016; 43 (5)


    The GE SIGNA PET/MR is a new whole body integrated time-of-flight (ToF)-PET/MR scanner from GE Healthcare. The system is capable of simultaneous PET and MR image acquisition with sub-400 ps coincidence time resolution. Simultaneous PET/MR holds great potential as a method of interrogating molecular, functional, and anatomical parameters in clinical disease in one study. Despite the complementary imaging capabilities of PET and MRI, their respective hardware tends to be incompatible due to mutual interference. In this work, the GE SIGNA PET/MR is evaluated in terms of PET performance and the potential effects of interference from MRI operation.The NEMA NU 2-2012 protocol was followed to measure PET performance parameters including spatial resolution, noise equivalent count rate, sensitivity, accuracy, and image quality. Each of these tests was performed both with the MR subsystem idle and with continuous MR pulsing for the duration of the PET data acquisition. Most measurements were repeated at three separate test sites where the system is installed.The scanner has achieved an average of 4.4, 4.1, and 5.3 mm full width at half maximum radial, tangential, and axial spatial resolutions, respectively, at 1 cm from the transaxial FOV center. The peak noise equivalent count rate (NECR) of 218 kcps and a scatter fraction of 43.6% are reached at an activity concentration of 17.8 kBq/ml. Sensitivity at the center position is 23.3 cps/kBq. The maximum relative slice count rate error below peak NECR was 3.3%, and the residual error from attenuation and scatter corrections was 3.6%. Continuous MR pulsing had either no effect or a minor effect on each measurement.Performance measurements of the ToF-PET whole body GE SIGNA PET/MR system indicate that it is a promising new simultaneous imaging platform.

    View details for DOI 10.1118/1.4945416

    View details for Web of Science ID 000378924200034

    View details for PubMedID 27147345

  • Evaluation of improved scatter correction with highly targeted 68Ga-labeled radiopharmaceuticals Deller, T., Khalighi, M., Lantos, J., Gulaka, P., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2016
  • Optimization of 15O-H2O dose for cerebral blood flow imaging on a time-of-flight PET/MR scanner Deller, T., Khalighi, M., Fan, A., Singh, P., Park, J., Hoehne, A., Shen, B., Chin, F., Zaharchuk, G. SOC NUCLEAR MEDICINE INC. 2016
  • Dynamic brain PET/MR using TOF reconstruction. EJNMMI physics Khalighi, M. M., Delso, G., Tohme, M., Iagaru, A., Zaharchuk, G. 2015; 2: A60-?

    View details for DOI 10.1186/2197-7364-2-S1-A60

    View details for PubMedID 26956320

  • Efficient bloch-siegert B1 (+) mapping using spiral and echo-planar readouts. Magnetic resonance in medicine Saranathan, M., Khalighi, M. M., Glover, G. H., Pandit, P., Rutt, B. K. 2013; 70 (6): 1669-1673


    The Bloch-Siegert (B-S) B(1) (+) mapping technique is a fast, phase-based method that is highly SAR limited especially at 7T, necessitating the use of long repetition times. Spiral and echo-planar readouts were incorporated in a gradient-echo based B-S sequence to reduce specific absoprtion rate (SAR) and improve its scan efficiency. A novel, numerically optimized 4 ms B-S off-resonant pulse at + 1960 Hz was used to increase sensitivity and further reduce SAR compared with the conventional 6 ms Fermi B-S pulse. Using echo-planar and spiral readouts, scan time reductions of 8-16 were achieved. By reducing the B-S pulse width by a factor of 1.5, SAR was reduced by a factor of 1.5 and overall sensitivity was increased by a factor of 1.33 due to the nearly halved resonance offset of the new B-S pulse. This was validated on phantoms and volunteers at 7 T. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24599

    View details for PubMedID 23401024

    View details for PubMedCentralID PMC3657582

  • Adiabatic RF pulse design for Bloch-Siegert B-1(+) mapping MAGNETIC RESONANCE IN MEDICINE Khalighi, M. M., Rutt, B. K., Kerr, A. B. 2013; 70 (3): 829-835


    The Bloch-Siegert (B-S) B 1+ mapping method has been shown to be fast and accurate, yet it suffers from high Specific Absorption Rate (SAR) and moderately long echo time. An adiabatic RF pulse design is introduced here for optimizing the off-resonant B-S RF pulse to achieve more B-S B 1+ measurement sensitivity for a given pulse width. The extra sensitivity can be used for higher angle-to-noise ratio B 1+ maps or traded off for faster scans. Using numerical simulations and phantom experiments, it is shown that a numerically optimized 2-ms adiabatic B-S pulse is 2.5 times more efficient than a conventional 6-ms Fermi-shaped B-S pulse. The adiabatic B-S pulse performance is validated in a phantom, and in vivo brain B 1+ mapping at 3T and 7T are shown. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24507

    View details for Web of Science ID 000323543600025

  • Small-tip-angle spokes pulse design using interleaved greedy and local optimization methods MAGNETIC RESONANCE IN MEDICINE Grissom, W. A., Khalighi, M., Sacolick, L. I., Rutt, B. K., Vogel, M. W. 2012; 68 (5): 1553-1562


    Current spokes pulse design methods can be grouped into methods based either on sparse approximation or on iterative local (gradient descent-based) optimization of the transverse-plane spatial frequency locations visited by the spokes. These two classes of methods have complementary strengths and weaknesses: sparse approximation-based methods perform an efficient search over a large swath of candidate spatial frequency locations but most are incompatible with off-resonance compensation, multifrequency designs, and target phase relaxation, while local methods can accommodate off-resonance and target phase relaxation but are sensitive to initialization and suboptimal local cost function minima. This article introduces a method that interleaves local iterations, which optimize the radiofrequency pulses, target phase patterns, and spatial frequency locations, with a greedy method to choose new locations. Simulations and experiments at 3 and 7 T show that the method consistently produces single- and multifrequency spokes pulses with lower flip angle inhomogeneity compared to current methods.

    View details for DOI 10.1002/mrm.24165

    View details for Web of Science ID 000310062300022

    View details for PubMedID 22392822

  • RF pulse optimization for Bloch-Siegert B-1(+) mapping MAGNETIC RESONANCE IN MEDICINE Khalighi, M. M., Rutt, B. K., Kerr, A. B. 2012; 68 (3): 857-862


    The Bloch-Siegert (B-S) method of B ₁⁺ mapping has been shown to be fast and accurate, yet has high SAR and moderately long TE. These limitations can lengthen scan times and incur signal loss due to B(0) inhomogeneity, particularly at high field. The B-S method relies on applying a band-limited off-resonant B-S radiofrequency pulse to induce a B ₁⁺-dependent frequency-shift for resonant spins. A method for optimizing the B-S radiofrequency pulse is presented here, which maximizes B-S B ₁⁺ measurement sensitivity for a given SAR and T(2) . A 4-ms optimized pulse is shown to have 35% less SAR compared with the conventional 6-ms Fermi pulse while still improving B ₁⁺ map angle-to-noise ratio by 22%. The optimized pulse performance is validated both in phantom and in vivo brain imaging at 7 T.

    View details for DOI 10.1002/mrm.23271

    View details for Web of Science ID 000308098100022

    View details for PubMedID 22144397

    View details for PubMedCentralID PMC3297726

  • Self-Refocused Adiabatic Pulse for Spin Echo Imaging at 7 T MAGNETIC RESONANCE IN MEDICINE Balchandani, P., Khalighi, M. M., Glover, G., Pauly, J., Spielman, D. 2012; 67 (4): 1077-1085


    Spin echo pulse sequences are used to produce clinically important T(2) contrast. However, conventional 180° radiofrequency pulses required to generate a spin echo are highly susceptible to the B(1) inhomogeneity at high magnetic fields such as 7 Tesla (7 T), resulting in varying signal and contrast over the region of interest. Adiabatic 180° pulses may be used to replace conventional 180° pulses in spin echo sequences to provide greater immunity to the inhomogeneous B(1) field at 7 T. However, because the spectral profile of an adiabatic 180° pulse has nonlinear phase, pairs of these pulses are needed for proper refocusing, resulting in increased radiofrequency power deposition and long minimum echo times. We used the adiabatic Shinnar Le-Roux method to generate a matched-phase adiabatic 90°-180° pulse pair to obviate the need for a second adiabatic 180° pulse for phase refocusing. The pulse pair was then reformulated into a single self-refocused pulse to minimize the echo time, and phantom and in vivo experiments were performed to validate pulse performance. The self-refocused adiabatic pulse produced transmit profiles that were substantially more uniform than those achieved using a conventional spin echo sequence.

    View details for DOI 10.1002/mrm.23089

    View details for Web of Science ID 000301533500021

    View details for PubMedID 21954048

    View details for PubMedCentralID PMC3548423