Clinical Focus

  • Diagnostic Radiology

Academic Appointments

  • Assistant Professor - Med Center Line, Radiology
  • Assistant Professor - Med Center Line (By courtesy), Neurosurgery
  • Assistant Professor - Med Center Line (By courtesy), Urology

Professional Education

  • Internship:Santa Clara Valley Medical Center Radiology Residency (2006) CA
  • Residency:Stanford University Hospital (2010) CA
  • Fellowship:Stanford University - CAPS (2011) CA
  • Board Certification: Diagnostic Radiology, American Board of Radiology (2010)
  • Medical Education:Stanford University (2005) CA

Research & Scholarship

Clinical Trials

  • Feasibility of ExAblate MRI Guided High Intensity Focused Ultrasound Tx of Soft Tissue Tumors Not Recruiting

    The goal of this project is to evaluate the safety and preliminary efficacy of ExAblate magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) surgery in the treatment of soft tissue tumors of the extremities.

    Stanford is currently not accepting patients for this trial. For more information, please contact Raffi Avedian, MD, 650-721-7618.

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  • MR Guided High Intensity Focused Ultrasound for Lumbar Back Pain Recruiting

    The primary purpose of this protocol is to assess the ExAblate 2100 MR guided high intensity focused ultrasound device as an intervention for treatment of facetogenic lower back pain.

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  • ExAblate Conformal Bone System Treatment of Metastatic Bone Tumors for the Palliation of Pain Not Recruiting

    A study to evaluate the safety and initial effectiveness of the ExAblate 2100 Conformal Bone System in the treatment of pain resulting from metastatic bone tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Fizaa Ahmed, 650-725-6409.

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  • ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors Not Recruiting

    The objective of this prospective, randomized, double-blind (to subjects, local site's blinded assessor and Tremor Core Lab assessors), crossover, multi-site, two-arm study (ExAblate treated arm Vs ExAblate Sham treated control arm) is to test the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in subjects with essential tremor (ET).

    Stanford is currently not accepting patients for this trial.

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  • Continued Access Protocol: ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors Not Recruiting

    The objective of this prospective, multi site, single-arm study is to capture the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in patients with essential tremor (ET).

    Stanford is currently not accepting patients for this trial. For more information, please contact Evalina Salas, 650-724-4131.

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  • Focal MR-Guided Focused Ultrasound Treatment of Localized Low-Intermediate Risk Prostate Cancer: Feasibility Study Recruiting

    The hypothesis of this feasibility study is that focal treatment with ExAblate MRgFUS has the potential to be a safe and effective non-invasive treatment for low to intermediate risk, organ-confined prostate cancer involving low incidence of morbidity. The study hypothesis will be tested by measuring treatment-related safety and initial effectiveness parameters in the ExAblate MRgFUS treated patients, as described above. Based on the result of this study, InSightec will initiate a larger study in an effort to approve low risk, organ-confined prostate cancer as an indication for its ExAblate MRgFUS device.

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  • A Phase IV Post Approval Clinical Study of ExAblate Treatment of Metastatic Bone Tumors for the Palliation of Pain Not Recruiting

    The study hypotheses is that the proportion of patients experiencing clinically significant pain relief will be at least 30% greater than the proportion experiencing worsening pain.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pam Gallant, 650-736-8965.

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  • ExAblate (Magnetic Resonance-guided Focused Ultrasound Surgery) Treatment of Metastatic Bone Tumors for the Palliation of Pain Not Recruiting

    A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Treatment of Metastatic Bone and Multiple Myeloma Tumors for the Palliation of Pain in Patients Who are not Candidates for Radiation Therapy

    Stanford is currently not accepting patients for this trial. For more information, please contact Kamil Unver, (650) 725 - 9810.

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  • ExAblate UF V2 System for the Treatment of Symptomatic Uterine Fibroids Not Recruiting

    The purpose of this study is to evaluate the safety and ablation efficacy of the ExAblate UF V2 System when treating symptomatic uterine fibroids. The ExAblate System is a medical device that involves a focused ultrasound system and an MRI scanner. ExAblate delivers a pulse of focused ultrasound energy, or sonication, to the targeted tissue. In this particular study, the targeted tissue is uterine fibroids. Each sonication is used to heat small spots in the fibroid much like a magnifying glass can be used to focus light to heat a spot. The heat created kills a portion of the fibroid with the goal of decreasing or eliminating uterine fibroid-related symptoms. Repeated sonications are performed until the entire fibroid is treated or the treated volume is determined to be appropriate. The ExAblate system is commercially approved in the United States to treat symptomatic uterine fibroids. The ExAblate UF V2 System is an experimental device and is being investigated in this study. While similar to the commercial system, the ExAblate UF V2 device includes the following major changes, among others, which are intended to improve device performance and safety: - Up and down movement of the ultrasound transducer, in an attempt to improve fibroid treatment by moving the ultrasound focal point within the targeted fibroid. - Ultrasound energy can be turned off for a specific area in an attempt to minimize amount of energy passing through sensitive areas of the body.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pejman Ghanouni, MD, 650-498-4485.

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  • ExAblate Treatment of Metastatic Bone Tumors for the Palliation of Pain Not Recruiting

    The purpose of this enhanced surveillance study ("ESS") is to collect information regarding chronic adverse events that are possibly related to the ExAblate® System ("ExAblate") that are received by InSightec ("InSightec") following PMA approval. This study will examine adverse events reported in patients undergoing the device procedure for the first two years of commercial experience. Other relevant data may be collected as well.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pamela Gallant, 650-736-8965.

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2017-18 Courses

Stanford Advisees


All Publications

  • 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-?


    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 (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

  • 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


    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-?


    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


    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


    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-?


    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


    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; 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., Butts Pauly, K., Grissom, W. A. 2016; 76 (1): 172-182


    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

  • 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

    View details for DOI 10.1002/mrm.25899

    View details for Web of Science ID 000384996900016

  • 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: -?


    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


    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


    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

  • 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


    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


    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-?


    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


    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 Web of Science ID 000356781000041

    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-?


    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


    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

  • 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


    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-?


    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

  • 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)


    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


    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

  • 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

    View details for DOI 10.1002/mrm.24695

    View details for Web of Science ID 000330769700036

  • 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


    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


    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

  • 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


    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 Web of Science ID 000295708400013

    View details for PubMedID 21961982

    View details for PubMedCentralID PMC3185301

  • 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


    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


    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

    View details for PubMedCentralID PMC4479407

  • 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


    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


    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


    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


    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 Web of Science ID 000245992200010

    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


    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


    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

  • 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


    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


    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 Web of Science ID 000168883700014

    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


    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


    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


    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


    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