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Meeting Report: Radiological Society of North America (RSNA) 2022

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Key Points The RSNA 108th Scientific Assembly and Annual Meeting was held in Chicago from November 27 through December 1, 2022. Focused ultrasound—related abstracts addressed histotripsy, tumor ablation, and several indications, including bone, brain, musculoskeletal, pancreatic cancer, prostate cancer, and uterine fibroids. RSNA’s 108th Scientific Assembly and Annual Meeting was held in Chicago from November 27 through December 1, 2022. There were at least 26 focused ultrasound–related abstracts, wherein attendees presented their research on histotripsy, tumor ablation, and several medical indications, including bone, brain, musculoskeletal, pancreatic cancer, prostate cancer, and uterine fibroids. The 26 abstracts and on demand educational content that may be of interest to the focused ultrasound community are listed below by topic area. Use the RSNA Online Planner tool to search and read the full text for each presentation. BoneMR-guided High Intensity Focused Ultrasound (MRgHIFU) in the Treatment of Bone Metastases: Safety of Sensitive Structures within 1 cm from Target Lesion by Valerio D’Agostino, MD (poster) Safety of MR-guided High Intensity Focused Ultrasound (MRgHIFU) in the Treatment of Osteoid Osteoma in Proximity of Sensitive Structures by Valerio D’Agostino, MD (oral presentation) BrainUltra High-Field MRI (7T) of the Thalamic Ventral Intermediate Nucleus (VIM) to Validate 3T Diffusion Tractography and 3T Anatomical Targeting for MR-Guided Focused Ultrasound (MRgFUS) of Essential Tremor (ET) by Brynmor Jones, FRCR, MRCP (oral presentation) How Diffusion Tensor Imaging Enables Direct Targeting for Focused Ultrasound Surgery by Hiroki Hori (on demand educational content) HistotripsyImpact of Non-invasive Histotripsy on Liver Tumor Treatment in a Rat Hepatocellular Carcinoma Model by Man Zhang, MD, PhD (oral presentation) Histotripsy Treatment of Veins as a Mechanism of Endothelial Damage by Amanda R. Smolock, MD, PhD (poster) A Phantom for Assessing Histotripsy Treatment Zones on Both Ultrasound and X-ray Imaging by Ayca Z. Kutlu, MD (poster) History of Histotripsy: Bench to Clinical Translation by Nathan E. Loudon, MD (on demand educational content) MusculoskeletalIn Vitro US-Triggered Drug Release from Polymer Film Pocket by Selin Isguven (poster) MSK Interventions: How I Do It by Matthew D. Bucknor, MD (on demand educational content) Pancreatic CancerFolfirinox plus High Intensity Focused Ultrasound for Pancreatic Ductal Adenocarcinoma: A Prospective Single Center Phase II Trial by Dong Ho Lee, MD (oral presentation) Synergistic Anticancer Effect of Pulsed Focused Ultrasound with Ultrasound-Sensitive Nanoparticle IMP301 on Pancreas Cancer Xenograft Model by Soojin Kim, MD (poster) ProstateAssessing Temporal Changes in Multi-parametric MRI and Analyzing MR Thermometry Parameters in Patients with Prostate Cancer Treated by Transurethral Ultrasound Ablation (TULSA): A Four-year Follow-up Study by Ali Bassir, MD (oral presentation) A Pilot Study of68Ga-PSMA11 and68Ga-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy by Heying Duan, MD (poster) Customized MR-guided Transurethral Ultrasound Ablation (TULSA) for Treatment of Localized Prostate Cancer and Concurrent Benign Prostate Hyperplasia: A Single Centre Retrospective Analysis of One Hundred Patients by Leonhard Steinmeister, MD (poster) MRI-Guided Focused Ultrasound (MRgFUS) Ablation for Localized Intermediate-Risk Prostate Cancer – Results of a Phase II Trial by Sangeet Ghai, MD (poster) Focal MRI-Guided Transurethral Ultrasound Ablation (TULSA) in Men with Prostate Cancer: Lessons Learned in 60+ Patients by Daniel N. Costa, MD (on demand educational content) MRI Guided Transurethral Ultrasound Ablation (TULSA) of Prostate: Initial Experience at Wellspan Hospital by Edward Steiner, MD (on demand educational content) Post-Treatment Prostatic Cancer: How to Perform an Adequate Imaging Evaluation by Vivien Bonadio, MD (on demand educational content) Minimally Invasive Image-Guided Treatment of Primary, Recurrent, and Metastatic Prostate Cancer by Daniel A. Adamo, MD (on demand educational content) Minimally Invasive Prostate Cancer Treatments – An Update by Riddhi M. Borse, MD (on demand educational content) Tumor AblationLow-Power MRgFUS Tumor Ablation upon Controlled Accumulation of Magnetic Nanoparticles by Cascade-Activated DNA Cross Linkers by Yi Zhu (poster) Uterine FibroidsDeep Learning Based Automatic Segmentation of the Uterus on T2-Weighted MRI for Volumetry in Patients with Uterine Fibroids Before and After High-Intensity Focused Ultrasound Therapy by Maike Theis, MSc (oral presentation) The Role of Boosting Algorithms in Machine Learning in Predicting the Treatment Outcome of High-Intensity Focused Ultrasound Ablation of Uterine Fibroids: Most Informative Perfusion MRI Features by Bilgin Keserci, PhD (poster) The Role of Machine Learning Algorithms in Predicting the Treatment Outcome of High-Intensity Focused Ultrasound Ablation of Uterine Fibroids with an Immediate Nonperfused Volume Ratio of at least 90% by Bilgin Keserci, PhD (poster) Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for Treatment of Uterine Fibroids: Patient Selection, Contraindications and Operative Execution by Monica Mattone, MD (on demand educational content) See the Meeting Website > Search the RSNA Online Planner Tool >
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Meeting Report: Society of Neuro-Oncology (SNO) Annual Meeting and Education Day

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Key Points SNO held its 27th annual meeting and education day November 16-20, 2022. Investigators presented abstracts on using focused ultrasound to treat brain metastases and recurrent glioblastoma. Focused ultrasound—enhanced liquid biopsy was discussed with other researchers in the liquid biopsy session. Devices from Insightec, Carthera, and Cordance Medical were represented. SNO held its 27th Annual Meeting and Education Day in Tampa Bay, Florida, from November 16–20, 2022. With an in-person attendance of 2,500, the conference broke its previous attendance record. Along with the Foundation, many other nonprofits and patient advocacy organizations that support brain tumor research were represented, which created productive networking and collaboration opportunities. Suzanne LeBlang, MD, the Foundation’s Director of Clinical Relationships, attended many sessions at SNO and said, “Overall, I was impressed by the number of studies presented by focused ultrasound researchers. New research efforts clearly show the potential of this incisionless technology to combat brain tumors with numerous mechanisms of action.” At the liquid biopsy meeting, Dr. LeBlang presented an update on the state of the field of focused ultrasound–enhanced liquid biopsy for brain tumors and how focused ultrasound blood-brain barrier opening in and around a brain tumor could enhance the quantity and perhaps quality of analytes detected in the peripheral blood. Investigators presented abstracts and posters on using focused ultrasound to treat glioblastoma, primary brain tumors, and brain metastases with blood-brain barrier opening as well as sonodynamic therapy as the mechanisms of action. Focused ultrasound—enhanced liquid biopsy, a mechanism of action that has the potential to make a big impact in brain cancer diagnosis and treatment, and drug delivery approaches were also presented. Hideho Okada, MD, PhD, from the University of California, San Francisco, presented “Immunotherapy for Patients with IDH-Mutant LGG,” a keynote lecture and mentioned that focused ultrasound has the potential to enhance chimeric antigen receptor (CAR) T cell delivery. Each abstract is listed below. The full text for each abstract can be found by searching the ID number on SNO’s program website. CTNI-10 – Randomized pivotal study of blood-brain barrier (BBB) disruption using Exablate Model 4000 with standard of care (SOC) therapy in non-small cell lung cancer (NSCLC) brain metastases: LIMITLESS trial (Multiple medical centers, Insightec) poster presented by Manmeet S. Ahluwalia CTNI-13 – A first-in-human phase 0/1 trial of 5-Aminolevulinic Acid Sonodynamic Therapy (5-ALA SDT) in recurrent glioblastoma (Barrow Neurological Institute and Ivy Brain Tumor Center) oral abstract presented by Nader Sanai CTNI-20 – Results of a phase 1/2 clinical trial of blood-brain barrier (BBB) opening with the SonoCloud-9 implantable ultrasound device in recurrent glioblastoma patients receiving IV carboplatin (Multiple medical centers, Carthera) poster presented by Michael Canney CTNI-37 – Repeated opening of the blood-brain barrier with the skull-implantable SonoCloud-9 (SC9) device: Phase 1 trial of nab-paclitaxel and SC9 in recurrent glioblastoma (multiple medical centers, Carthera) oral abstract presented by Adam Sonabend CTNI-46 – Pivotal study to evaluate safety and efficacy of Exablate model 4000 using microbubble resonators to temporarily mediate blood-brain barrier disruption for liquid biopsy in glioblastoma (LIBERATE) (Multiple medical centers, Insightec) poster presented by Manmeet S. Ahluwalia CTNI-64 – Focused ultrasound mediated blood-brain barrier penetrance to enable cell-free DNA (cfDNA) as a liquid biopsy in recurrent primary brain tumors (Memorial Sloan Kettering Cancer Center and Cordance Medical) – poster presented by Ryan Dittamore DDEL-10 – Ultrasound-enhanced drug delivery in humans alters endothelial phenotype and perturbs the ultrastructure of the blood-brain barrier (Northwestern University, Carthera) poster presented by Andrew Gould DDEL-13 – Ultrasound-enhanced delivery of liposomal doxorubicin across the blood brain barrier induces an IFN-g phenotype in microglia, macrophages, and T cells and improves response to PD-1 blockade in gliomas (Northwestern University, IIT Research Institute, Carthera) poster presented by Victor A. Arrieta See the Meeting Website >
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Focused Ultrasound for Pancreatic Cancer: Trial Results Prove Safety, Initial Efficacy

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Key Points The data from an initial clinical trial in Korea were critical for establishing safety, preliminary efficacy, and the protocol parameters for a larger study. Jae Young Lee, MD, PhD, used the ultrasound-guided Alpinion focused ultrasound device plus standard-of-care chemotherapy to decrease tumor size in patients with pancreatic cancer. A phase II clinical trial is now underway in Korea and nearing its enrollment goal. Early, proof-of-concept safety data and the protocol parameters from a pancreatic cancer focused ultrasound plus chemotherapy clinical trial have now been published. This small, 9-participant clinical trial, which completed enrollment in 2019, was critical for establishing safety, preliminary efficacy, and the protocol parameters for the phase II clinical trial that is now underway. All participants were pathologically diagnosed with unresectable pancreatic cancer. Jae Young Lee, MD, PhD, professor of Radiology and president at Seoul National University Medical Research Center in Korea, is the principal investigator for both (phase I and II) studies. He and his team are using the ultrasound-guided Alpinion focused ultrasound device and standard-of-care chemotherapy regimens to address pancreatic cancer that is unresectable (which is the case in about 80% of patients with pancreatic cancer). “Pancreatic cancer typically presents with a dense fibrous stroma and low vascularity, which limits drug delivery and efficacy,” said Dr. Lee in the publication. “Therefore, there is an urgent need to develop new treatment options to enhance drug delivery.” Dr. Lee hypothesizes that focused ultrasound can weaken the tumor’s dense stroma to allow chemotherapy to penetrate the cancer cells. As published in European Radiology, the nine participants in the phase I study were assigned to one of three predefined treatment intensity groups (low, intermediate, or high) for six combined treatments of focused ultrasound plus nab-paclitaxel plus gemcitabine chemotherapy. Although it was primarily a safety study, after treatment, the team also measured changes in tumor size, tumor response, tumor marker levels, patient-reported outcomes, and survival. The treatments were safe, and participants experienced no adverse effects. Tumor size decreased more than 15% in seven of the nine participants at both the immediate and 3-month follow-up computed tomography scans. Tumor marker levels decreased in all participants. The intermediate intensity treatment was the most effective, with this group showing the largest decreases in tumor size (more than 30%) and tumor markers plus a significant improvement in survival (p < 0.05). “A key point of the proof-of-concept study is that the Seoul National team showed that they were able to access the patients’ tumors and treat them without complications,” said Tim Meakem, MD, the Foundation’s Chief Medical Officer. “This was not a small issue to solve, because accessing the pancreas with focused ultrasound has been challenging. Some efforts to treat similar patients using MRI guidance have been difficult, simply due to the size and access limitations of the MRI. Dr. Lee used ultrasound guidance for this procedure, which avoided these issues. The safety and initial efficacy of this project were well received by his colleagues, and almost all of the participants for the phase II study have already been enrolled.” The phase II, 60-participant study is being funded by the Focused Ultrasound Foundation. For phase II, the team is using a FOLFIRINOX regimen of chemotherapy. Dr. Lee presented interim phase II results at the 8th International Symposium on Focused Ultrasound. See the Video > See European Radiology > Related StoriesPancreatic Cancer Clinical Trial Begins in Korea October 2021 Research Awards Update: 15 Projects Initiated in the First Six Months of 2021 September 2021
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Visiting Scholars Work to Accelerate the Field of Focused Ultrasound

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Key Points This fall, an intern and a visiting scholar joined the Foundation and took different approaches toward the same goal of advancing the field of focused ultrasound. Visiting scholar Yi-Hsiu Chen gained preclinical and clinical research experience that will help further the focused ultrasound program at her hospital in Taiwan. Fall intern Imogen Hequet explored machine learning and its intersection with focused ultrasound. Yi-Hsiu Chen is pursuing her PhD in Neuroscience at National Yang Ming Chiao Tung University/Taipei Veterans General Hospital. She joined the Foundation this fall as a short-term research scholar to gain experience that she will take back to her team in Taiwan to help further their focused ultrasound program. During her time at the Foundation, Yi-Hsiu observed preclinical studies and clinical treatments at the University of Virginia and the University of Maryland. Learn More About Her Experience “My experience [at the Foundation was] so amazing,” recalls Yi-Hsiu. “I met so many people here and discussed the research they were interested in and the next step of focused ultrasound research in our hospital in Taiwan. I have learned a lot from people I met here.” Imogen Hequet, a recent graduate of Imperial College of London, worked with the Foundation’s chief technology officer, Rick Hamilton, to explore machine learning and the role that it could play in medicine, specifically in the field of focused ultrasound. Learn More About Her Project “Hopefully something I have done during my internship will help to open conversations about machine learning and areas where it could add value in focused ultrasound,” says Imogen.
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Review Article: Immunotherapy Delivery for Alzheimer’s Disease

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Key Points This article provides a preclinical and clinical overview of using low-intensity ultrasound plus microbubbles to disrupt the blood-brain barrier for the delivery of immunotherapies in Alzheimer’s disease.It then compares in vitro and in vivo models, strategies for combining therapeutic agents with microbubbles, and techniques to understand observable bioeffects.The authors discuss questions on how in vitro studies can be translated to animal and human applications. Opportunities and Challenges in Delivering Biologics for Alzheimer’s Disease by Low-Intensity Ultrasound Source: Queensland Brain Institute In this review article, Jürgen Götz, PhD, and his team at Queensland Brain Institute first provide an overview of preclinical and clinical trials that have used low-intensity ultrasound plus microbubbles to disrupt the blood-brain barrier (BBB) for the delivery of immunotherapies in Alzheimer’s disease. The immunotherapies described are those that target either amyloid-beta peptides or tau proteins. The article then compares various models for in vitro BBB studies, strategies for combining therapeutic agents with microbubbles, and the impact of super-resolution microscopy on the field. In vitro BBB models may be cellular, two-dimensional, or three-dimensional, and there are many molecular imaging techniques that can be used to understand the bioeffects that occur during these types of experiments. To conclude, the group discusses several treatment development and optimization questions on how in vitro studies can be translated to animal and human applications. See Advanced Drug Delivery Reviews >
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Meeting Report: International Bubble Conference 2022 Meeting Report: European Society for Hyperthermic Oncology (ESHO) 2022 Clinical Trial of Sonodynamic Therapy for Glioblastoma Begins in Milan Call for Manuscripts: Special Collection on Histotripsy Research Awards Update: Five Preclinical Projects Initiated in the Third Quarter of 2022