Key Points
- The Foundation’s Research Awards Program recently initiated preclinical projects that use focused ultrasound to treat a wide variety of adult, pediatric, and veterinary diseases.
- Learn how to apply for funding.
The Foundation is pleased to announce that 14 new preclinical studies were launched in the first quarter of 2024. Beyond several general and brain technical projects, researchers are studying the use of various modes of focused ultrasound for the treatment of pancreatic cancer, brain tumors, neuroblastoma, Alzheimer’s disease (with gene therapy), uterine fibroids, sleep apnea, pain, and osteosarcoma in humans and dogs.
“These studies span three continents and nine diseases, showing the global impact of our diverse research portfolio,” said Joe Kilroy, PhD, the Foundation’s research program manager. “Importantly, the large number of projects at Virginia Tech were funded by state funding from the Commonwealth of Virginia as a result of the Foundation’s advocacy efforts.”
Each newly initiated project is listed below.
Pancreatic Cancer
Characterization of a Transesophageal Focused Ultrasound Transducer for Endoscopic Pancreatic Cancer Ablation by Eli Vlaisavljevich, PhD, at Fralin Biomedical Research Institute at Virginia Tech Carilion
For this project, researchers will evaluate the safety and feasibility of a trans-gastric approach for treating pancreatic tumors with cavitation-based focused ultrasound using a novel endoscopic focused ultrasound device. The device will be characterized for its ability to safely deliver cavitation to the pancreas with precise targeting to induce tissue destruction.
Brain Tumors
Low-Intensity Focused Ultrasound Delivery of PRMT5 Inhibitors for the Treatment of Glioblastoma by Kathleen Mulvaney, PhD, at Fralin Biomedical Research Institute at Virginia Tech Carilion
A collaborative team of researchers with expertise in PRMT5 biology/chemical inhibitor discovery, in vivo glioblastoma tumor modeling, and focused ultrasound drug delivery across the blood-brain barrier (BBB) is seeking to develop a therapeutic regimen that can be translated to humans and canine companion animals with glioblastoma. In vitro genomics screening will be used to determine effective drug combinations for GBM tumors that harbor a specific genetic mutation. A murine orthotopic glioblastoma brain tumor model will be used.
Cancer Immunotherapy for Pediatric Neuroblastoma
Combining High Intensity Focused Ultrasound Acoustic Cavitation and CAR T Cells for the Treatment of Pediatric Neuroblastoma by Gail ter Haar, PhD, from the Institute of Cancer Research
One form of cancer immunotherapy, CAR T cell therapy, has been largely ineffective for treating soft tissue tumors, partly due to a lack of CAR T cell response to tumor cells. Pilot data collected in a pediatric neuroblastoma model with suboptimal CAR T cell efficacy suggest that acoustic cavitation (microbubble-induced mechanical damage in the target) can enhance the anticancer effects of CAR T cells. For this project, researchers will conduct experiments to gain better understanding of the mechanisms involved in CAR T therapy, optimize treatment conditions, and use focused ultrasound to improve the activation of the CAR T cells with the goal of treating pediatric neuroblastoma.
Gene Therapy for Alzheimer’s Disease
Development of a Transcranial Focused Ultrasound System for Alzheimer’s Disease Stem Cell Therapy by Dong-Guk Paeng, PhD, at Jeju National University
Multipotent mesenchymal stem cells (MMSCs) are a potential novel type of cell therapy for Alzheimer’s disease, but the BBB hinders their delivery to the brain when administered systemically. The goal of this project is to investigate whether focused ultrasound can assist with MMSC delivery across the BBB in a transgenic pig model of Alzheimer’s disease.
In Vivo PET Imaging of Ultrasound-Assisted Therapies in Alzheimer’s Disease by Katherine Ferrara, PhD, at Stanford University
Because gene expression is reduced in later stages of Alzheimer’s disease, the goal of this study is to use therapeutic ultrasound and microbubbles to enhance delivery of adeno-associated viruses and antibodies in an Alzheimer’s disease model. Researchers will also develop and apply positron emission tomography (PET) and optical imaging methods to noninvasively quantify the delivery efficiency of their technique.
Uterine Fibroids
Ultrasound-Guided Histotripsy for the Complete and Rapid Ablation of Uterine Fibroids by Eli Vlaisavljevich, PhD, at Fralin Biomedical Research Institute at Virginia Tech Carilion
This project will investigate the use of ultrasound-guided histotripsy for rapid, efficient, and complete ablation of uterine fibroids. While histotripsy has already been shown to effectively ablate human uterine fibroids, new methods will be developed to enable more rapid treatment.
Sleep Apnea
Image-Guided Histotripsy for Sleep Apnea led by Jeremy Brown, PhD, at Dalhousie University
When fatty tissue accumulates at the base of the tongue, it can cause obstructive sleep apnea. This study will help determine whether histotripsy can be used to safely, efficiently, and noninvasively debulk fat from the base of the tongue as a treatment for sleep apnea. If successful, histotripsy could replace current surgical techniques that create wounds and carry a risk of bleeding, infection, speech impairment, and tongue paralysis.
Pain
Functional Ultrasound Imaging to Monitor Low-Intensity Focused Ultrasound Neuromodulation in Humans by Aiguo Han, PhD, at Virginia Polytechnic Institute and State University
Low-intensity focused ultrasound (LIFU) is a noninvasive technology to modulate neuronal activity that promises to treat multiple neurologic diseases. For this project, researchers will develop functional ultrasound (fUS) imaging methods to monitor the administration of LIFU in humans. If successful, fUS imaging could provide the high spatiotemporal resolution needed to confirm LIFU targeting and dosing.
Veterinary Program
Promoting an Anti-Tumor Immune Response by Combining Histotripsy with an Intratumoral Immune Stimulant, N-Dihydrogalactochitosan, in Osteosarcoma Therapy by Joanne Tuohy, PhD, DVM, at the Virginia-Maryland College of Veterinary Medicine
Osteosarcoma is the most common primary bone cancer in people and dogs. It metastasizes to other parts of the body and thus far has not been responsive to cancer immunotherapies. In this project, researchers are seeking to determine whether histotripsy plus an immune adjuvant can improve treatment response in dogs with osteosarcoma. The study will evaluate short- and long-term immune responses after the combination therapy, which pairs histotripsy ablation with intratumoral injection of N-dihydrogalactochitosan, a novel immunostimulant in osteosarcoma. The hope is that the combination treatment will make osteosarcoma responsive to immunotherapies.
Noninvasive Ablation and Liquid Biopsy of Canine Appendicular Osteosarcoma Using Histotripsy: Evaluation of Treatment Kinetics and Efficacy Using MRI and Raman Molecular Urinalysis by Joanne Tuohy, PhD, DVM, at the Virginia-Maryland College of Veterinary Medicine
To determine whether disease progression after histotripsy can be monitored with a novel liquid biopsy (LB) technique, researchers will evaluate a noninvasive, rapid, and economical urinalysis method for LB to evaluate tumor growth and progression with and without histotripsy treatment.
Brain Technical
Transcranial Ultrasound Aberration Correction by Florian Steinmeyer, PhD, at Nuremberg Technical University
In this study, researchers are seeking to determine whether real-time, ultrasound-echo skull characterization could replace, and surpass, CT-based skull correction. Transcranial ultrasound therapy relies on precise focusing of waves passing through skull bone. If it is possible, ultrasound-based aberration correction would accelerate treatment planning, could be repeated during treatment (e.g., as the skull heats up or if the patient moves), and may enhance patient eligibility. An ultrasound-based system would also be more time- and cost-efficient.
Sonobiopsy for Noninvasive Diagnosis of Diffuse Intrinsic Pontine Glioma (DIPG) by Hong Chen, PhD, at Washington University in St. Louis
To determine whether focused ultrasound–enabled liquid biopsy (sonobiopsy) can improve the genetic diagnosis of DIPG, researchers will test their proprietary techniques for releasing measurable tumor biomarkers into the bloodstream. The aim is to achieve sensitive diagnoses of DIPG genetic mutations by sonobiopsy without surgery.
General Technical
Simulations of Power Tuning Resonant Acoustic Vibrations for High Intensity Focused Ultrasound (HIFU) led by Rodney Herring, PhD, at the University of Victoria
This simulation study will determine whether dual-frequency, confocal ultrasound produces HIFU for cancer cell ablation. Researchers will measure the power/volume of the mixed acoustic beams at a far-focused probe position of 10 cm deep and also determine whether any enhanced power volume is found in off-target areas.
Development of Ultrasound-Guided High Intensity Focused Ultrasound (USgHIFU) Twin-Twin Transfusion Syndrome (TTTS) Clinical Training by Gail ter Haar, PhD, at the Institute of Cancer Research
In this project, researchers will develop a training phantom to optimize focusing, planning, and performing sham treatments of TTTS with USgHIFU. The project will also develop techniques for optimizing the placental vessel ultrasound imaging. The turnover of fetal medicine specialists (and the future potential to increase the number of users of the system) necessitates the development of a safe, inexpensive, and easily accessible method of training medical doctors in the use of the USgHIFU clinical systems for this application.