The Foundation has funded five new External Research Award projects for the 4th quarter of 2014. Three preclinical and two clinical studies will evaluate the use of focused ultrasound for:
- Papillary thyroid cancer (University of Virginia)
- Intranasal DNA nanoparticle delivery (Northeastern University in collaboration with Brigham and Women’s Hospital/Harvard University)
- Osteoarthritis joint pain (Rizzoli Institute in Italy)
- Neuromodulation and functional imaging (Vanderbilt University)
- Multiple sclerosis (University of Washington)
David Shonka, MD, University of Virginia clinical project: “A Pilot Study to Evaluate the Feasibility and Safety of High Intensity Focused Ultrasound for Treatment of Papillary Thyroid Cancer.”
The incidence of differentiated thyroid cancers, comprised primarily of PTC, has more than doubled over the last twenty years, due in part to increased detection of small (≤2cm) tumors. Total thyroidectomy remains the recommended treatment for these malignancies, but poses significant risks and lifelong hormone replacement for patients. A non-surgical alternative is needed for this rapidly growing patient population. The purpose of this two-stage study is to evaluate the feasibility and safety of HIFU for treating PTC.
Methodology: In Stage 1, HIFU ablation will be performed on biopsy-proven PTC thyroid nodules 9 weeks prior to thyroidectomy. Feasibility of HIFU is measured as completion of proposed therapy. Safety is evaluated by incidence of treatment-related adverse events. Efficacy is judged by serial diagnostic ultrasound (DUS) imaging performed every 3 weeks following HIFU and confirmed by histological exam of the target nodule following surgery. In Stage 2, subjects with small PTCs (≤2 cm) will be treated with HIFU ablation alone. Subjects will be followed for 12 months to assess residual disease and/or disease recurrence/progression. If a residual nodule of viable PTC persists after FUS treatment, or if patients exhibit evidence of progression, patients will have the option to undergo total thyroidectomy as a salvage procedure.
Barbara Waszczak, PhD, Northeastern University in collaboration with Nathan McDannold at Brigham and Women’s Hospital, preclinical project: “Focused Ultrasound for Increased Delivery of Intranasal DNA Nanoparticles to Rat Brain.”
We will investigate whether focused ultrasound (FUS) can increase delivery to the brain of a nonviral gene vector given by the intranasal route of administration. Aim 1 will examine different FUS treatment conditions to determine if FUS can increase total plasmid DNA nanoparticle (NP) delivery and transgene expression in the sonicated regions, the rat substantia nigra and striatum, two brain areas involved in Parkinson’s Disease (PD). Aim 2 will test whether FUS improves tissue penetration and alters cellular transfection patterns in the sonicated regions following intranasal doses of DNA NPs. If successful, FUS may enable agents with poor capabilities of crossing the blood-brain barrier (BBB), e.g. neurotrophic factors, viral and non-viral vectors encoding them, to become disease-altering therapies by a non-invasive route of administration.
Alberto Bazzocchi, MD, Rizzoli Institute (Italy), clinical project: “Magnetic Resonance guided Focused Ultrasound Surgery: a pilot study in the treatment of pain caused by osteoarthritis – hand and hip, challenging joints.”
Pain caused by osteoarthritis is a matter of huge impact, in terms of quality of life, social, and economic burdens. The aging of the population is even going to augment the problem. The hand is the most affected site in the upper limb, and the trapeziometacarpal joint is crucial for the prevalence of the disease and for determining significant limitations of function when involved. In the lower limb, the hip and the knee share the leading position in the clinical scenario, with the former being historically the most frequently submitted to joint replacement. At any site, the vast majority of joint replacement surgery procedures are performed because of pain. Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) has recently demonstrated a great potential in fighting pain caused by different medical conditions, including osteoarthritis. The aim of the work is to study the feasibility, the safety, and the potential efficacy of MRgFUS in treating pain from osteoarthritis in two “hot” spots: the hip and the trapeziometacarpal joint.
Charles Caskey, PhD, Vanderbilt University, preclinical project: “Noninvasive targeted neuromodulation and functional imaging in behaving macaques.”
All presently available neural stimulation methods are either invasive or can only be moderately localized, and a neurostimulation method that could overcome these limitations would be invaluable for the mapping of brain circuits, disease diagnosis in the brain, neurosurgery and therapy. Neural stimulation with magnetic resonance guided focused ultrasound (MRgFUS) is a promising technology that can noninvasively excite or inhibit neural activity in well-defined discrete volumes of the brain, subsequently enabling investigation of brain circuits with magnetic resonance imaging (MRI). In this study, we seek to explore ultrasonic neuromodulation in the frontal eye field of a macaque monkey, while measuring the effects of neuromodulation via event-related potentials, behavioral responses, and blood oxygen level dependent functional MRI.
Pierre Mourad, PhD, University of Washington, preclinical project: “Modulated focused ultrasound for treatment of demyelinating axons in multiple sclerosis lesions – pilot animal studies.”
Multiple sclerosis is a debilitating disease whose symptoms arise from demyelination of axons within brain tissue with an attendant loss of central and peripheral function. We, among others, have shown that transcranial delivery of pulsed focused ultrasound (pFU) can non-destructively activate central neural circuits. Others have shown enhanced myelin remodeling of axons activated by laser light in an optogenetic mouse model. We hypothesize that pFU activation of axons within MS lesions in a rodent model will decrease their demyelination and increase their re-myelination. If successful, this non-invasive therapy may lead to rapid advancements in the treatment of MS and other demyelinating neurological disorders.
Researchers who are interested in applying for an external research award should contact Matt Eames, PhD, Director of Extramural Research, (434) 326-9834 or firstname.lastname@example.org