Principal Investigator: Natalya Rapoport, Ph.D., D.Sc., Research Professor, Department of Bioengineering, University of Utah

Co-Investigators: Jill Shea, Ph.D., Research Associate, Department of Surgery, University of Utah; Allison Payne, Ph.D., Research Assistant Professor, Utah Center for Advanced Imaging Research, University of Utah; Nick Todd, Ph.D., Postdoctoral Fellow, Utah Center for Advanced Imaging Research, University of Utah; Courtney Scaife, M.D., Assistant Professor of Surgery, University of Utah School of Medicine; Dennis Parker, Ph.D., Professor of Radiology & Biomedical Informatics, Utah Center of Advanced Imaging Research, University of Utah; Douglas Christensen, Ph.D., Professor of Bioengineering & Electrical Engineering, University of Utah

Award: $99,967

Funding Period: April 15, 2011 – April 14, 2012

Abstract: It is still not known which mode of ultrasound action—thermal or mechanical—plays the predominant role in ultrasound-mediated drug delivery. This project will combine results from two powerful imaging modalities, MRI and RFP imaging, to better understand and quantify the major effects. Several experimental variables will be tested in vivo using RFP-transfected pancreatic cancer MiaPaCa2 subcutaneous tumors grown in nude mice, providing information to better understand the mechanisms involved in ultrasound-mediated drug delivery.

Progress Reports: 6-month progress report

Principal Investigator: Richard Price, Ph.D., Associate Professor of Biomedical Engineering, University of Virginia

Co-Investigators: G. Wilson Miller, Ph.D., Assistant Professor of Radiology, University of Virginia; Justin Hanes, Ph.D., Professor, Johns Hopkins University

Award: $100,000

Funding Period: April 1, 2011 – March 31, 2012

Abstract: Glioblastoma multiforme (GBM) has a 5-year survival rate of only 12%, due primarily to the
inability of chemotherapeutic drugs to cross the blood brain barrier (BBB). The goal of this proposal is
to improve GBM therapy by coupling MR-guided BBB opening via focused ultrasound (FUS) and
microbubbles (MBs) with drug-loaded nanoparticles that efficiently penetrate brain tissue. Here, we
will first define FUS pressure thresholds for safe and reversible BBB opening to an MR contrast agent
(gadolinium) in invasive intracranial brain tumors. Next, we will determine optimal conditions for
delivering brain penetrating nanoparticle (BPN) formulations. Once completed, these studies will have
provided the foundation for future studies in which therapeutic BPNs are delivered across the BBB to
inhibit tumor growth and improve animal survival.

Progress Reports:  6-month progress report

Principal Investigator: Charles L. Dumoulin, Ph.D., Professor & Director, Imaging Research Center, Cincinnati Children's Hospital Medical Center

Co-Investigator: Janaka Wansapura, Ph.D., Assistant Professor, Cincinnati Children's Hospital Medical Center; Michelle Foster, Ph.D., Post Doctoral Fellow, Cincinnati Children's Hospital Medical Center

Award: $100,000

Funding Period: March 15, 2011 – March 14, 2012

Abstract: The goal of this project is to develop a minimally invasive treatment for metabolic syndrome
associated with obesity. Metabolic syndrome includes diabetogenic, atherogenic, pro-thrombotic and
pro-inflammatory metabolic abnormalities; which often present during childhood. Patients with
obesity-induced metabolic syndrome have a high risk of cardiovascular disease and type 2 diabetes.
The most prevalent form of obesity-associated metabolic syndrome is related to the accumulation of
visceral fat, rather than subcutaneous fat or total body fat. Visceral fat and its resident macrophages
produce pro-inflammatory cytokines (e.g., necrosis factor-alpha, leptin, and interleukin-6) that are
implicated in chronic low-grade inflammation which subsequently lead to metabolic syndrome in the
obese. Recent animal studies show that loss of visceral fat may generate substantial improvements in
the metabolic risk factor profile. This notion has important clinical implications as it recognize visceral
adiposity as a therapeutic target for the management of metabolic syndrome in high-risk patients.

While lifestyle modifications in the form of caloric restriction, pharmacotherapy and bariatric surgery
have all been shown to provide improvement in metabolic risk factors associated with obesity, it is
not known if these improvements are maintained over time. Improvement also takes time, (i.e.,
several months to years) to show beneficial effects. More importantly none of the existing
interventions specifically target visceral fat which is thought to play a causative role in the metabolic
syndrome. Thus, in this application we will investigate de-bulking of visceral fat by thermal ablation as
a treatment option for obesity-induced metabolic syndrome.

We hypothesize that HIFU treatment of visceral fat can improve insulin action in obese rats and
provide a non-surgical alternative to visceral fat resection. To test this hypothesis, we will design,
build, and validate an MR-guided focused ultrasound system for the ablation of visceral fat in a
rodent model of metabolic syndrome.

Progress Reports: 6-month progress report

Principal Investigator: Mario Ries, Ph.D., Research Engineer, Laboratory for Functional and Molecular Imaging (IMF), Bordeaux