Principal Investigator: Marvin Doyley, PhD; Assistant Professor, Department of Electrical and
Computer Engineering, University of Rochester, Rochester, NY
Co-Investigator: Giovanni Schifitto, MD; Associate Professor, Department of Neurology and Imaging Sciences, University of Rochester School of Medicine, Rochester, NY
Specific Aims: The primary hypothesis that underpins this project is that magnetic resonance elastography (MRE) imaging can visualize structural changes in grey and white matter that occur when the human immunodeficiency virus (HIV) invades the central nervous system (CNS). The main biological hypothesis is that HIV infection causes both the micro and macroscopic changes in the structure of brain tissue, which will produce a local change in the mechanical properties (i.e., shear modulus, anisotropy, and interstitial pressure) of the grey and white brain matter. The requested grant support will be used to hire additional staff to develop a crucial component of the MRE data acquisition system, which this research team urgently needs to acquire additional preliminary data. The preliminary data will then be used to apply for federal funding at the R01 level to properly assess the role that MRE could play in identifying subjects with mild HIV-associated neurocognitive disease (HAND). The development of this novel method for assessing brain injury will advance clinical trials of novel therapeutics for HAND as well as the clinical management of persons with this disease, because there are presently no adequate biomarkers or stand alone imaging approaches that allow sensitive staging of disease progression. It is also expected to provide a method that can be adapted to other CNS diseases including traumatic brain injury (TBI). Finally, high performance computational (HPC) resources are essential for this project because of the large computational overhead which is required to solve the threedimensional inverse elastography problem on a highly resolved finite element mesh. The following hypothesis-driven specific aims are proposed:
Aim # 1: Can we develop a useful, versatile clinical prototype of a magnetic resonance elastography system to visualize the mechanical properties (i.e., shear modulus, anisotropy, and interstitial pressure) within the brain, with the specific goal of improving the evaluation of HIV-associated brain injury? . The sub-steps to achieve this aim are listed below.
1a Develop a mechanical actuation system to induce shear waves in brain tissue.
1b Implement a three-dimensional phase-contrast gradient echo pulse sequence on the 3T whole body magnetron (Siemens imaging system) that is located in the Rochester Center for Brain Imaging. This will be used to measure the phase and amplitude of the propagating shear waves under steady-state conditions.
1c Develop numerical methods to recover shear modulus, anisotropy and interstitial pressure from MRmeasured phase and amplitude maps. These parameters are expected to provide a measure of HIVinduced neuro-inflammatory changes in axonal architecture and gross tissue damage in brain regions of interest (with a resolution of 5 mm2, based on our preliminary studies in breast tissue).
Aim #2: Can magnetic resonance elastography
differentiate between the mechanical properties of HIVinfected brain
tissues with and without cognitive impairment?
We will perform MR elastographic imaging on16 HIV-infected volunteers, 8 with cognitive impairment and 8 without HAND and 8 HIV negative controls . Dr. Schifitto will recruit patients from ongoing NIH-supported cohorts assessing HIV-associated cognitive impairment, and patients from the infectious disease clinic who have been on a stable antiretroviral regimen for at least 12 weeks. Results from MRE imaging will be compared directly to more established techniques, although far from been considered gold standards, including MRI morphometry, spectroscopy and diffusion tensor imaging (DTI). The number of patients required for each group was based our preliminary studies in breast imaging and statistical analysis. For a 20% standard deviation, in order to observe a 30% increase in the mechanical properties, we require a minimum of 10 patients per group to obtain a power of 0.8 with a p-value of 0.05.