MSBI Thesis & Abstracts 2021-2022

Anna Bennett

Advisor: Dr. Peder Larson, PhD

Thesis Title: Improving Pyruvate Kinetic Measurements Using Variable Flip Angle Schemes in bSSFP Hyperpolarized Carbon-13 MR Imaging

Abstract: Hyperpolarized MR imaging of 13C-labeled probes provide increased sensitivity to investigate metabolic kinetics. The characterization of [1-13C]pyruvate kinetics has been correlated to increased aggressiveness of Renal Cell Carcinoma (RCC) and pyruvate kinetics have the potential to be a valuable tool for assessing disease burden. Increased signal-to-noise ratio (SNR) has already been proven through the use of balanced steady-state free precession (bSSFP) sequences over accelerated gradient echo (GRE) acquisitions. A sigmoid-based variable flip angle scheme was implemented in a pyruvate-specific 3D bSSFP dynamic imaging protocol to further optimize the SNR across multiple acquisitions. The effects of varying flip angle across a dynamic imaging study was first simulated with a physics-based 2-site pyruvate-lactate kinetic model and then evaluated using Monte Carlo simulations for sensitivities to kinetic and imaging parameters. An increase in early lactate signal as well as a delayed pyruvate signal peak and extended signal window were confirmed with subsequent animal studies on a healthy adult rat. The resulting signal changes present the possibility of improved spatial resolution and improved kPL fitting. Additional studies and simulations to optimize associated sequence parameters are needed to further characterize the use-case for sigmoid-based variable flip angle schemes.

Gabriella Ramil

Advisor: Dr. Galateia Kazakia, PhD

Thesis Title: Using Time-Lapse HR-pQCT for Bone Turnover Classification in CKD-MBD Patients

Abstract: Patients with chronic kidney disease – mineral and bone disorder, a disease that results in a high risk for bone fractures, can be classified based on the rate of total bone turnover. Currently, bone turnover rates are determined from iliac crest bone biopsies followed by quantitative histomorphometry. However, this method is painful, invasive, and performed in an area not typically prone to fractures. In this ongoing prospective study, we explore the use of time-lapse high resolution peripheral quantitative computed tomography (HR-pQCT) imaging as a non-invasive method to determine bone turnover in patients. Fifteen participants are expected to participate in this study. To date, six participants were recruited to undergo HR-pQCT scans at four different timepoints with two-month intervals. Three scans will be performed at the first timepoint and one scan will be performed at the three following timepoints. The three repeat baseline scans and each of the follow-up scans underwent time-lapse analysis to determine total bone turnover. For this thesis project, the objective was to establish methodology for this study, including determine the time-lapse threshold needed to detect <0.5% reproducibility differences, determine the more robust image processing pipeline between two processing techniques, determine the least significant change (LSC) from baseline repeat scans, and determine if there are detectable time-lapse changes in total bone turnover at two-months. The preliminary results determined that using a Laplace-Hamming image processing pipeline performed better than the standard analysis protocol, determined that a threshold of 525 mgHA/ccm led to <0.5% reproducibility differences, demonstrated a LSC of 0.088 and 0.040 for the radius and tibia respectively, and showed that after two months, time-lapse HR-pQCT could measure in vivo total bone turnover in patients but not greater than the LSC values. Since determining the optimal time to scan was an objective of this study, the continuation of the study and scanning at longer timeframes will uncover the period with which we can measure bone turnover greater than the LSC. The continuation of this study will also elucidate the relationship between time-lapse HR-pQCT results and the gold standard of bone biopsies and verify our initial conclusions.

Zachary Rossen

Advisor: Dr. Pratik Mukherjee, MD, PhD

Thesis Title: White Matter Microstructure and Connectivity in mTBI Patients with Distinct Neuropsychiatric Phenotypes

Abstract: Traumatic brain injury (TBI) is highly prevalent and difficult to characterize. Based on the Glasgow Coma Scale, the majority of TBI patients are diagnosed as mild TBI (mTBI), which can be associated with a wide array of outcomes ranging from full recovery to debilitating and long-lasting neurologic symptoms. These neurobehavioral symptoms have large deleterious impacts on not only the patients, but their families, colleagues, and the community. Recent work used a battery of cognitive and behavioral tests early postinjury to classify mTBI patients into phenotypes that predicted clinical outcomes later: patients of the neuropsychiatrically distressed (ND) phenotype exhibited degraded neuropsychological functioning while patients of the emotionally resilient (ER) phenotype recovered well over the first 6 months post-injury. This study aimed to seek a physical explanation of these phenotypes by analyzing diffusion MRI (dMRI) derived parameters including diffusion tensor imaging (DTI) and edge density imaging (EDI). Analyses of longitudinal data from a cohort of 68 patients (30 NDs and 38 ERs) and 40 uninjured controls showed that axial diffusivity (AD) was lower in certain white matter tracts at 6 month post-injury in the ER but not the ND patients. Edge density trended a longitudinal increase in the ND but not the ER patients. The variability of these parameters exhibited a complex pattern that would require future investigations. The current neuroimaging evidence revealed differences in the dynamic healing processes for the ND and ER patients.