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Single-sided magnetic resonance sensors for clinical detection of volume status
Several pathological processes affect the body's ability to regulate volume status. In each of these disease states, the body loses some ability to regulate fluid balance and maintain an euvolemic state. Deviations from euvolemia have been shown to increase morbidity and mortality. The ability to detect pre-symptomatic changes in volume status would allow for more responsive management of these conditions and prevention of higher-mortality complications. Direct evaluation and quantification of early-stage changes in volemic state is not currently a clinical measure. T2 relaxometry, a magnetic resonance imaging technique, may offer a feasible method to quantify volume status. In this work we explore the design of single-sided magnetic resonance sensors for the quantification of volume status, evaluate the clinical performance of the sensor, and elucidate further physiological considerations for fluid diagnostics.
The primary research question that motivated this thesis is: can a point-of-care relaxometer sensitively distinguish muscle interstitial fluid shifts in a single measurement? Several approaches are used to answer this question including instrumentation development, signal acquisition studies, and human subject studies. We describe the design of a point-of-care, single-sided magnetic resonance relaxometer. The constructed sensor can acquire slice-selective signal from 8mm above the instrument’s surface with a high signal-to-noise ratio. We review instrument performance on phantoms, ex-vivo tissue, and human subjects. Preliminary observational clinical studies of two cohorts, healthy athletes and in-patient hemodialysis patients, were conducted and validate the instrument is able to detect signal selectively from the muscle interstitial compartment and distinguish healthy adults and those with end stage renal disease with a single measurement. We discuss the implementation of multi-exponential fitting of acquired data. This enables analysis of individual muscle tissue compartments. We demonstrate strategies to double signal acquisition and improve T2 fitting accuracy through the simulation and implementation of linear frequency swept adiabatic radio frequency pulses. These decrease the sensitivity of applied RF pulses to B1 and B0 inhomogeneity and reduce the effects of stimulated echoes. Finally, we explore physiological considerations for the instrument’s clinical implementation with an MRI study of chronic kidney disease and healthy control subjects. This allows for the evaluation of physiological factors which may affect the device’s accuracy and offer further future areas for study.
The single-sided magnetic resonance sensor and signal acquisition and processing techniques described demonstrate high potential for quantitative clinical assessment of volume status. This work focuses exclusively on healthy subjects or adults with chronic kidney disease, but the principles demonstrated are agnostic to many underlying disease pathologies.
Thesis Supervisor:
Michael J. Cima, PhD
David H. Koch Professor of Engineering; Professor of Materials Science and Engineering, Massachusetts Institute of Technology
Thesis Committee Chair:
Elfar Adalsteinsson, PhD
Eaton-Peabody Professor, Electrical Engineering and Computer Science and Institute for Medical Engineering and Computer Science, Massachusetts Institute of Technology
Thesis Readers:
Matthew Rosen, PhD
Associate Professor of Radiology, Harvard Medical School; Associate Investigator, Athinoula A. Martinos Center for Biomedical Imaging, Mass General Research Institute; Kiyomi and Ed Baird MGH Research Scholar, Mass General Research Institute, Massachusetts General Hospital
Sagar Nigwekar, MD
Physician Investigator, Nephrology, Mass General Research Institute; Assistant Professor of Medicine, Harvard Medical School; Assistant Physician, Nephrology, Massachusetts General Hospital
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Topic: Sydney Sherman MEMP PhD Thesis Defense
Time: April 18, 2024, 1:00 PM Eastern Time (US and Canada)
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