Point-of-Care Diagnostics for Dementia
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that weakens patients’ muscles, leading to loss of physical function and death. Ice budget challenge, a few years ago, created awareness of its severity and growing prevalence. Most patients survive only 3 to 5 years after the onset of the disease. Unfortunately, no confirmatory diagnosis of ALS exists and at present, diagnosis by the method of elimination. Therefore, a confirmatory diagnosis is essential for early diagnosis of ALS with precision and early initiation of treatment, which is crucial in improving the survival rate and reducing the treatment cost. We are identifying ALS at an early stage through a blood test. The aim is to differentiate early stages of the disease by detecting structural changes of an enzyme, called superoxide dismutase (SOD1), in order to identify and monitor ALS. Pulsed dipolar electron spin resonance (ESR) spectroscopy can effectively measure the Cu2+-Cu2+ distance, but the accuracy to differentiate distances is lacking at the blood concentration level. It is due to the ill-posed nature of the mathematical inversion of the experimental data. We are developing a localized pseudo-inversion method that can capture the evolution of the distances and hence can distinguish various stages.
Measuring Oxygen Concentration for Radiation Therapy
Oxygen concentration in tissue has proven to be an excellent marker for tumor composition and can be effectively used to determine radiation dose. Electron Spin Resonance Imaging (ESRI) can quantify pO2 and have shown to be effective in live animals. However, the challenge has been to translate ESRI for imaging humans in clinical settings because the dosage of paramagnetic probe for high quality imaging exceeds the human safety levels and needs to be reduced by an order-of-magnitude to make ESRI for humans feasible. The reduction in paramagnetic probe dose weakens the signal strength and increases the noise presence, lowering the signal-to-noise ratio (SNR) and affecting the pO2 measurement accuracy. The poor quality ESRI image obtained may also become clinically irrelevant. We aim to enable clinical ESRI studies by enhancing its sensitivity at desired paramagnetic probe concentrations through advanced techniques of signal processing and adapting wavelet denoising methods.
Reducing Scan Time for Clinical MRI
Magnetic Resonance Imaging (MRI) is widely used as a clinical diagnostic tool. Over 30 million MRI scans are conducted each year in the US. However, patients in need of MRI scans often face long wait-times as a result of imaging facility backlogs. The per-patient scan-time is a fundamental bottleneck that limits daily throughput, and is one of the root causes of backlogs and long wait-times. We are developing a signal-processing based software approach for reducing MRI scan-times. Our technology is focused on the novel application of denoising raw MRI data in real-time prior to construction of the MRI image and can be integrated with existing instrumentation without requiring any hardware modifications.
Protein Dynamics Studies using ESR Spectroscopy
Many biological studies focus on structure determination of soluble and membrane proteins but the study of dynamics is vital to understand disease mechanisms, including their function and interaction with their environment. Electron Spin Resonance (ESR) spectroscopy is a powerful method for studying structural dynamics of proteins at physiological temperatures for a wide range of time scales and can provide a detailed description of motion that includes both dynamics as well as local structural ordering. To address this problem of sensitivity in physiological environments, we are developing computational methods based on wavelet transforms to remove noise for accurate signal recovery.