Research Projects

One of the aims of this research is to identify DNA variations, (genotype) by whole genome sequencing, that are associated with clinical, immunologic, and imaging traits (phenotype) of Multiple Sclerosis. Another goal of the research is to find genotype-phenotype associations in MS study subjects such as magnetic resonance imaging (MRI) measures of disease burden and/or severity and immunologic functions. The research will also identify or confirm markers of inflammation and neurodegeneration using a variety of techniques including biochemical and immunological assays, blood transcriptome analysis, plasma proteomics, neurocognitive testing, and quantitative MRI metrics. The research aims at analyzing the intestinal microbial composition and its association with immunological phenotypes in individuals with Multiple Sclerosis and with healthy controls with no clinical evidence of inflammatory or infectious diseases. By comparing MS subjects’ gut biome flora to healthy controls, we hope to pinpoint bacterial DNA that is specific to MS patients
Positron emission tomography (PET) offers the potential to complement MRI with quantitative measures of molecular specific markers of cellular and metabolic processes. PET radiotracers already available promise new insights into the dynamics of the innate immune response, neuronal function, neurodegeneration and remyelination. The aim of this project is to measure the reproducibility of PET measures of neuroinflammation associated with activated macrophages and microglial cells in the Central Nervous System using [11C]PBR28. Another aim of the research is to image microglial cells in vivo in multiple sclerosis and healthy control subjects. The research will derive [ 11C]PBR28 measurements in multiple sclerosis plaques, white matter and grey matter regions from co-registered high resolution MRI images. The research aims to determine whether [11C]PIB can be used as an in vivo marker for measuring myelin content in white matter in multiple sclerosis and healthy controls.
This is an observational study looking at the clinical applicability of newly developed pulse sequences for magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI) techniques by applying them to subjects with or at risk for MS recruited at the Yale MS Center and imaged at the Magnetic Resonance Research Center (MRRC). The motivation for increasing the magnetic field strength from the clinical 1.5 to high 3T and 7T ultra-high systems is mainly governed by the increased sensitivity, contrast and resolution at higher magnetic fields.

The AIMS lab functions as the central MRI core reading, coordinating and image processing unit for Johns Hopkins multi-center study titled, A Randomized Controlled Trial of Vitamin D supplementation in MS. In this ongoing project, the lab receives imaging data from various participating sites via electronic media. The researchers at the lab read brain MRI scans from MS patients to calculate white matter lesion counts. Specialized software developed at the lab is used to generate volumetric measures of brain atrophy and total disease burden. The post-processed imaging measures are sent to Johns Hopkins University.

Glutathione (GSH) is a critical antioxidant that plays a key role in protecting cells against oxidative damage by reactive oxygen species generated in the brain. In particular, GSH provides a first line of defense against singlet oxygen and hydroxyl radicals that are known to cause cellular damage and eventual cell death. Because GSH is consumed in this protective process, a reduction in GSH levels is noted in brain tissue undergoing oxidative stress. In non-disease condition, increased glutathione was observed after stimulation with extra-cellular glutamate, indicating that glutathione might also have a neuroprotective role to minimize glutamate toxicity.The primary objective of this research is to directly estimate the concentration of brain glutathione [glutathione] in vivo using H-MRS at 7T before and after initiation of Tecfidera in established MS patients considering switching therapy or being treatment-naive.