QUANTIFICATION OF WHITE MATTER VULNERABILITY USING MULTI-COMPONENT RELAXOMETRY (AND DIFFUSION TENSOR IMAGING): A POSSIBLE TOOL TO DETECT PRECURSORS TO NEURODEGENERATION

Abstract

Studies suggest overt white matter damage in aging, i.e., white matter hyperintensities (WMH), is driven by alterations in myelin integrity. In addition, demyelination is increasingly being associated with early markers of Alzheimer's disease (AD) and related dementias. Thus, quantification of white matter vulnerability (i.e., a measure of asymptomatic but nonetheless ‘at risk’ tissue that may transition to damaged white matter in the form of WMH) may provide a biomarker to assist with earlier diagnosis and intervention as well as preclinical detection of dementia including AD. MRI advances in multicomponent relaxometry (MCR) allow for the decomposition of the measured MR signal into contributions from discrete environments or ‘water pools’ based on their unique T1 and T2 relaxation rates. By quantifying the relaxation characteristics attributed to the ‘restricted’ water trapped within the lipid bilayers of the myelin sheath a surrogate marker of myelin integrity is calculated. We compared possible myelin probes of ‘at-risk’ tissue, defined as normal appearing white matter (NAWM), and ‘damaged’ tissue, defined as WMH, using MCR and diffusion tensor imaging (DTI) to determine cognitive and risk factor associate of myein integrity taken from a sample of 115 older adults. Non-demented/non-depressed older adults (age∼66+6; 50% female; 65% minority) participated in a cognitive assessment including learning/memory and attention/information processing speed. Participants were evaluated for vascular risks associated with dementia including AD and underwent brain MRI at 3T. T2-FLAIR was used to quantify NAWM and WMH. MCR-derived myelin water fraction (MWF) and DTI-derived radial diffusivity (RD) within NAWM and WMH were standardized relative to total white matter volume. As expected, MWF had an inverse relationship with RD within NAWM and WMH after controlling for relevant confounds including sex (Figure 1). Separate Steiger's Z-tests revealed that when compared to RD values MWF showed statistically more robust associations to (a) learning and memory in both NAWM and WMH and (b) vascular risk factors associated with dementia including AD within NAWM (Table 1). Given that myelin degradation may contribute to white matter damage associated with dementia including AD, MCR may be a more robust biomarker for pre-clinical detection of neurodegeneration. Myelin water fraction (MWF) was inversely related to radial diffusivity (RD) in normal appearing white matter (NAWM) and white matter hyperintensities (WMH).