Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

Abstract

There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.

Neuroimaging of Mouse Models of Alzheimer’s Disease

“…DTI lends itself to the assessment of regional microstructural integrity (or lack thereof) and is particularly well suited to the evaluation of white matter integrity [ 43 ]. In neurodegenerative diseases, such as AD, DTI has been especially useful in assessing gray and white matter brain pathology, as recently reviewed [ 44 ]. Luo and colleagues reported reduced DTI-derived fiber density in limbic tracts, corpus callosum and others in LOAD patients from two large separate databases [ 45 ].…”

Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection

“…34 Following preprocessing, we derived conventional diffusion tensor imaging (DTI) markers of white matter microstructure, i.e., fractional anisotropy (FA) and mean diffusivity (MD), which have been extensively used in neuroscientific and neuropsychological research. 35,36 Free-water imaging was employed to model an extracellular free-water compartment, sensitive to immune activation 37 and atrophy 38 , as well as a cellular tissue compartment (FA of the tissue, FAT), more closely reflecting myelin and axonal alterations than their DTI equivalents. 39 Fixel-based analysis, a novel multi-tissue model addressing more complex white matter compositions, was used to derive metrics of fiber density, fiber-bundle cross section (FC), fiber density and cross section (FDC), and complexity.…”

Microstructural white matter abnormalities in multiple sclerosis and neuromyelitis optica spectrum disorders: Evaluation by advanced diffusion imaging

“…Recently, free water (FW) imaging, which employs twocompartment model for diffusion data, has been used to calculates the contribution of isotropic FW and correct DTI values for the contribution of FW, suggesting the possibility of detecting demyelination-related abnormalities and distinguishing between neuroinflammation and neurodegeneration [18][19][20]. These FW-corrected measures are less susceptible to the partial volume effects of cerebrospinal fluid and water molecules accumulated in the extracellular spaces of the brain parenchyma [21,22].…”