Applications of Magnetic Resonance Cytography: Assessing Underlying Cytoarchitecture

In medical imaging, a wide variety of methods are used to interrogate structural and physiological differences between soft tissues. One of the most ubiquitous methods in clinical practice is Magnetic Resonance Imaging (MRI), which has the advantage of limited invasiveness, soft tissue discrimination, and adequate volumetric resolution. A myriad of advanced MRI methods exists to investigate the microstructural, physiologic and metabolic characteristics of tissue. For example, Dynamic Contrast Enhanced (DCE) and Dynamic Susceptibility Contrast (DSC) MRI non-invasively interrogates the dynamic passage of an exogenously administered MRI contrast agent through tissue to quantify local tracer kinetic properties like blood flow, vascular permeability and tissue compartmental volume fractions. Recently, an improved understanding of the biophysical basis of DSC-MRI signals in brain tumors revealed a new approach to derive multiple quantitative biomarkers that identify intrinsic sub-voxel cellular and vascular microstructure that can be used differentiate tumor sub-types. One of these characteristic biomarkers called Transverse Relaxivity at Tracer Equilibrium (TRATE), utilizes a combination of DCE and DSC techniques to compute a steady-state metric which is particularly sensitive to cell size, density, and packing properties. This work seeks to investigate the sensitivity and potential utility of TRATE in a range of disease states including Glioblastomas, Amyotrophic Lateral Sclerosis (ALS), and Duchenne’s Muscular Dystrophy (DMD). The MRC measures of TRATE showed the most promise in mouse models of ALS where TRATE values decreased with disease progression, a finding that correlated with reductions in myofiber size and area, as quantified by immunohistochemistry. In the animal models of cancer and DMD, TRATE results were more inconclusive, due to marked heterogeneity across animals and treatment state. Overall, TRATE seems to be a promising new biomarker but still needs further methodological refinement due to its sensitivity to contrast to noise and further characterization owing to its non-specificity with respect to multiple cellular features (e.g. size, density, heterogeneity) that complicate interpretation.