TRACKING ENLARGED PERIVASCULAR SPACES FROM CLINICAL MRI TO POST-MORTEM MRI GUIDED HISTOPATHOLOGY

While there is mounting evidence that enlargement of the perivascular space (ePVS) is associated with amyloid, vascular, and tau-based pathologies, their etiology and clinical relevance in the setting of progressive neurodegeneration is not established. Previous post-mortem studies have linked ePVS with amyloid, tau, and vascular pathologies, and our previous work has evaluated ePVS in the post-mortem human brain as a possible biomarker of impaired glymphatic function. However, the lack of targeted radiological/pathological association studies is a major limitation to understanding the clinical significance of radiologically visible ePVS. Here, we present ongoing work targeting the histopathology of MRI visible ePVS. Among brain donations received from previously active NIA-Oregon Alzheimer's Disease Center subjects with signed autopsy consent, we identified six cases for whom in vivo 3 Tesla brain MRI also were available (Table, Figure 1 left, 2, left). Ultra-high field post-mortem MRI for in-tact hemisphere imaging was completed with a previously presented protocol. Briefly, left hemispheres are immersed in Fluorinert inside a custom-fabricated vacuum-sealed container. T2, T1, PD, and T2* - weighted data are acquired axially on a 7 Tesla Siemens MAGNETOM MRI instrument rendering 3D imaging of the entire hemisphere (Figure 1, right, Figure 2, center). Hemispheres are then sliced into 6mm thick coronal slices and reimaged, bisected, photographed, and nonlinearly aligned to MR images from the same slice. Regions of interests are identified from the midline bisection plane and targeted sampling is completed using a custom-fabricated tissue punch (Figure 2, right). Cassettes from these punches are banked and processed for hypothesis-specific tissue staining protocols (Figure 3). Among all six cases, at least one ePVS observed on in vivo clinical imaging also was identified at post-mortem hemisphere imaging. Often, there were multiple ePVS visible, including those in juxtacortical, periventricular, and basal ganglia regions. In addition the intersection of ePVS and other pathologies of interest, including regions of white matter hyperintensity were present and co-sampled.