Multimodal Imaging Analysis for Brain Clearance: PET Imaging Based Clearance Slope, FASTT2 MRI‐based Parenchyma CSF fraction, and DTI‐based ALPS‐index

Abstract

AbstractBackgroundGlymphatic clearance is important to maintain brain health, which depends on two interconnected fluid systems: the novel glymphatic system and the traditional well‐characterized CSF system1. There are several imaging tools have been developed to evaluate the glymphatic function in the human brain, however each method providing only a limited perspective into glymphatic system2. A proper imaging tool should consider both circulation pathway of the bulk CSF flow, and a complex PVS network parallel to the microvascular structure. We developed and tested an imaging package including vCSF, CSFF, and DTI‐ALPS, to investigate the ventricular CSF turnover rate, perivascular CSF flow and brain parenchymal CSF fraction.MethodA total of 23 subjects (F=16, M=7, NL=17, MCI=6) age from 63 and 82 years (mean=69.3, std=5.1). PET MK6240 was acquired for lateral ventricle CSF clearance measure3 (vCSF), and MRI FASTT2 and DTI was acquired for CSF fraction4 (CSFF) and diffusion tensor imaging along perivascular spaces5 (DTI‐ALPS) index, respectively. Precisely, vCSF was calculated as the slope of 10 to 30min lateral ventricle TAC normalized by 1‐4min whole brain AUC. CSFF was fitted using three compartment model with 6 TEs = 0, 7.5, 17.5, 67.5, 147.5, 307.5 ms. DTI‐ALPS was calculated by mean(D𝑥_𝑝𝑟𝑜𝑗,D𝑥_𝑎𝑠𝑠𝑜𝑐)/mean (D𝑦_𝑝𝑟𝑜𝑗, D𝑧_𝑎𝑠𝑠𝑜𝑐), where Dx, Dy and Dz are the diffusivity along x‐, y‐ and x‐axis, and the projection, association regions.ResultFigure 4 shows Parenchymal CSFF negative correlates with DTI‐ALPS (r = ‐.51; p=.01 n=23), suggesting link between glymphatic system dysfunction and increased cerebral CSFF. 4 NL subjects with high CSFF and low DTI‐ALPS are amyloid positive. Figure 5 shows ventricular CSF turnover rate (vCSF) negative correlates CSFF (r = ‐.53; p=.01 n=23).ConclusionOur preliminary results showed that ventricular CSF turnover rate (vCSF), perivascular CSF flow (DTI‐ALPS) and brain parenchymal CSF fraction (CSFF) are correlated to each other and indicate the connection between the glymphatic system and the traditional CSF system. The complementary imaging approaches could lead to a much greater understanding of glymphatic clearance, and facilitate a more complete perspective on both glymphatic pathology and function alterations. Reference: 1. JM. Wardlaw,2020. 2. M. Niazi,2018. 3. Y. Li, 2022. 4. L. Zhou, 2021. 5. T. Taoka, 2017