Utilizing 3D Arterial Spin Labeling to Identify Cerebrovascular Leak and Glymphatic Obstruction in Neurodegenerative Disease.

Charles R Joseph

doi:10.3390/diagnostics11101888

Abstract

New approaches are required to successfully intervene therapeutically in neurodegenerative diseases. Addressing the earliest phases of disease, blood brain barrier (BBB) leak before the accumulation of misfolded proteins has significant potential for success. To do so, however, a reliable, noninvasive and economical test is required. There are two potential methods of identifying the BBB fluid leak that results in the accumulation of normally excluded substances which alter neuropil metabolism, protein synthesis and degradation with buildup of misfolded toxic proteins. The pros and cons of dynamic contrast imaging (DCI or DCE) and 3D TGSE PASL are discussed as potential early identifying methods. The results of prior publications of the 3D ASL technique and an overview of the associated physiologic challenges are discussed. Either method may serve well as reliable physiologic markers as novel therapeutic interventions directed at the vasculopathy of early neurodegenerative disease are developed. They may serve well in addressing other neurologic diseases associated with either vascular leak and/or reduced glymphatic flow.

Highlights

Diagnostics 2021, 11, 1888. https://In the wake of disappointing treatment trials of Alzheimer modifying drugs, a fresh therapeutic approach to this and other neurodegenerative diseases is necessary
Approaching the initial disease phase, the pathological leak of the blood brain barrier and consequent obstruction of glymphatic flow is worthy of therapeutic investigation
Looking at sporadic AD in stages, the initial insult is the blood brain barrier (BBB) leak, triggered by endothelial and pericyte damage resulting from circulating low level upregulated pro-inflammatory factors via several potential sources [1,3]

Summary

Introduction

In the wake of disappointing treatment trials of Alzheimer modifying drugs, a fresh therapeutic approach to this and other neurodegenerative diseases is necessary. If we view these pathways of disease development as being from the inside out as opposed to the outside in (sporadic disease), one must modify the lake analogy to the pollution source being within the lake itself This may have profound implications as to treatment strategies since stopping the BBB leak would theoretically be less efficacious in the familial group due to the continuous and inherent production of beta amyloid and its negative impact on vascular integrity and the BBB [33,34]. The Ktransfer of contrast into the parenchyma was calculated [44] This is a landmark study demonstrating via imaging clear evidence of the BBB disruption in the preclinical and clinical phases of the disease process [2,43]. This method requires infusion of gadolinium contrast, which is both costly and not without risk

Perfusion ASL

Results

Discussion