Page 69 - TI Journal 18-1

Technology and Innovation, Vol. 18, pp. 63-74, 2016 ISSN 1949-8241 • E-ISSN 1949-825X
Printed in the USA. All rights reserved. http://dx.doi.org/10.21300/18.1.2016.63
Copyright © 2016 National Academy of Inventors. www.technologyandinnovation.org

THE EMERGING FIELD OF PERIVASCULAR FLOW DYNAMICS:
BIOLOGICAL RELEVANCE AND CLINICAL APPLICATIONS

Jacob Huffman , Sarah Phillips , George T. Taylor , and Robert Paul 1,2
1
1
1,3
1 Behavioral Neuroscience Program, Department of Psychological Sciences, University of Missouri – St. Louis, MO, USA
2 Missouri Institute of Mental Health (MIMH), St. Louis, MO, USA
3 Interfakultäre Biomedizinische Forschungseinrichtung (IBF) der Universität Heidelberg, Heidelberg, Germany

Brain-wide pathways of perivascular flow help clear the brain of proteins and metabolic waste
linked to the onset and progression of neurodegenerative diseases. Recent studies on the
glymphatic system and novel lymphatic vessels of the meninges have prompted new insight
into the clinical significance of perivascular flow. Current techniques in both humans and
animals are unable to fully reveal the complex functional and anatomical features of these
clearance pathways. While much research has stemmed from fluorescence microscopy and MR
imaging, clinical and experimental investigations are hindered by the lack of more advanced
and precise technology. In this review, we discuss the biological relevance of the glymphatic
and perivascular clearance systems, the innovative technology that has defined these pathways,
and the potential for new studies to advance our understanding of degenerative brain diseases
using similar technology.
Key words: Perivascular space; Glymphatic; Imaging; Fluorescence; Contrast-enhance; MRI

INTRODUCTION differences among neurodegenerative disorders,
Maintaining homeostatic function of the central imaging modalities have been employed in both
nervous system (CNS) relies not only on the proper animal and human research to uncover the etiolog-
regulation and composition of cerebrospinal fluid ical mechanisms associated with neurodegenerative
(CSF) but its distribution and drainage from the brain. diseases.
The dynamic flow of CSF and interstitial fluid (ISF)
along brain-wide networks of fluid motion permit CSF AND PERIVASCULAR FLOW
the transport of molecules and substrates throughout Clinical evaluations of CSF production, flow, and
multiple brain regions (68). Dysfunction of these reabsorption in humans rely primarily on phase
delivery and clearance systems may render the brain contrast magnetic resonance imaging (PC-MRI)
vulnerable to the accumulation of metabolic waste (7,27,40,69). However, CSF moves with relatively
and aggregation of proteins, such as amyloid β (Aβ), low velocity and is confined to small anatomical areas;
possibly leading to the onset and/or progression therefore, a number of limitations arise with image
of diseases such as Alzheimer’s Disease (AD) and quality and accuracy. As a result, the vast majority
Cerebral Amyloid Angiopathy (CAA) (36,53,72). of studies focused on mechanisms of CSF physiol-
Due to the inherent physiological and behavioral ogy rely on animal models. A brief review of these
_____________________
Accepted December 10, 2015.
Address correspondence to Jacob Huffman, Behavioral Neuroscience/Psychology, University of Missouri – Saint Louis, One University Boulevard, St. Louis,
MO 63121, USA, Tel: +1 (314) 486-3407; Fax: (314) 516-5392, E-mail: jnhryb@mail.umsl.edu

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