Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer Disease
With beta amyloid and tau antibody treatment trial failures, avenues directed to other facets of the disease pathophysiology are being explored to treat in the preclinical or early clinical state. Clear evidence of blood–brain barrier (BBB) breakdown occurring early in the AD process has recently be...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/7/228 |
| _version_ | 1797561983397003264 |
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| author | Charles R Joseph |
| author_facet | Charles R Joseph |
| author_sort | Charles R Joseph |
| collection | DOAJ |
| description | With beta amyloid and tau antibody treatment trial failures, avenues directed to other facets of the disease pathophysiology are being explored to treat in the preclinical or early clinical state. Clear evidence of blood–brain barrier (BBB) breakdown occurring early in the AD process has recently been established. Likewise, the glymphatic system regulating water and solute inflow and outflow in parallel with the vascular system is affected causing delayed clearance of fluid waste. Its dysfunction as a component of AD along with BBB leak are reasonable candidates to explore for future treatments. Ideally, human medication trials require a minimally invasive method of quantifying both improvements in BBB integrity and glymphatic fluid clearance correlated with clinical outcomes. We will review the known physiology and anatomy of the BBB system, and its relationship to the glymphatic system and the microglial surveillance system. Dysfunction of this tripart system occurring in preclinical Alzheimer disease (AD) will be reviewed along with existing MRI tools for identifying altered flow dynamics useful for monitoring improved functionality with future treatments. High-resolution dynamic contrast enhanced MRI imaging demonstrating BBB leak and the recently reported non-invasive 3D PASL MRI pilot study demonstrating significant delay in glymphatic clearance in AD subjects appear to be the best candidates. |
| first_indexed | 2024-03-10T18:22:15Z |
| format | Article |
| id | doaj.art-e5b78a3128a74800bdf2e05a4ac2e1f9 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T18:22:15Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-e5b78a3128a74800bdf2e05a4ac2e1f92023-11-20T07:17:47ZengMDPI AGBiomedicines2227-90592020-07-018722810.3390/biomedicines8070228Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer DiseaseCharles R Joseph0Department of Internal Medicine, Liberty University College of Osteopathic Medicine, Lynchburg, VA 24502, USAWith beta amyloid and tau antibody treatment trial failures, avenues directed to other facets of the disease pathophysiology are being explored to treat in the preclinical or early clinical state. Clear evidence of blood–brain barrier (BBB) breakdown occurring early in the AD process has recently been established. Likewise, the glymphatic system regulating water and solute inflow and outflow in parallel with the vascular system is affected causing delayed clearance of fluid waste. Its dysfunction as a component of AD along with BBB leak are reasonable candidates to explore for future treatments. Ideally, human medication trials require a minimally invasive method of quantifying both improvements in BBB integrity and glymphatic fluid clearance correlated with clinical outcomes. We will review the known physiology and anatomy of the BBB system, and its relationship to the glymphatic system and the microglial surveillance system. Dysfunction of this tripart system occurring in preclinical Alzheimer disease (AD) will be reviewed along with existing MRI tools for identifying altered flow dynamics useful for monitoring improved functionality with future treatments. High-resolution dynamic contrast enhanced MRI imaging demonstrating BBB leak and the recently reported non-invasive 3D PASL MRI pilot study demonstrating significant delay in glymphatic clearance in AD subjects appear to be the best candidates.https://www.mdpi.com/2227-9059/8/7/228preclinical Alzheimer diseaseblood–brain barrierparavascular outflowglymphatic systemhigh definition dynamic contrast enhanced (DCE) imaging MRI3D pulsed arterial spin labeling (PASL) MRI |
| spellingShingle | Charles R Joseph Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer Disease Biomedicines preclinical Alzheimer disease blood–brain barrier paravascular outflow glymphatic system high definition dynamic contrast enhanced (DCE) imaging MRI 3D pulsed arterial spin labeling (PASL) MRI |
| title | Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer Disease |
| title_full | Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer Disease |
| title_fullStr | Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer Disease |
| title_full_unstemmed | Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer Disease |
| title_short | Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer Disease |
| title_sort | novel mri techniques identifying vascular leak and paravascular flow reduction in early alzheimer disease |
| topic | preclinical Alzheimer disease blood–brain barrier paravascular outflow glymphatic system high definition dynamic contrast enhanced (DCE) imaging MRI 3D pulsed arterial spin labeling (PASL) MRI |
| url | https://www.mdpi.com/2227-9059/8/7/228 |
| work_keys_str_mv | AT charlesrjoseph novelmritechniquesidentifyingvascularleakandparavascularflowreductioninearlyalzheimerdisease |