Contrast enhanced MRI for the measurement of dynamic signal changes in the CSF and cerebral lymphatic vessels

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Date
2022-09-08
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Johns Hopkins University
Abstract
Cerebrospinal fluid (CSF) circulation is critical for waste clearance from the brain parenchyma. Dysfunction of the system has been linked to abnormal protein deposition in patients with Alzheimer’s (Aβ, tau) and Parkinson’s (alpha-synuclein) disease. The cerebral lymphatic vessels communicate with routes for CSF circulation and are believed to play a crucial role in the drainage of CSF from brain tissues to cervical lymph nodes. The study of CSF flow in cerebral lymphatic vessels can provide critical information regarding the clearance of abnormal proteins and metabolites from brain tissues. Accumulating evidence has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. Contrast-enhanced MRI is currently the most promising method for imaging CSF flow in the cerebral lymphatic vessels in humans. However, as most existing human MRI scans take > 5 minutes, the temporal resolution is poor for tracking dynamic changes in these vessels. The first contribution of this thesis is the development of MRI techniques for the measurement of dynamic susceptibility contrast changes in CSF (cDSC) in the human brain. With the cDSC method developed in this thesis, dynamic signal changes after Gd injection in the CSF can be detected at several locations where cerebral lymphatic vessels were identified in previous studies. The concentration of Gd in CSF in these regions was estimated to be approximately 0.2 mmol/L. To date, most imaging methods can only measure blood or lymphatic vessels separately. The second contribution of this thesis is that we further expanded the MRI method for simultaneously dynamic imaging of small blood and lymphatic vessels in the human brain with dynamic dual-spin-echo perfusion (DDSEP) MRI. The proposed DDSEP method showed consistent results in human brains as previous studies using separate methods. To the best of our knowledge, this may be the first study in which the temporal difference in Gd-induced signal changes from small blood and lymphatic vessels after intravenous Gd-injection was measured in the same human subjects.
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MRI, cerebral lymphatic vessels, Gd
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