Ultra-long-TE arterial spin labeling reveals rapid and brain-wide blood-to-CSF water transport in humans

The study of brain clearance mechanisms is an active area of research. While we know that the cerebrospinal fluid (CSF) plays a central role in one of the main existing clearance pathways, the exact processes for the secretion of CSF and the removal of waste products from tissue are under debate. CSF is thought to be created by the exchange of water and ions from the blood, which is believed to mainly occur in the choroid plexus. This exchange has not been thoroughly studied in vivo. We propose a modified arterial spin labeling (ASL) MRI sequence and image analysis to track blood water as it is transported to the CSF, and to characterize its exchange from blood to CSF. We acquired six pseudo-continuous ASL sequences with varying labeling duration (LD) and post-labeling delay (PLD) and a segmented 3D-GRASE readout with a long echo train (8 echo times (TE)) which allowed separation of the very long-T2 CSF signal. ASL signal was observed at long TEs (793 ms and higher), indicating presence of labeled water transported from blood to CSF. This signal appeared both in the CSF proximal to the choroid plexus and in the subarachnoid space surrounding the cortex. ASL signal was separated into its blood, gray matter and CSF components by fitting a triexponential function with T2s taken from literature. A two-compartment dynamic model was introduced to describe the exchange of water through time and TE. From this, a water exchange time from the blood to the CSF (Tbl->CSF) was mapped, with an order of magnitude of approximately 60 s

Blood-Brain Barrier Permeability of Normal Appearing White Matter in Relapsing-Remitting Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS). METHODOLOGY/PRINCIPAL FINDINGS: Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before and after injection of Gd-DTPA. The pre-injection baseline T1 of NAWM (945±55 [SD] ms) was prolonged in RR-MS relative to healthy controls (903±23 ms, p = 0.028). Gd-DTPA injection shortened T1 to a similar extent in both groups. Mean T1 of NAWM was 866±47 ms in the NAWM of RR-MS patients and 824±13 ms in the white matter of healthy controls. The regional variability of T1 values expressed as the coefficient of variation (CV) was comparable between the two groups at baseline, but not after injection of the contrast agent. After intravenous Gd-DTPA injection, T1 values in NAWM were more variable in RR-MS patients (CV = 0.198±0.046) compared to cerebral white matter of healthy controls (CV = 0.166±0.018, p = 0.046). CONCLUSIONS/SIGNIFICANCE: We found no evidence of a global BBB disruption within the NAWM of RR-MS patients undergoing immunomodulatory treatment. However, the increased variation of T1 values in NAWM after intravenous Gd-DTPA injection points to an increased regional inhomogeneity of BBB function in NAWM in relapsing-remitting MS

Reduced NAA-Levels in the NAWM of Patients with MS Is a Feature of Progression. A Study with Quantitative Magnetic Resonance Spectroscopy at 3 Tesla

Reduced N-acetyl-aspartate (NAA) levels in magnetic resonance spectroscopy (MRS) may visualize axonal damage even in the normal appearing white matter (NAWM). Demyelination and axonal degeneration are a hallmark in multiple sclerosis (MS).To define the extent of axonal degeneration in the NAWM in the remote from focal lesions in patients with relapsing-remitting (RRMS) and secondary progressive MS (SPMS).H-MR-chemical shift imaging (TR = 1500ms, TE = 135ms, nominal resolution 1ccm) operating at 3Tesla to assess the metabolic pattern in the fronto–parietal NAWM. Ratios of NAA to creatine (Cr) and choline (Cho) and absolute concentrations of the metabolites in the NAWM were measured in each voxel matching exclusively white matter on the anatomical T2 weighted MR images.No significant difference of absolute concentrations for NAA, Cr and Cho or metabolite ratios were found between RRMS and controls. In SPMS, the NAA/Cr ratio and absolute concentrations for NAA and Cr were significantly reduced compared to RRMS and to controls.In our study SPMS patients, but not RRMS patients were characterized by low NAA levels. Reduced NAA-levels in the NAWM of patients with MS is a feature of progression

Association between MRI parameters and the MS severity scale: a 12 year follow-up study

Contains fulltext : 80250.pdf (publisher's version ) (Closed access)BACKGROUND: Several magnetic resonance imaging (MRI) parameters are known to be associated with short-term outcome in multiple sclerosis (MS) patients. MS-related disability typically progresses over decades, stressing the need for longer follow-up studies. Until now, these studies are relatively sparse and, therefore, the predictive value of MRI parameters for clinical disability remains largely unknown. OBJECTIVE: To assess the predictive value of brain MRI parameters, which are obtained during the first 3.3 years of the study for overall disease severity as measured by the MS Severity Score (MSSS) after 12.2 years follow-up. METHODS: Forty-six MS patients were included in the study. MRI parameters included both lesion loads and atrophy measures. Average and change parameters were calculated for MRI parameters and subsequently used as independent variables in regression models, while MSSS was the dependent variable. RESULTS: Follow-up (FU) was obtained in 43/46 patients (94%) and median expanded disability status scale (EDSS) score increased significantly from 2.5 to 4.0. At last FU median MSSS was 4.3 (range 2.2-6.9). In univariate analyses, both change and cross-sectional T1-hypointense lesion load and ventricular atrophy measures were associated with MSSS. A multiple regression model included the change parameter of hypointense T1-lesion load (BHLL). This model explained 20% of variance in MSSS, which increased to 34% when type of disease (relapsing remitting or secondary progressive), age, and sex were entered additionally. CONCLUSION: MRI measures of axonal loss are associated with higher overall disease severity in MS patients