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Non-contrast MR imaging of blood-brain barrier permeability to water.

ABSTRACT: PURPOSE:Many brain diseases are associated with an alteration in blood-brain barrier (BBB) and its permeability. Current methods using contrast agent are primarily sensitive to major leakage of BBB to macromolecules, but may not detect subtle changes in BBB permeability. The present study aims to develop a novel non-contrast MRI technique for the assessment of BBB permeability to water. METHODS:The central principle is that by measuring arterially labeled blood spins that are drained into cerebral veins, water extraction fraction (E) and permeability-surface-area product (PS) of BBB can be determined. Four studies were performed. We first demonstrated the proof-of-principle using conventional ASL with very long post-labeling delays (PLD). Next, a new sequence, dubbed water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST), and its Look-Locker (LL) version were developed. Finally, we demonstrated that the sensitivity of the technique can be significantly enhanced by acquiring the data under mild hypercapnia. RESULTS:By combining a strong background suppression with long PLDs (2500-4500 ms), ASL spins were reliably detected in the superior sagittal sinus (SSS), demonstrating the feasibility of measuring this signal. The WEPCAST sequence eliminated partial voluming effects of tissue perfusion and allowed quantitative estimation of E?=?95.5?±?1.1% and PS?=?188.9?±?13.4?mL/100?g/min, which were in good agreement with literature reports. LL-WEPCAST sequence shortened the scan time from 19?min to 5?min while providing results consistent with multiple single-PLD acquisitions. Mild hypercapnia increased SNR by 78?±?25% without causing a discomfort in participants. CONCLUSION:A new non-contrast technique for the assessment of global BBB permeability was developed, which may have important clinical applications.

SUBMITTER: Lin Z

PROVIDER: S-EPMC6097906 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Non-contrast MR imaging of blood-brain barrier permeability to water.

Lin Zixuan Z Li Yang Y Su Pan P Mao Deng D Wei Zhiliang Z Pillai Jay J JJ Moghekar Abhay A van Osch Matthias M Ge Yulin Y Lu Hanzhang H

Magnetic resonance in medicine 20180301 4

<h4>Purpose</h4>Many brain diseases are associated with an alteration in blood-brain barrier (BBB) and its permeability. Current methods using contrast agent are primarily sensitive to major leakage of BBB to macromolecules, but may not detect subtle changes in BBB permeability. The present study aims to develop a novel non-contrast MRI technique for the assessment of BBB permeability to water.<h4>Methods</h4>The central principle is that by measuring arterially labeled blood spins that are drai ...[more]

PMID: 29498097

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Project description:Key pointsThe blood-brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system. BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant Ki . Here evidence is provided that Ki as measured by DCE-MRI behaves as expected for a marker of overall BBB leakage. These results support the use of DCE-MRI for in vivo studies of human BBB permeability in health and disease.AbstractBlood-brain barrier (BBB) leakage can be measured using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as the influx constant Ki . To validate this method we compared measured Ki with biological expectations, namely (1) higher Ki in healthy individual grey matter (GM) versus white matter (WM), (2) GM/WM cerebral blood volume (CBV) ratio close to the histologically established GM/WM vascular density ratio, (3) higher Ki in visibly enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher Ki in MS NAWM versus healthy individual NAWM. We recruited 13 healthy individuals and 12 patients with MS and performed whole-brain 3D DCE-MRI at 3 T. Ki and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. Ki was higher in control GM versus WM (P = 0.001). CBV was higher in GM versus WM (P = 0.005, mean ratio 1.9). Ki was higher in visibly enhancing MS lesions versus MS NAWM (P = 0.002), and in MS NAWM versus controls (P = 0.014). Bland-Altman analysis showed no significant difference between ROI and segmentation methods (P = 0.638) and an intra-class correlation coefficient showed moderate single measure consistency (0.610). Ki behaves as expected for a compound marker of permeability and surface area. The GM/WM CBV ratio measured by this technique is in agreement with the literature. This adds evidence to the validity of Ki measured by DCE-MRI as a marker of overall BBB leakage.

Project description:PurposeAssessment of the blood-brain barrier (BBB) permeability without the need for contrast agent is desirable, and the ability to measure the permeability to small molecules such as water may further increase the sensitivity in detecting diseases. This study proposed a time-efficient, noncontrast method to measure BBB permeability to water, evaluated its test-retest reproducibility, and compared it with a contrast agent-based method.MethodsA single-delay water extraction with phase-contrast arterial spin tagging (WEPCAST) method was devised in which spatial profile of the signal along the superior sagittal sinus was used to estimate bolus arrival time, and the WEPCAST signal at the corresponding location was used to compute water extraction fraction, which was combined with global cerebral blood flow to estimate BBB permeability surface area product to water. The reliability of WEPCAST sequence was examined in terms of intrasession, intersession, and inter-vendor (Philips [Ingenia, Best, the Netherlands] and Siemens [Prisma, Erlangen, Germany]) reproducibility. Finally, we compared this new technique to a contrast agent-based method.ResultsSingle-delay WEPCAST reduced the scan duration from approximately 20 min to 5 min. Extract fraction values estimated from single-delay WEPCAST showed good consistency with the multi-delay method (R = 0.82, P = .004). Group-averaged permeability surface area product values were found to be 137.5 ± 9.3 mL/100 g/min. Intrasession, intersession, and inter-vendor coefficient of variation of the permeability surface area product values were 6.6 ± 4.5%, 6.9 ± 3.7%, and 8.9 ± 3.0%, respectively. Finally, permeability surface area product obtained from WEPCAST MRI showed a significant correlation with that from the contrast-based method (R = .73, P = .02).ConclusionSingle-delay WEPCAST MRI can measure BBB permeability to water within 5 min with an intrasession, intersession, and inter-vendor test-retest reproducibility of 6% to 9%. This method may provide a useful marker of BBB breakdown in clinical studies.

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Non-contrast MR imaging of blood-brain barrier permeability to water.

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Non-contrast MR imaging of blood-brain barrier permeability to water.

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