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    Dynamic monitoring of blood-brain barrier integrity using water exchange index (WEI) during mannitol and CO2 challenges in mouse brain

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    Authors
    Huang, Shuning
    Farrar, Christian T
    Dai, Guangping
    Kwon, Seon Joo
    Bogdanov, Alexei A. Jr.
    Rosen, Bruce R.
    Kim, Young R.
    UMass Chan Affiliations
    Department of Radiology
    Document Type
    Journal Article
    Publication Date
    2013-04-01
    Keywords
    Cardiovascular System
    Investigative Techniques
    Nervous System
    Radiology
    
    Metadata
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029920/
    Abstract
    The integrity of the blood-brain barrier (BBB) is critical to normal brain function. Traditional techniques for the assessment of BBB disruption rely heavily on the spatiotemporal analysis of extravasating contrast agents. However, such methods based on the leakage of relatively large molecules are not suitable for the detection of subtle BBB impairment or for the performance of repeated measurements in a short time frame. Quantification of the water exchange rate constant (WER) across the BBB using strictly intravascular contrast agents could provide a much more sensitive method for the quantification of the BBB integrity. To estimate WER, we have recently devised a powerful new method using a water exchange index (WEI) biomarker and demonstrated BBB disruption in an acute stroke model. Here, we confirm that WEI is sensitive to even very subtle changes in the integrity of the BBB caused by: (i) systemic hypercapnia and (ii) low doses of a hyperosmolar solution. In addition, we have examined the sensitivity and accuracy of WEI as a biomarker of WER using computer simulation. In particular, the dependence of the WEI-WER relation on changes in vascular blood volume, T1 relaxation of cellular magnetization and transcytolemmal water exchange was explored. Simulated WEI was found to vary linearly with WER for typically encountered exchange rate constants (1-4 Hz), regardless of the blood volume. However, for very high WER ( > 5 Hz), WEI became progressively more insensitive to increasing WER. The incorporation of transcytolemmal water exchange, using a three-compartment tissue model, helped to extend the linear WEI regime to slightly higher WER, but had no significant effect for most physiologically important WERs (WER < 4 Hz). Variation in cellular T1 had no effect on WEI. Using both theoretical and experimental approaches, our study validates the utility of the WEI biomarker for the monitoring of BBB integrity.
    Source
    NMR Biomed. 2013 Apr;26(4):376-85. doi: 10.1002/nbm.2871. Epub 2012 Oct 11. Link to article on publisher's site
    DOI
    10.1002/nbm.2871
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/48604
    PubMed ID
    23055278
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1002/nbm.2871
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