Original Article

Journal of Cerebral Blood Flow & Metabolism (2005) 25, 583–592. doi:10.1038/sj.jcbfm.9600053 Published online 16 February 2005

Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI

This work was supported by NINDS Grants PO1 NS23393, RO1 NS38292, RO1 NS43324, and HL64766.

Quan Jiang1,2, James R Ewing1,2, Guang Liang Ding1, Li Zhang1, Zheng Gang Zhang1, Lian Li1, Polly Whitton1, Mei Lu3, Jiani Hu4, Qing Jiang Li1, Robert A Knight1,2 and Michael Chopp1,2

  1. 1Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan, USA
  2. 2Department of Physics, Oakland University, Rochester, Michigan, USA
  3. 3Department of Biostatistics and Research Epidemiology, Henry Ford Health Sciences Center, Detroit, Michigan, USA
  4. 4Harper Hospital, MR Center, Detroit, Michigan, USA

Correspondence: Dr M Chopp, Neurology Department, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. E-mail: chopp@neuro.hfh.edu

Received 1 August 2004; Revised 3 September 2004; Accepted 15 September 2004; Published online 16 February 2005.

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Abstract

We sought to identify magnetic resonance imaging (MRI) parameters that can identify as well as predict disruption of the blood–brain barrier (BBB) after embolic stroke in the rat. Rats subjected to embolic stroke with (n=13) and without (n=13) rt-PA treatment were followed with MRI using quantitative permeability-related parameters, consisting of: transfer constant (Ki) of Gd- DTPA, the distribution volume (Vp) of the mobile protons, and the inverse of the apparent forward transfer rate for magnetization transfer (kinv), as well as the apparent diffusion coefficient of water (ADCw), T2, and cerebral cerebral blood flow (CBF). Tissue progressing to fibrin leakage resulting from BBB disruption and adjacent tissue were then analyzed to identify MRI markers that characterize BBB disruption. Animals were killed after final MRI measurements at 24 h after induction of embolic stroke and cerebral tissues were perfused and stained to detect fibrin leakage. Ki, Vp, and kinv were the most sensitive early (2 to 3 h) indices of the cerebral tissue that progresses to fibrin leakage. Cerebral blood flow was not significantly different between ischemic tissue with a compromised and an intact BBB. Our data indicate that compromise of the BBB can be sensitively predicted using a select set of MR parameters.

Keywords:

blood–brain barrier, cerebral ischemia, magnetic resonance imaging, magnetization transfer, permeability, thrombolysis

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