Original Article

Journal of Cerebral Blood Flow & Metabolism (2006) 26, 1366–1377. doi:10.1038/sj.jcbfm.9600288; published online 1 March 2006

Ischemic cerebral tissue response to subventricular zone cell transplantation measured by iterative self-organizing data analysis technique algorithm

This work was supported by NINDS Grants PO1 NS23393, PO1 NS42345, RO1 NS48349, RO1 NS38292, RO1 NS43324 and HL64766.

Lian Li1, Quan Jiang1, Li Zhang1, Guangliang Ding1, Lei Wang1, Ruilan Zhang1, Zheng G Zhang1, Qingjiang Li1, James R Ewing1, Alissa Kapke2, Mei Lu2 and Michael Chopp1,3

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

Correspondence: Dr M Chopp, Henry Ford Hospital, Neurology Department, E&R 3056, 2799 West Grand Boulevard, Detroit, MI 48202, USA. E-mail: chopp@neuro.hfh.edu

Received 22 December 2005; Revised 23 January 2006; Accepted 23 January 2006; Published online 1 March 2006.

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Abstract

To investigate the changes of the ischemic lesion in rat brain after subventricular zone (SVZ) cell transplantation and the influence of the grafted cells on the appearance of angiogenesis, SVZ cells, superparamagnetically labeled, were intracisternally transplanted into the rat brain 48 h after onset of embolic stroke. A complete set of magnetic resonance (MR) images was acquired for all animals with (n=8) and without (n=3) cell grafting at approximately 24 h, 72 h, and weekly for 6 weeks after stroke. Transplanted cells were tracked by high-resolution three-dimensional gradient-echo images and the interaction between the cells and ischemic lesion was detected by ISODATA (Iterative Self-Organizing Data Analysis Technique Algorithm) calculated from T1, T2 and T1sat maps. Tissue status from ISODATA was characterized by a specific signature, which represents the deviation from normal tissue in the feature space. Transplanted SVZ cells selectively migrated towards the ischemic side of the rat brain and approached the lesion boundary within 1-week after grafting. Cell treated rats exhibited a significant reduction of average lesion size compared with control rats (P<0.05). A significant reduction of tissue signature (P<0.001) induced by cell transplantation was localized to the position of grafted cells, and these sites exhibited stably restored cerebral blood flow (CBF) (approximately 85% of normal CBF). Angiogenesis was present in sites either immediately adjacent to or surrounded by the grafted cells. Our data indicate that map-ISODATA accurately and dynamically characterizes the ischemic lesion and its response to cell therapy.

Keywords:

angiogenesis, cerebral ischemia, ISODATA, MRI, subventricular zone cell transplantation

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