Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI

Quan Jiang, Gang Zhang Zheng, Liang Ding Guang, Li Zhang, James R. Ewing, Lei Wang, Rui Lan Zhang, Lian Li, Mei Lu, He Meng, Ali Syed Arbab, Jiani Hu, Jiang Li Qing, Siamak Pourabdollah Nejad D, Hemanthkumar Athiraman, Michael Chopp

Research output: Contribution to journalArticlepeer-review

147 Scopus citations


Using MRI, we investigated dynamic changes of brain angiogenesis after neural progenitor cell transplantation in the living adult rat subjected to embolic stroke. Neural progenitor cells isolated from the subventricular zone (SVZ) of the adult rat were labeled by superparamagnetic particles and intracisternally transplanted into the adult rat 48 h after stroke (n = 8). Before and after the transplantation, an array of MRI parameters were measured, including high resolution 3D MRI and quantitative T1, T 1sat (T1 in the presence of an off-resonance irradiation of the macromolecules of brain), T2, the inverse of the apparent forward transfer rate for magnetization transfer (kinv), cerebral blood flow (CBF), cerebral blood volume (CBV), and blood-to-brain transfer constant (Ki) of Gd-DTPA. The von Willerbrand factor (vWF) immunoreactive images of coronal sections obtained at 6 weeks after cell transplantation were used to analyze vWF immunoreactive vessels. MRI measurements revealed that grafted neural progenitor cells selectively migrated towards the ischemic boundary regions. In the ischemic boundary regions, angiogenesis confirmed by an increase in vascular density and the appearance of large thin wall mother vessels was coincident with increases of CBF and CBV (CBF, P < 0.01; CBV, P < 0.01) at 6 weeks after treatment, and coincident with transient increases of Ki with a peak at 2 to 3 weeks after cell therapy. Relative T1, T1sat, T2, and k inv decreased in the ischemic boundary regions with angiogenesis compared to that in the non-angiogenic ischemic region (T1, P < 0.01 at 6 weeks; T1sat, P < 0.05 at 2 to 6 weeks; T2, P < 0.05 at 3 to 6 weeks; kinv P < 0.05 at 6 weeks). Of these methods, Ki appear to be the most useful MR measurements which identify and predict the location and area of angiogenesis. CBF, CBV, T 1sat, T1, T2, and kinv provide complementary information to characterize ischemic tissue with and without angiogenesis. Our data suggest that select MRI parameters can identify the cerebral tissue destined to undergo angiogenesis after treatment of embolic stroke with cell therapy.

Original languageEnglish (US)
Pages (from-to)698-707
Number of pages10
Issue number3
StatePublished - Nov 15 2005
Externally publishedYes


  • Angiogenesis
  • CBF
  • CBV
  • Cerebral ischemia
  • Magnetic resonance imaging
  • Molecular imaging
  • Permeability

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


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