TY - JOUR
T1 - Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI
AU - Jiang, Quan
AU - Zheng, Gang Zhang
AU - Guang, Liang Ding
AU - Zhang, Li
AU - Ewing, James R.
AU - Wang, Lei
AU - Zhang, Rui Lan
AU - Li, Lian
AU - Lu, Mei
AU - Meng, He
AU - Arbab, Ali Syed
AU - Hu, Jiani
AU - Qing, Jiang Li
AU - Nejad D, Siamak Pourabdollah
AU - Athiraman, Hemanthkumar
AU - Chopp, Michael
N1 - Funding Information:
This work was supported by NIH grants RO1 NS48349, RO1 NS38292, RO1 NS43324, RO1 HL64766, RO1 HL70023, PO1 NS23393, and PO1 NS42345.
PY - 2005/11/15
Y1 - 2005/11/15
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - CBF
KW - CBV
KW - Cerebral ischemia
KW - Magnetic resonance imaging
KW - Molecular imaging
KW - Permeability
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U2 - 10.1016/j.neuroimage.2005.06.063
DO - 10.1016/j.neuroimage.2005.06.063
M3 - Article
C2 - 16112879
AN - SCOPUS:27544488427
SN - 1053-8119
VL - 28
SP - 698
EP - 707
JO - NeuroImage
JF - NeuroImage
IS - 3
ER -