Korean J Radiol.  2008 Jun;9(3):196-204. 10.3348/kjr.2008.9.3.196.

Tracking of Neural Stem Cells in Rats with Intracerebral Hemorrhage by the Use of 3T MRI

• Chang NK
• Jeong YY
• Park JS
• Jeong HS
• Jang S
• Jang MJ
• Lee JH
• Shin SS
• Yoon W
• Chung TW
• Kang HK

• KMID: 1758452
• DOI: http://doi.org/10.3348/kjr.2008.9.3.196

Abstract

OBJECTIVE
To access the feasibility of clinically available 3T MRI to detect the migration of labeled neural stem cells (NSCs) in intracerebral hemorrhage (ICH) in a rat model. MATERIALS AND METHODS: The ethics committee of our institution approved this study. ICH was induced by the injection of collagenase type IV into the right striatum of ten Sprague-Dawley rats. Human NSCs conjugated with Feridex (super-paramagnetic iron oxide: SPIO) were transplanted into the left striatum one week after ICH induction. MRI was performed on a 3T scanner during the first, second, third, fourth, and sixth weeks post-transplantation. MRI was obtained using coronal T2- and T2*-weighted sequences. Two rats were sacrificed every week after in vivo MRI in order to analyze the histological findings. RESULTS: ICH in the right striatum was detected by MRI one and two weeks after transplantation without migration of the NSCs. There was no migration of the NSCs as seen on the histological findings one week after transplantation. The histological findings two weeks after transplantation showed a small number of NSCs along the corpus callosum. On MRI three weeks after transplantation, there was a hypointense line along the corpus callosum and decreased signal intensity in the right periventricular region. Histological findings three weeks after transplantation confirmed the presence of the hypointense line representing SPIO-labeled NSCs. MRI four and six weeks after transplantation showed a hypointense spot in the right periventricular region. The histological findings four and six weeks after transplantation showed the presence of prominent NSCs in the right periventricular region. CONCLUSION: 3T MRI can detect the migration of NSCs in rats with ICH along the corpus callosum. Therefore, 3T MRI could be feasible for detecting the migration of NSCs in the clinical setting of stem cell therapy.

Keyword

Stem cells; Magnetic resonance (MR); Ferumoxides

MeSH Terms

Animals
Cell Movement/*physiology
Cerebral Hemorrhage/*pathology
Corpus Callosum/pathology
Humans
Iron/diagnostic use
Magnetic Resonance Imaging/*methods
Neurons/*physiology
Oxides/diagnostic use
Rats
Rats, Sprague-Dawley
Stem Cell Transplantation
Stem Cells/*physiology
Time Factors

Figure

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  Fig. 1 Prussian blue staining of neural stem cells (objective magnification: × 40). A. Unlabeled neural stem cells without blue spots. B. SPIO-labeled neural stem cells show blue spots located inside cells, suggesting presence of iron oxide particles.

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  Fig. 2 In vitro T2*-weighted images of neural stem cells. A-D. 250 neural stem cells in 2% gelatin tube (A), 5 × 103 neural stem cells (B), 5 × 104 neural stem cells (C), 2 × 105 neural stem cells (D). In B, C, and D, T2*-weighted images (TR/TE = 231/10 msec) show linear, hypointense cluster in bottom of tubes (arrows), representing SPIO-labeled neural stem cells.

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  Fig. 3 MR and histological findings one week after implantation of neural stem cells. A. T2-weighted image (TR/TE = 3,000/100 msec) shows hypointense, SPIO-labeled, neural stem cells (curved arrow) in left striatum and hyperintense lesion (arrows) in right striatum, representing intracerebral hemorrhage. B. T2*-weighted image (TR/TE = 231/10 msec) reveals hypointense, SPIO-labeled neural stem cells (curved arrow) in left cerebral hemisphere. C. Hematoxylin and eosin staining (objective magnification: × 4) shows intracerebral hemorrhage (arrows) in right striatum with mass effect to corpus callosum and right lateral ventricle (LV). D. Prussian blue staining (objective magnification: × 4) shows no migration of SPIO-labeled neural stem cells. E. Immunohistochemical staining (objective magnification: × 4) shows no migration of neural stem cells.

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  Fig. 4 MR and histological findings two weeks after implantation of neural stem cells. A. On T2-weighted image (TR/TE = 3,000/100 msec), size of intracerebral hemorrhage (arrow) in right cerebral hemisphere is smaller than it was one week after implantation of neural stem cells. B. T2*-weighted image (TR/TE = 231/10 msec) shows slightly decreased size of hypointense spot (curved arrow) in left cerebral hemisphere. There is no migration of neural stem cells. C. Prussian blue staining (objective magnification: × 4) shows small number of neural stem cells in corpus callosum (arrows). D. Immunohistochemical staining (objective magnification: × 4) shows migration of small number of neural stem cells into corpus callosum (arrows).

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  Fig. 5 MR and histological findings three weeks after implantation of neural stem cells. A. T2-weighted image (TR/TE = 3,000/100 msec) shows decreased size (arrow) of intracerebral hemorrhage two weeks after implantation of neural stem cells. B. T2*-weighted image (TR/TE = 231/10 msec) shows decreased size of hypointense spot (curved arrow) in left striatum. Linear low signal intensity (arrows) along corpus callosum is considered to represent SPIO-labeled neural stem cells. There is small, hypointense spot in right, periventricular region (arrowheads), suggestive of migrated neural stem cells. C. Prussian blue staining (objective magnification: × 2) shows large number of SPIO-labeled, neural stem cells in corpus callosum (arrows). D. Immunohistochemical staining (objective magnification: × 2) shows neural stem cells in corpus callosum (arrows).

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  Fig. 6 MR and histological findings four weeks after implantation of neural stem cells. A. T2-weighted image (TR/TE = 3,000/100 msec) shows decreased size of intracerebral hemorrhage three weeks after implantation of neural stem cells. B. T2*-weighted image (TR/TE = 231/10 msec) shows decreased size of hypointense spot (curved arrow) in left striatum. Clusters of hypointensity (arrows) are seen in right periventricular region. C. Prussian blue staining (objective magnification: × 4) shows inhomogeneous distribution of neural stem cells around right ventricle (arrows). D, E. Immunohistochemical staining (objective magnification: × 4 and × 10) shows neural stem cells in right, periventricular region (arrows).

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  Fig. 7 Signal intensity ratio changes in MR images of right periventricular region and of left striatum. Significant decrease of signal intensity ratio between two weeks and three weeks after implantation of neural stem cells is seen in right periventricular region, suggesting massive migration of SPIO-labeled neural stem cells from left striatum into right periventricular region.

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