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Precise Characterization of the Penumbra Revealed by MRI: A Modified Photothrombotic Stroke Model Study.

Qian C, Li PC, Jiao Y, Yao HH, Chen YC, Yang J, Ding J, Yang XY, Teng GJ - PLoS ONE (2016)

Bottom Line: One hour after occlusion, the low perfusion areas on the perfusion-weighted imaging interlaced with the hypointense areas on the apparent diffusion coefficient map, demonstrating that the penumbra was located both surrounding and inside the lesions.This phenomenon was subsequently confirmed by the c-fos and heart shock protein 90 staining.At early stages, the lesions were clearly identified on the apparent diffusion coefficient map; the volumes of the lesions on the diffusion-weighted imaging and T2-weighted imaging did not reach a maximum until 12 hours.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.

ABSTRACT

Aims: To precisely characterize the penumbra by MRI based on a modified photothrombotic stroke mouse model.

Methods: The proximal middle cerebral artery was occluded by a convenient laser system in conjunction with an intravenous injection of Rose Bengal in mice. And the suture MCAO model was performed in seven mice as a comparison of the reproducibility. One hour after occlusion, the penumbra was defined in six random photothrombotic stroke mice by mismatch between perfusion-weighted imaging and the apparent diffusion coefficient map on a home-made workstation. After imaging, three random mice of them were chosen to perform the reperfusion surgery. And the other three mice were sacrificed to stain for several potential penumbra markers, such as c-fos and heart shock protein 90. In the remaining mice, the evolution of the lesions was detected on the apparent diffusion coefficient map, diffusion-weighted imaging and T2-weighted imaging at 1, 3, 6, 12 and 24 hours. After evaluating the neurological deficit scores, the brains were sectioned and stained by triphenyltetrazolium chloride and Nissl.

Results: The mice subjected to photothrombosis showed significant behavioral deficits. One hour after occlusion, the low perfusion areas on the perfusion-weighted imaging interlaced with the hypointense areas on the apparent diffusion coefficient map, demonstrating that the penumbra was located both surrounding and inside the lesions. This phenomenon was subsequently confirmed by the c-fos and heart shock protein 90 staining. The final T2-weighted images of the mice subjected to the reperfusion surgery were also consistent with the penumbra images at one hour. At early stages, the lesions were clearly identified on the apparent diffusion coefficient map; the volumes of the lesions on the diffusion-weighted imaging and T2-weighted imaging did not reach a maximum until 12 hours. The coefficient of variation (CV) of the final lesions in the photothrombotic stroke mice was 21.7% (0.08 of 0.37) on T2-weighted imaging and 27.8% (0.10 of 0.35) on triphenyltetrazolium chloride, representing a high reproducibility (n = 7). While the CV of the lesions in the MCAO stroke mice was only 70% (0.24 of 0.34, n = 4).

Conclusions: This study has provided a precise imaging definition of the penumbra based on a reproducible photothrombotic stroke mouse model.

No MeSH data available.


Related in: MedlinePlus

The penumbra at one hour after occlusion on MRI.A) Representative slices from one mouse. Red colored areas represented low perfusion areas on the CBF map or hypointense areas on the ADC map, respectively. On the same map, meanwhile, the light blue colored areas represented the matching areas, which were regarded as the infarct lesions; while the negative mismatch areas were showed in dark blue. And the yellow colored areas represented the mismatching areas, this indicated the penumbra. The penumbra was shown as not only surrounding the lesions but also in the lesions. B) The CBF map on PWI showed considerably larger averaged relative lesion volumes (in percent of ipsilateral hemisphere) (*p<0.05; versus the ADC map). Several potential penumbra markers stains were performed to confirm the location of the penumbra, such as c-fos (C) and HSP-90 (D). The ipsilateral hemispheric slices were taken with a 2.5× objective lens. And the peri-infarct and the infarct areas were taken with a 10× lens indicated by triangle and pentacle, respectively. In both the peri-infarct and infarct areas, c-fos was readily detected, which was also consistent with the HSP-90 staining.
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pone.0153756.g004: The penumbra at one hour after occlusion on MRI.A) Representative slices from one mouse. Red colored areas represented low perfusion areas on the CBF map or hypointense areas on the ADC map, respectively. On the same map, meanwhile, the light blue colored areas represented the matching areas, which were regarded as the infarct lesions; while the negative mismatch areas were showed in dark blue. And the yellow colored areas represented the mismatching areas, this indicated the penumbra. The penumbra was shown as not only surrounding the lesions but also in the lesions. B) The CBF map on PWI showed considerably larger averaged relative lesion volumes (in percent of ipsilateral hemisphere) (*p<0.05; versus the ADC map). Several potential penumbra markers stains were performed to confirm the location of the penumbra, such as c-fos (C) and HSP-90 (D). The ipsilateral hemispheric slices were taken with a 2.5× objective lens. And the peri-infarct and the infarct areas were taken with a 10× lens indicated by triangle and pentacle, respectively. In both the peri-infarct and infarct areas, c-fos was readily detected, which was also consistent with the HSP-90 staining.

Mentions: The penumbra was visualized in vivo at one hour after occlusion. As the representative slices from one mouse were showed in Fig 4A, red colored areas indicated low perfusion areas on the cerebral blood flow (CBF) map or hypointense areas on the ADC map, respectively. Then, on the same map, the matching areas between the CBF and ADC maps were showed in light blue, while the mismatching areas were showed in yellow, and the negative mismatch areas were showed in dark blue. In detail, the relative volume of low blood flow areas on CBF map appeared considerably larger than the hypointense areas on the ADC map (0.48±0.01vs 0.33±0.08, p< 0.05) (Fig 4A and 4B). Interestingly, the mismatch areas, representing the penumbra, could be detected not only surrounding but also in the lesions (Fig 4A). This phenomenon was also confirmed by several potential penumbra markers, c-fos and HSP-90. C-fos was readily observed in both the peri-infarct and infarct areas, which was also consistent with HSP-90 staining (Fig 4C and 4D). The T2-weighted images at 24 hours showed small lesions in the mice subjected to reperfusion, which matched well with the penumbra images at one hour (S2 Fig).


Precise Characterization of the Penumbra Revealed by MRI: A Modified Photothrombotic Stroke Model Study.

Qian C, Li PC, Jiao Y, Yao HH, Chen YC, Yang J, Ding J, Yang XY, Teng GJ - PLoS ONE (2016)

The penumbra at one hour after occlusion on MRI.A) Representative slices from one mouse. Red colored areas represented low perfusion areas on the CBF map or hypointense areas on the ADC map, respectively. On the same map, meanwhile, the light blue colored areas represented the matching areas, which were regarded as the infarct lesions; while the negative mismatch areas were showed in dark blue. And the yellow colored areas represented the mismatching areas, this indicated the penumbra. The penumbra was shown as not only surrounding the lesions but also in the lesions. B) The CBF map on PWI showed considerably larger averaged relative lesion volumes (in percent of ipsilateral hemisphere) (*p<0.05; versus the ADC map). Several potential penumbra markers stains were performed to confirm the location of the penumbra, such as c-fos (C) and HSP-90 (D). The ipsilateral hemispheric slices were taken with a 2.5× objective lens. And the peri-infarct and the infarct areas were taken with a 10× lens indicated by triangle and pentacle, respectively. In both the peri-infarct and infarct areas, c-fos was readily detected, which was also consistent with the HSP-90 staining.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4836676&req=5

pone.0153756.g004: The penumbra at one hour after occlusion on MRI.A) Representative slices from one mouse. Red colored areas represented low perfusion areas on the CBF map or hypointense areas on the ADC map, respectively. On the same map, meanwhile, the light blue colored areas represented the matching areas, which were regarded as the infarct lesions; while the negative mismatch areas were showed in dark blue. And the yellow colored areas represented the mismatching areas, this indicated the penumbra. The penumbra was shown as not only surrounding the lesions but also in the lesions. B) The CBF map on PWI showed considerably larger averaged relative lesion volumes (in percent of ipsilateral hemisphere) (*p<0.05; versus the ADC map). Several potential penumbra markers stains were performed to confirm the location of the penumbra, such as c-fos (C) and HSP-90 (D). The ipsilateral hemispheric slices were taken with a 2.5× objective lens. And the peri-infarct and the infarct areas were taken with a 10× lens indicated by triangle and pentacle, respectively. In both the peri-infarct and infarct areas, c-fos was readily detected, which was also consistent with the HSP-90 staining.
Mentions: The penumbra was visualized in vivo at one hour after occlusion. As the representative slices from one mouse were showed in Fig 4A, red colored areas indicated low perfusion areas on the cerebral blood flow (CBF) map or hypointense areas on the ADC map, respectively. Then, on the same map, the matching areas between the CBF and ADC maps were showed in light blue, while the mismatching areas were showed in yellow, and the negative mismatch areas were showed in dark blue. In detail, the relative volume of low blood flow areas on CBF map appeared considerably larger than the hypointense areas on the ADC map (0.48±0.01vs 0.33±0.08, p< 0.05) (Fig 4A and 4B). Interestingly, the mismatch areas, representing the penumbra, could be detected not only surrounding but also in the lesions (Fig 4A). This phenomenon was also confirmed by several potential penumbra markers, c-fos and HSP-90. C-fos was readily observed in both the peri-infarct and infarct areas, which was also consistent with HSP-90 staining (Fig 4C and 4D). The T2-weighted images at 24 hours showed small lesions in the mice subjected to reperfusion, which matched well with the penumbra images at one hour (S2 Fig).

Bottom Line: One hour after occlusion, the low perfusion areas on the perfusion-weighted imaging interlaced with the hypointense areas on the apparent diffusion coefficient map, demonstrating that the penumbra was located both surrounding and inside the lesions.This phenomenon was subsequently confirmed by the c-fos and heart shock protein 90 staining.At early stages, the lesions were clearly identified on the apparent diffusion coefficient map; the volumes of the lesions on the diffusion-weighted imaging and T2-weighted imaging did not reach a maximum until 12 hours.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.

ABSTRACT

Aims: To precisely characterize the penumbra by MRI based on a modified photothrombotic stroke mouse model.

Methods: The proximal middle cerebral artery was occluded by a convenient laser system in conjunction with an intravenous injection of Rose Bengal in mice. And the suture MCAO model was performed in seven mice as a comparison of the reproducibility. One hour after occlusion, the penumbra was defined in six random photothrombotic stroke mice by mismatch between perfusion-weighted imaging and the apparent diffusion coefficient map on a home-made workstation. After imaging, three random mice of them were chosen to perform the reperfusion surgery. And the other three mice were sacrificed to stain for several potential penumbra markers, such as c-fos and heart shock protein 90. In the remaining mice, the evolution of the lesions was detected on the apparent diffusion coefficient map, diffusion-weighted imaging and T2-weighted imaging at 1, 3, 6, 12 and 24 hours. After evaluating the neurological deficit scores, the brains were sectioned and stained by triphenyltetrazolium chloride and Nissl.

Results: The mice subjected to photothrombosis showed significant behavioral deficits. One hour after occlusion, the low perfusion areas on the perfusion-weighted imaging interlaced with the hypointense areas on the apparent diffusion coefficient map, demonstrating that the penumbra was located both surrounding and inside the lesions. This phenomenon was subsequently confirmed by the c-fos and heart shock protein 90 staining. The final T2-weighted images of the mice subjected to the reperfusion surgery were also consistent with the penumbra images at one hour. At early stages, the lesions were clearly identified on the apparent diffusion coefficient map; the volumes of the lesions on the diffusion-weighted imaging and T2-weighted imaging did not reach a maximum until 12 hours. The coefficient of variation (CV) of the final lesions in the photothrombotic stroke mice was 21.7% (0.08 of 0.37) on T2-weighted imaging and 27.8% (0.10 of 0.35) on triphenyltetrazolium chloride, representing a high reproducibility (n = 7). While the CV of the lesions in the MCAO stroke mice was only 70% (0.24 of 0.34, n = 4).

Conclusions: This study has provided a precise imaging definition of the penumbra based on a reproducible photothrombotic stroke mouse model.

No MeSH data available.


Related in: MedlinePlus