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. 2015 Feb 6;10(2):e0117290.
doi: 10.1371/journal.pone.0117290. eCollection 2015.

Temporal evolution of ischemic lesions in nonhuman primates: a diffusion and perfusion MRI study

Xiaodong Zhang  1 , Frank Tong  2 , Chun-Xia Li  1 , Yumei Yan  1 , Doty Kempf  1 , Govind Nair  3 , Silun Wang  1 , E Chris Muly  4 , Stuart Zola  5 , Leonard Howell  4
Affiliations

Temporal evolution of ischemic lesions in nonhuman primates: a diffusion and perfusion MRI study

Xiaodong Zhang et al. PLoS One. .

Erratum in

Abstract

Background and purpose: Diffusion-weighted imaging (DWI) and perfusion MRI were used to examine the spatiotemporal evolution of stroke lesions in adult macaques with ischemic occlusion.

Methods: Permanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10-21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1-6, 48, and 96 hours post occlusion and validated with H&E staining.

Results: The stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours) (n = 7) in the hyperacute phase (1-6 hours). The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI) and increased to 3.9±2.9 ml (n = 5, by T2W) after 48 hours, and to 4.7±2.2ml (n = 3, by T2W) after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01) at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4). In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion.

Conclusion: The infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Stroke lesion evolution.
Top: Axial DWI images of Subject RJJ3 at 48 hours post stroke show the entire infarct territory. Bottom: representative DWI images of RJJ3 demonstrate the infarct evolution at different time point (in hours) post MCA occlusion.
Fig 2
Fig 2. Temporal volumetric changes of stroke infarct in each subject during the hyperacute phase (1–6 hours).
A natural logarithmic fitting was performed for each data set. Y-axis: volume (ml); X-axis: hours post MCA occlusion.
Fig 3
Fig 3. Serial axial CBF maps illustrate temporal perfusion changes in Subject RFA5 after permanent MCA occlusion.
Fig 4
Fig 4. CBF ratio of ipsilateral/contralateral in infarction core (left) and penumbra (right) post MCA occlusion.
Error bar: mean + Standard error.
Fig 5
Fig 5. The stroke lesion is illustrated in the perfusion (CBF), diffusion (DWI), T2W images and H&E stained slice of the stroke monkey brain (RVG4).
Fig 6
Fig 6. Illustration of ischemic lesions on T2W images and histology sections.
Top: Axial T2W images of Subject RVG4. Middle: Reconstructed coronal T2W images of the same stroke monkey. Bottom: H&E staining of this stroke monkey brain sample.
See this image and copyright information in PMC

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