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Author Notes:

Email: xzhang8@emory.edu.

Conceived and designed the experiments: FT SZ LH XZ. Performed the experiments: FT CL DK GN ECM XZ. Analyzed the data: YY CL SW ECM XZ. Wrote the paper: XZ.

The authors thank Sudeep Patel for C-arm operation and MRI data collection, Ruth Connelly, Wendy Williamson Coyne, Juliet Brown, Dr Fawn Connor-Stroud (DVM), Jean Ksiazek for animal care in MRI, surgery and post stroke, and Dr Anapatricia Garcia for necropsy, Marcelia Maddox for H&E staining, and Drs Shan Ping Yu, Byron Ford, Manuel Yepes, Ling Wei, Yoji Tanaka, Stelios Smirnakis for their thoughtful suggestions.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This project was supported in part by NCRR and currently by the Office of Research Infrastructure Programs (P51RR000165 and OD P51OD011132), DA 031246 (LH), and by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454 (XZ).

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • FOCAL CEREBRAL-ISCHEMIA
  • STROKE MODEL
  • RESONANCE SPECTROSCOPY
  • ARTERY OCCLUSION
  • SERIAL DIFFUSION
  • RHESUS MACAQUE
  • INFARCT VOLUME
  • TISSUE SODIUM
  • SYMPTOM ONSET
  • WEIGHTED MRI

Temporal Evolution of Ischemic Lesions in Nonhuman Primates: A Diffusion and Perfusion MRI Study

Tools:

Journal Title:

PLoS ONE

Volume:

Volume 10, Number 2

Publisher:

, Pages e0117290-e0117290

Type of Work:

Article | Final Publisher PDF

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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© 2015 Zhang et al.

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