This proposal is a competitive renewal of R01NS045879 "Stroke Imaging of Conscious Rats." In the previous grant cycle, we reported over two dozen peer-reviewed publications and leveraged multiple foundation grants to expand stroke research. Stroke remains to be the third leading cause of death and the leading cause of long-term disability. Our previous goals were to establish a rat stroke model with reproducible perfusion-diffusion mismatch (which approximates the ischemic penumbra), and to develop and apply quantitative perfusion, diffusion MRI and analysis methods to characterize pixel-by-pixel the spatiotemporal progression of diffusion and perfusion characteristics under different middle cerebral artery occlusion (MCAO) durations in the acute phase. Imaging measures were compared with histology. Gratifying progress was made on all previously proposed aims. In this competitive renewal, we seek to develop novel multimodal MRI approaches to probe the "physiological" and "functional" characteristics of the ischemic tissue at risk in stroke rats. These studies will focus on using blood-oxygenation-level dependent (BOLD) and cerebral blood flow (CBF) fMRI of physiologic (hypercapnic and oxygen) challenge and functional (stimulation and resting state) activity to probe perfusion and diffusion abnormality at 7 Tesla.
We aim to apply these methodologies to study both acute and chronic stroke. Together, through an artificial neural-network predictive model, we will examine different MRI measures to accurately predict acute infarction and chronic recovery. Our central hypothesis is - through improved understanding of the physiological and functional profiles of ischemic tissue at risk and their spatiotemporal characteristics - tissue viability and functional recovery can be accurately predicted using only acute MRI data.
This proposal aims to develop novel multimodal MRI approaches to probe the "physiological" and "functional" characteristics of the ischemic tissue at risk in stroke rats. These non-invasive translational methodologies will provide a comprehensive anatomical, physiological and functional profile of ischemic tissue at risk and their spatiotemporal characteristics in a reproducible rat stroke model. These findings have the potential to positively impact stroke research, including testing of novel therapeutic strategies, as well as enhance clinical decision making in the treatment of acute stroke.
|Li, Wei; Long, Justin Alexander; Watts, Lora et al. (2016) Spatiotemporal changes in diffusion, T2 and susceptibility of white matter following mild traumatic brain injury. NMR Biomed 29:896-903|
|Sun, Y; Shen, Q; Watts, L T et al. (2016) Multimodal MRI characterization of experimental subarachnoid hemorrhage. Neuroscience 316:53-62|
|Talley Watts, Lora; Long, Justin Alexander; Boggs, Robert Cole et al. (2016) Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury. J Neurotrauma 33:194-202|
|Shen, Qiang; Duong, Timothy Q (2016) Magnetic Resonance Imaging of Cerebral Blood Flow in Animal Stroke Models. Brain Circ 2:20-27|
|Tiwari, Yash Vardhan; Jiang, Zhao; Sun, Yuhao et al. (2016) Effects of stroke severity and treatment duration in normobaric hyperoxia treatment of ischemic stroke. Brain Res 1635:121-9|
|Jiang, Zhao; Duong, Timothy Q (2016) Methylene blue treatment in experimental ischemic stroke: a mini review. Brain Circ 2:48-53|
|Shen, Qiang; Huang, Shiliang; Duong, Timothy Q (2016) T2*-weighted fMRI time-to-peak of oxygen challenge in ischemic stroke. J Cereb Blood Flow Metab 36:283-91|
|Zhou, Yongxia; Yu, Fang; Duong, Timothy Q et al. (2015) White matter lesion load is associated with resting state functional MRI activity and amyloid PET but not FDG in mild cognitive impairment and early Alzheimer's disease patients. J Magn Reson Imaging 41:102-9|
|Long, Justin A; Watts, Lora T; Li, Wei et al. (2015) The effects of perturbed cerebral blood flow and cerebrovascular reactivity on structural MRI and behavioral readouts in mild traumatic brain injury. J Cereb Blood Flow Metab 35:1852-61|
|Shen, Qiang; Huang, Shiliang; Duong, Timothy Q (2015) Ultra-high spatial resolution basal and evoked cerebral blood flow MRI of the rat brain. Brain Res 1599:126-36|
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