White matter damage precedes that in gray matter despite similar magnetic resonance imaging changes following cerebral hypoxia-ischemia in neonatal rats

NRC publication: Ye

Magnetic resonance imaging of differential gray versus white matter injury following a mild or moderate hypoxic-ischemic insult in neonatal rats

NRC publication: Ye

Early T1- and T2-weighted MRI signatures of transient and permanent middle cerebral artery occlusion in a murine stroke model studied at 9.4T.

Early reperfusion following stroke results in reduced tissue injury. Paradoxically, restoration of blood flow under certain conditions may also cause delayed neuronal damage (reperfusion injury). The interrelationship of changes in T1, T2 and diffusion weighted images of tissue water were studied in mouse models of permanent and transient focal cerebral ischemia. A sham surgery or either permanent or transient (30 min) middle cerebral artery occlusion (MCAO) were induced in 14 mice. Magnetic resonance (MR) images of the brain were acquired including: T2 maps, T1 maps and diffusion weighted spin-echo images to produce apparent diffusion coefficient of water apparent diffusion coefficient (ADC) maps. Images were collected on average 90 min after MCAO in both the transient and permanent ischemia groups. Scans were repeated at 24h post-occlusion in mice with transient ischemia. Permanent MCAO resulted in decreases in ADC and no significant change in T2 acutely following MCAO. There were increases in T1 compared to sham controls within the ischemic region in mice following either transient or permanent MCAO (P<0.001). In contrast to permanent MCAO, there were increases in T2 (P<0.001) in the infarct area present in the reperfusion phase within 90 min of transient MCAO. There was considerable infarct growth at 24h (P<0.001). This study demonstrates that following either type of occlusion there are early increases in T1 suggesting an elevated water content in the stroke lesion, while only following transient MCAO are there early increases in T2, indicative of early vasogenic oedema with breakdown of the blood-brain barrier

Imaging Corticospinal Degeneration in Neonatal Rats with Unilateral Cerebral Infarction

Recent human studies indicate that magnetic resonance (MR) imaging, particularly diffusion weighted imaging, detects abnormalities within the descending cortico-spinal tract following stroke. Whether these changes are directly related to processes of axonal degeneration and how MR changes (e.g. apparent diffusion coefficient of water (ADC) and T 2) vary in their diagnostic utility over time is not known. The present study demonstrates that a commonly used rat model of neonatal transient unilateral hypoxia-ischemia provides similar diffusion weighted and ADC changes in the cerebral peduncle as those observed in human neonates clinically. Imaging the descending cortico-spinal tract in this model at defined acute (1-3days) and chronic (1 and 4weeks) time points demonstrates increased T 2 and progressive changes in ADC within the descending cortico-spinal tract in the first days to weeks following hypoxia-ischemia with a normalization by 1week and further increases in ispilateral cerebral cortex by 4weeks. These imaging changes are associated with reduced axonal neurofilament staining both at the subacute and more chronic time points. This demonstrates directly the utility of ADC and T 2 MRI to detect acute changes in axons associated with early Wallerian degeneration. \ua9 2011.Peer reviewed: YesNRC publication: Ye

The effect of coating of Fe

Magnetic Resonance Imaging (MRI) that provides superior soft tissue contrast is commonly used for diagnosis of many diseases. However specificity of MRI cancer diagnosis can be further increased by application of target contrast agents comprising superparamagnetic nanoparticles (NPs) synthesised with biological objects, which deliver the contrast to the specific cancer cells. These superparamagnetic NPs shorten T2 relaxation time thus change contrast to noise ratio for tumor tissues. Therefore the impact of Fe3O4 size and silica coating for Fe3O4/silica core/shell superparamagnetic nanoparticles (NPs) on T2 relaxation time was studied at 9.4 T. The magnetic resonance imaging (MRI) studies were performed using homogenous agar solution of NPs. Naked Fe3O4NPs with a mean core diameter of 10.0 ± 1.3 (mean ± SD), 15.0 ± 2.5 and 20.0 ± 0.9 nm were analyzed. Silica coated Fe3O4 NPs with core size of 10.0 ± 1.3 nm and the shell thickness of 16.7 ± 1.8, 25.3 ± 2.7 and 33.9 ± 4.0 nm were also investigated. The T2 values of agar solutions with different NPs were calculated using a single slice multi echo method and single exponential fitting of the echo train. The measurements showed linear correlation between T2 and Fe3O4 core diameter as well as shell thickness. Silica coating, while improving functionalization and potentially reducing toxicity of NPs, decreases the impact of the magnetic core on T2, thus decreasing MRI contrast efficacy

Functional MRI of the rat lumbar spinal cord involving painful stimulation and effect of peripheral joint mobilization

NRC publication: Ye

Transient blood pressure changes affect the functional magnetic resonance imaging detection of cerebral activation

NRC publication: Ye

Evaluating endogenous repair of focal cartilage defects in C57BL/6 and MRL/MpJ mice using 9.4 T magnetic resonance imaging: A pilot study

The use of magnetic resonance imaging (MRI) for evaluating joint injuries is often considered superior to radiography due to the capacity of MRI for visualizing both soft and hard tissues. While longitudinal studies regarding cartilage repair have been undertaken on patients and in larger animal models, a method has yet to be developed for mouse cartilage to be repeatedly and non-invasively evaluated over time. The aim of this pilot study was to investigate if morphological changes following a focal cartilage injury in mice could be measured by 9.4T magnetic resonance imaging. Focal cartilage defects were induced in the left knee of 4-6weeks old C57BL/6 and MRL/MpJ mice. At endpoints 0, 2, and 4weeks post-injury, legs were dissected out and imaged ex vivo. The defect could be detected by MRI immediately after injury, appearing as a hyperintense focal point and with size similar to that of the surgical tool used. Defects were visible in both strains up to 4weeks post-injury, although signal intensity decreased over time. One C57BL/6 in particular, displayed extensive fibrosis in the patellar tendon at 4weeks as assessed by histology, while the MR images of the same animal displayed a clear, structural distinction between the patella and the new tissue growth. Overall, our results suggest that MRI could be used for longitudinal studies in murine cartilage injury models to evaluate certain characteristics of repair not detectable through histology.Canadian Stem Cell Network, Natural Sciences and Engineering Research Council of Canada and Canadian Institutes of Health ResearchYe

Development of a model of recurrent stroke consisting of a mild transient stroke followed by a second moderate stroke in rats

Recurrent stroke often consists of a transient ischemic attack or mild stroke followed by a moderate stroke. Lacking is knowledge of the mechanisms of interaction of such multiple ischemic insults. Our aim was to develop a rat model of recurrent stroke and to test whether such multiple insults would enhance brain injury. A mild focal ischemic insult was produced by transient (40min) occlusion of the middle cerebral artery (MCAO) and this resulted in scattered necrosis and areas of increased labeling of astrocytes with glial fibrillary acidic protein. Additional animals were subjected to a moderate stroke alone or a recurrent stroke-a mild stroke followed 3 days later by a moderate stroke (60min MCAO). Damage was dependent on the proximal or distal cerebral cortical location from the occlusion (P<0.007) and the type of stroke insult (mild, moderate or recurrent, P<0.002). Following recurrent stroke, the cumulative injury score was similar to a mild stroke in distal parietal cortex but enhanced proximally. Recurrent stroke also resulted in changes in magnetic resonance imaging T(2), in neuronal microtubule associated protein2, in reactive astrocytes and in microglia/macrophages that were enhanced in proximal but not distal parietal cortex. This model demonstrates that when a minor stroke is combined with a second stroke, both distributed within the same middle cerebral artery territory, there are different injury processes regionally. Proximally, damage exceeds that of the first insult whereas distally the response is consistent with a tolerance to the second insult.Peer reviewed: YesNRC publication: Ye