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Biomedical subjects

A de Crespigny

Publications and source records attributed to A de Crespigny.

24 records · Page 2Linked to original sources

Hyperglycemia delays terminal depolarization and enhances repolarization after peri-infarct spreading depression as measured by serial diffusion MR mapping.

We investigated the effect of hyperglycemia on the initiation and propagation of spreading depression-like peri-infarct ischemic depolarization (SD) induced by focal cerebral ischemia in rats. Peri-infarct SD were monitored during the initial 15 minutes after remotely induced middle cerebral artery occlusion (MCAO) using serial diffusion weighted magnetic resonance imaging. Maps of the apparent diffusion coefficient (ADC) were calculated and ADC decreases were monitored over time. Hyperglycemic rats (n = 6) had a significant prolongation of the time from induction of MCAO to the start of the ADC decrease as compared with normoglycemic control rats. The time to the maximal ADC decrease was significantly delayed and recovery of transient ADC declines in the area adjacent to the ischemic core was significantly faster in hyperglycemic rats. We conclude that hyperglycemia delays the terminal depolarization in the ischemic core and supports a faster repolarization in severely mal-perfused penumbral tissue after SD, which reflects the increased availability of energy substrates in the state of hyperglycemia.

Animals↗

Time-course and treatment response with SNX-111, an N-type calcium channel blocker, in a rodent model of focal cerebral ischemia using diffusion-weighted MRI.

Diffusion-weighted magnetic resonance imaging (DWI) is capable of noninvasively imaging acute cerebral ischemia. We demonstrate the utility of this technique by evaluating SNX-111, a novel N-type calcium channel blocker with potential neuroprotective properties, in a rodent model of transient focal ischemia. Twenty-four Sprague-Dawley rats weighing between 310-350 g underwent occlusion of the middle cerebral artery (MCAO) for 105 min followed by 22.5 h of reperfusion. Thirty minutes following MCAO, animals were randomized to receive SNX-111 5 mg/kg intravenously over 1 h vs. placebo. DWI and T2-weighted MRIs (T2W) were performed at 0.5, 1.5 and 24 h after the onset of ischemia. Area fractions of increased signal intensity on the DWI and T2W images were measured. DWI area fractions at 1.5 and 24 h were also normalized to the initial, pre-treatment scans. Apparent diffusion coefficients (ADC) were calculated from fitted maps. Tri-phenyl tetrazolium chloride (TTC) staining was performed on brains at 24 h and infarct area fractions were measured. SNX-111 treated animals showed significantly improved 1.5-h DWI scan ratios compared to controls (ratios of 1.06 +/- 0.25 vs. 2.98 +/- 0.78 SNX vs. controls respectively, P < 0.05). A trend toward improved DWI ratios was seen by 24 h in the SNX-111 group (2.5 +/- 0.75 vs. 4.12 +/- 1.6, N.S.) DWI, T2W and TTC area fractions at 24 h also showed trends favoring a neuroprotective effect of SNX-111. Bright areas on DWI corresponded to ADC decreases of about 30% compared to the non-ischemic hemisphere. These decreases were the same in both treatment groups and at each time point. DWI, T2W and TTC area fractions at 24 h were strongly correlated (r = 0.98, DWI and TTC; r = 0.99, T2W and TTC; r = 0.97, T2W and DWI, P < 0.0001). We conclude that in this ischemic model, SNX-111 provides early neuroprotection and that serial DWI is a useful way of demonstrating this.

Animals↗

Diffusion-weighted interleaved echo-planar imaging with a pair of orthogonal navigator echoes.

This work describes a diffusion-weighted (DW) interleaved echo-planar imaging (IEPI) method for use on either conventional whole-body scanners or scanners equipped with high-speed gradient and receiver hardware. In combination with cardiac gating and motion correction with a pair of orthogonal navigator echoes, the presented method is time-efficient, compensates for patient motions, and is less sensitive to image distortions than single-shot methods. The motion-correction scheme consists of correction for constant and linear phase terms found from the orthogonal navigator echoes. The correction for the linear phase term in the phase-encode direction includes gridding the data to the Cartesian grid. The DW IEPI was used to image a phantom rotating about the slice-select direction, and motion correction was performed to eliminate ghost artifacts arising from motion in either the readout- or phase-encoding directions. DW IEPI with motion correction was performed on a normal volunteer and on a patient with a 26-day-old region of ischemia over much of the right hemisphere.

Algorithms↗

Acute and chronic stroke: navigated spin-echo diffusion-weighted MR imaging.

PURPOSE: The authors evaluated a phase-navigated spin-echo (SE) motion-correction sequence for use at diffusion-weighted (DW) magnetic resonance (MR) imaging after cerebral infarction. MATERIALS AND METHODS: Twenty-nine patients underwent 32 conventional T2-weighted fast SE and SE DW imaging after stroke (n=25), transient ischemic attack (n=3), or reversible ischemic neurologic deficit (n=1). Imaging was performed in a standard head holder with standard padding. Apparent diffusion coefficient (ADC) maps were constructed. RESULTS: DW images depicted high signal intensity compatible with localization of the ischemic symptoms in all cases. Lesions were depicted more clearly on DW than on T2-weighted images. On DW images, acute infarct ADC values were uniformly low (mean, 0.401x10(-5) cm2/sec =+/- 0.143 [standard deviation]) compared with control ADC values (mean, 0.754x10(-5) cm2/sec +/- 0.201). ADC values of chronic infarcts were supranormal (mean, 1.591x10(-5) cm2/sec +/- 0.840) compared with control values (mean, 0.788x10(-5) cm2/sec +/- 0.166). DW imaging did not show a change after transient ischemic attack. with reversible ischemic neurologic deficit, however, hyperintensity on DW images and low ADC resolved after symptoms abated. CONCLUSION: Clinical phase-navigated SE DW imaging improved early diagnosis of stroke and helped differentiate acute from chronic stroke. Changes on DW images are reversed after symptoms resolve.

Acute Disease↗

Endogenous susceptibility contrast in myocardium during apnea measured using gradient recalled echo planar imaging.

Gradient recalled echo planar imaging was used to monitor changes in myocardial and left ventricular chamber blood intensity during apnea in rats. Significant signal loss in both blood (to 62 +/- 5% and 51 +/- 6% of baseline) and myocardium (to 79 +/- 2% and 76 +/- 3% of baseline) was observed at 45 and 90 s apnea while O2 saturation decreased from 98 +/- 1% to 62 +/- 7% and 36 +/- 9%, respectively. These results show that myocardial intensity is modulated by alterations in blood oxygenation.

Animals↗

Clinical aspects of DWI.

Diffusion-weighted MR imaging (DWI) is capable of imaging ischemia-induced changes in water protons in either animal or man. Technical developments are described that allow the routine clinical utility of DWI in a stroke setting to provide objective criteria beyond the neurological exam by which the pathophysiology of stroke can be evaluated. To date, DWI has provided unique information concerning detection and evaluation of acute, symptomatic lesions from older, chronic strokes, detection and localization of small deep infarcts and reversible ischemic neurologic deficits and transient ischemia. Clinical DWI studies suggest that the temporal behaviour of ADC can critically improve the evaluation of clinical ischemia.

Aged↗