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ABSTRACT: The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model and to compare tissue plasminogen activator (tPA)-based clot lysis with and without recombinant Annexin-2 (rA2).
In experiment 1 we used in vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50 μL in 250 μL blood. In experiment 2, we used in vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot imaging were conducted before and during treatment with vehicle (n=6), tPA (n=8), or rA2 plus tPA (n=8) at multiple time points. Brains were removed for ex vivo clot localization.
Clots created with 25 μL Magnevist were the most stable and provided the highest contrast-to-noise ratio. In the vehicle group, clot length as assessed by T1-weighted imaging correlated with histology (r=0.93). Clot length and cerebral blood flow-derived ischemic lesion volume were significantly smaller than vehicle at 15 minutes after treatment initiation in the rA2 plus tPA group, whereas in the tPA group no significant reduction from vehicle was observed until 30 minutes after treatment initiation. The rA2 plus tPA group had a significantly shorter clot length than the tPA group at 60 and 90 minutes after treatment initiation and significantly smaller cerebral blood flow deficit than the tPA group at 90 minutes after treatment initiation.
We introduce a novel MRI-based clot imaging method for in vivo monitoring of clot lysis. Lytic efficacy of tPA was enhanced by rA2.
Stroke 03/2011; 42(4):1110-5. · 5.73 Impact Factor
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ABSTRACT: In hyperpolarized xenon magnetic resonance imaging (HP (129)Xe MRI), the inhaled spin-1/2 isotope of xenon gas is used to generate the MR signal. Because hyperpolarized xenon is an MR signal source with properties very different from those generated from water-protons, HP (129)Xe MRI may yield structural and functional information not detectable by conventional proton-based MRI methods. Here we demonstrate the differential distribution of HP (129)Xe in the cerebral cortex of the rat following a pain stimulus evoked in the animal's forepaw. Areas of higher HP (129)Xe signal corresponded to those areas previously demonstrated by conventional functional MRI (fMRI) methods as being activated by a forepaw pain stimulus. The percent increase in HP (129)Xe signal over baseline was 13-28%, and was detectable with a single set of pre and post stimulus images. Recent innovations in the production of highly polarized (129)Xe should make feasible the emergence of HP (129)Xe MRI as a viable adjunct method to conventional MRI for the study of brain function and disease.
PLoS ONE 01/2011; 6(7):e21607. · 4.09 Impact Factor
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ABSTRACT: One issue with amplitude binning list-mode studies in SPECT for respiratory motion correction is that variation in the patient's respiratory pattern will result in binned motion states with little or no counts at various projection angles. The reduced counts result in limited-angle reconstruction artifacts which can impact the accuracy of the necessary motion estimation needed to correct the images. In this work, the authors investigate a method to overcome the effect of limited-angle reconstruction artifacts in SPECT when estimating respiratory motion.
In the first pass of the reconstruction method, only the projection angles with significant counts in common between the binned respiratory states are used in order to better estimate the motion between them. After motion estimation, the estimates are used to correct for motion within iterative reconstruction using all of the acquired projection data.
Using simulated SPECT studies based on the NCAT phantom, the authors demonstrate the problem caused by having data available for only a limited number of angles when estimating motion and the utility of the proposed method in diminishing this error. For NCAT data sets with a clinically appropriate level of Poisson noise, the average registration error for motion with the proposed method was always less with the use of their algorithm, the reduction being statistically significant (p<0.05) in the majority of cases. The authors illustrate the ability of their method to correct the degradations caused by respiratory motion in short-axis slices and polar maps of the NCAT phantom for cases with 1 and 2 cm amplitudes of respiratory motion. In four cardiac-perfusion patients acquired on the same day, the authors demonstrate the large variability of the number of counts in the amplitude-binned projections. Finally, the authors demonstrate a visual improvement in the slices and polar maps of patient studies with the algorithm for respiratory motion correction.
The authors' method shows promise in reducing errors in respiratory motion estimation despite the presence of limited-angle reconstruction effects due to irregularity in respiration. Improvements in image quality were observed in both simulated and clinical studies.
Medical Physics 12/2010; 37(12):6453-65. · 2.83 Impact Factor
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ABSTRACT: Perfusion imaging is crucial in imaging of ischemic stroke to determine 'tissue at risk' for infarction. In this study we compared the volumetric quantification of the perfusion deficit in two rat middle-cerebral-artery occlusion (MCAO) models using two gadolinium-based contrast agents (P1152 (Guerbet) and Magnevist (Bayer-Schering, Pittsburgh, PA, USA)) as compared with our well established continuous arterial spin labeling (CASL) perfusion imaging technique. Animals underwent either permanent MCAO or transient MCAO with 80-min reperfusion. Imaging was performed at four different time points after MCAO. A region-of-interest (ROI) analysis of the subregions of the ischemic zone (core, penumbra, transient reversal (TR), and sustained reversal (SR)) using P1152 showed significant reduction in blood flow in the core and TR subregions relative to the penumbral and SR subregions while occluded. After reperfusion, a significant increase in blood flow was recorded at all time points after reperfusion in all regions except TR. From the ROI analysis the threshold for the penumbra was determined to be -62+/-11% and this value was subsequently used for quantification of the volumetric deficit. The ischemic volume as defined by dynamic susceptibility contrast (DSC), was only statistically different from the CASL-derived ischemic volume when using Magnevist at post-reperfusion time points.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 10/2009; 30(2):336-42. · 5.46 Impact Factor
