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ABSTRACT: Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood-brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke.
We recruited patients with lacunar and mild cortical stroke. We assessed BBB leak in gray matter, white matter, and cerebrospinal fluid, at least 1 month after stroke, using magnetic resonance imaging before and after intravenous gadolinium. We measured tissue enhancement for 30 minutes after intravenous gadolinium by two image analysis approaches (regions of interest and tissue segmentation). We compared the enhancement (leak) between lacunar and cortical patients, and associations with key variables, using general linear modeling.
We recruited 51 lacunar and 46 cortical stroke patients. Signal enhancement after gadolinium was higher in lacunar than cortical stroke patients in white matter (p < 0.001) and cerebrospinal fluid (p < 0.003) by both analysis methods, independent of other variables. Signal enhancement after gadolinium was also associated with increasing age and enlarged perivascular spaces, but these did not explain the lacunar-cortical difference.
Patients with lacunar stroke have subtle, diffuse BBB dysfunction in white matter. Further studies are required to determine the relative contributions of BBB dysfunction and/or ischemia to the microvascular and brain abnormalities in lacunar stroke.
Annals of Neurology 02/2009; 65(2):194-202. · 11.09 Impact Factor
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ABSTRACT: Lacunar stroke is associated with endothelial dysfunction and histologically with intrinsic cerebral microvascular disease of unknown cause. Endothelial dysfunction could impair blood-brain barrier integrity. We assessed background blood-brain barrier leakage in patients with lacunar ischemic stroke compared with cortical stroke controls.
We recruited patients with lacunar or mild cortical ischemic stroke and assessed generalized cerebral blood-brain barrier leak with MRI and intravenous gadolinium at least 1 month after stroke. We used detailed image processing to compare signal change before and for 30 minutes postcontrast throughout gray matter, white matter, and cerebrospinal fluid with summary analyses and general linear modeling.
Among 48 patients (29 lacunar, 19 cortical), postcontrast enhancement was significantly higher in cerebrospinal fluid (P=0.04, Mann-Whitney U), and nonsignificantly higher in white matter, in lacunar than in cortical strokes, with no difference in gray matter. General linear modeling confirmed significantly greater postcontrast enhancement in cerebrospinal fluid in lacunar patients than in cortical controls (t=3.37, P<0.0008).
These preliminary data suggest that the blood-brain barrier may be dysfunctional throughout subcortical white matter (white matter drains via interstitial spaces to cerebrospinal fluid) in patients with lacunar stroke. Further studies are required to confirm these findings and determine whether abnormal blood-brain barrier might predate development of lacunar disease. Blood-brain barrier dysfunction may be an important mechanism for brain damage in cerebral microvascular disease.
Stroke 04/2008; 39(4):1327-32. · 5.73 Impact Factor
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ABSTRACT: (1)H MR spectroscopy (MRS) can identify metabolite abnormalities in age-related, neurological diseases. However, there is little information on how metabolites change with healthy aging.
We systematically reviewed the literature on MRS, from 1980 to 2006, for studies where healthy young subjects (<60 years) were compared to healthy older subjects (>60 years). We extracted metabolite data reported as "no change", "increase" or "decrease" for each metabolite by brain region and, where data were available, meta-analysed mean metabolite concentrations (mM) for young versus old subjects.
Eighteen studies met the inclusion criteria (total n=703 subjects, 284 >60 years old). Most data came from the frontal region, and reported "no change" in older subjects; however, a meta-analysis revealed a decrease in frontal NAA (p=0.05) and increases in parietal choline (p=0.003) and creatine (p<0.001).
These data suggest that NAA may decrease and choline and creatine increase with age. Therefore, more data are needed from older subjects to characterise age effects better and ratios in older subjects should be interpreted with caution.
Neurobiology of aging 08/2007; 30(3):353-63. · 5.94 Impact Factor
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ABSTRACT: Trials of new treatments for neurological disorders like stroke require imaging as part of the patient assessment, but need to be large enough to obtain reliable results if treatment effects are likely to be modest. However, multicentre trials use many different scanners in different hospitals and present complex problems for image data collection, interpretation and analysis and long-term secure archiving.
NeuroGrid aims to develop and test grid technologies for collecting, analysing and interpreting, and secure archiving of neuroimaging data for large multicentre trials in common neurological and psychiatric disorders.
A 3-year multicentre consortium of clinicians, neuroimaging centres and e-scientists are designing a Grid storage network, mechanisms for uploading, curating and retrieving image and metadata, combining image data from different scanners and an analysis tool box. Three clinical exemplars--stroke, dementia and psychosis--provide the data and 'real-world' clinical trial applications, and a set of specific and typical problems encountered with image data in multicentre trials for NeuroGrid to address. The stroke exemplar is using image data from two multicentre stroke trials: Third International Stroke Trial and Efficacy of Nitric Oxide in Stroke.
The final product is intended to appear as an integrated capability consisting of services, both database and analyses, accessed through simple portals. These will include image submission, automated scan quality control, appropriate metadata linkage, streamlined image review and coding tools and long-term secure storage for future multicentre stroke trials.
International Journal of Stroke 03/2007; 2(1):63-9. · 2.38 Impact Factor
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ABSTRACT: A magnetic resonance proton spectroscopic imaging (SI) technique was developed to measure regional brain temperatures in human subjects. The technique was validated in a homogeneous phantom and in four healthy volunteers. Simulations and calculations determined the theoretical measurement precision as approximately +/-0.3 degrees C for individual 1-ml voxels. In healthy volunteers, repeated measurements on individual voxels had an S.D. = 1.2 degrees C. In a clinical study, 40 patients with acute ischemic stroke were imaged within 26 h (mean, 10 h) of onset. Temperatures were highest in the region that appeared abnormal (i.e., ischemic) on diffusion-weighted imaging (DWI) compared with a normal-appearing brain. The mean temperature difference between the DWI "lesion" area and the "normal brain" was 0.17 degrees C [P < 10(-3); range, 2.45 degrees C (hotter)-2.17 degrees C (cooler)]. Noninvasive temperature measurement by SI has sufficient precision to be used in studies of pathophysiology in stroke and in other brain disorders and to monitor therapies.
Magnetic Resonance Imaging 08/2006; 24(6):699-706. · 1.99 Impact Factor
