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Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke.

BACKGROUND: Hyperbaric oxygen therapy is considered an important stroke treatment strategy. BACKGROUND: To determine whether normobaric oxygen is neuroprotective, and, if so, what the therapeutic time window is. METHODS: Experiment 1-Serial diffusion- and perfusion-weighted MRI (DWI and PWI) was performed after middle cerebral artery filament occlusion (MCAO) in rats randomized to FiO(2) 30% (normoxia) or FiO(2) 100% (hyperoxia). Experiment 2-48-hour lesion volumes were analyzed in rats subjected to 2-hour MCAO and randomized to normoxia or hyperoxia starting 15, 30, or 45 minutes after MCAO and ending 15 minutes after reperfusion. RESULTS: Experiment 1-Lesion apparent diffusion coefficient (ADC) values were persistently low in normoxic animals. In hyperoxia-treated rats, ADC values in cortical border zones showed progressive recovery from 66 +/- 3% of contralateral before hyperoxia, to 104 +/- 20% at approximately 2 hours. Striatal ADC values showed early but ill-sustained improvement. ADC lesion volumes increased progressively in the normoxia group. In the hyperoxia group, ADC lesion volumes tended to decrease after starting hyperoxia; however, lesions later increased in size, and 2-hour lesion volumes were not significantly different from baseline. PWI showed stable right MCA hypoperfusion in all animals. Experiment 2-Hyperoxia within 30 minutes significantly reduced total and cortical lesion volumes at 48 hours after stroke. Striatal lesion volumes were significantly reduced in the hyperoxia-15 group. CONCLUSION: In rats subjected to transient stroke, 100% oxygen administered within 30 minutes salvages ischemic brain tissue, especially in the cerebral cortex. Reducing the time to treatment enhances the degree of neuroprotection.

Animals↗

Imaging of postthalamic visual fiber tracts by anisotropic diffusion weighted MRI and diffusion tensor imaging: principles and applications.

Diffusion weighted MRI offers the possibility to study the course of the cerebral white matter tracts. In the present manuscript, the basics, the technique and the limitations of diffusion tensor imaging and anisotropic diffusion weighted MRI are presented and their applications in various neurological and neurosurgical diseases are discussed with special emphasis on the visual system. A special focus is laid on the combination of fiber tract imaging, anatomical imaging and functional MRI for presurgical planning and intraoperative neuronavigation of lesions near the visual system.

Brain Diseases↗

Heterogeneous mechanisms of early edema formation in cerebral contusion: diffusion MRI and ADC mapping study.

Severe cerebral contusion is sometimes associated with early edema formation within 24-48 hours post-trauma, and this frequently results in progressive ICP elevation and clinical deterioration. To investigate the underlying mechanisms of such severe contusion edema, diffusion imaging and ADC mapping were performed in 20 patients with cerebral contusion, employing 1.5 T echo planar MRI. Within 24 hours post-trauma, the diffusion images demonstrated a low intensity core in the central area and a high intensity rim in the peripheral area of contusion. The ADC value increased in the central area (ADC ratio (contusion/normal brain) = 1.13 +/- 0.13) and decreased in the peripheral area (ADC ratio = 0.83 +/- 0.13). This suggested that intra- and extracellular components underwent disintegration and homogenization within the central area, whereas cellular swelling was predominant in the peripheral area. A crescent-shaped zone of very high ADC value (ADC ratio = 1.38-1.61) was observed at the border between these two areas during the period of 24-48 hours post-trauma in some cases, apparently indicating that edema fluid was accumulated within a space formed by homogenization. The ADC values in the peripheral area shifted to an increase after 48-72 hours post-trauma. These findings imply that multiple mechanisms operate in early edema formation in cerebral contusion. It appears that the capacity for edema fluid accumulation increases in the central area and resistance for edema fluid propagation is elevated by cellular swelling in the peripheral area. We suggest that a combination of such events facilitates edema fluid accumulation in the central area and contributes, together with the cellular swelling in the peripheral area, to the mass effect of contusion edema. Diffusion MRI and ADC mapping represent powerful tools for investigating spatially as well as temporally heterogeneous mechanisms of contusion edema.

Brain↗

Ultra-early study of edema formation in cerebral contusion using diffusion MRI and ADC mapping.

OBJECTIVE: Our previous studies have reported that heterogeneous mechanisms exist in early edema formation in cerebral contusion, and cytotoxic edema plays an important role within 48 hours post-trauma. It is remains unclear, when edema begins to develop following injury. In order to determine the time course of edema development, diffusion imaging and ADC (apparent diffusion co-efficient) mapping was performed in 10 patients within 24 hours post-trauma with cerebral contusion. METHODS: Diffusion imaging and ADC mapping were performed employing 1.0 T echo planar MRI. ADC values were indicated as a ration relative to the values of intact brain areas. RESULTS: Within 3 hours post-trauma, diffusion MRI showed no remarkable changes, and the ADC values were within normal limit (ADC ratio (=contused/normal brain) = 1.00 +/- 0.21, (mean +/- SD)). At 6 hours post-trauma, diffusion images demonstrated a low intensity core in the contusion proper and a high intensity rim in the peripheral area of contusion. The ADC value increased in the contusion proper (ADC ratio = 1.26 +/- 0.13) and decreased in the peripheral area (ADC ratio = 0.58 +/- 0.19). CONCLUSIONS: These findings indicated that early cellular swelling in the peripheral area of contusion begins within 6 hours following injury. This delayed occurrence of contusion-induced cellular swelling suggests that the CBF does not decrease to ischemic level immediately following injury.

Brain Edema↗

q-Space high b value diffusion MRI of hemi-crush in rat spinal cord: evidence for spontaneous regeneration.

The development of the damage following hemi-crush trauma in rat spinal cord was studied ex vivo using high b value (bmax = 1 x 10(7) s cm(-2)) q-space diffusion weighted MRI (DWI) at five days, ten days and six weeks post-trauma. Rat spinal cord trauma, produced by hemi-crush of 15s and 60s duration, was studied. The water signal decay in these diffusion experiments was found to be non mono-exponential and was analyzed using the q-space approach. The q-space MRI parameters were compared with T1 and T2 MR images, behavioral tests and histopathological osmium staining. A very good anatomical correlation was found between the q-space MRI parameters and the osmium staining. Interestingly, we found that in the 15s hemi-crush model significant recovery was observed in both the q-space MR images and the osmium staining six weeks post-trauma. However, in the 60s hemi-crush trauma model very little recovery was observed. These results paralleled those obtained from behavioral tests demonstrating that partial spontaneous recovery seems to occur in the 15s hemi-crush spinal cord model, which should be taken in consideration when using it to evaluate new therapies.

Animals↗

Diffusion MRI studies of experimental animal models and patients with stroke.

PURPOSE: This overview summarises the diffusion magnetic resonance imaging (MRI) results both from the experimental animal model studies and clinical investigations in acute cerebral ischemic stroke. DATA SOURCES: An English literature searched using MEDLINE (1990-1997). STUDY SELECTION: Over 80 papers and reviews published in the last eight years and our partial results were selected. RESULTS AND CONCLUSIONS: Diffusion weighted magnetic resonance imaging (DWI) has been extensively used to study acute cerebral ischemia both in experimental animal models and in patients. DWI yields signal intensity contrast modulated by water molecular self-diffusion. By recording a series of DWI with different amplitudes of the displacement encoding gradient, the apparent diffusion coefficient (ADC) can be quantitatively mapped. DWI combined with quantitative ADC mapping can provide earlier and more precise evaluation of the ischemic zones. However, the biophysical mechanisms behind the decreased ADC in acute cerebral ischemia are still not fully understood.

Animals↗

High b value q-space-analyzed diffusion MRI in vascular dementia: a preliminary study.

High b value diffusion weighted magnetic resonance imaging (high-b DWI) was used to characterize white matter changes in the brain of patients with vascular dementia (VaD). Hyperintense white matter areas detected by T2-weighted magnetic resonance imaging (MRI) represent lesions, also termed leukoaraiosis that are very common in VaD as well as in other types of dementia. Therefore, the role of white matter changes in the cognitive and memory decline that occurs in VaD patients is still under debate. High-b DWI, analyzed using the q-space approach, is a more sensitive MRI method for detection of white matter changes. High-b DWI revealed massive white matter loss in VaD patients that surpassed the boundaries of T2 hyperintensities. This technique, therefore, might serve as a better indication for the extensive nerve fiber loss in the white matter that is caused by vascular disease.

Aged↗

Cellular volume determination of alginate-entrapped hepatocytes by MRI diffusion measurements.

Cellular volume of hepatocytes entrapped in alginate gel beads were evaluated under in vivo conditions in samples having different cell densities by applying mathematical models to the diffusion data obtained by magnetic resonance imaging (MRI). The calculated average volume is in good agreement with the values from the literature-- being closer to the data relative to living tissue than to isolated cells. The non invasive characteristics of magnetic resonance imaging make this method particularly well suited to obtain information from the intact system.

Alginates↗

Noninvasive temperature imaging using diffusion MRI.

Efficacy and safety considerations for cancer therapy with hyperthermia require accurate temperature measurements throughout the heated volume. We report the use of molecular diffusion, whose temperature dependence is well known. A dedicated hyperthermia applicator was built, combining a MRI gradient coil and a rf coil. Diffusion and derived temperature images were obtained with a 1 x 2 mm pixel size on a polyacrylamide gel phantom using a clinical 1.5-T whole body MRI system. Temperatures determined from these images using 1 cm2 regions of interest were found to be within 0.2 degrees C of those recorded from the thermocouples and fiber-optic probes placed inside the gel.

Body Temperature↗

The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis: a serial diffusion MRI study.

The idea that the initiating event in the formation of all new multiple sclerosis lesions is a focal blood-brain barrier (BBB) leakage associated with perivascular inflammation has been challenged recently by the observation of subtle abnormalities in some quantitative magnetic resonance (MR) parameters (including the magnetization transfer ratio) prior to lesion enhancement. MR diffusion imaging can non-invasively quantify the average apparent diffusion coefficient (ADC(av)), a measure of water molecule random motion that is sensitive to pathological change in multiple sclerosis lesions and to abnormalities in the normal-appearing white matter (NAWM). We therefore used MR diffusion imaging to investigate the dynamic evolution of water diffusion measurements in new enhancing multiple sclerosis lesions, in the NAWM from which they arise, and in anatomically matched contralateral NAWM regions from which no visible lesions develop. Gadolinium diethylenetriaminepentaacetic acid (Gd)-enhanced MRI and MR diffusion studies were performed monthly for 1 year in five multiple sclerosis patients with clinically and radiologically active disease. The ADC(av) was calculated at each time point of the study (before, during and after lesion appearance on Gd-enhanced scans) for each new enhancing lesion, and for regions matched for size and position in the contralateral NAWM. A steady and moderate increase in ADC(av) in prelesion NAWM was observed, which was followed by a rapid and marked increase at the time of Gd enhancement and a slower decay after the cessation of enhancement. In matched contralateral NAWM regions there was a significant but milder increase in ADC(av) at the time of the first noted lesion enhancement. These findings indicate that new focal lesions associated with frank BBB leakage are preceded by subtle, progressive alterations in tissue integrity beyond the resolution of conventional MRI. The increases in ADC(av) in anatomically matched contralateral regions after lesions have appeared supports the concept that structural damage in lesions causes damage or dysfunction in connected areas of NAWM.

Adult↗

Diffusion MRI radiomics in meningiomas: imaging correlates of tumor grade and intraoperative consistency.

OBJECTIVE: Despite advancements in imaging studies, the preoperative prediction of the biological behavior and intraoperative consistency of intracranial meningiomas remains limited. This study evaluated the association of volumetric diffusion-based and texture-derived radiomic features extracted from routine MRI with histopathological aggressiveness and intraoperative tumor consistency. METHODS: Ninety-seven intracranial meningiomas resected at two tertiary centers were retrospectively analyzed. Volumetric segmentation was performed on contrast-enhanced T1-weighted MRI and coregistered to apparent diffusion coefficient (ADC) maps. Data on first-order diffusion metrics and selected texture features were collected. The associations between World Health Organization (WHO) grade and Ki-67 index were assessed using nonparametric tests and Spearman correlation analysis. Independent factors associated with intraoperative tumor consistency (Zada grades 1-5) were evaluated via multivariate ordinal logistic regression analysis that adjusted for tumor volume, skull base location, calcification status, and WHO grade. Secondary receiver operating characteristic (ROC) curve analyses were performed to differentiate solid (Zada grades 4-5) from soft (Zada grades 1-2) tumors. ROC analyses were performed within the study cohort and were intended as exploratory assessments of discriminative performance. RESULTS: The mean ADC (ADCmean) and the 10th percentile of the ADC decreased significantly with increasing WHO grade (p < 0.001). ADCmean had a moderate inverse correlation with the Ki-67 index (r = -0.42, p < 0.001) and intraoperative tumor consistency (r = -0.45, p < 0.001). In the multivariate analysis, the ADCmean remained independently associated with increasing tumor firmness. Each 0.1 &#xd7; 10-3 mm2/sec increase corresponded to a 38% reduction in the odds of belonging to a higher consistency category (OR 0.62, 95% CI 0.51-0.74, p < 0.001). The ROC analysis showed good discrimination for solid tumors (area under the curve 0.847, 95% CI 0.742-0.953) and soft tumors (area under the curve 0.824, 95% CI 0.714-0.935). Texture features had weaker associations with intraoperative tumor consistency. CONCLUSIONS: Volumetric diffusion-derived metrics, particularly ADCmean, are associated with both histopathological aggressiveness and intraoperative tumor firmness in meningiomas. Diffusion imaging may reflect a graded microstructural continuum rather than a purely dichotomous property, providing complementary preoperative insights into surgical complexity.

Humans↗

Correlation of diffusion MRI and heat shock protein in a rat embolic stroke model.

The expression of 70 kDa heat shock protein (HSP-70) in focal ischemia occurs in regions that sustain sub-lethal ischemic injury, and may therefore be considered as a biological marker of the ischemic penumbra. In a rat embolic stroke model, using fibrin-rich emboli, we correlated the expression of HSP-70 mRNA with diffusion magnetic resonance imaging (MRI) to determine if HSP-70 mRNA expression was associated with alterations in the apparent diffusion coefficient (ADC) of brain tissue water, a putative early marker of cytotoxic injury that is readily measured in vivo. Serial ADC measurements were made for 120 min following embolic infarction in the right carotid artery territory. HSP-70 mRNA expression was observed at the boundaries of the densely ischemic zone, as judged by diffusion imaging. ADC values observed in HSP-70 mRNA-positive regions were intermediate between those observed in the ischemic core or in control regions. In addition, the volume of HSP-70 mRNA-positive tissue correlated positively with the volume of tissue showing intermediate ADC values at 120 min. These findings suggest that intermediate ADC values occur in penumbral regions. Heterogeneity of ischemic cellular injury is suggested as the basis for the intermediate ADC values observed in these regions.

Animals↗

The role of isotropic diffusion MRI in children under 2 years of age.

Our objective was to determine the contribution of diffusion MR imaging to standard MR imaging in the neuroradiological evaluation of children less than 2 years of age. Echo-planar diffusion MR imaging was added to standard MR exams in 75 consecutive patients under the age of 2 years. Single-shot echo-planar spin-echo T2 weighted images (EPSE-T2) were acquired. Isotropic diffusion-weighted images (DWI), attenuation coefficient maps (ACM), and apparent diffusion co-efficient (ADC) maps were calculated offline from images obtained with diffusion gradients (b = 1000 s/mm2) in three orthogonal directions. Two neuroradiologists determined if EPSE-T2, DWI, or ACM contributed new information to spin-echo proton density (SE PD) and T2 studies. In 15 of 18 abnormalities detected in 8 patients with symptoms less than 1 week in duration, DWI and/or ACM added information to SE PD and T2. Diffusion sequences detected five new lesions, showed six lesions with greater conspicuity, and identified four lesions with different diffusion character. In patients with symptoms of more than 7 days duration, diffusion studies added no information. Isotropic diffusion MR contributed to lesion detection and characterization in infants when symptoms were less than 1 week in duration. Diffusion MR is useful in patients with leukodystrophies, metabolic disorders, and patients with acute ischemic lesions.

Adult↗

High temporal resolution diffusion MRI of global cerebral ischemia and reperfusion.

Although brain ischemia has been extensively studied using diffusion-weighted magnetic resonance imaging, most studies performed so far have not had adequate time resolution to follow the temporal changes in the water apparent diffusion coefficient (ADC) in hyperacute ischemia. Using diffusion echo planar imaging, we obtained ADC maps (calculated from measurements made with 8 b-values) with a time resolution of 43 s in a feline model of global brain ischemia and reperfusion. Different protocols were performed: 10-min hypoperfusion, 10- and 22-min ischemia followed by reperfusion, and cardiac arrest. ADC values were obtained from white matter of the internal capsule and from the thalamus. Cortical gray matter measurements were not deemed reliable due to the close proximity of CSF in the cortical sulci. Following occlusion, the ADC declined in the thalamus to < 2 SD of its normal baseline value within 1.5-2.5 min. This decay was exponential with a time constant (tau +/- SD) of 6.0 +/- 2.6 min; no further decrease in the ADC was observed 10 min following ischemia. Following reperfusion, in animals that showed ADC recovery, the ADC began increasing immediately, returning to its preischemic value in approximately 15 min. No significant ADC changes were observed during hypoperfusion. Following cardiac arrest, the decay of ADC was more rapid in the thalamus (tau = 2.6 +/- 0.6 min) than in white matter (tau = 6.6 +/- 1.8 min). We observed that the ADC at 40 min after cardiac arrest was similar to the ADC at 10 min after ischemia. Given that all animals subjected to 10-min ischemic episodes showed ADC recovery with reperfusion, doubt is cast on whether it is possible to define a threshold value of the ADC below which brain tissue is irreversibly damaged. Finally, despite variability in the time constants of the ADC decay induced by ischemia, the ADC values at 10 min were very similar in all the animals. This suggests that when blood flow is diminished sufficiently to induce an ADC reduction, differences in perfusion affect the rapidity of the decrease but not the final asymptotic value reached.

Animals↗

Mild hypothermia decreases the incidence of transient ADC reduction detected with diffusion MRI and expression of c-fos and hsp70 mRNA during acute focal ischemia in rats.

The effects of mild hypothermia on the apparent diffusion coefficient of water (ADC) and expression of c-fos and hsp70 mRNA were examined during acute focal cerebral ischemia. Young adult rats were subjected to 60-min middle cerebral artery occlusion under either normothermia (37.5 degrees C) or hypothermia (33 degrees C). Diffusion-weighted echo-planar magnetic resonance imaging was used to monitor changes in ADC throughout the ischemic period. Perfusion MRI with dysprosium contrast was used at the end of the ischemic period to verify that the occlusion was successful. C-fos and hsp70 mRNA expression were examined with in situ hybridization at the end of the ischemic period. The results indicate that the size of the region that exhibited reduced ADC was smaller during hypothermia than during normothermia. Hypothermia also decreased the frequency of occurrence of transient ADC reductions, especially in dorsal aspects of cortex. Expression of both c-fos and hsp70 mRNA were markedly reduced by hypothermia. Transient ADC reduction and c-fos expression are associated with spreading depression, which is believed to contribute to lesion expansion during acute focal ischemia. The results suggest that part of the neuroprotective effect of hypothermia may be due to a reduced incidence of spreading depression.

Animals↗

Rapid three-dimensional diffusion MRI facilitates the study of acute stroke in mice.

MRI studies using mouse brain models of ischemia are becoming a valuable tool for understanding the mechanism of stroke, since transgenic models are now available. However, the small size of the mouse brain and the surgical complexity of creating ischemia in mice make it technically challenging to obtain high-quality MRI data. Therefore, there are few reports of MRI studies in murine cerebral ischemia. In this project a newly developed rapid 3D diffusion-weighted imaging (DWI) technique was applied to study experimental stroke in a mouse model of reversible middle cerebral artery occlusion (MCAO). Ischemic volumes were successfully delineated using this 3D whole-brain imaging technique with high spatial (0.34 x 0.5 x 1.0 mm(3) before zero-filling) and temporal (7 min) resolution. The 3D observation revealed the characteristic evolution of stroke after transient MCAO. There was a temporarily high diffusion constant in the cortex during early reperfusion, followed by a secondary energy failure in the cortex and caudate-putamen at 6 and 21 h of reperfusion. Magn Reson Med 46:183-188, 2001.

Animals↗