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Alteration of intracellular metabolite diffusion in rat brain in vivo during ischemia and reperfusion.

BACKGROUND AND PURPOSE: Diffusion-weighted MRI can demonstrate decreases of the apparent diffusion coefficient (ADC) of brain tissue water shortly after the onset of ischemia. To further elucidate underlying mechanisms, this study extended diffusion assessment to intracellular metabolites in rat brain in vivo before, during, and after ischemia. METHODS: Changes in molecular mobility were studied in a rat model of global forebrain ischemia (n = 8, 20-minute occlusion, 120-minute reperfusion) with the use of diffusion-weighted localized proton MR spectroscopy. During ischemia and early reperfusion the time course of ADC changes was monitored by strongly diffusion-weighted spectra. ADC values of N-acetylaspartate, creatines, cholines, and myo-inositol were evaluated from series of differently diffusion-weighted spectra before ischemia, 90 minutes after reperfusion, and 60 minutes postmortem. RESULTS: Parallel to a rise in diffusion-weighted water signal (133 +/- 20%), pertinent intensities of all brain metabolites increased during ischemia. Changes were most pronounced for myo-inositol (46 +/- 9%) and smallest for N-acetylaspartate (12 +/- 4%). During reperfusion water ADC values returned to basal values, whereas metabolite ADC values were decreased by 22% (after 40 minutes). Postmortem ADC values (after 60 minutes) were reduced by 46% for water and 38% for metabolites. CONCLUSIONS: The present findings indicate that water ADC changes during ischemic stroke are accompanied by significant alterations in intracellular mobility in both neuronal and glial cell populations as reflected by N-acetylaspartate and myo-inositol, respectively. Altered metabolite ADC values during reperfusion are consistent with irreversible tissue damage in this model and offer new means to assess circulatory and metabolic compromise.

Animals↗

Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging.

The authors performed a serial study of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS) who presented with diffusion-weighted MRI (DWI). DWI demonstrated a higher apparent diffusion coefficient in the lesion than in the control region during the acute stage of stroke. Vasogenic edema is present in stroke-like episodes in MELAS.

Blood-Brain Barrier↗

Reperfusion differentially induces caspase-3 activation in ischemic core and penumbra after stroke in immature brain.

BACKGROUND AND PURPOSE: Different strategies for neuroprotection of neonatal stroke may be required because the developing brain responds differently to hypoxia-ischemia than the mature brain. This study was designed to determine the role of caspase-dependent injury in the pathophysiology of pure focal cerebral ischemia in the immature brain. METHODS: Postnatal day 7 rats were subjected to permanent or transient middle cerebral artery (MCA) occlusion. Diffusion-weighted MRI was used during occlusion to noninvasively map the evolving ischemic core. The time course of caspase-3 activation in ischemic brain tissue was determined with the use of an Asp-Glu-Val-Asp-aminomethylcoumarin cleavage assay. The anatomy of caspase-3 activation in the ischemic core and penumbra was mapped immunohistochemically with an anti-activated caspase-3 antibody in coronal sections that matched the imaging planes on diffusion-weighted MRI. RESULTS: A marked increase in caspase-3 activity occurred within 24 hours of reperfusion after transient MCA occlusion. In contrast, caspase-3 activity remained significantly lower within 24 hours of permanent MCA occlusion. Cells with activated caspase-3 were prominent in the penumbra beginning at 3 hours after reperfusion, while a more delayed but marked caspase-3 activation was observed in the ischemic core by 24 hours after reperfusion. CONCLUSIONS: In the neonate, caspase-3 activation is likely to contribute substantially to cell death not only in the penumbra but also in the core after ischemia with reperfusion. Furthermore, persistent perfusion deficits result in less caspase-3 activation and appear to favor caspase-independent injury.

Animals↗

MR perfusion imaging in Moyamoya Syndrome: potential implications for clinical evaluation of occlusive cerebrovascular disease.

BACKGROUND AND PURPOSE: Ischemic symptoms in patients with moyamoya syndrome (MMS) are usually due to hemodynamically mediated perfusion failure, and identification of abnormal tissue perfusion in these patients is therefore clinically important. Although dynamic susceptibility contrast (DSC) MRI can be used to study tissue perfusion, there are potential technical problems in MMS. This study investigates the scope and limitations of perfusion MRI in the clinical evaluation of such patients. METHODS: Thirteen patients with bilateral MMS were studied with the use of structural, diffusion, and perfusion MRI. The DSC MRI data were analyzed both visually and by a quantitative regional analysis, and the relationship between perfusion status and clinical symptoms was investigated. RESULTS: Extensive bilateral DSC MRI abnormalities were observed in all the patients. There was a very heterogeneous distribution of bolus arrival time. The areas of abnormality included the major arterial border zones in all cases, although these usually appeared normal on structural and diffusion MRI. Only the most clinically unstable patients had peak width (defined as time to peak minus bolus arrival time) >5 seconds on the quantitative regional analysis. Several technical limitations of perfusion quantification in MMS are described, as well as the implications of these limitations in patients with other forms of occlusive large-vessel disease. CONCLUSIONS: The technical limitations of DSC MRI described in this study are important for the accurate interpretation of perfusion MRI in MMS. Despite these limitations, these preliminary findings suggest that the use of quantitative regional analysis of summary parameters may provide clinically useful information in patients with MMS.

Adolescent↗

Perfusion-weighted magnetic resonance imaging in patients with vasospasm: a useful new tool in the management of patients with subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm (VSP) is one of the most important risk factors for the development of a delayed neurological deficit after subarachnoid hemorrhage (SAH). Perfusion-weighted magnetic resonance imaging (pwMRI) provides the possibility of detecting tissue at risk for infarction. The objective of our study was to evaluate the feasibility and impact of pwMRI in the management of SAH patients. METHODS: From a consecutive series of 180 patients experiencing SAH and treated at our institution over a 3-year period, we identified 20 who underwent pwMRI during their acute illness. For these 20 patients, the results of pwMRI were compared with the results of diffusion-weighted MRI, transcranial Doppler sonography, and neurological examinations performed at the same time and with repeated pwMRI examinations of the same patient at different times. RESULTS: Nineteen of 20 patients showed perfusion changes predominantly in the time maps. Fifteen of 19 patients with changes in pwMRI had a neurological deficit at the same time. In 7 of 15 patients with neurological deterioration, transcranial Doppler sonography showed signs of VSP, whereas all 15 patients showed alterations in pwMRI. The areas of perfusion changes in pwMRI correlated well with the neurological deficits of the patients and were larger than the areas of changed diffusion in diffusion-weighted MRI performed at the same time. There were no clinical complications with regard to the pwMRI examinations. CONCLUSION: pwMRI is safe and helpful in the management of patients with VSP after SAH. The sensitivity of pwMRI is higher than that of transcranial Doppler sonography in the detection of decreased perfusion as a result of VSP. pwMRI can detect tissue at risk before definitive infarction occurs and therefore may lead to a change of therapy in those patients.

Adult↗

Lung MRI at 3.0 T: a comparison of helical CT and high-field MRI in the detection of diffuse lung disease.

The purpose of this study was to evaluate the feasibility of high-field magnetic resonance imaging (MRI) of the lung using a T2-weighted fast-spin echo (TSE) sequence. Comparison was made with helical computed tomography CT findings in patients with diffuse pulmonary diseases. Prospective segment-wise analysis of high-field MR imaging findings in 15 patients with diffuse pulmonary diseases was made using helical CT and HRCT as the standard of reference. The MR studies were performed on a 3.0-T whole body system (Intera 3T, Philips Medical Systems) using a T2w TSE sequence with respiratory and cardiac gating (TE 80 ms TR 1,500-2,500 ms; turbo factor 17; 22 slices with 7/2-mm slice thickness and gap; 256x192 matrix). MR artifacts were graded on a three-point scale (low, moderate, high). Lung MR studies were prospectively analyzed segment-by-segment and diagnosed as healthy or pathological; results were compared with helical CT findings. In all 15 patients, MR imaging of the lung was successful. All 15 MR studies were compromised by artifacts; however, the severity of these artifacts was classified as low or moderate in 8/15, respectively, 7/15 cases. A total of 143/285 lung segments showed diffuse lung disease in helical CT. With MRI, 133 of these 143 segments (93%) were judged to be diseased. The ten segments that received false negative MR diagnoses displayed non-acute pulmonary lesions with inherently low proton density (scars, granulomas). MRI at 3.0 T can detect diffuse pulmonary disease with a high sensitivity. Based on this experience, further pulmonary studies with high-field systems appear justified and promising.

Adult↗

In vivo isotropic 3D diffusion tensor mapping of the rat brain using diffusion-weighted 3D MP-RAGE MRI.

The purpose of this study was to examine the potential of diffusion-weighted (DW) three-dimensional (3D) MP-RAGE MRI for diffusion-tensor mapping of the rat brain in vivo. A DW-3D-MP-RAGE (3D-DWI) sequence was implemented at 2.0 T using six gradient orientations and a b value of 1000 s/mm2. In this sequence, the preparation sequence with a "90 degrees RF-motion proving gradient (MPG): MPG-180 degrees RF-MPG-90 degrees RF" pulse train (DW driven equilibrium Fourier transform) was used to sensitize the magnetization to diffusion. A centric k-space acquisition order was necessary to minimize saturation effects (T1 contamination) from tissues with short relaxation time. The image matrix was 128x128x128 (interpolated from 64x64x64 acquisitions), which resulted in small isotropic DW image data (voxel size: 0.273x0.273x0.273 mm3). Moreover, 3D-DWI-derived maps of the fractional anisotropy (FA), relative anisotropy (RA) and main-diffusion direction were completely free of susceptibility-induced signal losses and geometric distortions. Two well-known commissural fibers, the corpus callosum and anterior commissure, were indicated and shown to be in agreement with the locations of these known stereotaxic atlases. The experiment took 45 min, and shorter times should be possible in clinical application. The 3D-DWI sequence allows for in vivo 3D diffusion-tensor mapping of the rat brain without motion artifacts and susceptibility to distortion.

Animals↗

Diffusion-weighted echo-planar MRI: a valuable tool for differentiating primary parotid gland tumors?

PURPOSE: To investigate the feasibility of using diffusion-weighted (DW) echo-planar imaging (EPI) for differentiating primary parotid gland tumors. MATERIAL AND METHODS: Fifty consecutive patients with a suspected primary tumor of the parotid gland were examined with a DW EPI sequence (TR 1,500 msec, TE 77 msec, field of view 250 x 250 mm, pixel size 2.10 x 1.95 mm, section thickness 5 mm). The b factors used were 0, 500, and 1,000 sec/mm (2). Apparent diffusion coefficient (ADC) maps were digitally transferred to MRIcro (Chris Rorden, University of Nottingham, Great Britain) and evaluated with a manually placed irregular region of interest (ROI) containing the entire tumor. Additionally, the contralateral, non affected parotid gland was measured and a circular ROI containing 100 - 200 pixels was placed in the cerebrospinal fluid (CSF) next to the spinal cord in every patient. For comparison of the results, the two-tailed Student's t test was used, based on the median ADC values for each patient, and a p-value <.05 was determined to indicate statistical significance. RESULTS: In 45 patients, a primary neoplasm of the parotid gland could be histologically verified. For the non-affected parotid glands of all 45 evaluated patients, the mean ADC value was 1.14 x 10 ( - 3) mm (2)/sec +/- 0.12 x 10 ( - 3) mm (2)/sec (mean +/- standard deviation). Seven different entities of parotid gland tumors were histologically discriminated. Pleomorphic adenomas (2.14 x 10 ( - 3) mm (2)/sec +/- 0.11 x 10 ( - 3) mm (2)/sec), Warthin tumors (0.85 x 10 ( - 3) mm (2)/sec +/- 0.1 x 10 ( - 3) mm (2)/sec), and mucoepidermoid carcinomas (1.04 x 10 ( - 3) mm (2)/sec +/- 0.3 x 10 ( - 3) mm (2)/sec) showed statistically significant different ADC values in comparison to all other evaluated tumors (p .001), and also among each other (p <.001). Additionally, ADC values presented by lipomas were statistically significant compared to all other entities (p <.001 to .015). Among all other [corrected] primary malignant parotid gland tumors, no statistically significant ADC values could be observed (p .18 to 1). CONCLUSION: Diffusion-weighted echo-planar MRI seems to be a valuable tool for differentiating benign from malignant primary parotid gland tumors.

Adolescent↗

The role of diffusion tensor imaging in the evaluation of ischemic brain injury - a review.

Water diffusion in brain tissue is affected by the presence of barriers to translational motion such as cell membranes and myelin fibers. The measured water apparent diffusion coefficient (ADC) value is therefore frequently anisotropic and varies depending upon the orientation of restricting barriers (such as white matter tracts) relative to the diffusion-sensitive-gradient direction. Anisotropic water diffusion can be specified using indices of diffusion anisotropy [e.g. standard deviation of the individual ADC values, fractional anisotropy (FA), lattice index (LI)], which are derived from measurements of the full diffusion tensor. The rotationally invariant nature of particular diffusion anisotropy indices (e.g. FA, LI) allows orientation-independent comparisons of these parameters between different subjects. Pathophysiological processes (such as cerebral ischemia) that modify the integrity of the tissue microstructure result in significant alterations in tissue anisotropy and make this metric a useful endpoint for characterizing the temporal evolution of the disease. Diffusion-tensor imaging (DTI) studies of both experimental and human stroke suggest that DTI may provide additional information about the evolution of the disease that is not available from diffusion-weighted MRI (DWI) alone. Acute reductions in the average diffusivity [ = (lambda(1) + lambda(2) + lambda(3))/3 where lambda(1), lambda(2), and lambda(3) are the eigenvalues of the diffusion tensor] following the onset of cerebral ischemia are often accompanied by increases in diffusion anisotropy. In the transition from acute to sub-acute and chronic stroke, renormalizes and subsequently increases whereas diffusion anisotropy measures (e.g. FA) decline and remained reduced in chronic infarcts. Overall isotropic ADC changes during infarct evolution have been observed to be greater in white matter (WM) than in gray matter (GM) lesions (although there have been conflicting reports on this issue) and GM lesions tend to renormalize prior to WM lesions as the infarct evolves. Ischemic WM exhibits a significant decrease in diffusion anisotropy (relative to normal WM) during ischemic evolution whereas that of ischemic GM remains statistically unchanged. Furthermore, the percentage decrease in ischemic WM is largely determined by reductions in lambda(1), the eigenvalue that coincides with the long axis of the WM fiber tract. Variations in unidirectional ADC or over the ischemic time course limit the usefulness of this parameter alone as a predictor of ischemic injury. Consequently, ADC information has been combined with that of other MR parameters (including DTI) to unambiguously stage and predict ischemic brain injury over its entire temporal evolution. Combined and diffusion anisotropy measurements have identified three phases of diffusion abnormality: (1) reduced and elevated anisotropy; (2) reduced and reduced anisotropy; and (3) elevated and reduced anisotropy. However, variations in the differential patterns of and diffusion anisotropy evolution have been observed by a number of investigators and more work is needed to clarify the role of these measurements in characterizing the severity of the ischemic insult as well as the potential outcome in response to the initial ischemic injury. The use of DTI, in combination with more sophisticated analysis methods for performing multiparametric segmentation, such as multispectral analysis, may enhance the use of MRI for accurate diagnosis and prognosis of stroke. Furthermore, these techniques may also play an important role in the clinical evaluation of new stroke treatments.

Animals↗

Postural headache in a patient with Marfan's syndrome.

A 26-year-old man with Marfan's syndrome had postural headache. Brain MRI with gadolinium showed diffuse pachymeningeal enhancement. MRI myelography revealed bilateral multiple large meningeal diverticula at sacral nerve roots level. He was suspected to have spontaneous intracranial hypotension syndrome. Eight days later headache improved with bed rest and hydration. One month after the onset he was asymptomatic and 3 months later brain MRI showed no evidence of diffuse pachymeningeal enhancement. The 1-year follow-up revealed no neurological abnormalities. The intracranial hypotension syndrome likely resulted from a CSF leak from one of the meningeal diverticula. In conclusion patients with spinal meningeal diverticula (frequently seen in Marfan's syndrome) might be at increased risk of developing CSF leaks, possibly secondary to Valsalva maneuver or minor unrecognized trauma.

Adult↗

Status of the neonatal rat brain after NMDA-induced excitotoxic injury as measured by MRI, MRS and metabolic imaging.

Intrastriatal injection of the excitotoxin N-methyl-D-aspartate (NMDA) in neonatal rat brain resulted in an acute ipsilateral decrease of the apparent diffusion coefficient (ADC) of brain tissue water, as measured with diffusion-weighted MRI. The early diffusion changes were accompanied by only mild changes in the overall metabolic status as measured by in vivo 1H MRS and 31P MRS and metabolic imaging of brain sections. Minimal decreases in the high-energy phosphate levels and a small hemispheric acidosis were observed in the first 6 h after NMDA administration. In addition, there was very modest lactate accumulation. Twenty-four hours after the induction of the excitotoxic injury the tissue energy status was still only moderately affected, whereas an overall decrease of 1H MRS-detected brain metabolites was found. Treatment with the non-competitive NMDA-antagonist MK-801 given within 90 min after NMDA injection rapidly reversed the NMDA-induced changes in the entire ipsilateral hemisphere. The effect of the competitive NMDA-antagonist D-CPPene was restricted to the cortical areas and was accomplished on a slower time scale. Our results indicate that; (i) early excitotoxicity in the neonatal rat brain does not lead to profound changes in the metabolic status; and (ii) brain tissue water ADC changes are not necessarily associated with a metabolic energy failure.

Animals↗

[Acute disseminated encephalomyelitis (ADEM) associated with cytomegalovirus infection--a case report].

A 60-year-old woman was admitted to our hospital because of developing fever, visual loss, weakness in right upper limb, walking difficulty and difficulties of urination and defecation. There were memory disturbance, optic neuritis, ataxia and myelopathy. CSF cells and protein were increased. Cytomegalovirus (CMV) antibodies in the CSF were increased. T2-weighted images of brain MRI showed diffuse high signal intensity lesions in white matter. Gadolinium-enhanced MRI of cervical spinal cord showed diffuse spotty enhanced lesions. Corticosteroid treatment improved clinical symptoms and anti-CMV antibodies in the CSF. This is the first case report of ADEM associated with CMV infection.

Antibodies, Viral↗

Predicting and monitoring response to chemotherapy by 1,3-bis(2-chloroethyl)-1-nitrosourea in subcutaneously implanted 9L glioma using the apparent diffusion coefficient of water and 23Na MRI.

PURPOSE: To examine the effects of the alkylating anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on (23)Na MRI and the water apparent diffusion coefficient (ADC) in subcutaneously- (sc-) implanted 9L glioma in rats. MATERIALS AND METHODS: (23)Na MRI and (1)H water ADC measurements were performed on sham-treated control (N = 6) and BCNU-treated (N = 15) Fisher rats one day before BCNU injection and then one, three, and five days after BCNU injection. RESULTS: The BCNU-treated tumors were divided into BCNU-responsive (R(BCNU)) and BCNU-nonresponsive (NR(BCNU)) groups depending on the tumor volume changes that occurred after therapy. The pretreatment (23)Na MRI signal intensity (SI) and water ADC values were higher in R(BCNU) tumors compared to NR(BCNU) tumors. (23)Na MRI SI and water ADC increased with tumor growth in control and NR(BCNU) groups, but these changes were interrupted by BCNU therapy in R(BCNU) group. CONCLUSION: (23)Na MRI and water ADC measurements may be useful for predicting and monitoring response to chemotherapy in some tumors. However, the changes that occurred in (23)Na MRI SI and water ADC in sc-implanted 9L tumors are in contrast to previously published results for BCNU therapy of orthotopic 9L tumors. This may have important implications for monitoring therapy response in tumors.

Animals↗

Diffusion- and perfusion-weighted MRI in a patient with a prolonged reversible ischaemic neurological deficit.

We report acute and follow-up diffusion- and perfusion-weighted MRI (DWI, PWI) findings in a patient with a prolonged reversible ischaemic neurological deficit. PWI 12 h after the patient was last seen to be without symptoms revealed a large perfusion deficit in the left posterior MCA territory with a relatively inconspicuous and much smaller abnormality on DWI. Follow-up showed resolution of abnormalities on both DWI and PWI, and conventional MRI was normal, apart from a very slight abnormality, visible only on FLAIR images, at the centre of the initially DWI-positive region. These findings demonstrate the utility of PWI when be used in combination with DWI to investigate the pathophysiology of transient ischemic syndromes.

Aged↗

Role of diffusion-weighted echo-planar MRI in distinguishing between brain brain abscess and tumour: a preliminary report.

Our purpose was to evaluate diffusion-weighted (DW) echo-planar MRI in differentiating between brain abscess and tumour. We examined two patients with surgically confirmed pyogenic brain abscess and 18 with metastatic brain tumours or high-grade glioma, using a 1.5 T system. The apparent diffusion coefficient (ADC) of each necrotic or solid contrast-enhancing lesion was measured with two different b values (20 and 1200 s/mm2). All capsule-stage brain abscesses (4 lesions) and zones of cerebritis (2 lesions) were identified on high-b-value DWI as markedly high-signal areas of decreased ADC (range, 0.58-0.70 [(10-3 mm2/s; mean, 0.63)]). All cystic or necrotic portions of brain tumours (14 lesions) were identified on high-b-value DWI as low-signal areas of increased ADC (range, 2.20-3.20 [(10-3 mm2/s; mean, 2.70)]). Solid, contrast-enhancing portions of brain tumours (19 lesions) were identified on high-b-value DWI as high-signal areas of sightly decreased or increased ADC (range, 0.77-1.29 [(10-3 mm2/s; mean, 0.94)]). Our preliminary results indicate that DW echo-planar MRI be used for distinguishing between brain abscess and tumour.

Aged↗

PROPELLER EPI: an MRI technique suitable for diffusion tensor imaging at high field strength with reduced geometric distortions.

A technique suitable for diffusion tensor imaging (DTI) at high field strengths is presented in this work. The method is based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) k-space trajectory using EPI as the signal readout module, and hence is dubbed PROPELLER EPI. The implementation of PROPELLER EPI included a series of correction schemes to reduce possible errors associated with the intrinsically higher sensitivity of EPI to off-resonance effects. Experimental results on a 3.0 Tesla MR system showed that the PROPELLER EPI images exhibit substantially reduced geometric distortions compared with single-shot EPI, at a much lower RF specific absorption rate (SAR) than the original version of the PROPELLER fast spin-echo (FSE) technique. For DTI, the self-navigated phase-correction capability of the PROPELLER EPI sequence was shown to be effective for in vivo imaging. A higher signal-to-noise ratio (SNR) compared to single-shot EPI at an identical total scan time was achieved, which is advantageous for routine DTI applications in clinical practice.

Algorithms↗

MRI measurements of water diffusion: impact of region of interest selection on ischemic quantification.

OBJECTIVE: To investigate the effect of ADC heterogeneity on region of interest (ROI) measurement of isotropic and anisotropic water diffusion in acute (< 12 h) cerebral infarctions. METHODS AND MATERIALS: Full diffusion tensor images were retrospectively analyzed in 32 patients with acute cerebral infarction. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured in ischemic lesions and in the corresponding contralateral, normal appearing brain by using four ROIs for each patient. The 2 x 2 pixel square ROIs were placed in the center, the lateral rim and the medial rim of the infarction. In addition, the whole volume of the infarction was measured using a free hand method. Each ROI value obtained from the ischemic lesion was normalized using contralateral normal ROI values. RESULTS: The localization of the ROIs in relation to the ischemic lesion significantly affected ADC measurement (P < 0.01, using Friedman test), but not FA measurement (P = 0.25). Significant differences were found between ADC values of the center of the infarction versus whole volume (P < 0.01), and medial rim versus whole volume of infarction (P < 0.001) with variation of relative ADC values up to 11%. The differences of absolute ADC for these groups were 22 and 23%, respectively. The lowest ADC was found in the center, followed by medial rim, lateral rim and whole volume of infarction. CONCLUSION: ADC quantification may provide variable results depending on ROI method. The ADC and FA values, obtained from the center of infarction tend to be lower compared to the periphery. The researchers who try to compare studies or work on ischemic quantification should be aware of these differences and effects.

Adolescent↗