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Diffusion magnetic resonance imaging study of a rat hippocampal slice model for acute brain injury.

Diffusion magnetic resonance imaging (MRI) provides a surrogate marker of acute brain pathology, yet few studies have resolved the evolution of water diffusion changes during the first 8 hours after acute injury, a critical period for therapeutic intervention. To characterize this early period, this study used a 17.6-T wide-bore magnet to measure multicomponent water diffusion at high b-values (7 to 8,080 s/mm(2)) for rat hippocampal slices at baseline and serially for 8 hours after treatment with the calcium ionophore A23187. The mean fast diffusing water fraction (Ffast) progressively decreased for slices treated with 10-microM/L A23187 (-20.9 +/- 6.3% at 8 hours). Slices treated with 50-micromol/L A23187 had significantly reduced Ffast 80 minutes earlier than slices treated with 10-microM/L A23187 (P < 0.05), but otherwise, the two doses had equivalent effects on the diffusion properties of tissue water. Correlative histologic analysis showed dose-related selective vulnerability of hippocampal pyramidal neurons (CA1 > CA3) to pathologic swelling induced by A23187, confirming that particular intravoxel cell populations may contribute disproportionately to water diffusion changes observed by MRI after acute brain injury. These data suggest diffusion-weighted images at high b-values and the diffusion parameter Ffast may be highly sensitive correlates of cell swelling in nervous issue after acute injury.

Acute Disease↗

[A case of Binswanger's disease in which an acute infarcted lesion was detected by diffusion-weighted magnetic resonance imaging].

Diffusion-weighted magnetic resonance imaging (DWI) was carried out on a patient with Binswanger's disease suffering from acute cerebral infarction. Though an acute infarcted lesion was demonstrated as a high signal area on the T2-weighted image, it was impossible to determine whether it was acute or chronic because of extensive deep white matter lesions (periventricular hyperintensity and white matter hyperintensity lesions). However, only the acute infarcted lesion was detected on DWI which showed it as a high signal area, suggesting reduced molecular diffusion of water. The apparent diffusion coefficient (ADC), a physiological parameter that characterizes the self-diffusion on water in tissue, was lower in the acute lesion and higher in the chronic lesion. DWI can differentiate acute from chronic infarcts, which is not possible by conventional CT and MRI.

Acute Disease↗

In vivo monitoring of age-related changes in rat brain using quantitative diffusion magnetic resonance imaging and magnetic resonance relaxometry.

Diffusion-weighted magnetic resonance imaging (MRI) has been proven to be a sensitive diagnostic tool to examine age associated acute and chronic changes in brain tissue. The aim of our study was to examine whether there are differences in brain diffusion and transverse relaxation time between young and adult rats. In an experimental MR scanner, 24 young (age: 3 months) and 26 adult rats (age: 12 months) were examined using diffusion-weighted and transverse relaxation time (T2)-weighted MRI sequences. There were no differences in the T2 relaxation time between the two animal groups, either local or global. However, the mean apparent diffusion coefficient (ADC) within the whole brain was significantly lower (P<0.0005) in the adult animals (765+/-35 x 10(-6) mm(2)/s) than in the young animals (829+/-45 x 10(-6) mm(2)/s). ADC decrease was mainly found in the cerebral cortex. These results can be attributed to an activity-related or central nervous system damage-related internal water shift from the extracellular to the intracellular space without a net increase in water content in brain tissue. Our study also shows that age-related changes in diffusion should be considered when performing longitudinal studies in rats.

Aging↗

Diffusion magnetic resonance imaging of solid vestibular schwannomas.

Six patients with solid vestibular schwannomas were studied by diffusion magnetic resonance imaging to assess if this modality adds new information for these tumors, because there is no previous report in the relevant literature. The sizes of the tumors ranged from 2.2 to 4.7 cm with respect to their largest diameters. They were isointense to the normal brain parenchyma on b = 1,000 s/mm2 images. The apparent diffusion coefficient (ADC) values in the tumors were high (range: 1.14-1.72 x 10(-3) mm2/s, mean = 1.42 +/- 0.17 x 10(-3) mm2/s) compared with normal brain parenchyma ADC values (mean = 0.80 +/- 0.11 x 10(-3) mm2/s). High ADC values of solid vestibular schwannomas were in conformity with increased diffusion rates, indicating the presence of increased amounts of extracellular water (a relatively loose tissue) in the tumor matrix.

Adult↗

Canavan disease: diffusion magnetic resonance imaging findings.

A 15-month-old boy with Canavan disease is reported in whom a restricted diffusion pattern on diffusion magnetic resonance imaging (MRI) (high signal on b = 1,000 mm2/s images and low apparent diffusion coefficient [ADC] values) was evident in the affected regions of the brain, including the peripheral white matter, globi pallidi, thalami, brainstem, dorsal pons, and dentate nuclei. The ADC values at these regions ranged from 0.42 to 0.56 x 10(-3) mm2/s compared with the normal ADC values from the uninvolved deep frontal white matter (0.68-0.92 x 10(-3) mm2/s). The known histopathologic features in Canavan disease include edematous and gelatinous brain tissue associated with diffuse vacuolization. Considering these and the diffusion MRI findings in this patient, it is likely that existence of a gel (gelatinous) state rather than the usual sol state of water molecules in the affected brain regions accounted for the restricted diffusion pattern in Canavan disease.

Brain↗

Non-invasive thermometry using magnetic resonance diffusion imaging: potential for application in hyperthermic oncology.

The proposition to use non-invasive thermometry based on magnetic resonance diffusion imaging for applications in therapeutic hyperthermia is examined. The measurement of proton motion predominantly associated with the self-diffusion of water can be characterized by a Boltzmann temperature dependence (i.e. e-Ea/kT). The activation energy (Ea) is on the order of 0.2 eV and, for a restricted range (approximately 30 degrees) at a base temperature of approximately 300 K, the relationship between the effective diffusion coefficient and temperature is approximately linear. This response has been empirically demonstrated in water-based gel phantoms using magnetic resonance imaging (MRI). Additionally, it is feasible to have compatibility between radiofrequency (RF) heating devices and MRI equipment. An MRI-compatible heating applicator that includes a hexagonal array of coherently phased dipoles was assembled. This heating array easily fits into a standard 1.5 T head imaging coil (diameter 28 cm). The RF fields associated with heating (130 MHz) and imaging (64 MHz) were decoupled using bandpass filters providing isolation in excess of 100 dB. This isolation was sufficient to allow simultaneous imaging and RF heating without deterioration of the image signal-to-noise ratio. In this report temperature, spatial and time resolution achieved in phantom are examined in order to assess the potential for using this non-invasive temperature measurement in applications of hyperthermic oncology. Using this system and conventional multi-slice imaging techniques, 0.5 degrees C resolution in a voxel size of less than 1 cm3 has been achieved using an acquisition time of 4.15 min.

Diffusion↗

Diffusion nuclear magnetic resonance imaging in experimental stroke. Correlation with cerebral metabolites.

BACKGROUND AND PURPOSE: Diffusion-weighted nuclear magnetic resonance imaging has been shown to detect early ischemia-related alterations in experimental stroke. This raises the question of whether the observed increase in signal intensity is correlated with changes in cerebral metabolism. After middle cerebral artery occlusion, nuclear magnetic resonance diffusion images were recorded and compared with the regional concentration of cerebral metabolites and with histology of identical planes. METHODS: Seven anesthetized Fischer rats were subjected to permanent occlusion of the middle cerebral artery. T1, T2, and diffusion images (b factors ranging from 0 to 1500 s/mm2) were measured in three to five planes after 7 hours. Thereafter, brains were frozen in situ for histology and quantitative bioluminescence imaging of ATP, glucose, lactate, and for fluorescence imaging of tissue pH. RESULTS: Seven hours after middle cerebral artery occlusion, the apparent diffusion coefficient was reduced from 615 +/- 97 x 10(-6).mm2.s-1 (contralateral brain) to 359 +/- 42 x 10(-6).mm2.s-1 (ischemic brain; mean +/- SD, P < .01). A precise topical coincidence was demonstrated between changes in nuclear magnetic resonance diffusion images, pattern of histological damage, ATP-depleted areas, and local tissue acidosis, the lesion area amounting to between 24.1% and 27.6% of the hemisphere at the level of the caudate-putamen. The area of elevated brain lactate clearly exceeded the acidic core of the infarct and included the slightly alkaline border zone. CONCLUSIONS: The data demonstrate that after 7-hour middle cerebral artery occlusion, the reduction of the apparent diffusion coefficient in nuclear magnetic resonance diffusion images reflects precisely the region of histological injury, breakdown of energy metabolism, and tissue acidosis.

Adenosine Triphosphate↗

The relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow and hypoxia in an animal stroke model.

This study examined the relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow (99mTc-hexamethylpropylene amine oxime) and cerebral hypoxia (125I-iodoazomycin arabinoside) in a rat model of stroke. Middle cerebral artery occlusion in the rat was performed using an intraluminal suture approach. Diffusion, hypoxia, and blood flow maps were acquired 2 hr following occlusion, and were compared with T2 images and histology at 7 hr. Two hours following middle cerebral artery occlusion the lesion distributions from the diffusion maps and hypoxic autoradiographs were similar. The blood flow threshold for increased uptake of the hypoxic marker was approximately 34 +/- 7% of the normal flow. The combination of diffusion or hypoxic images with perfusion maps allowed differentiation between four regions: 1) normal tissue; 2) a region of decreased perfusion but normal diffusion and normal uptake of hypoxic marker; 3) a region of decreased perfusion, decreased diffusion and increased uptake of hypoxic marker; 4) a region of decreased perfusion, decreased diffusion and low uptake of hypoxic marker. The areas for increased uptake of hypoxic marker and decreased diffusion are equivalent, indicating similar blood flow thresholds. Regions of oligaemic misery perfusion, ischaemic misery perfusion and lesion core may be delineated with the combination of diffusion or hypoxic images and perfusion maps.

Animals↗

Etiology of perfusion-diffusion magnetic resonance imaging mismatch patterns.

BACKGROUND AND PURPOSE: Diffusion-and perfusion-weighted magnetic resonance imaging (DWI and PWI) are useful tools for the assessment of brain ischemia. Discrepancies between the extent of DWI and PWI abnormalities are thought to depend pre dominantly on time from symptom onset to magnetic resonance imaging (MRI) examination. However, underlying ischemic stroke etiology can also be important. A mismatch may indicate the presence of tissue at risk for infarction, whereas the relevance of other DWI/PWI patterns is uncertain. The authors therefore investigated the etiology of brain ischemia in patients with different DWI/PWI patterns. METHODS: Retrospective study of 130 patients with acute brain ischemia and detailed stroke workup, including MRI within a week after symptom onset (40 +/- 39 hours). Patients were divided into the following groups: mis-match (PWI > DWI), reverse mismatch (DWI > PWI), and match (<25% difference between PWI and DWI). RESULTS: Mismatch occurred in 49% of patients, whereas 22% had reverse mis-match and 29% matched lesions. Time from symptom onset to MRI examination was similar between the 3 groups. Largeartery atherosclerosis increased by almost 4-fold the odds of mismatch (odds ratio: 3.89, 95% confidence interval: 1.72-8.78; P < .001), whereas patients with reverse mismatch were likely to have cryptogenic stroke. Patients with matched lesions were similarly distributed among different stroke subtypes. CONCLUSIONS: Ischemic stroke etiology appears to influence the development of specific DWI/PWI patterns. Prospective studies are needed to confirm these observations.

Aged↗

Phenylketonuria: diffusion magnetic resonance imaging and proton magnetic resonance spectroscopy.

Two patients with phenylketonuria are reported with white matter lesions. Diffusion magnetic resonance (MR) imaging revealed restricted diffusion patterns (high signal) on b = 1000 s/mm2 images associated with low apparent diffusion coefficient values ranging between 0.44 x 10-3 mm2/s and 0.56 x 10-3 mm2/s. On proton MR spectroscopy obtained in 1 of the patients, a prominent peak resonating at approximately 3.80 ppm was consistently present attributable to the peak rising from the alpha-proton of the phenylalanine molecule.

Adult↗

Sturge-Weber syndrome: diffusion magnetic resonance imaging and proton magnetic resonance spectroscopy findings.

We report on the diffusion magnetic resonance imaging (MRI) and proton MR spectroscopy findings of a 26-year-old female patient with Sturge-Weber syndrome. Echo-planar trace diffusion MRI revealed mildly high signal intensity changes at parieto-occipital lobes on b = 1000 s/mm2 images, suggesting restricted diffusion. On corresponding apparent diffusion coefficient maps, those areas had moderately high signal intensity and high apparent diffusion coefficient values (around 0.9 x 10(-3) mm2/s) compared with the contralateral symmetrical normal side of the brain (0.776 x 10(-3) mm2/s). This finding was consistent with increased motion of water molecules (disintegration of the neural tissue) in these regions. Proton MR spectroscopy revealed decreased N-acetyl aspartate and increased choline peaks, indicating disintegration of neural tissue associated with neuronal loss as well.

Adult↗

Diffusion magnetic resonance imaging patterns in metabolic and toxic brain disorders.

PURPOSE: To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI). MATERIAL AND METHODS: Echo-planar diffusion MRI examinations were obtained in 34 pediatric patients with metabolic and toxic brain disorders proved by appropriate laboratory studies. The MRI unit operated at 1.5 T with a gradient strength of 30 mT/ meter, and a rise time of 600 micros. b=1000s/mm2 images and apparent diffusion coefficient (ADC) maps with ADC values were studied. RESULTS: Three patterns were observed: 1. A restricted diffusion pattern (high signal on b = 1000 s/mm2 images and low ADC values); 2. an elevated diffusion pattern (normal signal on b = 1000s/mm2 images and high ADC values); and 3. a mixed pattern (coexistent restricted and increased diffusion patterns in the same patient). Disorders manifesting with a restricted diffusion pattern included metachromatic leukodystrophy (n = 2), phenylketonuria (n = 3), maple syrup urine disease (intermediate form) (n = 1), infantile neuroaxonal dystrophy (n = 1), Leigh (n = 2), Wilson (n = 3), and Canavan disease (n = 1). Disorders with an elevated diffusion pattern included phenylketonuria (n = 1), adrenoleukodystrophy (n = 1), merosin-deficient congenital muscular dystrophy (n = 2), mucopolysaccharidosis (n = 2), Lowe syndrome (n = 1), Leigh (n = 2), Alexander (n = 1), Pelizaeus-Merzbacher (n = 1), and Wilson (n = 3) disease. Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n = 2), non-ketotic hyperglycinemia (n = 1), infantile neuroaxonal dystrophy (n =2), maple syrup urine disease (n = 1), and Leigh (n = 1) disease. CONCLUSION: The findings suggested that the three different diffusion patterns reflect the histopathological changes associated with the disorders and different stages of a particular disorder. It is likely that the restricted diffusion pattern corresponds to abnormalities related to myelin, and the elevated diffusion pattern to disintegration of the tissue. The mixed pattern has contributions from both myelin abnormalities related to myelin disintegration of the tissue.

Adolescent↗

Detection of wallerian degeneration in a newborn by diffusion magnetic resonance imaging (MRI).

We present the case of an infant with hypoxic-ischemic encephalopathy in whom wallerian degeneration is demonstrated in white-matter fiber tracts by diffusion magnetic resonance imaging (MRI). MRI was undertaken on days 2 and 9 and then at 9 months of age. On day 2, conventional MRI was normal, but diffusion MRI showed bioccipital abnormalities. On day 9, diffusion MRI showed marked abnormalities in the deep white matter of the occipital regions (left > right), corpus callosum, left posterior limb of the internal capsule, and left cerebral peduncle. Water apparent diffusion coefficient values showed a significant reduction in the left occipital white matter and corpus callosum between days 2 and 9 while demonstrating the expected pseudonormalization in cortical gray matter. Images at 9 months showed left occipital porencephaly and atrophy of the left cerebral peduncle, with the infant displaying right hemiplegia at 18 months of age. In this case, the time course of diffusion changes differed between white and gray matter, with diffusion MRI showing delayed wallerian degeneration of the cerebral white matter. This case characterizes this degeneration with clinical and follow-up MRI at 9 months of age.

Asphyxia Neonatorum↗

Evaluation of cancer therapy using diffusion magnetic resonance imaging.

Assessment of the effectiveness of cancer therapy traditionally relies on comparison of tumor images acquired before and after therapeutic intervention by inspection of gross anatomical images to evaluate changes in tumor size. The potential for imaging to provide additional insights related to the therapeutic impact would be enhanced if a specific parameter or combination of parameters could be identified that reflect tissue changes at the cellular or physiological level. This information could also provide a more sensitive and earlier indicator of treatment response in an individual animal or patient. Diffusion magnetic resonance imaging can detect relatively small changes in tissue structure at the cellular level and thus provides an opportunity to quantitatively and serially follow therapeutic-induced changes in solid tumors. This article provides an overview of the use of diffusion magnetic resonance imaging as a surrogate marker for quantitating treatment responsiveness in both preclinical and clinical studies.

Animals↗

Role of diffusion-weighted magnetic resonance imaging in diffuse axonal injury.

PURPOSE: To determine whether the signal changes on magnetic resonance imaging (MRI), including fluid attenuated inversion recovery (FLAIR), T2*-weighted gradient echo (GE) imaging, and diffusion-weighted imaging (DWI) in diffuse axonal injury (DAI) patients correlate with the clinical outcome. MATERIAL AND METHODS: We diagnosed patients with DAI based on the following criteria: 1) a loss of consciousness from the time of injury that persisted beyond 6 h; 2) no apparent hemorrhagic contusion on computed tomography (CT); 3) the presence of white matter injury on MRI. Twenty-one DAI patients were analyzed (19 M, 2 F, mean age 34 years) with MRI (FLAIR, T2*-weighted GE imaging, and DWI). RESULTS: 325 abnormalities were detected by MRI within a week after injury. The T2*-weighted GE imaging was significantly more sensitive than FLAIR and DWI in diagnosing DAI. DWI detected only 32% of all lesions, but could depict additional shearing injuries not visible on either T2*-weighted GE imaging or FLAIR. The mean number of lesions in brainstem detected by DWI in the favorable group (good recovery/moderately disabled) was significantly smaller than in the unfavorable group (severely disabled/vegetative survival/death). This trend was not observed on the T2*-weighted GE imaging and FLAIR findings. CONCLUSION: DWI cannot detect all DAI-related lesions, but is a potentially useful imaging modality for both diagnosing and assessing patients with DAI.

Adolescent↗

In vivo monitoring of acute flavivirus (Modoc) encephalitis with regional and whole-brain quantitative diffusion magnetic resonance imaging.

In vivo imaging of structural changes in the brain of patients with encephalitis has become an important aid in diagnostic and therapeutic procedures. Diffusion-weighted magnetic resonance imaging (DWI) was employed to quantitate regional and whole-brain diffusion-weighted MRI changes in a hamster model for acute flavivirus encephalitis. The regional apparent diffusion coefficient (ADC) was determined in hyperintense regions seen on T2-weighted images (i.e., the thalamic area and the temporal lobe), but anatomical variation and structural heterogeneity of encephalitic lesions severely impeded the placement of regions of interest (ROI). Therefore, quantitative whole-brain diffusion-weighted imaging was carried out and revealed a significantly reduced ADC (P = .02) in the brain of hamsters with acute encephalitis (n = 7) as compared to that of healthy, uninfected controls (n = 3). Furthermore, the ADC histogram demonstrated a reduced peak height and center of gravity during the acute encephalitis. Our findings could further support the use of diffusion-weighted imaging for in vivo monitoring of acute flavivirus encephalitis and for the study of therapeutic approaches.

Animals↗

Tumor extension in high-grade gliomas assessed with diffusion magnetic resonance imaging: values and lesion-to-brain ratios of apparent diffusion coefficient and fractional anisotropy.

PURPOSE: To determine whether the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) can distinguish tumor-infiltrated edema in gliomas from pure edema in meningiomas and metastases. MATERIAL AND METHODS: Thirty patients were studied: 18 WHO grade III or IV gliomas, 7 meningiomas, and 5 metastatic lesions. ADC and FA were determined from ROIs placed in peritumoral areas with T2-signal changes, adjacent normal appearing white matter (NAWM), and corresponding areas in the contralateral healthy brain. Values and lesion-to-brain ratios from gliomas were compared to those from meningiomas and metastases. RESULTS: Values and lesion-to-brain ratios of ADC and FA in peritumoral areas with T2-signal changes did not differ between gliomas, meningiomas, and metastases (P = 0.40, P = 0.40, P = 0.61, P = 0.34). Values of ADC and FA and the lesion-to-brain ratio of FA in the adjacent NAWM did not differ between tumor types (P = 0.74, P = 0.25, and P = 0.31). The lesion-to-brain ratio of ADC in the adjacent NAWM was higher in gliomas than in meningiomas and metastases (P = 0.004), but overlapped between tumor types. CONCLUSION: Values and lesion-to-brain ratios of ADC and FA in areas with T2-signal changes surrounding intracranial tumors and adjacent NAWM were not helpful for distinguishing pure edema from tumor-infiltrated edema when data from gliomas, meningiomas, and metastases were compared.

Adult↗