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In vivo differentiation of edematous changes after stroke in spontaneously hypertensive rats using diffusion weighted MRI.

Apparent diffusion coefficients (ADCs) of tissue water were determined in chronic brain lesions of a rat stroke model, the stroke-prone spontaneously hypertensive rat, and compared with histology. ADCs increased in the order normal < edema < gliosis < cyst. The differences between individual groups were statistically significant. The increase in ADC is thought to mainly reflect a relative increase in the extracellular space in brain tissue. ADC may be a new parameter for tissue characterization.

Animals

Time-course and treatment response with SNX-111, an N-type calcium channel blocker, in a rodent model of focal cerebral ischemia using diffusion-weighted MRI.

Diffusion-weighted magnetic resonance imaging (DWI) is capable of noninvasively imaging acute cerebral ischemia. We demonstrate the utility of this technique by evaluating SNX-111, a novel N-type calcium channel blocker with potential neuroprotective properties, in a rodent model of transient focal ischemia. Twenty-four Sprague-Dawley rats weighing between 310-350 g underwent occlusion of the middle cerebral artery (MCAO) for 105 min followed by 22.5 h of reperfusion. Thirty minutes following MCAO, animals were randomized to receive SNX-111 5 mg/kg intravenously over 1 h vs. placebo. DWI and T2-weighted MRIs (T2W) were performed at 0.5, 1.5 and 24 h after the onset of ischemia. Area fractions of increased signal intensity on the DWI and T2W images were measured. DWI area fractions at 1.5 and 24 h were also normalized to the initial, pre-treatment scans. Apparent diffusion coefficients (ADC) were calculated from fitted maps. Tri-phenyl tetrazolium chloride (TTC) staining was performed on brains at 24 h and infarct area fractions were measured. SNX-111 treated animals showed significantly improved 1.5-h DWI scan ratios compared to controls (ratios of 1.06 +/- 0.25 vs. 2.98 +/- 0.78 SNX vs. controls respectively, P < 0.05). A trend toward improved DWI ratios was seen by 24 h in the SNX-111 group (2.5 +/- 0.75 vs. 4.12 +/- 1.6, N.S.) DWI, T2W and TTC area fractions at 24 h also showed trends favoring a neuroprotective effect of SNX-111. Bright areas on DWI corresponded to ADC decreases of about 30% compared to the non-ischemic hemisphere. These decreases were the same in both treatment groups and at each time point. DWI, T2W and TTC area fractions at 24 h were strongly correlated (r = 0.98, DWI and TTC; r = 0.99, T2W and TTC; r = 0.97, T2W and DWI, P < 0.0001). We conclude that in this ischemic model, SNX-111 provides early neuroprotection and that serial DWI is a useful way of demonstrating this.

Animals

Identification of collaterally perfused areas following focal cerebral ischemia in the rat by comparison of gradient echo and diffusion-weighted MRI.

Diffusion-weighted (DW) and gradient echo (GE) magnetic resonance images were acquired before and after occlusion of the middle cerebral artery (MCA) in the rat. Upon occlusion, an increase in DW imaging signal intensity was observed in a core area within the MCA territory, most likely reflecting cytotoxic edema. The signal from GE images, which is sensitive to changes in the absolute amount of deoxyhemoglobin, decreased following ischemia within a region that extended beyond the core area observed with DW imaging. This hypointensity is attributed to increases in blood volume and/or oxygen extraction fraction, which result from a decrease in perfusion pressure in the collaterally perfused area. The evolution of the GE imaging signal intensity from different regions was studied for 3.5 h following the occlusion. In the core area, the GE imaging signal returned towards baseline values after approximately 1-2 h, while it remained stable in the surrounding area. This feature may reflect a decrease in hematocrit due to microcirculatory defect and/or a decrease in the oxygen extraction fraction due to ongoing infarction of the tissue and may indicate that tissue recovery is severely compromised. The combined use of DW and GE imaging offers great promise for the noninvasive identification of specific pathological events with high spatial resolution.

Animals

Diffusion of an innovation: adoption of MRI.

"Diffusion of Innovation" is a marketing theory that predicts the pattern of adoption of new products, with specific characteristics of the product determining the rate of adoption. This article attempts to determine whether MRI fits the predicted pattern. A computer Medline search to assess the number of articles printed on MRI shows that MRI is being adopted more slowly than CT, but like CT, MRI is following the pattern predicted by the Diffusion Theory.

Communication

Abnormal diffusion-weighted MRI in medulloblastoma: does it reflect small cell histology?

A 12-year-old boy presented with the classic CT and MRI findings of medulloblastoma and the unusual finding of increased signal on diffusion MRI. The small-cell histology of medulloblastoma may account for the increased signal seen on diffusion MRI. Diffusion MRI with echoplanar technique may be useful in evaluation of these tumors and metastatic disease.

Brain Neoplasms

Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI.

Quantitative-diffusion-tensor MRI consists of deriving and displaying parameters that resemble histological or physiological stains, i.e., that characterize intrinsic features of tissue microstructure and microdynamics. Specifically, these parameters are objective, and insensitive to the choice of laboratory coordinate system. Here, these two properties are used to derive intravoxel measures of diffusion isotropy and the degree of diffusion anisotropy, as well as intervoxel measures of structural similarity, and fiber-tract organization from the effective diffusion tensor, D, which is estimated in each voxel. First, D is decomposed into its isotropic and anisotropic parts, [D] I and D - [D] I, respectively (where [D] = Trace(D)/3 is the mean diffusivity, and I is the identity tensor). Then, the tensor (dot) product operator is used to generate a family of new rotationally and translationally invariant quantities. Finally, maps of these quantitative parameters are produced from high-resolution diffusion tensor images (in which D is estimated in each voxel from a series of 2D-FT spin-echo diffusion-weighted images) in living cat brain. Due to the high inherent sensitivity of these parameters to changes in tissue architecture (i.e., macromolecular, cellular, tissue, and organ structure) and in its physiologic state, their potential applications include monitoring structural changes in development, aging, and disease.

Animals

Measurement of tumor vascular volume and mean microvascular random flow velocity magnitude by dynamic Gd-DTPA-albumin enhanced and diffusion-weighted MRI.

Tumor vascular volume fraction and the magnitude of the mean microvascular random flow velocity were measured in an animal tumor model by combining dynamic Gd-DTPA-albumin enhanced MRI and diffusion-weighted MRI in conjunction with a compartmental modeling analysis. The vascular volume fraction maps were obtained from the dynamic Gd-DTPA-albumin enhanced MRI measurement. It was found that the vascular volume fraction for Walker 256 tumor was higher within the outgrowing rim and decreased towards the central region. The average value obtained from five animals was 0.062 +/- 0.009 ml/g. By using the vascular volume fraction from the Gd-DTPA-albumin enhanced MRI measurement, maps of the magnitude of the mean microvascular random flow velocity were obtained from the diffusion-weighted MRI measurements with the compartmental modeling analysis. The relative extravascular and intravascular contributions to the diffusion-weighted MRI signal were determined for three tissue groups with different Gd-DTPA-albumin enhancement characteristics, and the flow and molecular diffusion-induced attenuation factors for the intravascular compartment were also compared. The mean microvascular random flow velocity magnitude maps were obtained with an average value of 0.67 +/- 0.06 mm/s.

Albumins

MRI of "diffusion" in the human brain: new results using a modified CE-FAST sequence.

"Diffusion-weighted"MRI in the normal human brain and in a patient with a cerebral metastasis is demonstrated. The method employed was a modified CE-FAST sequence with imaging times of only 6-10 s using a conventional 1.5-T whole-body MRI system (Siemens Magnetom). As with previous phantom and animal studies, the use of strong gradients together with macroscopic motions in vivo causes unavoidable artifacts in diffusion-weighted images of the human brain. While these artifacts are shown to be considerably reduced by averaging of 8-16 images, the resulting diffusion contrast is compromised by unknown signal losses due to motion.

Aged

Effects of a novel NMDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion-weighted MRI.

We employed diffusion-weighted MRI (DWI) to identify regions of focal brain ischemia during the first 3 hours after permanent occlusion of the middle cerebral artery in rats. Using DWI as early as 30 minutes after the onset of ischemia, it was possible to identify the areas of brain destined to progress to infarction over the next 24 hours in untreated animals, as demonstrated by postmortem evaluation. DWI studies revealed the cerebroprotective effects of a noncompetitive N-methyl-D-aspartate receptor antagonist, CNS 1102, administered 15 minutes postocclusion, both on the cortical and caudoputaminal regions during the initial 3 hours of ischemia. Although the treatment effect lessened over the next 21 hours in a few animals with lower plasma drug levels at 3 hours, postmortem studies demonstrated a 66% reduction in the total volume of infarcted tissue with the treatment and confirmed the DWI results. T2-weighted MRI obtained at similar times revealed little or no abnormality. These results suggest that DWI provides a sensitive in vivo measure of focal cerebral ischemic injury and can assess the beneficial effects of cytoprotective therapy. DWI may be useful in the early evaluation of human stroke patients and in monitoring the effects of cerebroprotective therapies in the clinical setting.

Animals

MR spectroscopic imaging and diffusion-weighted MRI for early detection of kainate-induced status epilepticus in the rat.

Previous studies have shown that reduction of N-acetyl-aspartate (NAA) is correlated with the degree of neuronal loss at 3 days after kainate-induced status epilepticus in the rat. In this study, magnetic resonance spectroscopic imaging (MRSI), measurement of NAA and lactate, T2-weighted MRI, and diffusion-weighted MRI were used to study early alterations in rat piriform cortex at 12 and 26 h after kainate administration. The major findings are that decreased NAA signal, increased lactate signal, and decreased apparent diffusion coefficient (ADC) were observed at 12 h, with little evidence of histological and T2-weighted MRI changes. These results support the hypothesis that NAA, lactate signals, and ADC provide sensitive methods for detection of early and minimal brain damage in vivo.

Animals

[Diffusion images on brain MRI in Creutzfeldt-Jakob disease].

We report a 72-year-old man with Creutzfeldt-Jakob disease. He showed a progressive dementia, myoclonus, and other neurological symptoms. DNA analysis showed a normal variation of prion gene (codon 129, Met/Met: codon 219, Glu/Glu). He had periodic synchronous discharge on electroencephalogram and brain atrophy on CT scan and MRI. Diffusion images on his brain MRI revealed a marked increase in signal intensity in the caudate nuclei, putamen, and cerebral cortices. These changes may represent spongy changes of the brain and seem to be a feature of brain MRI in Creutzfeldt-Jakob disease.

Aged

CT and MRI of diffuse liver disease.

CT and MRI contribute important information to the clinical evaluation of diffuse liver disease. In some cases, these modalities can establish a diagnosis that was not ascertained histologically, which is often the case when sampling errors prevent a definitive tissue diagnosis. Characteristic alterations of liver attenuation on CT, signal changes on MRI, and morphological changes appreciated with both modalities can be used to diagnose fatty infiltration, some parenchymal deposition diseases, and cirrhosis. Furthermore, hepatocellular disease can be confirmed in the setting of indeterminate clinical and laboratory findings. Significant overlap in the imaging findings of this wide range of disorders continues to limit specificity; however, at a minimum, these techniques provide a rapid means to a noninvasive evaluation that often guides clinical decisions. Faster scanning techniques available with CT and MRI may provide additional information by assessing contrast dynamics. This review of CT and MRI in diffuse liver disease considers the diagnostic utility and clinical implications of these modalities. Pathological findings relevant to imaging considerations are discussed.

Fatty Liver

Differentiation of recent and old cerebral infarcts by diffusion-weighted MRI.

We performed MRI, including diffusion-weighted imaging, in 15 patients with recurrent strokes with acute ischaemia and at least one old lesion according to the clinical history and/or CT. Routine MRI showed similar signal intensity changes in both situations. Diffusion-weighted images, however, were positive in all acute or subacute infarcts. The high signal of acutely disturbed diffusion due to intracellular oedema could also be identified in small brain stem lesions. Spatial resolution was increased by applying separate gradients in each axis instead of creating anisotropy-independent trace images.

Adult

Early detection of cerebral ischemic lesion using diffusion-weighted MRI.

We performed serial diffusion-weighted imaging (DWI) in a patient with right middle cerebral arterial occlusion using 1.0 T MRI. The initial DWI demonstrated suppression of water diffusion in the gray matter in the ischemic lesion as a high signal area 4 h after stroke onset, when T2-weighted imaging failed to detect any parenchymal injury. Repeat DWI 9 h after onset demonstrated the whole infarct, whereas it was not demonstrated by T2-weighted imaging until 48 h. Furthermore, the regional apparent diffusion coefficient (ADC) had already decreased significantly in both the gray and white matters of the ischemic lesion 4 h after onset, even though hyperintensity was not visible in the white matter on the DWI. The features in this case indicate that DWI in conjunction with the assessment of regional ADC can provide important information regarding the evolving infarct at a very early stage even when a relatively low tesla clinically available MRI unit is used.

Brain Ischemia

Anisotropy in diffusion-weighted MRI.

Diffusional anisotropy of water protons, induced by nonrandom, directional barriers which hinder or retard water motion, is measurable by MRI. Faster water diffusion was observed when the diffusion-sensitizing gradient direction paralleled the long axes of white matter tracts, indicative of fewer barriers to water motion. Diffusion perpendicular to this axis was as much as four times slower. Anisotropy was seen pre- and postmortem in all axial, sagittal, and coronal planes, with and without cardiac gating. Ordering has also been observed in feline optic nerve and in human peripheral nerves. Utilization of this technique can greatly improve understanding and assessment of demyelinating disorders, of white matter infarcts and neoplasms, and of neonatal brain and spinal cord development.

Animals

Diffusion-weighted MRI in sporadic Creutzfeldt-Jakob disease.

Diffusion-weighted MRI (DWI) was used in three patients with autopsy-proven sporadic Creutzfeldt-Jakob disease (CJD) to provide a rapid noninvasive way to make this sometimes confusing diagnosis. DWI prompted the diagnosis of CJD at an early stage and appears to be particularly useful for monitoring the progression of the disease. We suggest that patients with suspected CJD and no abnormalities on T2- and proton density-weighted images may have cortical involvement on DWI.

Aged

Normal diffusion-weighted MRI during stroke-like deficits.

BACKGROUND: Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic brain injury. However, this is not always the case. OBJECTIVE: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. METHODS: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. RESULTS: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TIA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). CONCLUSIONS: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality.

Aged

[Study of diffusion weighted magnetic resonance imaging in Wilson's disease].

We analyzed diffusion weighted magnetic resonance images (diffusion MRI) of the basal ganglia, which were obtained from four patients with Wilson's disease, and compared them with the images from ten age-matched normal individuals. In all patients, T2-MRI of the basal ganglia disclosed low or iso-signals, but diffusion MRI revealed abnormal high signals in some areas of the basal ganglia in each case. Pathological changes except for copper and/or iron deposits are difficult to estimate by T2-MRI because the low signal on T2-MRI emphatically reflects the deposits, while the abnormal high signal on diffusion MRI is thought to reflect parenchymal lesions such as cell loss, demyelination and/or increase of the extracellular fluid. From our results, we confirmed that diffusion MRI was very useful for estimating parenchymal lesions with metal deposits.

Adult