Looking into the functional architecture of the brain with diffusion MRI.
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Brain↗
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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↗
[MRI-diffusion weighted images of encephalopathy associated with human herpesvirus 6 infection].
Encephalopathy associated with human herpes virus 6 infection (HHV-6 encephalopathy) is not rare. The pathophysiology of HHV-6 encephalopathy has not been clearly established and diagnosis in the early stages is difficult. To elucidate the diagnostic value of MRI in the early stages of HHV-6 encephalopathy, we performed MRI including diffusion weighted imaging (DWI) on 6 patients. No abnormalities were found in the T1, T2 weighted images and fluid attenuated inversion recovery (FLAIR) images of any of the patients. DWI revealed an increase of signal in the subcortical white matter of the frontal lobes during the acute phase in all 6 patients. Follow-up MRI in two patients showed lesions expanded to the cortical regions, and disappearance of high signal-lesions followed by atrophy of the corresponding areas in 2 patients. To our knowledge, these findings have not previously been reported in acute encephalopathy and encephalitis and may be characteristic of HHV-6 encephalopathy. DWI may be a useful diagnostic procedure in the early stages of HHV-6 encephalopathy.
Acute Disease↗
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↗
Perfusion and diffusion MRI of glioblastoma progression in a four-year prospective temozolomide clinical trial.
PURPOSE: This study was performed to determine the impact of perfusion and diffusion magnetic resonance imaging (MRI) sequences on patients during treatment of newly diagnosed glioblastoma. Special emphasis has been given to these imaging technologies as tools to potentially anticipate disease progression, as progression-free survival is frequently used as a surrogate endpoint. METHODS AND MATERIALS: Forty-one patients from a phase II temolozomide clinical trial were included. During follow-up, images were integrated 21 to 28 days after radiochemotherapy and every 2 months thereafter. Assessment of scans included measurement of size of lesion on T1 contrast-enhanced, T2, diffusion, and perfusion images, as well as mass effect. Classical criteria on tumor size variation and clinical parameters were used to set disease progression date. RESULTS: A total of 311 MRI examinations were reviewed. At disease progression (32 patients), a multivariate Cox regression determined 2 significant survival parameters: T1 largest diameter (p < 0.02) and T2 size variation (p < 0.05), whereas perfusion and diffusion were not significant. CONCLUSION: Perfusion and diffusion techniques cannot be used to anticipate tumor progression. Decision making at disease progression is critical, and classical T1 and T2 imaging remain the gold standard. Specifically, a T1 contrast enhancement over 3 cm in largest diameter together with an increased T2 hypersignal is a marker of inferior prognosis.
Analysis of Variance↗
3He diffusion MRI of the lung.
RATIONALE AND OBJECTIVES: MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. RESULTS: We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. METHODS: Techniques for purging and imaging excised lungs are discussed.
Diffusion Magnetic Resonance Imaging↗
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 × 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↗
Functional pathway-defined MRI diffusion measures reveal increased transverse diffusivity of water in multiple sclerosis.
The diffusion properties of water are sensitive to microscopic changes in the white matter of multiple sclerosis (MS) patients. Typical MRI measures of disease burden in MS demonstrate modest to poor correlation with disability. Functional MRI and DTI-based fiber tracking were used to define the interhemispheric white matter pathway connecting bilateral supplementary motor areas (SMA) in 16 MS patients sand 16 control subjects. Fractional anisotropy (FA), mean diffusivity (MD), longitudinal (lambda(1)) and transverse diffusivity (lambda(2)) were measured along this pathway in all subjects. Mean FA was 0.587 +/- 0.032 for patients and 0.608 +/- 0.020 for controls (P < 0.02). Mean MD was (0.821 +/- 0.055) x 10(-3) mm(2) s(-1) for patients and (0.770 +/- 0.020) x 10(-3) mm(2) s(-1) for controls (P < 0.004). Mean lambda(1) values were (1.462 +/- 0.099) x 10(-3) mm(2) s(-1) for patients and (1.400 +/- 0.034) x 10(-3) mm(2) s(-1) for controls (P < 0.02). Mean lambda(2) values were (0.500 +/- 0.047) x 10(-3) mm(2) s(-1) for patients and (0.454 +/- 0.027) x 10(-3) mm(2) s(-1) for controls (P < 0.001). In addition, the correlation between the Multiple Sclerosis Functional Composite (MSFC) and transverse diffusivity was -0.341 (P < 0.05). The component test of the MSFC most related to the SMA pathway studied with our MRI method (Nine-hole Peg Test) showed significant correlation with transverse diffusivity (r = 0.392, P < 0.02), indicating that probing functional pathways with MRI measures can lead to a better reflection of disease status.
Adult↗
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↗
Diffusion MRI findings in neonatal brain abscess.
In neonates and infants, bacterial brain abscess is rare, and the diffusion weighted MR imaging appearance of such abscesses has not been reported. We report the diffusion weighted MR findings of a brain abscess in a 25-day-old boy. The lesion initially had a large cystic component with some high-signal pyogenic material inside on diffusion-weighted (b=1000 sec/mm(2))images. The ADC value of this material was low (0.59 x 10(-3) mm(2)/sec), compared to the value from normal cerebellar parenchyma (0.78 x 10(-3) mm(2)/sec). The unusual initial appearance mimicked a cystic tumor. The lesion markedly decreased in size over 20 days after antibiotic therapy with persistent high-signal pyogenic material. In addition, at the initial presentation b=1000 sec/mm(2) images revealed high-signal changes in the brain parenchyma compressed by markedly dilated ventricles, consistent with ischemia. Also, ADC values of perilesional vasogenic edema (1.74 x 10(-3) mm(2)/sec), and that of transependymal resorption of CSF (1.56 x 10(-3) mm(2)/sec) were noted at the initial stage.
Anti-Bacterial Agents↗
Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in tumor microenvironment in response to inhibition of HIF-1alpha using PX-478.
PX-478 is a new agent known to inhibit the hypoxia-responsive transcription factor, HIF-1alpha, in experimental tumors. The current study was undertaken in preparation for clinical trials to determine which noninvasive imaging endpoint(s) is sensitive to this drug's actions. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) were used to monitor acute effects on tumor hemodynamics and cellularity, respectively. Mice bearing human xenografts were treated either with PX-478 or vehicle, and imaged over time. DW imaging was performed at three b values to generate apparent diffusion coefficient of water (ADCw) maps. For DCE-MRI, a macromolecular contrast reagent, BSA-Gd-DTPA, was used to determine vascular permeability and vascular volume fractions. PX-478 induced a dramatic reduction in tumor blood vessel permeability within 2 hours after treatment, which returned to baseline by 48 hours. The anti-VEGF antibody, Avastin, reduced both the permeability and vascular volume. PX-478 had no effect on the perfusion behavior of a drug-resistant tumor system, A-549. Tumor cellularity, estimated from ADCw, was significantly decreased 24 and 36 hours after treatment. This is the earliest significant response of ADC to therapy yet reported. Based on these preclinical findings, both of these imaging endpoints will be included in the clinical trial of PX-478.
Animals↗
[MR image (diffusion MRI and perfusion MRI)].
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Brain Ischemia↗
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↗