Water Diffusion In Brain Research Articles

Diffusion tensor changes in patients with amnesic mild cognitive impairment and various dementias

White matter damage and its contribution to clinical manifestations in patients with dementia have been increasingly recognized. To explore white matter changes in different types of dementia, we examined brain water diffusivity with diffusion tensor imaging (DTI). We measured fractional anisotropy and mean diffusivity of multiple white matter regions in patients with amnesic mild cognitive impairment (MCI, n = 10), Alzheimer's disease (AD, n = 30), subcortical ischemic vascular dementia (SIVD, n = 18), frontotemporal dementia (FTD, n = 7), and control subjects ( n = 20). We performed pairwise comparisons in each region of interest between patients and controls. MCI patients showed diffusion tensor change (DTC) in the left anterior periventricular (PV) area, possibly in the right posterior PV area, and the genu of the corpus callosum. AD patients showed DTC in the corpus callosum, and in frontal and parieto-occipital subcortical and anterior PV areas. In SIVD patients, DTC occurred in the genu of the corpus callosum, and in bilateral frontal subcortical and PV areas. FTD patients differed from controls in showing DTC in the temporal and frontal subcortical areas, the genu of the corpus callosum and PV areas. The degree of DTC correlated with the clinical severity of dementia as assessed by the clinical dementia rating (CDR). Mean diffusivity was diffusely and positively associated with the CDR scores. Fractional anisotropy of the PV areas was negatively associated with the CDR scores, suggesting a critical role of the lateral cholinergic pathways.

Voxel‐based diffusion tensor magnetic resonance imaging evaluation of low‐grade hepatic encephalopathy

To quantify the changes in brain water diffusivity in hepatic encephalopathy (HE) associated with cirrhosis using diffusion tensor imaging (DTI) and to correlate with neuropsychological (NP) scores. DTI was performed in 14 patients with low-grade HE and age/gender-comparable 16 healthy controls. Whole brain mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated, normalized to common space, smoothed, and compared voxel-by-voxel between groups using analysis of covariance with age included as a covariate. The average MD and FA values were also calculated from individual subjects for selected brain regions and correlated with the neuropsychological scores. Patients with HE showed increased MD in the cortical gray and white matter and the internal capsule. Less extensive brain regions with decreased FA were observed in the bilateral frontal and occipital white matter. MD values from the corpus callosum correlated inversely with several NP scores among HE patients and controls. Positive correlations were observed with FA values and cognitive scores. Voxel-based DTI analysis showed widespread brain regions with increased MD values, indicating enhanced water content and decreased FA in cirrhotic patients with HE. The MD and FA values from selected regions correlated with the NP scores.

Diffusion-Weighted Imaging: Can it Play a Role in the Evaluation of Patients with Epilepsy?

Diffusion-Weighted and Perfusion MRI Demonstrates Parenchymal Changes in Complex Partial Status Epilepticus Szabo K, Poepel A, Pohlmann-Eden B, Hirsch J, Back T, Sedlaczek O, Hennerici M, Gass A Brain 2005;128(Pt 6):1369–1376 Diffusion-weighted MRI (DWI) and perfusion MRI (PI) have been mainly applied in acute stroke, but may provide information in the peri-ictal phase in epilepsy patients. Both transient reductions of brain water diffusion, namely a low apparent diffusion coefficient (ADC), and signs of hyperperfusion have been reported in experimental and human epilepsy case studies. We studied 10 patients with complex partial status epilepticus (CPSE) with serial MRI, including DWI and PI. All patients showed regional hyperintensity on DWI, and a reduction of the ADC in (i) the hippocampal formation and the pulvinar region of the thalamus (six out of 10 patients), (ii) the pulvinar and cortical regions (two out of 10), (iii) the hippocampal formation only (one out of 10), and (iv) the hippocampal formation, the pulvinar and the cortex (one out of 10). In all patients, a close spatial correlation of focal hyperperfusion with areas of ADC/DWI change was present. In two patients, hyperperfusion was confirmed in additional SPECT (single photon emission computed tomography) studies. All patients received follow-up MRI examinations showing partial or complete resolution of diffusion and perfusion abnormalities depending on the length of the follow-up interval. The clinical course, EEG, and SPECT results all indicate that MRI detected changes related to prolonged epileptic activity. Combined PI and DWI can visualize haemodynamic and tissue changes after CPSE in the hippocampus, thalamus, and affected cortical regions.

Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy†

Brain water may increase in hepatic encephalopathy (HE). Diffusion tensor imaging was performed in patients with cirrhosis with or without HE to quantify the changes in brain water diffusivity and to correlate it with neuropsychological (NP) tests. Thirty-nine patients with cirrhosis, with minimal (MHE) or overt HE, were studied and compared to 18 controls. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in corpus callosum, internal capsule, deep gray matter nuclei, periventricular frontal, and occipital white matter regions in both cerebral hemispheres. The MD and FA values from different regions in different groups were compared using analysis of variance and Spearman's rank correlation test. In 10 patients with MHE, repeat studies were performed after 3 weeks of lactulose therapy to look for any change in MD, FA, and NP scores. Significantly increased MD was found with insignificant changes in FA in various regions of brain in patients with MHE or HE compared with controls, indicating an increase in interstitial water in the brain parenchyma without any microstructural changes. A significant correlation was found between MD values from corpus callosum, internal capsule, and NP test scores. After therapy, MD values decreased significantly and there was a corresponding improvement in NP test scores. Further analysis showed that MD values were different for different grades of minimal or overt HE. In conclusion, the increase in MD with no concomitant changes in FA in cirrhosis with minimal or early HE indicates the presence of reversible interstitial brain edema.

Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus

Diffusion-weighted MRI (DWI) and perfusion MRI (PI) have been mainly applied in acute stroke, but may provide information in the peri-ictal phase in epilepsy patients. Both transient reductions of brain water diffusion, namely a low apparent diffusion coefficient (ADC), and signs of hyperperfusion have been reported in experimental and human epilepsy case studies. We studied 10 patients with complex partial status epilepticus (CPSE) with serial MRI including DWI and PI. All patients showed regional hyperintensity on DWI, and a reduction of the ADC in (i) the hippocampal formation and the pulvinar region of the thalamus (six out of 10 patients), (ii) the pulvinar and cortical regions (two out of 10), (iii) the hippocampal formation only (one out of 10), and (iv) the hippocampal formation, the pulvinar and the cortex (one out of 10). In all patients a close spatial correlation of focal hyperperfusion with areas of ADC/DWI change was present. In two patients hyperperfusion was confirmed in additional SPECT (single photon emission computed tomography) studies. All patients received follow-up MRI examinations showing partial or complete resolution of diffusion and perfusion abnormalities depending on the length of the follow-up interval. The clinical course, EEG and SPECT results all indicate that MRI detected changes related to prolonged epileptic activity. Combined PI and DWI can visualize haemodynamic and tissue changes after CPSE in the hippocampus, thalamus and affected cortical regions.

Increased frontal white matter diffusion is associated with glial metabolites and psychomotor slowing in HIV

Diffusion-weighted imaging (DWI) measures brain water diffusion that is sensitive to microscopic brain injury. A total of 11 HIV seropositive patients were compared to 14 seronegative subjects using DWI, proton magnetic resonance spectroscopy ( 1H MRS), and neuropsychological tests. The apparent diffusion coefficient (ADC) was significantly increased in the HIV patients, primarily in the frontal white matter (FWM; +5%, p=0.01). Diffusivity correlated positively with the glial marker myo-inositol ( r=0.5, p=0.008) and negatively with cognitive performance (NPZ-8 composite score; r=−0.43, p=0.05). These findings suggest increased brain water diffusion may reflect increased glial activation or inflammation, which in turn, may contribute to the cognitive deficits in HIV patients.

269 Secondary Energy Failure in a Model of Hypoxic Ischaemic Brain Injury Assessed by Serial Phosphorous Magnetic Resonance Spectroscopy, Water Apparent Diffusion and Electrophysiology: A Pilot Study

Background: The electroencephalogram (EEG) provides a sensitive means of predicting outcome early after perinatal hypoxia-ischaemia (HI). The amplitude integrated EEG (aEEG), a compressed, rectified and filtered form of 1-channel EEG, is increasingly used clinically to define infants who may benefit from neuroprotective intervention following perinatal HI. The precise relationship between electrophysiology and brain energetics remains unclear however. Phosphorous-31 magnetic resonance spectroscopy (31P MRS) and magnetic resonance imaging measurements of the apparent diffusion coefficient of water (ADC) provide useful information about local tissue energetics following HI. Objective: (i) To compare electro-cortical activity to cerebral energetics and ADC during the evolution of secondary energy failure (SEF); (ii) To assess the correlation between aEEG and standard EEG during HI and SEF. Methods: A newborn piglet was studied under general anaesthesia (isoflurane & fentanyl) before, during and after acute HI (carotid occlusion and reduction of FiO2 to 12% for 45min). The standard EEG (8 surface electrodes, 10–20 system) and aEEG were recorded for 30min before, immediately following and approximately every 4hrs after HI. Whole-brain 31P MRS spectra and ADC maps from the central axial slice were also obtained. Results: Changes in the EEG are summarised in Table 1.The corresponding aEEG recordings are shown in Fig.1. Abnormal burst (4hrs post-HI) and seizure activity (11hrs post-HI) were transformed into similar appearing traces on aEEG. The density of high voltage activity was highest during seizures. Energetic status assessed by phosphocreatine to inorganic phosphate ratio ([PCr]/[Pi]) and ATP to total exchangeable phosphate pool ([ATP]/[EPP]) is shown in Table 1. ADC was reduced as early as 4hrs after the insult, initially in the deep grey matter and watershed deep white matter, extending throughout the brain by 15hrs (Table 1 & Fig.1). Conclusion: Changes in electro-cortical activity, brain energy metabolism and water diffusion were observed during the evolution of SEF. The aEEG trace was sufficiently sensitive to capture globally abnormal cortical activity in this pilot study. We recorded abnormal burst activity many hours before PCr/Pi decreased. Future work aims to fully characterise the relationship between electrophysiology and brain energetics during SEF. Such information will facilitate the selection of infants who may benefit from neuroprotective strategies.

Editorial Comment—Specificity of Stroke Imaging

Brain imaging in acute stroke patients can be effective on 6 different levels:1 (1) It will reduce health care costs, if it prevents disability and death of stroke victims. (2) Brain imaging will improve the clinical outcome of stroke patients, if it identifies the patients who benefit from specific treatment. (3) To identify these patients, brain imaging must provide relevant information that is unavailable from other sources for the appropriate choice of treatment. (4) This could be brain images that allow the exclusion of brain hemorrhage and other diseases that mimic ischemic stroke, and allow assessment of ischemic edema and perfusion disturbance, mass effect, arterial wall pathology, and obstruction. (5) The imaging modality should be sensitive and specific for stroke pathology early after symptom onset. (6) This requires the imaging modality to have the technical capacity to reliably detect the relevant stroke pathology. In this issue, Schramm et al2 compare computed tomography (CT) and MRI (MRI) techniques that assessed brain perfusion, brain water diffusion, and the resulting ischemic infarct in acute stroke patients. In a group of 22 patients, among them 9 patients without a brain infarct on follow-up CT, Schramm et al did not detect a statistical difference …

Normal and Abnormal Water Diffusion in the Brain

Normal and Abnormal Water Diffusion in the Brain

Changes in brain water diffusion during the 1st year of life.

To evaluate the normal water diffusion changes that occur during the 1st year of life. Diffusion-weighted imaging was performed in 40 subjects (age range, birth to 1 year) in whom both magnetic resonance imaging and neurologic assessment results were normal at the time of imaging and, where available, at follow-up. Apparent diffusion coefficient (ADC) was calculated in four areas of white matter (anterior and posterior subcortical and internal capsule) and four of gray matter (cortex, thalamus, head of the caudate nucleus, and lentiform nucleus). Linear regression was used to examine the effect of age on ADC, and analysis of variance was used to compare ADC within different brain regions. ADC decreased with age in all regions (P <.01). Data best fit with a logarithmic decline (r(2) = 0.20-0.63). ADC was significantly higher in white (113 x 10(-5) mm(2)/sec) than in gray matter (102 x 10(-5) mm(2)/sec; P <.001). Significant differences were seen among three white matter regions (subcortical, 188 x 10(-5) mm(2)/sec at birth; anterior limb of internal capsule, 130 x 10(-5) mm(2)/sec; posterior limb of internal capsule, 109 x 10(-5) mm(2)/sec) and three gray matter regions (cortex, 134 x 10(-5) mm(2)/sec at birth; head of caudate nucleus, 134 x 10(-5) mm(2)/sec at birth; and thalamus and lentiform nucleus, 120 x 10(-5) mm(2)/sec; P <.01). Results suggest that in neonates and infants, water diffusion is highly dependent on both subject age and brain location.

Reversible posterior leukoencephalopathy syndrome: evaluation with diffusion-tensor MR imaging.

To characterize the changes in brain water diffusion caused by reversible posterior leukoencephalopathy syndrome (RPLS). Twelve patients with the clinical features and conventional magnetic resonance (MR) imaging findings of RPLS underwent diffusion-tensor echo-planar MR imaging. The isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) were measured in posterior regions of diffusion abnormality and in anterior areas of normal-appearing brain. Across all 12 subjects, the mean D of (1.09 +/- 0.13 [SD]) x 10(-3) mm(2)/sec in affected posterior regions was 26% greater than its value of (0.87 +/- 0.07) x 10(-3) mm(2)/sec in normal-appearing anterior regions. The mean A(sigma) of 0.15 +/- 0.03 in posterior regions was 35% less than its value of 0.23 +/- 0.02 in anterior regions (t(11) = 9.58; P <.001). There was a significant inverse correlation between D and A(sigma) in posterior regions (r = -0.67; P <.018) but not in anterior regions (r = -0.12; P =.719). A follow-up study performed in one patient after resolution of symptoms documented reversal of elevated isotropic diffusion and at least partial recovery of anisotropy loss. The increased magnitude of brain water diffusion characteristic of RPLS is accompanied by reduced A(sigma). The magnitudes of these two effects are correlated and may be reversible. These observations support the proposal that vasogenic edema due to cerebrovascular autoregulatory dysfunction is the underlying pathophysiologic mechanism in uncomplicated RPLS.

Diffusion time dependence of the apparent diffusion tensor in healthy human brain and white matter disease.

The diffusion time dependence of the brain water diffusion tensor provides information regarding diffusion restriction and hindrance but has received little attention, primarily due to limitations in gradient amplitude available on clinical MRI systems, required to achieve short diffusion times. Using new, more powerful gradient hardware, the diffusion time dependence of tensor-derived metrics were studied in human brain in the range 8-80 ms, which encompasses the shortest diffusion times studied to date. There was no evidence for a change in mean diffusivity, fractional anisotropy, or in the eigenvalues with diffusion time in healthy human brain. The findings are consistent with a model of unrestricted, but hindered water diffusion with semipermeable membranes, likely originating from the extracellular space in which the average extracellular separation is less than 7 microns. Similar findings in two multiple sclerosis plaques indicated that the size of the water diffusion space in the lesion did not exceed this dimension.

Vessel size imaging.

Vessel size imaging is a new method that is based on simultaneous measurement of the changes Delta R(2) and Delta R(2)(*) in relaxation rate constants induced by the injection of an intravascular superparamagnetic contrast agent. Using the static dephasing approximation for Delta R(2)(*) estimation and the slow-diffusion approximation for Delta R(2) estimation, it is shown that the ratio Delta R(2)/Delta R(2)(*) can be expressed as a function of the susceptibility difference between vessels and brain tissue, the brain water diffusion coefficient, and a weighted mean of vessel sizes. Comparison of the results with 1) the Monte Carlo simulations used to quantify the relationship between tissue parameters and susceptibility contrast, 2) the experimental MRI data in the normal rat brain, and 3) the histologic data establishes the validity of this approach. This technique, which allows images of a weighted mean of the vessel size to be obtained, could be useful for in vivo studies of tumor vascularization. Magn Reson Med 45:397-408, 2001.

Distinguishing between cellular and vasogenic edema in head injured patients with focal lesions using magnetic resonance imaging.

Having determined that edema and not vascular engorgement is the major factor leading to traumatic brain swelling, the objective of this study was to determine which type of edema, cellular or vasogenic, is responsible for increased tissue water in patients with focal lesions. Severely head injured patients (GCS 8 or less) were transported to imaging suites for measurement of brain water and apparent diffusion coefficient (ADC) using magnetic resonance technique. Cerebral blood flow by stable Xenon method was also measured in the regions of interest. Brain water was increased significantly in the hemisphere with lesion. The increase in water was associated with reduced ADC signifying a predominant cellular edema. The ADC in the contralateral hemisphere was near normal value. Cerebral blood flow values in the regions of interest were above ischemic levels suggesting that factors other than ischemia are responsible for the cytotoxic swelling in patients with focal injury.

Changes in brain water diffusion during childhood.

We studied the changes in brain water diffusion in childhood as seen on diffusion-weighted MRI in 30 children from 1 day of life to 17 years to provide a data base and to investigate the correlation of diffusion changes with known patterns of white matter maturation. The apparent diffusion coefficient (ADC) and apparent anisotropy (AA) were calculated in numerous regions of the brain to include major white matter tracts and gray matter. ADC and AA values were directly related to the structural maturity and compactness of the white matter tracts and changed with aging in a way that predated early myelination markers such as signal change on T1- or T2-weighted images. Diffusion of water is sensitive to structural changes in the brain such as white matter maturation and may be useful in investigating white matter disorders.

Brain water diffusion in normal and creatine-supplemented rats during transient global ischemia.

Brain water diffusion in response to transient global ischemia (12 min), reperfusion (60 min), and cardiac arrest was monitored by localized proton magnetic resonance spectroscopy. The trace of the apparent diffusion coefficient tensor (ADC(Av)) was determined at high temporal resolution (10 sec) to assess the putative neuroprotective potential of oral creatine (Cr) in rats that received 2.2 g Cr-monohydrate per kg body weight per day for 10 days (n = 8) relative to controls (n = 9). Cr-fed rats revealed a statistically significant increase of the cerebral concentration ratio of Cr to choline-containing compounds (20%). The decrease of the ADC(Av) value during acute ischemia showed a three-phasic behavior in line with energy depletion, cytotoxic edema, and brain cooling. In Cr-fed rats, slightly less severe and mildly delayed diffusion changes during ischemia and similar beneficial trends during early reperfusion did not reach statistical significance. Magn Reson Med 42:798-802, 1999.

Brain water diffusion in normal and creatine‐supplemented rats during transient global ischemia

Brain water diffusion in response to transient global ischemia (12 min), reperfusion (60 min), and cardiac arrest was monitored by localized proton magnetic resonance spectroscopy. The trace of the apparent diffusion coefficient tensor (ADCAv) was determined at high temporal resolution (10 sec) to assess the putative neuroprotective potential of oral creatine (Cr) in rats that received 2.2 g Cr-monohydrate per kg body weight per day for 10 days (n = 8) relative to controls (n = 9). Cr-fed rats revealed a statistically significant increase of the cerebral concentration ratio of Cr to choline-containing compounds (20%). The decrease of the ADCAv value during acute ischemia showed a three-phasic behavior in line with energy depletion, cytotoxic edema, and brain cooling. In Cr-fed rats, slightly less severe and mildly delayed diffusion changes during ischemia and similar beneficial trends during early reperfusion did not reach statistical significance. Magn Reson Med 42:798–802, 1999. © 1999 Wiley-Liss, Inc.

Water diffusion in rat brain in vivo as detected at very large b values is multicompartmental

The diffusion-weighted signal attenuation of water in rat brain was measured with pulsed-field gradient nuclear magnetic resonance methods in a single voxel under in vivo and global ischemic conditions. The diffusion-attenuated water signal was observed in vivo at b values of 300 ms/μm2 (strength of diffusion weighting) and diffusion times up to 400 ms. A series of constant diffusion time (CT) experiments with varied gradient directions and diffusion times revealed a multiexponential decay with apparent diffusion coefficients (ADC) covering two orders of magnitude from 1 to 0.01 μm2/ms. In a four-exponential fit, the observed changes during global ischemia could be fully explained by changes in the relative volume fractions only with unchanged ADCs. An anisotropy of the ADC, detected at small b values, was not observed for the ADC at large b values, but for the concomitant volume fractions. An inverse Laplace Transform of the CT curves, performed with CONTIN, resulted in continuously distributed diffusion coefficients, for which the term ‘diffusogram’ is proposed. This approach was more appropriate than a discrete exponential model with four to six components, being related to the morphology of brain tissue and its cell size distribution. On the basis of an analytical, quantitative model, it is suggested that the measured ADC at small b values reflects mainly properties of the restricting boundaries, i.e. the relative volume fractions and the extracellular tortuosity, while the intrinsic intracellular diffusion constant and the exchange time are predicted to have minor influence.

Water diffusion in rat brain in vivo as detected at very large b values is multicompartmental.

The diffusion-weighted signal attenuation of water in rat brain was measured with pulsed-field gradient nuclear magnetic resonance methods in a single voxel under in vivo and global ischemic conditions. The diffusion-attenuated water signal was observed in vivo at b values of 300 ms/microm2 (strength of diffusion weighting) and diffusion times up to 400 ms. A series of constant diffusion time (CT) experiments with varied gradient directions and diffusion times revealed a multiexponential decay with apparent diffusion coefficients (ADC) covering two orders of magnitude from 1 to 0.01 microm2/ms. In a four-exponential fit, the observed changes during global ischemia could be fully explained by changes in the relative volume fractions only with unchanged ADCs. An anisotropy of the ADC, detected at small b values, was not observed for the ADC at large b values, but for the concomitant volume fractions. An inverse Laplace Transform of the CT curves, performed with CONTIN, resulted in continuously distributed diffusion coefficients, for which the term 'diffusogram' is proposed. This approach was more appropriate than a discrete exponential model with four to six components, being related to the morphology of brain tissue and its cell size distribution. On the basis of an analytical, quantitative model, it is suggested that the measured ADC at small b values reflects mainly properties of the restricting boundaries, i.e. the relative volume fractions and the extracellular tortuosity, while the intrinsic intracellular diffusion constant and the exchange time are predicted to have minor influence.

New nuclear magnetic resonance data in epilepsy.

Nuclear magnetic resonance methods as a whole have contributed as much to the study and treatment of epilepsy as to any branch of medicine. The pace of the progress in this field increases as recently developed nuclear magnetic resonance techniques mature into practical tools for epilepsy research and management. Recent examples of such progress include new data on seizure-related brain water diffusion changes, brain metabolic abnormalities in epileptic patients, and pharmacologic manipulation of brain gamma-aminobutyric acid.