Assessment of automatic decision-support systems for detecting active T2 lesions in multiple sclerosis patients.

BACKGROUND: Active (new/enlarging) T2 lesion counts are routinely used in the clinical management of multiple sclerosis. Thus, automated tools able to accurately identify active T2 lesions would be of high interest to neuroradiologists for assisting in their clinical activity. OBJECTIVE: To compare the accuracy in detecting active T2 lesions and of radiologically active patients based on different visual and automated methods. METHODS: One hundred multiple sclerosis patients underwent two magnetic resonance imaging examinations within 12 months. Four approaches were assessed for detecting active T2 lesions: (1) conventional neuroradiological reports; (2) prospective visual analyses performed by an expert; (3) automated unsupervised tool; and (4) supervised convolutional neural network. As a gold standard, a reference outcome was created by the consensus of two observers. RESULTS: The automated methods detected a higher number of active T2 lesions, and a higher number of active patients, but a higher number of false-positive active patients than visual methods. The convolutional neural network model was more sensitive in detecting active T2 lesions and active patients than the other automated method. CONCLUSION: Automated convolutional neural network models show potential as an aid to neuroradiological assessment in clinical practice, although visual supervision of the outcomes is still required.

Quantitative comparison of subcortical and ventricular volumetry derived from MPRAGE and MP2RAGE images using different brain morphometry software.

OBJECTIVE: In brain volume assessment with MR imaging, it is of interest to know the effects of the pulse sequence and software used, to determine whether they provide equivalent data. The aim of this study was to compare cross-sectional volumes of subcortical and ventricular structures and their repeatability derived from MP2RAGE and MPRAGE images using MorphoBox, and FIRST or ALVIN. MATERIALS AND METHODS: MPRAGE and MP2RAGE T1-weighted images were obtained from 24 healthy volunteers. Back-to-back scans were performed in 12 of them. Volumes, coefficients of variation, concordance, and correlations were determined. RESULTS: Significant differences were found for volumes derived from MorphoBox and FIRST. Ventricular volumes determined by MorphoBox and ALVIN were similar. Differences between volumes obtained using MPRAGE and MP2RAGE were significant for a few regions. Coefficients of variation, ranged from 0.2 to 9.1%, showed a significant inverse correlation with the mean volume. There was a correlation between volume measures, but agreement was rated as poor for most regions. CONCLUSION: MP2RAGE sequences and MorphoBox are valid options for assessing subcortical and ventricular volumes, in the same way as MPRAGE and FIRST or ALVIN, accepted tools for clinical research. However, caution is needed when comparing volumes obtained with different tools.

Assessment of brain volumes obtained from MP-RAGE and MP2RAGE images, quantified using different segmentation methods.

OBJECTIVE: For clinical purposes and research projects in neurological disease, it is of interest to evaluate the performance and comparability of available sequences and software packages for brain volume assessment to determine whether they provide equivalent results. This study compares cross-sectional brain volume values derived from images obtained with MP-RAGE or MP2RAGE sequences, using SIENA/X, SPM, or MorphoBox. MATERIALS AND METHODS: MP-RAGE and MP2RAGE T1-weighted images were obtained from 24 healthy volunteers. Back-to-back scans were performed in 12 of them. Brain volumes, coefficients of variation, and concordance coefficients were determined. RESULTS: Significant differences were found for most brain volumes derived from MP-RAGE and MP2RAGE images. MP2RAGE-derived measures showed a non-significant trend to larger coefficients of variation. There were statistical differences between brain volumes determined with the three software packages, whereas coefficients of variation were comparable for most brain volumes. Correlation and concordance values were lower for CSF and brain parenchyma fraction measures. CONCLUSION: The results obtained advise caution when comparing brain volumes obtained by different sequences and software packages. Of note, for most brain volume measures, the MP2RAGE and MorphoBox coefficients of variation were similar to those obtained with MP-RAGE, SIENA/X or SPM, accepted tools for clinical research.

Brain magnetic resonance in experimental acute-on-chronic liver failure.

BACKGROUND & AIM: Acute-on-chronic liver failure is the term that refers to sustained liver injury with acute decompensation, usually induced by a precipitating factor. A common link between ensuing failures of various organs is impairment of the vascular supply, which may also induce vasogenic oedema in the brain. The aim of this study was to perform magnetic resonance (MR) study of the brain in a rat model combining bile duct ligation (BDL) and lipopolysaccharide (LPS) administration to investigate brain oedema in liver failure. METHODS: Bile duct-ligated rats underwent in vivo brain MR imaging at 4, 5 and 6 weeks, and after superimposed administration of LPS. The MR techniques applied enabled assessment of brain metabolites, and intra- or extracellular water distribution. Brain water content was assessed by gravimetry. RESULTS: MR spectroscopy showed an increase in brain glutamine and a decrease in myo-inositol and choline in relation to progression of liver disease. BDL rats showed a slight, progressive increase in the amount of cortical brain water that was significant after LPS injection. These changes did not modify the apparent diffusion coefficient, supporting a mixed origin of brain oedema (vasogenic and cytotoxic). CONCLUSIONS: The mechanisms leading to the development of brain oedema in an experimental liver disease model were related to the time course of liver failure and to pro-inflammatory stimuli. MR findings support the presence of cytotoxic and vasogenic mechanisms in induced brain oedema in BDL rats exposed to LPS.

Can Cognitive training Reignite Compensatory Mechanisms in Advanced Multiple Sclerosis Patients? An Explorative Morphological Network Approach.

Multiple Sclerosis (MS) has been shown to significantly impair brain connectivity, as alterations in functional and structural networks have been identified and associated with clinical status, particularly cognitive deficits. We aimed to identify structural connectivity changes in grey matter networks following cognitive rehabilitation (CR) in persons with MS (PwMS). Fifteen long-standing PwMS underwent a 5-week CR-program and five healthy controls (HC) were also investigated. T1-weighted MRI scans and neuropsychological tests were obtained before and after CR. T1-weighted scans were used to examine grey matter networks with graph analytic parameters [betweenness centrality (BC), degree (D), clustering (Cl), path length (PL) and small world properties: connectedness, gamma and lambda values]. Results were analysed at the whole brain level and for each brain lobe. Before CR, PwMS displayed lower values for D in the left parietal lobe (p = 0.009) compared to HC. After CR, significant increases in Cl located in frontal (p = 0.024) and temporal (p = 0.026) regions in PwMS were accompanied by significant decreases in PL located in the right parietal lobe (p = 0.025) and BC globally (p = 0.010). Overall, CR may prevent a network worsening in long-standing PwMS by increasing local efficiency of the brain and therefore facilitating compensation mechanisms.

Diffusion tensor imaging supports the cytotoxic origin of brain edema in a rat model of acute liver failure.

BACKGROUND & AIMS: Brain edema is a severe complication of acute liver failure (ALF) that has been related to ammonia concentrations. Two mechanisms have been proposed in the pathogenesis: vasogenic edema that is secondary to the breakdown of the blood-brain barrier and cytotoxic edema caused by ammonia metabolites in astrocytes. METHODS: We applied magnetic resonance techniques to assess the intracellular or extracellular distribution of brain water and metabolites in a rat model of devascularized ALF. The brain water content was assessed by gravimetry and blood-brain barrier permeability was determined from the transfer constant of (14)C-labeled sucrose. RESULTS: Rats with ALF had a progressive decrease in the apparent diffusion coefficient (ADC) in all brain regions. The average decrease in ADC was significant in precoma (-14%) and coma stages (-20%). These changes, which indicate an increase of the intracellular water compartment, were followed by a significant increase in total brain water (coma 82.4% +/- 0.3% vs sham 81.6% +/- 0.3%; P = .0001). Brain concentrations of glutamine (6 hours, 540%; precoma, 851%; coma, 1086%) and lactate (6 hours, 166%; precoma, 998%; coma, 3293%) showed a marked increase in ALF that paralleled the decrease in ADC and neurologic outcome. In contrast, the transfer constant of (14)C-sucrose was unaltered. CONCLUSIONS: The pathogenesis of brain edema in an experimental model of ALF involves a cytotoxic mechanism: the metabolism of ammonia in astrocytes induces an increase of glutamine and lactate that appears to mediate cellular swelling. Therapeutic measures should focus on removing ammonia and improving brain energy metabolism.

Hepatic encephalopathy is associated with posttransplant cognitive function and brain volume.

Hepatic encephalopathy (HE) is a common complication of cirrhosis that is associated with brain atrophy and may participate in impaired cognitive function after liver transplantation. This study analyzes the relationship of HE with cognitive function and brain volume after transplantation. A total of 52 consecutive patients with cirrhosis (24 alcohol abuse, 24 prior HE, 14 diabetes mellitus) completed a neuropsychological assessment before liver transplantation and again, 6 to 12 months after transplantation. In 24 patients who underwent the posttransplant assessment, magnetic resonance imaging was performed in addition, with measurement of brain volume and relative concentration of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr), a neuronal marker, by magnetic resonance spectroscopy. Neuropsychological assessment prior to transplantation identified minimal HE in 28 patients. All cognitive indexes improved after liver transplantation, but 7 patients (13%) showed persistent mild cognitive impairment. Global cognitive function after transplantation was poorer in patients with the following variables before liver transplantation: alcohol etiology, diabetes mellitus, and HE. Brain volume after transplantation was smaller in patients with prior HE. Brain volume correlated to NAA/Cr values (r = 0.498, P = 0.013) and poor motor function (r = 0.41, P = 0.049). In conclusion, the association of HE with cognitive function and brain volume suggests that having experienced HE before liver transplantation impairs the posttransplantation neurological outcome.

Decreased white matter lesion volume and improved cognitive function after liver transplantation.

UNLABELLED: Focal T2-weighted white matter lesions (WML) on brain magnetic resonance imaging (MRI), mimicking those seen in cerebrovascular small-vessel disease described in patients with persistent hepatic encephalopathy, decreased in volume with the improvement of hepatic encephalopathy. This outcome has been interpreted as a decrease in the edema that it is proposed to be involved in the pathogenesis of hepatic encephalopathy. We designed a study to further investigate potential changes in focal WML in the brains of patients with cirrhosis following liver transplantation and to study the relationship between these changes and overall cognitive function. We used MRI to measure the volume of supratentorial focal WML and a neuropsychological examination to assess cognitive function before and after liver transplantation in 27 patients with cirrhosis without signs of overt hepatic encephalopathy. Baseline MRI identified focal T2-weighted lesions in 19 patients (70.3%). The presence of WML was associated with older age but not with vascular risk factors, severity of liver function, or psychometric tests. A significant reduction in lesion volume was observed after liver transplantation (from a median of 1.306 cm(3) to 0.671 cm(3), P = 0.001). This decrease correlated with an improvement in an index of global cognitive function (r = -0.663; P < 0.001). This evolution indicates that lesion volume is partially related to a reversible type of tissue damage, which is compatible with brain edema. CONCLUSION: Focal WML probably induced by age-related microvascular injury can decrease their volume with liver transplantation. The associated improvement of cognitive function supports a relationship between brain edema and minimal hepatic encephalopathy.

Classic Block Design "Pseudo"-Resting-State fMRI Changes After a Neurorehabilitation Program in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: The goal of this study was to assess changes in the resting-state networks (RSNs) of patients with multiple sclerosis (MS) after a cognitive rehabilitation program (CRP), by retrospectively analyzing functional magnetic resonance imaging (fMRI) studies using the classical block design. METHODS: Fifteen patients with MS (2 primary progressive, 3 relapsing-remitting, 10 secondary progressive) were scanned before and after the CRP on a 1.5T MRI scanner. In addition, patients underwent pre- and post-CRP neuropsychological assessment using a battery of standardized tests. Five healthy individuals were scanned at the same time points to confirm the test-retest reliability of the imaging technique. For each study, the individual fMRI blocks of rest were merged to produce a "pseudo"-resting-state (pseudo-RS) of 3 minutes duration. RS studies were analyzed with the MELODIC toolbox. A dual regression analysis was applied to estimate the longitudinal changes in RSNs of patients and test controls relative to a set of predefined RSNs used as templates. RESULTS: In healthy individuals, there were no significant differences in RSN results between the two time points studied. In the group of patients with MS, significant differences were found post-CRP in the visual medial, cerebellar, auditory, and frontal-executive RSNs. Furthermore, synchronization increases in the frontal-executive RSN were associated with cognitive improvement on neuropsychological testing. CONCLUSIONS: Results obtained using a pseudo-RS approach to analyze data from block-design fMRI studies suggest that a CRP of 5 weeks' duration induces measurable changes in specific RSNs of patients with MS.

Delineation of microhemorrhage in acute hepatic encephalopathy using susceptibility-weighted imaging.

INTRODUCTION: Microhemorrhages (MH's) in patients with acute hepatic encephalopathy (AHE) have scarcely been described. This study set out to assess if MH's occur in characteristic locations and frequency in patients with AHE superimposed on chronic liver failure, and to determine if such findings correlate with the clinical and MRI severity. MATERIALS AND METHODS: Over a 4.5-year period, AHE patients with SWI MRI were included. The maximum plasma ammonia level (PAL), number and location of "frank" hemorrhages (>5mm size) or MH's (<5mm) on SWI, and severity of DWI and FLAIR were recorded. Susceptibility foci in the basal ganglia were disregarded, as those changes might represent common mineralization. The presence of MH's was correlated with the MRI and clinical severity. RESULTS: Punctate MH foci were found in 18/38 (47.4%) patients. The most common locations were periventricular white matter (6/38 patients, 15.8%) and cerebral cortex (5/38, 13.2%). Of 47 MH's, only a tiny minority (8.5%) occurred in regions of abnormality on FLAIR or DWI. Both the MRI severity on FLAIR (r=0.420, p=0.013) and DWI (r=0.320, p=0.045) mildly correlated with clinical outcome, but the correlation was not significant after Bonferroni correction. No significant correlation was found between the number of MH's and the clinical score, clinical outcome, FLAIR severity, or DWI severity (range r=-0.083-0.152, p=0.363-0.618). The number of MH's was not significantly different among various vasculopathies. Foci on SWI improved in two patients following liver transplantation. CONCLUSION: SWI-positive foci outside of the basal ganglia (presumed MH's) are present in nearly half of AHE patients, but do not portend outcome. Regions with the most observed MH's were the periventricular white matter, cortical gray matter, and subcortical white matter.

Serial diffusion-weighted MR imaging and proton MR spectroscopy of acute large demyelinating brain lesions: case report.

We present the serial MR studies of two patients with symptomatic acute large demyelinating lesions that initially showed a drop in apparent diffusion coefficient values. Baseline proton MR spectroscopy showed a slight decrease in N-acetylaspartate and a normal choline level. An excess of lactate was observed at the first examinations and completely disappeared by the final examinations. The time-course evolution of the lesions shown by MR imaging and proton MR spectroscopic examinations suggests that the initial drop in apparent coefficient diffusion may have been related to dense inflammatory cell infiltration and scant tissue destruction or to reversible reduced vascular supply due to the severity of the inflammatory process.

Brain tumor classification by proton MR spectroscopy: comparison of diagnostic accuracy at short and long TE.

BACKGROUND AND PURPOSE: Different TE can be used for obtaining MR spectra of brain tumors. The purpose of this study was to determine the influence of the TE used in brain tumor classification by comparing the performance of spectra obtained at two different TE (30 ms and 136 ms). METHODS: One hundred fifty-one studies of patients with brain tumors (37 meningiomas, 12 low grade astrocytomas, 16 anaplastic astrocytomas, 54 glioblastomas, and 32 metastases) were retrospectively selected from a series of 378 consecutive examinations of brain masses. Single voxel proton MR spectroscopy at TE 30 ms and 136 ms was performed with point-resolved spectroscopy in all cases. Fitted areas of nine resonances of interest were normalized to water. Tumors were classified into four groups (meningioma, low grade astrocytoma, anaplastic astrocytoma, and glioblastoma-metastases) by means of linear discriminant analysis. The performance of linear discriminant analysis at each TE was assessed by using the leave-one-out method. RESULTS: Tumor classification was slightly better at short TE (123 [81%] of 151 cases correctly classified) than at long TE (118 [78%] of 151 cases correctly classified). Meningioma was the only group that showed higher sensitivity and specificity at long TE. Improved results were obtained when both TE were considered simultaneously: the suggested diagnosis was correct in 105 (94%) of 112 cases when both TE agreed, whereas the correct diagnosis was suggested by at least one TE in 136 (90%) of 151 cases. CONCLUSION: Short TE provides slightly better tumor classification, and results improve when both TE are considered simultaneously. Meningioma was the only tumor group in which long TE performed better than short TE.

Brain magnetic resonance in hepatic encephalopathy.

The term hepatic encephalopathy (HE) covers a wide spectrum of neuropsychiatric abnormalities caused by portal-systemic shunting. The diagnosis requires demonstration of liver dysfunction or portal-systemic shunts and exclusion of other neurologic disorders. Most patients with this condition have liver dysfunction caused by cirrhosis, but it also occurs in patients with acute liver failure and less commonly, in patients with portal-systemic shunts that are not associated with hepatocellular disease. Various magnetic resonance (MR) techniques have improved our knowledge about the pathophysiology of HE. Proton MR spectroscopy and T1-weighted imaging can detect and quantify accumulations of brain products that are normally metabolized or eliminated such as glutamine and manganese. Other MR techniques such as T2-weighted and diffusion-weighted imaging can identify white matter abnormalities resulting from disturbances in cell volume homeostasis secondary to brain hyperammonemia. Partial or complete recovery of these abnormalities has been observed with normalization of liver function or after successful liver transplantation. MR studies have undoubtedly improved our understanding of the mechanisms involved in the pathogenesis of HE, and some findings can be considered biomarkers for monitoring the effects of therapeutic measures focused on correcting this condition.

1H magnetic resonance spectroscopy in multiple sclerosis and related disorders.

Proton magnetic resonance spectroscopy ((1)H-MRS) is an unconventional technique that allows noninvasive characterization of metabolic abnormalities in the central nervous system. (1)H-MRS provides important insights into the chemical-pathologic changes that occur in patients with multiple sclerosis (MS). In this review article we present the main brain and spinal cord (1)H-MRS features in MS, their diagnostic value in differentiating pseudotumoral demyelinating lesions from primary brain tumors, and their relationship with clinical variables. Last, some data related to the use of (1)H-MRS in therapeutic trials is presented.

Magnetic resonance monitoring of lesion evolution in multiple sclerosis.

Disease activity in multiple sclerosis (MS) is strongly linked to the formation of new lesions, which involves a complex sequence of inflammatory, degenerative, and reparative processes. Conventional magnetic resonance imaging (MRI) techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences, are highly sensitive in demonstrating the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Hence, these techniques can provide quantitative assessment of disease activity in patients with MS, and they are commonly used in monitoring treatment efficacy in clinical trials and in individual cases. However, the correlation between conventional MRI measures of disease activity and the clinical manifestations of the disease, particularly irreversible disability, is weak. This has been explained by a process of exhaustion of both structural and functional redundancies that increasingly prevents repair and recovery, and by the fact that these imaging techniques do not suffice to explain the entire spectrum of the disease process and lesion development. Nonconventional MRI techniques, such as magnetization transfer imaging, diffusion-weighted imaging, and proton magnetic resonance spectroscopy, which can selectively measure the more destructive aspects of MS pathology and monitor the reparative mechanisms of this disease, are increasingly being used for serial analysis of new lesion formation and provide a better approximation of the pathological substrate of MS plaques. These nonconventional MRI-based measures better assess the serial changes in newly forming lesions and improve our understanding of the relationship between the damaging and reparative mechanisms that occur in MS.

Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy.

Brain magnetic resonance (MR) study has shown metabolic abnormalities and changes in water distribution of the brain tissue that may relate to the pathogenesis of hepatic encephalopathy (HE). We designed a study to investigate the disturbances in brain water and metabolites during episodic HE using a 3-T MR scanner. Cirrhotic patients with different grades of HE underwent MR during hospitalization (n=18). The MR was repeated at 6 weeks' follow-up (n=14). The results were compared with those of a group of healthy volunteers (n=8). During episodic HE, brain diffusion-weighted imaging showed a high apparent diffusion coefficient (ADC) (12% to 14%) that decreased during follow-up (-1% to -4%). These disturbances were accompanied by high glutamine (581%), low choline (-31%), and low myo-inositol (-86%) peaks on MR spectroscopy. In overt HE, patients showed high glutamine that decreased during follow-up (-22%). In addition, these patients exhibited a rise in plasma S100 beta and enlargement of brain white-matter lesions. In conclusion, several disturbances detected by MR support the presence of impaired brain water homeostasis during episodic HE. Although astrocytes have a major role in this condition, brain edema during episodic HE may be extracellular and does not appear to be directly responsible for the development of neurologic manifestations.

Reprint of: Neuroimaging in acute liver failure.

Acute liver failure (ALF) is frequently complicated by the development of brain edema that can lead to intracranial hypertension and severe brain injury. Neuroimaging techniques allow a none-invasive assessment of brain tissue and cerebral hemodynamics by means of transcranial Doppler ultrasonography, magnetic resonance and nuclear imaging with radioligands. These methods have been very helpful to unravel the pathogenesis of this process and have been applied to patients and experimental models. They allow monitoring the outcome of patients with ALF and neurological manifestations. The increase in brain water can be detected by observing changes in brain volume and disturbances in diffusion weighted imaging. Neurometabolic changes are detected by magnetic resonance spectroscopy, which provides a pattern of abnormalities characterized by an increase in glutamine and a decrease in myo-inositol. Disturbances in cerebral blood flow are depicted by SPECT or PET and can be monitored and the bedside by assessing the characteristics of the waveform provided by transcranial Doppler ultrasonography. Neuroimaging methods, which are rapidly evolving, will undoubtedly lead to future diagnostic and therapeutic progress that could be very helpful for patients with ALF.

Neuroimaging in acute liver failure.

Acute liver failure (ALF) is frequently complicated by the development of brain edema that can lead to intracranial hypertension and severe brain injury. Neuroimaging techniques allow a none-invasive assessment of brain tissue and cerebral hemodynamics by means of transcranial Doppler ultrasonography, magnetic resonance and nuclear imaging with radioligands. These methods have been very helpful to unravel the pathogenesis of this process and have been applied to patients and experimental models. They allow monitoring the outcome of patients with ALF and neurological manifestations. The increase in brain water can be detected by observing changes in brain volume and disturbances in diffusion weighted imaging. Neurometabolic changes are detected by magnetic resonance spectroscopy, which provides a pattern of abnormalities characterized by an increase in glutamine and a decrease in myo-inositol. Disturbances in cerebral blood flow are depicted by SPECT or PET and can be monitored and the bedside by assessing the characteristics of the waveform provided by transcranial Doppler ultrasonography. Neuroimaging methods, which are rapidly evolving, will undoubtedly lead to future diagnostic and therapeutic progress that could be very helpful for patients with ALF.

A long-term study of changes in the volume of brain ventricles and white matter lesions after successful liver transplantation.

BACKGROUND: A prolonged survival in liver transplant recipients due to a better management exposes them to multiple factors that can impair neurologic function in the long term. METHODS: Twenty-two patients were studied by brain magnetic resonance and completed a neuropsychologic assessment shortly before liver transplant, 6 to 12 months after (short term), and 6 to 9 years (long term) after liver transplant. Thirteen healthy controls matched by age were studied in parallel. RESULTS: An enlargement in the ventricular size (an indirect measure of brain volume) was observed in the short term (+8%) and in the long term after liver transplant (+22%); the size of ventricles was larger than in healthy controls. In addition, a progression in the volume of focal T2 white matter lesions (an index of small vessel cerebrovascular disease) was detected in the long term (+49%) and was related to vascular risk factors in those with larger increases (>12.5% per year). Neuropsychologic function showed a significant improvement after liver transplant and remained stable in the long term, except for memory loss in those patients with larger increases in white matter lesions. CONCLUSIONS: Improvement in neuropsychologic function after successful liver transplant can be demonstrated up to 9 years. However, these patients experience a progressive accumulation of focal T2 brain lesions and show a smaller brain volume than controls, which can be related to their previous cirrhosis. A good management to minimize brain injury before transplantation and an accurate treatment of vascular risk factors may be important to prevent consequences on cognitive function.

Noncirrhotic portal vein thrombosis exhibits neuropsychological and MR changes consistent with minimal hepatic encephalopathy.

Hepatic encephalopathy can arise from portal-systemic shunting in the absence of intrinsic liver disease. However, there are few descriptions of this form of encephalopathy. Portal vein thrombosis is an infrequent disease that causes portal-systemic shunting. Episodic hepatic encephalopathy has been described in patients with portal vein thrombosis, but it is not known if these patients develop minimal hepatic encephalopathy. We designed a study to investigate the neurological consequences of portal vein thrombosis in patients without cirrhosis and no clinical signs of encephalopathy. For this purpose, 10 patients underwent neuropsychological tests, an oral glutamine challenge test, and brain magnetic resonance (MR) imaging. The results were compared with those obtained in 10 healthy controls. Patients with portal vein thrombosis exhibited abnormalities in the results of neuropsychological tests, oral glutamine challenge test, and MR similar to those described in hepatic encephalopathy associated with cirrhosis. MR spectroscopy revealed a decrease in myo-inositol and an increase in glutamine. The increase in glutamine correlated with an increase in ammonia following the oral glutamine challenge test, signs of increased brain water (decrease in magnetization transfer ratio), and impairment of attention tests. In conclusion, patients with noncirrhotic portal vein thrombosis develop subclinical neurological abnormalities compatible with minimal hepatic encephalopathy. These disturbances, which include signs of increase in brain water and a compensatory osmotic response (decrease in brain myo-inositol), appear to be secondary to brain exposure to ammonia induced by portal-systemic shunting.