Juli Alonso

MR Imaging Findings in Hepatic Encephalopathy

SUMMARY: The term hepatic encephalopathy (HE) includes a spectrum of neuropsychiatric abnormalities occurring in patients with liver dysfunction. Most cases are associated with cirrhosis and portal hypertension or portal-systemic shunts, but the condition can also be seen in patients with acute liver failure and, rarely, with portal-systemic bypass and no associated intrinsic hepatocellular disease. Although HE is a clinical condition, several neuroimaging techniques, particularly MR imaging, may eventually be useful for the diagnosis because they can identify and measure the consequences of central nervous system (CNS) increase in substances that under normal circumstances, are efficiently metabolized by the liver. Classic MR imaging abnormalities include high signal intensity in the globus pallidum on T1-weighted images, likely a reflection of increased tissue concentrations of manganese, and an elevated glutamine/glutamate peak coupled with decreased myo-inositol and choline signals on proton MR spectroscopy, representing disturbances in cell-volume homeostasis secondary to brain hyperammonemia. Recent data have shown that white matter abnormalities, also related to increased CNS ammonia concentration, can also be detected with several MR imaging techniques such as magnetization transfer ratio measurements, fast fluid-attenuated inversion recovery sequences, and diffusion-weighted images. All these MR imaging abnormalities, which return to normal with restoration of liver function, probably reflect the presence of mild diffuse brain edema, which seems to play an essential role in the pathogenesis of HE. It is likely that MR imaging will be increasingly used to evaluate the mechanisms involved in the pathogenesis of HE and to assess the effects of therapeutic measures focused on correcting brain edema in these patients.

The development of low-grade cerebral edema in cirrhosis is supported by the evolution of 1H-magnetic resonance abnormalities after liver transplantation

BACKGROUND/AIMS Liver failure may cause brain edema through an increase in brain glutamine. However, usually standard neuroimaging techniques do not detect brain edema in cirrhosis. We assessed magnetization transfer ratio and (1)H-magnetic resonance (MR) spectroscopy before and after liver transplantation to investigate changes in brain water content in cirrhosis. METHODS Non-alcoholic cirrhotics without overt hepatic encephalopathy (n=24) underwent (1)H-MR of the brain and neuropsychological tests. (1)H-MR results were compared with those of healthy controls (n=10). In a subgroup of patients (n=11), the study was repeated after liver transplantation. RESULTS Cirrhotic patients showed a decrease in magnetization transfer ratio (31.5+/-3.1 vs. 37.1+/-1.1, P<0.01) and an increase in glutamine/glutamate signal (2.22+/-0.47 vs. 1.46+/-0.26, P<0.01). The increase in glutamine/glutamate signal was correlated to the decrease in magnetization transfer ratio and to neuropsychological function. Following liver transplantation, there was a progressive normalization of magnetization transfer ratio, glutamine/glutamate signal and neuropsychological function. Accordingly, correlations between these variables were lost after liver transplantation. CONCLUSIONS Cirrhotic patients show reversible changes in magnetization transfer ratio that are compatible with the development of low-grade cerebral edema. Minimal hepatic encephalopathy and low-grade cerebral edema appear to be the consequences of the metabolism of ammonia in the brain.

Towards a method for automated classification of 1H MRS spectra from brain tumours

Recent studies have shown that MRS can substantially improve the non‐invasive categorization of human brain tumours. However, in order for MRS to be used routinely by clinicians, it will be necessary to develop reliable automated classification methods that can be fully validated. This paper is in two parts: the first part reviews the progress that has been made towards this goal, together with the problems that are involved in the design of automated methods to process and classify the spectra. The second part describes the development of a simple prototype system for classifying 1H single voxel spectra, obtained at an echo time (TE) of 135 ms, of the four most common types of brain tumour (meningioma (MM), astrocytic (AST), oligodendroglioma (OD) and metastasis (ME)) and cysts. This system was developed in two stages: firstly, an initial database of spectra was used to develop a prototype classifier, based on a linear discriminant analysis (LDA) of selected data points. Secondly, this classifier was tested on an independent test set of 15 newly acquired spectra, and the system was refined on the basis of these results. The system correctly classified all the non‐astrocytic tumours. However, the results for the the astrocytic group were poorer (between 55 and 100%, depending on the binary comparison). Approximately 50% of high grade astrocytoma (glioblastoma) spectra in our data base showed very little lipid signal, which may account for thepoorer results for this class. Consequently, for the refined system, the astrocytomas were subdivided into two subgroups for comparison against other tumour classes: those with high lipid content and those without.

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. (HEPATOLOGY 2006;43:707–714.)

1H Magnetic Resonance in the Study of Hepatic Encephalopathy in Humans

Abstract1H magnetic resonance (1H MR) studies of the brain in patients with liver diseases have shown several abnormalities that may be relevant for the pathogenesis of hepatic encephalopathy. 1H magnetic resonance imaging shows a typical pallidal hyperintensity on T1-weighted images. This abnormality appears to be secondary to the accumulation of manganese in basal ganglia because of portal-systemic shunting. No direct correlation between the magnitude of pallidal hyperintensity and the grade of hepatic encephalopathy has been found, but some studies have related pallidal hyperintensity to parkinsonism. 1H magnetic resonance spectroscopy shows relative to creatine an increase in glutamine/glutamate (Glx) signal and a decrease of choline containing compounds (Cho) and myo-inositol. Abnormalities in the Glx signal have been interpreted as an increase in brain glutamine secondary to the metabolism of ammonia in astrocytes. Disturbances of Cho and myo-inositol have been interpreted as a compensatory response to the increase in intracellular osmolality caused by the accumulation of glutamine in astrocytes. In addition, magnetization transfer imaging shows signs compatible with low-grade cerebral edema. Altogether, 1H MR studies suggest the accumulation of manganese and the development of osmotic abnormalities in the brain of patients with cirrhosis. These abnormalities appear to participate in some of the neurological manifestations of hepatic encephalopathy.

Proton MR Spectroscopy Improves Discrimination between Tumor and Pseudotumoral Lesion in Solid Brain Masses

BACKGROUND AND PURPOSE: Differentiating between tumors and pseudotumoral lesions by conventional MR imaging may be a challenging question. This study aims to evaluate the potential usefulness and the added value that single-voxel proton MR spectroscopy could provide on this discrimination. MATERIALS AND METHODS: A total of 84 solid brain lesions were retrospectively included in the study (68 glial tumors and 16 pseudotumoral lesions). Single-voxel spectra at TE 30 ms (short TE) and 136 ms (long TE) were available in all cases. Two groups were defined: “training-set” (56 cases) and “test-set” (28 cases). Tumors and pseudotumors were compared in the training-set with the Mann-Whitney U test. Ratios between resonances were defined as classifiers for new cases, and thresholds were selected with receiver operating characteristic (ROC) curves. The added value of spectroscopy was evaluated by 5 neuroradiologists and assessed with the Wilcoxon signed-rank test. RESULTS: Differences between tumors and pseudotumors were found in myo-inositol (mIns); P < .01) at short TE, and N-acetylaspartate (NAA; P < .001), glutamine (Glx; P < .01), and choline (CHO; P < .05) at long TE. Classifiers suggested tumor when mIns/NAA ratio was more than 0.9 at short TE and also when CHO/NAA ratio was more than 1.9 at long TE. Classifier accuracy was tested in the test-set with the following results: short TE, 82% (23/28); long TE, 79% (22/28). The neuroradiologists’ confidence rating of the test-cases on a 5-point scale (0–4) improved between 5% (from 2.86–3) and 27% (from 2.25–2.86) with spectroscopy (mean, 17%; P < .01). CONCLUSIONS: The proposed ratios of mIns/NAA at short TE and CHO/NAA at long TE provide valuable information to discriminate between brain tumor and pseudotumor by improving neuroradiologists’ accuracy and confidence.

The basal ganglia: a substrate for fatigue in multiple sclerosis

IntroductionThe origin of fatigue in multiple sclerosis (MS) remains uncertain. However, the use of nonconventional magnetic resonance techniques has increased our understanding of this problem. We aimed to study the relationship between fatigue in MS and the presence of focal dysfunction in the basal ganglia and frontal white matter.MethodsIncluded in the study were 41 patients with relapsing–remitting MS with mild disability and 20 healthy controls. Fatigue was assessed by the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Patients were classified as “fatigued” when they expressed a subjective feeling of fatigue, and the FSS score was ≥5.0 and/or the MFIS score was >38. Patients with no subjective fatigue were classified as “nonfatigued” when the FSS score was <4.0. Proton magnetic resonance spectra were obtained from two different regions: the frontal white matter and the lentiform nucleus. The relationships between fatigue and NAA/Cr, NAA/Cho and Cho/Cr ratios were analysed.ResultsA significant decrease in NAA/Cr in the lentiform nucleus region in patients with fatigue was observed. No differences between the groups were found in the frontal white matter.ConclusionAlthough confirmatory studies are needed, our results would support the idea that a specific dysfunction or involvement of the basal ganglia might partly contribute to the development of MS-related fatigue.

Decreased White Matter Lesion Volume and Improved Cognitive Function After Liver Transplantation

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 cm3 to 0.671 cm3, 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. (HEPATOLOGY 2007.)

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.

Decrease in the Volume of White Matter Lesions with Improvement of Hepatic Encephalopathy

SUMMARY: MR imaging has found abnormalities compatible with low-grade edema in the brain of patients with cirrhosis that have been related to hepatic encephalopathy. We present 3 patients with hepatic encephalopathy who exhibit supratentorial focal or diffuse white matter lesions compatible with small-vessel brain disease. The volume and number of white matter lesions reduced with the improvement of hepatic encephalopathy, suggesting the participation of the blood-brain barrier in the pathogenesis of brain edema in hepatic encephalopathy.