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

Abstract

Purpose: 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. Materials and Methods: 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. Results: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. LOW-GRADE CEREBRAL EDEMA is considered to be responsible for the neuropsychological abnormalities in cirrhotic patients with chronic hepatic encephalopathy (HE) (1). The brain water changes result in enlargement of astrocytes, a feature interpreted differently by various groups using electron microscopy. Kimelberg (2) described these changes as astrogliosis due to astrocyte hypertrophy resulting in increased cell size without an increase in intracellular water; others have interpreted these changes as astrocyte swelling (1). The changes in the astrocyte are brought about by the chronic hyperammonemia in patients with HE. ConclusionHE is potentially reversible at each stage, provided the precipitating factors responsible for this condition are eliminated. Low-grade HE is associated with poor quality of life and increased work disability; both improve after hepatic transplantation. Patients with HE may appear overtly normal because mental changes are slight and do not necessarily affect their basic life activities. However, neurocognitive changes in patients with HE are observable with testing and include executive dysfunction, reduced psychomotor speed and attention, with a relative sparing of short-term, delayed, and procedural memories that could affect daily routine activities (3).A majority of patients with HE show no visible abnormalities on conventional magnetic resonance imaging (MRI), except for hyperintensities on T 1 -weighted images in the deep gray matter due to the deposition of manganese in varying proportions (4). Currently, a number of MR techniques are available to quantify brain water noninvasively including proton MR spectroscopy (5-7), magnetization transfer (MT) (8), diffusion-weighted imaging (DWI) (9,10), diffusion tensor imaging (DTI) (11), and T 1 -weighted imaging (12). Results from these techniques suggest that increased brain water content correlates with some neuropsycho-

Measuring Myelin Repair and Axonal Loss with Diffusion Tensor Imaging

“…Cerebral edema from hepatic encephalopathy is associated with increased MD and variable changes in FA. 21,22 After lactulose therapy for hepatic encephalopathy, MD decreased while FA did not change. 22 Peritumoral edema shows both a decrease in FA and an increase in apparent diffusion coefficient (which is comparable with MD).…”

Identification of Minimal Hepatic Encephalopathy in Patients with Cirrhosis Based on White Matter Imaging and Bayesian Data Mining

“…16 In addition, positron-emission tomography studies have indicated that an altered glial cell state, an important cause of MHE, occurs in the frontal WM and in the corpus callosum. 36 The frontal and parietal WM and corpus callosum (particularly the anterior part) are the regions most commonly reported to demonstrate increased water content 11 or diffusivity 9,10,12,15,16 and decreased FA. 15 When patients with cirrhosis in the intermediate state are excluded, Sugimoto et al 16 reported 70%-90% sensitivity and 85%-90% specificity in classification of MHE and NHE, based on a frontal or parietal WM ADC metric.…”

“…One limitation of our study is that we confined our analysis to WM regions, where brain edema predominantly occurs in MHE 11,15 ; however, several studies have indicated that other cerebral regions, such as subcortical nuclei, 9,10 may also manifest low-grade edema. The second limitation is that we used a suboptimal DTI sequence with 6 diffusion-encoding gradient directions, due to the finite capability of our MR imaging scanner.…”

“…These WM abnormalities are believed to be responsible for poor neurologic performances 12,15,16 and brain dysfunctions 17,18 in MHE and to be associated with HE development, 9,11,16 suggesting that WM imaging may be useful in characterizing potential MHE biomarkers. Of WM imaging techniques, diffusion tensor imaging, measuring the appropriate metrics such as mean diffusivity (MD), reflecting water movement across cell membranes, and fractional anisotropy (FA), reflecting microstructural in-tegrity of WM, is demonstrated to reveal the neuropathologic processes of MHE through group-level comparison.…”

“…Of WM imaging techniques, diffusion tensor imaging, measuring the appropriate metrics such as mean diffusivity (MD), reflecting water movement across cell membranes, and fractional anisotropy (FA), reflecting microstructural in-tegrity of WM, is demonstrated to reveal the neuropathologic processes of MHE through group-level comparison. 8,9,12,14,15,17 To date, however, there is no study using DTI-derived feature maps to discriminate patients with and without MHE in cirrhosis at the individual level; this discrimination remains an important question for clinicians. 6,19 The only related study is the report of Sugimoto et al, 16 which used a DWI-based metric (apparent diffusion coefficient) instead of DTI to classify patients with or without MHE, but in which patients in the intermediate state were excluded; this method obviously results in inadequate assessment.…”