Michael A. Thomas

Encephalopathy assessment in children with extra-hepatic portal vein obstruction with MR, psychometry and critical flicker frequency

BACKGROUND & AIMS Mild cognitive and psychomotor deficit has been reported in patients with extra-hepatic portal vein obstruction. This prospective study was done to ascertain the presence of minimal hepatic encephalopathy by neuropsychological testing and its correlation with diffusion tensor imaging derived metrics, T1 signal intensity, brain metabolites in (1)H magnetic resonance spectroscopy, blood ammonia and critical flicker frequency in patients with extra-hepatic portal vein obstruction. METHODS Neuropsychological tests, critical flicker frequency, blood ammonia, diffusion tensor imaging, T1 signal intensity and (1)H magnetic resonance spectroscopy were determined in 22 extra-hepatic portal vein obstruction and 17 healthy children. Bonferroni multiple comparison post hoc analysis was done to compare controls with patient groups. RESULTS Based on neuropsychological tests, 7/22 patients had minimal hepatic encephalopathy, and significantly increased Glx/Cr ratio, blood ammonia, mean diffusivity and globus pallidus T1 signal intensity with decreased critical flicker frequency in comparison to controls and in those without minimal hepatic encephalopathy. Cho/Cr, mI/Cr ratio and fractional anisotropy were unchanged in patient groups compared to controls. A significant inverse correlation of neuropsychological test with mean diffusivity, Glx/Cr ratio and blood ammonia and a positive correlation among mean diffusivity, blood ammonia and Glx/Cr ratio was seen. CONCLUSIONS Extra-hepatic portal vein obstruction is a true hyperammonia model with porto-systemic shunting and normal liver functions that results in minimal hepatic encephalopathy in one-third of these children. Hyperammonia results in generalized low grade cerebral edema and cognitive decline as evidenced by increased Glx/Cr ratio, mean diffusivity values and abnormal neuropsychological tests.

Quantification of cerebral edema on diffusion tensor imaging in acute-on-chronic liver failure.

Cerebral edema is a major complication of acute liver failure but may also be seen in other forms of liver failure such as acute‐on‐chronic liver failure (ACLF) and chronic liver failure (CLF). ACLF develops in patients with previously well‐compensated chronic liver disease following acute hepatitis A or E superimposed on underlying liver cirrhosis. The aim of this study was to detect the occurrence, and determine the nature, of cerebral edema in patients with the defined subset of ACLF using diffusion tensor imaging (DTI) metrics. Twenty‐three patients with ACLF were studied and compared with 15 healthy controls and 15 patients with CLF. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), linear anisotropy (CL), planar anisotropy (CP), and spherical isotropy (CS) were calculated by selecting regions of interest in the white matter and deep grey matter of the brain. Significantly decreased FA and increased CS were observed in the anterior limb (ALIC) and posterior limb (PLIC) of the internal capsule and frontal white matter (P < 0.05) in patients with different grades (1–4) of ACLF when compared with healthy controls. No significant changes in MD and CP were seen in any brain region. However, significantly decreased CL was observed in the PLIC, caudate nuclei and putamen. In patients with CLF, significantly decreased FA with increased CS in the ALIC and PLIC along with significantly increased MD in the ALIC and caudate nuclei were observed. The presence of significantly decreased FA and CL and increased CS along with no significant change in MD and CP suggests the presence of both intracellular and extracellular components of cerebral edema in patients with ACLF. Copyright

Effect of surgical portosystemic shunt on prevalence of minimal hepatic encephalopathy in children with extrahepatic portal venous obstruction: assessment by magnetic resonance imaging and psychometry.

Objective: The aim of this study was to evaluate the effect of surgical portosystemic shunt (PSS) on the prevalence of minimal hepatic encephalopathy (MHE) in patients with extrahepatic portal venous obstruction. Patients and Methods: Forty-two children with extrahepatic portal venous obstruction (17 with surgical PSS, 25 without surgical shunt) and 20 healthy children were evaluated with blood ammonia (BA), psychometry, 1H magnetic resonance spectroscopy, critical flicker frequency (CFF), and diffusion tensor imaging. Serum tumor necrosis factor-α and interleukin-6 were measured in 10 patients and 8 controls. Results: Patients with surgical PSS had significantly higher BA and glutamine/creatine on 1H-MR spectroscopy than those without surgical shunt. Both groups of patients had significantly higher BA and glutamate/creatine than controls. Myoinositol was reduced in patients with surgical PSS. MHE was present in 41% cases with and 32% cases without surgical PSS (p-ns). Raised mean diffusivity on diffusion tensor imaging signifying low-grade cerebral edema was seen only in MHE cases. Patients had significantly higher serum tumor necrosis factor-α and interleukin-6 levels than controls. CFF was abnormal in 5 of 15 patients with MHE. Conclusions: Patients with surgical PSS have significantly higher BA and Glx/creatine than those without surgical PSS. MHE prevalence was higher in surgically shunted than in the nonshunted patients, but the difference was not significant. Cerebral edema is present in patients with MHE. CFF has limited diagnostic utility for MHE in children.

Accelerated five-dimensional echo planar J-resolved spectroscopic imaging: Implementation and pilot validation in human brain

To implement an accelerated five‐dimensional (5D) echo‐planar J‐resolved spectroscopic imaging sequence combining 3 spatial and 2 spectral encoding dimensions and to apply the sequence in human brain.

Serum proinflammatory cytokines correlate with diffusion tensor imaging derived metrics and 1H-MR spectroscopy in patients with acute liver failure

Hyperammonemia and inflammation are major contributing factors in the development of cerebral edema (CE) in acute liver failure (ALF). Aim of this study was to look for the relationship between proinflammatory cytokines with diffusion tensor imaging (DTI) derived metrics and 1H-MR spectroscopy (1H-MRS) derived Glutamate/Glutamine (Glx). Fourteen patients with ALF and 14 age/sex matched controls were included in this study. All subjects had undergone clinical, biochemical, MR imaging and 1H-MRS studies. Serum proinflammatory cytokines (IL-6 and TNF-α), blood ammonia level and Glx were computed for independent t-test and Pearson correlation. Serum proinflammatory cytokines, blood ammonia level and brain Glx were significantly increased in ALF patients as compared to controls. Blood ammonia level and Glx showed significant positive correlation with proinflammatory cytokines. Spectroscopy voxel derived spherical anisotropy (CS) showed positive correlation with Glx while mean diffusivity (MD) showed negative correlation. Proinflammatory cytokines showed positive correlation with CS and negative correlation with MD in various brain regions including spectroscopy voxel. Significant correlation of Glx, CS and MD with proinflammatory cytokines suggests that both DTI derived metrics and 1H-MRS measure the synergistic effect of hyperammonemia and proinflammatory cytokines and may be used as non-invasive tools for understanding the pathogenesis of CE in ALF.

Pro-inflammatory cytokines are raised in extrahepatic portal venous obstruction, with minimal hepatic encephalopathy

Background and Aims:  Minimal hepatic encephalopathy (MHE) and hyperammonemia are seen in patients with extrahepatic portal venous obstruction (EHPVO). Inflammation has been shown to play an important role in the pathogenesis of hepatic encephalopathy in cirrhotics. This study assessed serum pro‐inflammatory cytokines and their correlation with hyperammonemia, 1H‐magnetic resonance (MR) spectroscopy‐derived brain glutamine, and diffusion tensor imaging (DTI)‐derived metrics in patients with EPHVO, with and without MHE.

Brain MR Imaging and 1H-MR Spectroscopy Changes in Patients with Extrahepatic Portal Vein Obstruction from Early Childhood to Adulthood

BACKGROUND AND PURPOSE: MR imaging and 1H-MR spectroscopy changes are well reported in cirrhotic patients, whereas they are inadequately reported in EHPVO. The aim of this study was to investigate age-related changes in brain MR imaging and metabolite profile in EHPVO with and without MHE and to explore any correlation of imaging and 1H-MR spectroscopy parameters with blood ammonia. MATERIALS AND METHODS: Sixty-three patients with EHPVO (children, 7–12 years [n = 22], adolescents, 13–18 years [n = 15] and adults, 19–41 years [n = 26]) and 47 healthy age/sex-matched volunteers were studied. Neuropsychological tests, MR imaging, 1H-MR spectroscopy, and blood ammonia estimation were performed in all subjects. RESULTS: Of 63 EHPVO patients, 25 (40%) who had MHE showed significantly increased MD, Glx, and blood ammonia in all 3 age groups; however, myo-inositol was significantly lower only in adults when compared with controls. MD positively correlated with blood ammonia and Glx in all age groups. Brain choline levels were normal in all patients with different age groups. CONCLUSIONS: Increases in brain MD, Glx, and blood ammonia were associated with MHE in all age groups. Normal brain choline in EHPVO signifies healthy liver and may serve as a diagnostic marker for its differentiation from cirrhosis-induced encephalopathy. Significant decrease of myo-inositol in adults is probably due to cellular osmoregulation secondary to long-standing hyperammonemia.

Serial evaluation of children with ALF with advanced MRI, serum proinflammatory cytokines, thiamine, and cognition assessment.

Objectives: This prospective, sequential study was done to understand changes in cerebral edema (CE) on magnetic resonance imaging and magnetic resonance spectroscopy, liver functions, and neurocognitive testing (NCT) in children with acute liver failure (ALF). Methods: A total of 11 ALF and 8 healthy controls were evaluated with advanced magnetic resonance (MR) imaging, blood proinflammatory cytokines (PCs), thiamine levels, liver functions, and NCT. Reevaluation was done at 43.5 ± 26.9 days (first follow-up, n = 8) and 157.3 ± 52.3 days (second follow-up, n = 6) after discharge. Results: At diagnosis, patients with ALF had vasogenic and cytotoxic CE, raised brain glutamine (23.2 ± 3.4 vs 15.3 ± 2.7), and serum PCs (tumor necrosis factor [TNF]-&agr; 40.1 ± 8.9 vs 7.2 ± 2.7 pg/mL, interleukin [IL]-6 29.2 ± 14.4 vs 4.7 ± 1.2 pg/mL). The mammillary bodies (MBs) were smaller, and brain choline (1.9 ± 0.36 vs 2.6 ± 0.6) and blood thiamine (55.2 ± 6.7 vs 81.8 ± 10.2 nmol/L) were lower than controls. At first follow-up, the brain glutamine and CE recovered. Brain choline and MBs volume showed improvement and thiamine levels normalized. Significant reduction in TNF-&agr; and IL-6 was seen. The patients performed poorly on NCT, which normalized at second follow-up. Liver biochemistry and thiamine levels were normal and TNF-&agr; and IL-6 showed further reduction at second follow-up. Conclusions: Patients with ALF have CE contributed by raised brain glutamine and PCs. MBs are small because of thiamine deficiency and show recovery in follow-up. CE and brain glutamine recover earlier than normalization of NCT and liver functions. Persistence of raised cytokines up to 6 months after insult suggests possible contribution from liver regeneration.

Non-water-suppressed short-echo-time magnetic resonance spectroscopic imaging using a concentric ring k-space trajectory.

Water‐suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non‐water‐suppressed MRS spectrum is used for artefact correction, reconstruction of phased‐array coil data and metabolite quantification. Here, a two‐scan metabolite‐cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short‐echo (TE = 14 ms), two‐dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite‐cycling is counterbalanced by a time‐efficient concentric ring k‐space trajectory. To validate the technique, water‐suppressed MRSI acquisitions were also performed for comparison. The proposed non‐water‐suppressed metabolite‐cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high‐resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non‐water‐suppressed and water‐suppressed techniques. The achieved spectral quality, signal‐to‐noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in‐plane resolution of 10 × 10 mm2 in 8 min and with a Cramér‐Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non‐water‐suppressed technique enabled voxel‐wise single‐scan frequency, phase and eddy current correction. These findings demonstrate that our non‐water‐suppressed metabolite‐cycling MRSI technique can perform robustly on 3 T MRI systems and within a clinically feasible acquisition time.

Accelerated echo planar J-resolved spectroscopic imaging in prostate cancer: a pilot validation of non-linear reconstruction using total variation and maximum entropy

The overlap of metabolites is a major limitation in one‐dimensional (1D) spectral‐based single‐voxel MRS and multivoxel‐based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two‐dimensional (2D) J‐resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four‐dimensional (4D) echo planar J‐resolved spectroscopic imaging (EP‐JRESI). The goal of the present work was to validate two different non‐linear reconstruction methods independently using compressed sensing‐based 4D EP‐JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty‐two patients with PCa with a mean age of 63.8 years (range, 46–79 years) were investigated in this study. A 4D non‐uniformly undersampled (NUS) EP‐JRESI sequence was implemented on a Siemens 3‐T MRI scanner. The NUS data were reconstructed using two non‐linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non‐cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo‐inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP‐JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites. Copyright