Sudhakar K. Venkatesh

Magnetic Resonance Elastography of Liver: Technique, Analysis and Clinical Applications

Many pathological processes cause marked changes in the mechanical properties of tissue. MR elastography (MRE) is a noninvasive MRI based technique for quantitatively assessing the mechanical properties of tissues in vivo. MRE is performed by using a vibration source to generate low frequency mechanical waves in tissue, imaging the propagating waves using a phase contrast MRI technique, and then processing the wave information to generate quantitative images showing mechanical properties such as tissue stiffness. Since its first description in 1995, published studies have explored many potential clinical applications including brain, thyroid, lung, heart, breast, and skeletal muscle imaging. However, the best‐documented application to emerge has been the use of MRE to assess liver disease. Multiple studies have demonstrated that there is a strong correlation between MRE‐measured hepatic stiffness and the stage of fibrosis at histology. The emerging literature indicates that MRE can serve as a safer, less expensive, and potentially more accurate alternative to invasive liver biopsy which is currently the gold standard for diagnosis and staging of liver fibrosis. This review describes the basic principles, technique of performing a liver MRE, analysis and calculation of stiffness, clinical applications, limitations, and potential future applications. J. Magn. Reson. Imaging 2013;37:544–555.

MR Elastography of Liver Tumors: Preliminary Results

OBJECTIVE The purpose of this study was to evaluate the potential value of MR elastography (MRE) in the characterization of solid liver tumors. MATERIALS AND METHODS Forty-four liver tumors (14 metastatic lesions, 12 hepatocellular carcinomas, nine hemangiomas, five cholangiocarcinomas, three cases of focal nodular hyperplasia, and one hepatic adenoma) were evaluated with MRE. MRE was performed with a 1.5-T system with a modified phase-contrast gradient-echo sequence to collect axial wave images sensitized along the through-plane motion direction. The tumors were identified on T2- and T1-weighted and gadolinium-enhanced T1-weighted images, and the MRE images were obtained through the tumor. A stiffness map (elastogram) was generated in an automated process consisting of an inversion algorithm. The mean shear stiffness of the tumor was calculated with a manually specified region of interest over the tumor in the stiffness map. The stiffness value of tumor-free hepatic parenchyma was calculated. Statistical analysis was performed on the stiffness values for differentiation of normal liver, fibrotic liver, benign tumors, and malignant tumors. RESULTS Malignant liver tumors had significantly greater mean shear stiffness than benign tumors (10.1 kPa vs 2.7 kPa, p < 0.001), fibrotic liver (10.1 kPa vs 5.9 kPa, p < 0.001), and normal liver (10.1 kPa vs 2.3 kPa, p < 0.001). Fibrotic livers had stiffness values overlapping both the benign and the malignant tumors. A cutoff value of 5 kPa accurately differentiated malignant tumors from benign tumors and normal liver parenchyma in this preliminary investigation. CONCLUSION MR elastography is a promising noninvasive technique for assessing solid liver tumors. Use of MRE may lead to new quantitative tissue characterization parameters for differentiating benign and malignant liver tumors.

Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: a systematic review and meta-analysis of individual participant data.

BACKGROUND & AIMS Magnetic resonance elastography (MRE) is a noninvasive tool for staging liver fibrosis. We conducted a meta-analysis of individual participant data collected from published studies to assess the diagnostic accuracy of MRE for staging liver fibrosis in patients with chronic liver diseases (CLD). METHODS Through a systematic literature search of multiple databases (2003-2013), we identified studies on diagnostic performance of MRE for staging liver fibrosis in patients with CLD with native anatomy, using liver biopsy as the standard. We contacted study authors to collect data on each participants age, sex, body mass index (BMI), liver stiffness (measured by MRE), fibrosis stage, staging system used, degree of inflammation, etiology of CLD, and interval between MRE and biopsy. Through a pooled analysis, we calculated cluster-adjusted area under the receiver-operating curve, sensitivity, and specificity of MRE for any fibrosis (≥stage 1), significant fibrosis (≥stage 2), advanced fibrosis (≥stage 3), and cirrhosis (stage 4). RESULTS We analyzed data from 12 retrospective studies, comprising 697 patients (mean age, 55 ± 13 y; 59.4% male; mean BMI, 26.9 ± 6.7 kg/m(2); 92.1% with <1 year interval between MRE and biopsy; and 47.1% with hepatitis C). Overall, 19.5%, 19.4%, 15.5%, 15.9%, and 29.7% patients had stage 0, 1, 2, 3, and 4 fibrosis, respectively. The mean area under the receiver-operating curve values (and 95% confidence intervals) for the diagnosis of any (≥stage 1), significant (≥stage 2), advanced fibrosis (≥stage 3), and cirrhosis, were as follows: 0.84 (0.76-0.92), 0.88 (0.84-0.91), 0.93 (0.90-0.95), and 0.92 (0.90-0.94), respectively. A similar diagnostic performance was observed in stratified analysis based on sex, obesity, and etiology of CLD. The overall rate of failure of MRE was 4.3%. CONCLUSIONS Based on a pooled analysis of data from individual participants, MRE has a high accuracy for the diagnosis of significant or advanced fibrosis and cirrhosis, independent of BMI and etiology of CLD. Prospective studies are warranted to better understand the diagnostic performance of MRE.

Feasibility of In Vivo MR Elastographic Splenic Stiffness Measurements in the Assessment of Portal Hypertension

OBJECTIVE Liver stiffness is associated with portal hypertension in patients with chronic liver disease. However, the relation between spleen stiffness and clinically significant portal hypertension remains unknown. The purposes of this study were to determine the feasibility of measuring spleen stiffness with MR elastography and to prospectively test the technique in healthy volunteers and in patients with compensated liver disease. MATERIALS AND METHODS Spleen stiffness was measured with MR elastography in 12 healthy volunteers (mean age, 37 years; range, 25-82 years) and 38 patients (mean age, 56 years; range, 36-60 years) with chronic liver disease of various causes. For patients with liver disease, laboratory findings, spleen size, presence and size of esophageal varices, and liver histologic results were recorded. Statistical analyses were performed to assess all measurements. RESULTS MR elastography of the spleen was successfully performed on all volunteers and patients. The mean spleen stiffness was significantly lower in the volunteers (mean, 3.6 +/- 0.3 kPa) than in the patients with liver fibrosis (mean, 5.6 +/- 5.0 kPa; range, 2.7-19.2 kPa; p < 0.001). In addition, a significant correlation was observed between liver stiffness and spleen stiffness for the entire cohort (r(2) = 0.75; p < 0.001). Predictors of spleen stiffness were splenomegaly, spleen volume, and platelet count. A mean spleen stiffness of 10.5 kPa or greater was identified in all patients with esophageal varices. CONCLUSION MR elastography of the spleen is feasible and shows promise as a quantitative method for predicting the presence of esophageal varices in patients with advanced hepatic fibrosis.

Dynamic Postprandial Hepatic Stiffness Augmentation Assessed With MR Elastography in Patients With Chronic Liver Disease

OBJECTIVE MR elastography (MRE) is an MRI-based technique for quantitatively assessing tissue stiffness by studying shear wave propagation through tissue. The goal of this study was to test the hypothesis that hepatic MRE performed before and after a meal will result in a postprandial increase in hepatic stiffness among patients with hepatic fibrosis because of transiently increased portal pressure. SUBJECTS AND METHODS Twenty healthy volunteers and 25 patients with biopsyproven hepatic fibrosis were evaluated. Preprandial MRE measurements were performed after overnight fasting. A liquid test meal was administered, and 30 minutes later a postprandial MRE acquisition was performed. Identical imaging parameters and analysis regions of interest were used for pre- and postprandial acquisitions. RESULTS The results in the 20 subjects without liver disease showed a mean stiffness change of 0.16 ± 0.20 kPa (range, -0.12 to 0.78 kPa) or 8.08% ± 10.33% (range, -5.36% to 41.7%). The hepatic stiffness obtained in the 25 patients with hepatic fibrosis showed a statistically significant increase in postprandial liver stiffness, with mean augmentation of 0.89 ± 0.96 kPa (range, 0.17-4.15 kPa) or 21.24% ± 14.98% (range, 7.69%-63.3%). CONCLUSION MRE-assessed hepatic stiffness elevation in patients with chronic liver disease has two major components: a static component reflecting structural change or fibrosis and a dynamic component reflecting portal pressure that can increase after a meal. These findings will provide motivation for further studies to determine the potential value of assessing postprandial hepatic stiffness augmentation for predicting the progression of fibrotic disease and the development of portal hypertension. The technique may also provide new insights into the natural history and pathophysiology of chronic liver disease.

Spectroscopic increase in choline signal is a nonspecific marker for differentiation of infective/inflammatory from neoplastic lesions of the brain

We report in vivo proton magnetic resonance (MR) spectroscopic findings in three benign infective/inflammatory lesions (one case each of tuberculoma, fungal granuloma, and xanthogranuloma), which showed high choline along with the presence of lipid/lactate, a feature characteristically described in neoplastic lesions. Histopathology of the lesions showed inflammatory cellular infiltrates with areas of necrosis/caseation. The spectroscopic‐visible increased choline resonance in these lesions is probably the result of cellularity. We conclude that increased choline, along with the presence of lipid/lactate is a nonspecific finding and may not be of much value in the differentiation of neoplastic from nonneoplastic infective/inflammatory intracranial mass lesions. J. Magn. Reson. Imaging 2001;14:8–15.

Imaging of hepatocellular carcinoma: diagnosis, staging and treatment monitoring.

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Imaging is important for establishing a diagnosis of HCC. Several imaging modalities including ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and angiography are used in evaluating patients with chronic liver disease and suspected HCC. CT, MRI and contrast-enhanced US have replaced biopsy for diagnosis of HCC. Dynamic multiphase contrast-enhanced CT or MRI is the current standard for imaging diagnosis of HCC. Functional imaging techniques such as perfusion CT and diffusion-weighted MRI provide additional information about tumor angiogenesis that may be useful for treatment. Techniques evaluating tissue mechanical properties such as magnetic resonance elastography, and acoustic radiation force impulse imaging are being explored for characterizing liver lesions. The role of PET in the evaluation of HCC is evolving with promise seen especially with the use of a hepatocyte-specific PET tracer. Imaging is also critical for assessment of treatment response and detection of recurrence following locoregional treatment. Knowledge of the post-treatment appearance of HCC is essential for correct interpretation. This review article provides an overview of the role of imaging in the diagnosis, staging and post-treatment follow-up of HCC.

CT Appearance of Pyogenic Liver Abscesses Caused by Klebsiella pneumoniae

PURPOSE To retrospectively compare the computed tomographic (CT) features of liver abscesses caused by Klebsiella pneumoniae with those caused by other bacterial pathogens. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, with waiver of informed consent. Hospital records of all patients with a diagnosis of liver abscess between July 2003 and July 2010 were retrieved from an electronic hospital database. One hundred and thirty-one consecutive patients with confirmed pyogenic liver abscesses were studied. Data on clinical presentation, comorbid conditions, septic hematogenous complications, hospitalization duration, and abscess-related mortality were obtained. CT characteristics of abscesses including number, distribution, unilocular or multilocular appearance, cystic or solid appearance, gas in cavity, pylephlebitis, thrombophlebitis, and pneumobilia were reviewed. Etiology was established by pus and/or blood culture. Patients were placed into a monomicrobial K pneumoniae liver abscess group and a comparison group. A comparison of the CT features and clinical findings between the two groups was performed. The χ(2) analysis or Fisher exact test was used for categorical variables, and Student t and log-rank tests were used for continuous variables. A P value of less than .05 was considered to indicate a significant difference. RESULTS Monomicrobial K pneumoniae liver abscesses were present in 92 cases (70.2%). On CT images, characteristics more likely to be associated with monomicrobial K pneumoniae liver abscesses than other pyogenic liver abscesses were a single abscess (79.3% vs 56.4%, P = .01), unilobar involvement (82.6% vs 61.5%, P = .01), solid appearance (57.6% vs 35.9%, P = .03), multilocular (94.6% vs 71.8%, P = .01), association with thrombophlebitis (30.4% vs 5.1%, P < .01), and hematogenous complications (28.3% vs 7.7%, P < .01). Thrombophlebitis was associated with higher incidence of hematogenous septic complications (50.0% vs 13.9%, P < .001). Monomicrobial K pneumoniae liver abscesses were associated with significantly shorter duration of antibiotic treatment (P = .018) and hospital stay (P = .005), but there was no significant difference in incidence of septic shock and abscess-related mortality as compared with other pyogenic liver abscesses. CONCLUSION Monomicrobial K pneumoniae liver abscesses appear as single, solid, or multiloculated liver abscesses and are associated with thrombophlebitis and septic hematogenous complications.

Role of magnetic resonance elastography in compensated and decompensated liver disease

BACKGROUND & AIMS Non-invasive predictors identifying subjects with compensated liver disease at highest risk for transitioning to a decompensated state are lacking. We hypothesized that liver shear stiffness as measured by magnetic resonance elastography is an important non-invasive predictor of hepatic decompensation. METHODS Among patients with advanced fibrosis undergoing magnetic resonance elastography (2007-2011), a baseline cohort and follow up cohort (compensated liver disease) were established. Cause specific cox proportional hazards analysis adjusting for competing risks was utilized to determine the association between elevated liver shear stiffness and development of decompensation (hepatic encephalopathy, ascites, variceal bleeding). RESULTS In the baseline cohort (n=430), subjects with decompensated liver disease had a significantly higher mean liver shear stiffness (6.8kPa, IQR 4.9-8.5) as compared to subjects with compensated liver disease (5.2kPa, IQR 4.1-6.8). After adjustment for Model for End Stage Liver Disease score, hepatitis C, age, gender, albumin, and platelet count, the mean liver shear stiffness (OR=1.13, 95% CI 1.03-1.27) was independently associated with decompensated cirrhosis at baseline. Over a median follow up of 27months (n=167), 7.2% of subjects with compensated disease experienced hepatic decompensation. In the follow up cohort, the hazard of hepatic decompensation was 1.42 (95% CI 1.16-1.75) per unit increase in liver shear stiffness over time. The hazard of hepatic decompensation was 4.96 (95% CI 1.4-17.0, p=0.019) for a subject with compensated disease and mean LSS value ⩾5.8kPa as compared to an individual with compensated disease and lower mean LSS values. CONCLUSION Baseline liver shear stiffness assessed by magnetic resonance elastography is independently associated with decompensated liver disease.

Feasibility of using 3D MR elastography to determine pancreatic stiffness in healthy volunteers

To evaluate the feasibility of using three‐dimensional (3D) MR elastography (MRE) to determine the stiffness of the pancreas in healthy volunteers.