Elastography for detecting hepatic fibrosis: options and considerations.

The elasticity of human liver varies by several orders of magnitude when measured by ex vivo stress–strain experiments. In the presence of acute injury, the liver may display contractile properties related to the activation of cellular elements including myofibroblasts.1 Emerging data further suggest that increased liver stiffness occurs even before collagen deposition takes place,2 implying that tissue stiffness is a prerequisite for injury responses such as stellate cell activation. With the development of chronic liver disease, however, the increased stiffness observed in vivo is primarily dictated by the presence of fibrosis.3 Conventional medical imaging modalities have been developed to detect changes over much smaller ranges.4 In the past decade, several investigative groups have developed methods for imaging tissue elasticity, recognizing the incremental diagnostic value of characterizing mechanical properties when assessing for the presence of disease. Proposed techniques using ultrasonography or magnetic resonance (MR) platforms employ methods consistent with classical approaches where stress is applied to tissue and the resulting strain distribution is measured. Transient elastography (FibroScan, Echosens, Paris, France) utilizes an ultrasound transducer probe mounted on the axis of a vibrator. Low-frequency (50 Hz) vibrations are transmitted into the skin by manual placement of the probe between the rib interspace where biopsy would be performed, inducing a shear wave that propagates into the liver. A pulse-echo acquisition is then used to measure the propagating wave's velocity, which is proportional to tissue stiffness represented by the equation for Young's elastic modulus E (expressed as E = 3ρv2, where v is the shear velocity and ρ is the density of tissue, assumed to be constant). Dedicated, machine-based software determines whether each measurement (quantified in units of kiloPascals) is successful or not. Requirements for accurate calculations of average liver stiffness include (1) an interquartile range for measurements within 30% of the median value and (2) a ratio of successful measurements to the total number of acquisitions ≥60%.5 Magnetic resonance elastography (MRE) directly visualizes and quantitatively measures propagating acoustic shear waves progressing through liver tissue.6 By using an electromagnetic or passive pneumatic driver placed directly on the patient for longitudinal shear wave generation, a phase-contrast magnetic resonance imaging pulse sequence detects the shear wave displacement patterns that are observed. Subsequently, the shear stiffness values are calculated from wave displacement patterns and displayed as color-encoded images (elastograms) that depict tissue elasticity. At our institution, region of interest analysis throughout 4 cross-sectional slices of liver (avoiding vascular structures) is performed to calculate mean liver stiffness. Elasticity quantification by MRE is based on the formula representing shear modulus, which is equivalent to one third of the Young's modulus reported with transient elastography.7,8 MRE is operator independent in terms of generating wave propagation and is compatible with many phased-array torso coils, offering the possibility of multimodal hepatic imaging, including perfusion assessment. The results of individual and combined results from clinical investigations of transient elastography demonstrate high sensitivity (>85%) and specificity (>90%) for detecting advanced hepatic fibrosis in patients with chronic hepatitis C.9 Single-center studies with MRE have also reported high degrees of accuracy for detecting advanced fibrosis in patients with various disease etiologies as well. Furthermore, the expanded application of MRE is noted for detecting stages 2–4 hepatic fibrosis with sensitivity and specificity values in the 85%–90% range, respectively.7,8 Because both technologies are likely to become available in the United States in the near future, a direct comparison between modalities to assess performance and clinical utility will be inevitable. In this month's issue of Gastroenterology, Huwart et al10 report on 141 patients who underwent blinded assessments with transient elastography, MRE, and aspartate aminotransferase to platelet ratio index (APRI) after liver biopsy to assess which method could most accurately predict the degree of hepatic fibrosis. Individual patients underwent both imaging examinations and it was noted that the technical success rate for MRE was significantly higher than for transient elastography (94% vs 84%). Reasons for incomplete transient elastography included the presence of minimal ascites (n = 13) and obesity (n = 10), defined as a body mass index ≥28 kg/m2. Incomplete MRE studies were related to claustrophobia, inability to enter the MR scanner owing to body habitus, and low hepatic signal from elevated hepatic iron content. Of the 96 patients with suitable results from noninvasive fibrosis examinations and liver biopsy, nearly 65% had chronic hepatitis C and the average body mass index was 26 kg/m2. The distribution of fibrosis on liver histology was stage 0, 23%; 1, 23%; 2, 20%; 3, 15%; and 4, 19%, with a mean specimen length of 30 mm. The authors report that all 3 noninvasive modalities provided measurements that correlated with fibrosis stage, but the strongest relationship was observed with MRE (r = 0.84; P < .001). The diagnostic performance of MRE was also greater than transient elastography and APRI for the detection of fibrosis stages 2–4 vs stages 0–1 based on receiver operating characteristic curve analyses. Notably, the sensitivity and specificity for detecting stages 2–4 hepatic fibrosis by MRE were 100% and 91%, respectively. Finally, the performance of MRE in detecting hepatic fibrosis remained higher when compared to the combination of transient elastography and APRI. Advantages of the reported study design include (1) the use of consecutive patients for identifying study participants, (2) blinding of all test strategy results to interpreters, (3) a high frequency of suitable liver histology specimens, which minimized sampling error, (4) excellent interobserver hepatopathologist reproducibility for staging fibrosis, and (5) the use of advanced statistical methods for examining diagnostic performance. Potential limitations of the investigation include (1) the exclusion of patients with unsuitable liver biopsies and imaging study results, which could result in bias toward higher performance rates and (2) the inability to successfully examine greater numbers of patients with obesity (only 12% with body mass index ≥28 kg/m2) and nonalcoholic fatty liver disease with transient elastography. Although the underlying principles for both transient elastography and MRE seem similar, there are key differences in these methods that should be considered when interpreting the results they produce. Specific issues are related to the concepts of reproducibility, accuracy, and fibrosis stage misclassification.