How efficient is acoustic radiation force impulse elastography for the evaluation of liver stiffness?

Background

In chronic liver diseases, a correct estimation of the severity of liver fibrosis is important for recommendations regarding the treatment. Nowadays, evaluation of fibrosis is done by noninvasive methods such as biochemical scores and transient elastography instead of liver biopsy. The lack of sensitivity to detect fibrosis, because of its heterogeneity is a drawback of liver biopsy (LB).

Objectives

To compare transient elastography (TE) and acoustic radiation force impulse (ARFI) for the evaluation of liver stiffness (LS), against percutaneous LB.

Patients and Methods

Our study comprised of 223 subjects; 52 without fibrosis (38 volunteers and 14 patients with F0 on LB), 36 with F1, 40 with F2, 26 with F3 and 69 with liver cirrhosis (46 with LB and 23 with signs of cirrhosis). For each patient we performed in the same session 10 TE and 5 ARFI measurements. The median values were calculated.

Results

A strong linear correlation (Spearman rho = 0.870) was found between TE and fibrosis (P < 0.0001); there was also a weaker correlation between ARFI and fibrosis (Spearman rho = 0.646; P < 0.0001). TE measurements were also correlated with ARFI measurements (Spearman rho = 0.733, P < 0.0001). The best test for predicting significant fibrosis (F ≥ 2) was TE with a cut-off value of 7.1 kPa (AUROC 0.953). For ARFI, the cut-off value was 1.27 m/s-area under ROC curve (AUROC): 0.890, sensitivity (Se) of 88.7%, specificity (Sp) of 67.5%, positive predictive value (PPV) of 64.5%, and negative predictive value (NPV) of 90% (P = 0.0044). For predicting cirrhosis (F = 4), the optimum cut-off values were 14.4 kPa for TE (AUROC: 0.985, Se: 95.6%, Sp: 94.7%, PPV: 89.2%, NPV: 98%) and 1.7 m/s for ARFI (AUROC: 0.931, Se: 93%, Sp: 86.7%, PPV: 73.6%, NPV: 96.9%) (P = 0.0102).

Conclusions

LS evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis. ARFI is an accurate test for the diagnosis of cirrhosis.     

Simplified follow-up of patients with mild chronic hepatitis C in areas with limited access to antiviral therapy

Background and aimsIn some areas of the world, antiviral therapy for chronic hepatitis C (CHC) is not available for all patients. The optimal interval for liver stiffness measures (LSM) and noninvasive scores to assess fibrosis progression has not been studied. We evaluated the usefulness of consecutive LSM, APRI, FIB-4 and Forns scores to predict disease progression.MethodsPatients with CHC and at least two annual LSM within 3 years were followed for a minimum of 5 years. Noninvasive scores were assessed. Evolution of LSM and scores were expressed as change/year (Delta).Results623 non-cirrhotic patients were included. Median baseline LSM was 6.6 kPa (IQR 5.4–8.4). During a median follow-up of 6 years, 61(9.7%) patients developed cirrhosis. Baseline LSM ≥ F2 and Forns ≥ 6.9 were the main predictors of cirrhosis (C-index 0.97). The addition of Delta variables did not improve its prediction. In patients with mild fibrosis (F0-1), progression to ≥F2 occurred in 80 (23%) within the first 3 years. Baseline BMI ≥ 24 kg/m² and LSM ≥ 5.9 kPa were associated to progression.ConclusionsBaseline LSM and Forns are highly predictive of cirrhosis development. In patients with mild CHC, BMI < 24 and LSM < 5.9, the likelihood of progression is very low, allowing for a significant spacing of noninvasive assessments over time.     

Breast ultrasound elastography—Results of 193 breast lesions in a prospective study with histopathologic correlation

Purpose

To evaluate the diagnostic performance of ultrasound elastography in breast masses.

Material and methods

193 lesions (129 benign, 64 malignant) were analyzed with the EUB 8500 Logos-ultrasonic-unit (Hitachi Medical, Japan) and a linear-array-transducer of 7.5-13-MHz. Standard of reference was cytology (FNAfine needle aspiration) or histology (core biopsy). The elastic-score was classified according to a 6-point colour-scale (Ueno classification; 1-3 = benign, 4-5 = malignant). Conventional B-mode ultrasound (US) findings were classified according to the BI-RADS classification. Statistical analysis included sensitivity, specificity, ROC-analysis and kappa-values for intra-/interobserver reliability.

Results

The mean score for elasticity was 4.1 ± 0.9 for malignant lesions, and 2.1 ± 1.0 for benign lesions (p < 0.001). With a best cut-off point between elasticity scores 3 and 4, sensitivity was 96.9%, and specificity 76%. Setting a best cut-off point for conventional US between BI-RADS 4 and 5, sensitivity was 57.8%, and specificity 96.1%. Elastography provided higher sensitivity and lower specificity than conventional US, but two lesions with elasticity score 1 were false negative, whereas no lesion scored BI-RADS 1-3 were false negative. ROC-curve was 0.884 for elastography, and 0.820 for conventional US (p < 0.001). Weighted kappa-values for intra-/interobserver reliability were 0.784/0.634 for BI-RADS classification, and 0.720/0.561 for elasticity scores.

Conclusion

In our study setting, elastography does not have the potential to replace conventional B-mode US for the detection of breast cancer, but may complement conventional US to improve the diagnostic performance.     

Towards an acoustic model-based poroelastic imaging method: II. experimental investigation

Soft biological tissue contains mobile fluid. The volume fraction of this fluid and the ease with which it may be displaced through the tissue could be of diagnostic significance and may also have consequences for the validity with which strain images can be interpreted according to the traditional idealizations of elastography. In a previous paper, under the assumption of frictionless boundary conditions, the spatio-temporal behavior of the strain field inside a compressed cylindrical poroelastic sample was predicted (Berry et al. 2006). In this current paper, experimental evidence is provided to confirm these predictions. Finite element modeling was first used to extend the previous predictions to allow for the existence of contact friction between the sample and the compressor plates. Elastographic techniques were then applied to image the time-evolution of the strain inside cylindrical samples of tofu (a suitable poroelastic material) during sustained unconfined compression. The observed experimental strain behavior was found to be consistent with the theoretical predictions. In particular, every sample studied confirmed that reduced values of radial strain advance with time from the curved cylindrical surface inwards towards the axis of symmetry. Furthermore, by fitting the predictions of an analytical model to a time sequence of strain images, parametric images of two quantities, each related to one or more of three poroelastic material constants were produced. The two parametric images depicted the Poisson's ratio (nu(s)) of the solid matrix and the product of the aggregate modulus (H(A)) of the solid matrix with the permeability (k) of the solid matrix to the pore fluid. The means of the pixel values in these images, nu(s) = 0.088 (standard deviation 0.023) and H(A)k = 1.449 (standard deviation 0.269) x 10(-7) m(2) s(-1), were in agreement with values derived from previously published data for tofu (Righetti et al. 2005). The results provide the first experimental detection of the fluid-flow-induced characteristic diffusion-like behavior of the strain in a compressed poroelastic material and allow parameters related to the above material constants to be determined. We conclude that it may eventually be possible to use strain data to detect and measure characteristics of diffusely distributed mobile fluid in tissue spaces that are too small to be imaged directly.     

Dynamic changes in liver stiffness during the course of acute hepatitis A

Abstract

Objective. Several recent studies have suggested that hepatic necroinflammation can alter the results of liver stiffness measurements (LSMs) obtained using the FibroScan device. However, the precise relationship between acute hepatic inflammation and LSMs remains unclear. The aim of this study was therefore to evaluate the dynamic changes in LSMs during the course of acute hepatic inflammation. Material and methods. Thirty-one patients with acute hepatitis A (AHA) were enrolled in this study (mean ± SD age 29 ± 7 years; 32.3% male). Only AHA patients who visited our hospital before their alanine aminotransferase (ALT) levels peaked were included. The day when AHA-associated symptoms began was considered as Day 0. Serum levels of ALT and bilirubin (BIL), and the international normalized ratio (INR) were measured every 2 days, as were LSMs, until the peak levels of all parameters were identified. Subsequently, these parameters were measured every 1–2 weeks until they had normalized. Results. Peak serum levels of ALT and BIL, the INR, and LSMs were 3723 ± 1513 IU/l, 5.8 ± 2.4 mg/dl, 1.3 ± 0.3, and 11.9 ± 5.7 kPa, respectively. The time taken for LSMs to peak from Day 0 (8 ± 2 days) differed significantly from that for ALT (5 ± 1 days), BIL (10 ± 4 days), and INR (5 ± 1 days). LSMs had normalized (≤ 5.5 kPa) in all patients at 34 ± 17 days after Day 0. ALT level and the INR were significantly associated with peak LSMs and BIL level and the INR with the time taken for normalization of LSMs. Conclusions. LSMs changed dynamically during the course of AHA. The pattern of change appears to be related to the severity of hepatic necroinflammation.     

Three-Dimensional Elastography for Cervical Lymph Node Volume Measurements: A Study to Investigate Feasibility,Accuracy and Reliability

This study investigated the feasibility of using three-dimensional (3-D) elastography in measuring cervical lymph node volume and compared the accuracy and reliability of 3-D elastography and 3-D grayscale ultrasound in measurement of ill-defined cervical nodes. Eighteen porcine lymph nodes from the neck were embedded in tissue-mimicking phantoms and scanned with the two ultrasound techniques. Ultrasound measurements were compared with the volume determined by water-displacement method to evaluate measurement accuracy. Inter-observer reproducibility and intra-observer repeatability of measurements were evaluated. Four patients with enlarged neck nodes were included to evaluate intra-observer repeatability of ultrasound measurements. Results demonstrated that lymph nodes that appeared ill-defined on grayscale ultrasound showed well-defined boundaries on elastography. 3-D elastography has higher measurement accuracy (84.2%), reproducibility (intraclass correlation coefficient, ICC = 0.909) and repeatability (ICC = 0.964–0.988) than does 3-D grayscale ultrasound (62.2%, 0.777 and 0.863–0.906 respectively). As a conclusion, 3-D elastography is accurate and reliable in volume measurement of ill-defined lymph nodes and has potential for accurate assessment of lymph node volume.     

Renal Transplant Elasticity Ultrasound Imaging: Correlation Between Normalized Strain and Renal Cortical Fibrosis

After transplantation, over a widely variable time course, the cortex of the transplanted kidney becomes stiffer as interstitial fibrosis develops and renal function declines. Elasticity ultrasound imaging (EUI) has been used to assess biomechanical properties of tissue that change in hardness as a result of pathologic damage. We prospectively assessed the hardness of the renal cortex in renal transplant allograft patients using a normalized ultrasound strain procedure measuring quasi-static deformation, which was correlated with the grade of renal cortical fibrosis. To determine cortical strain, we used 2-D speckle-tracking software (EchoInsight, Epsilon Imaging, Ann Arbor, MI, USA) to perform offline analysis of stored ultrasound loops capturing deformation of renal cortex and its adjacent soft tissue produced by pressure applied using the scanning transducer. Normalized strain is defined as the mean developed strain in the renal cortex divided by the overall mean strain measured in the soft tissues from the abdominal wall to pelvic muscles. Using the Banff scoring criteria for renal cortical fibrosis as the gold standard, we classified 20 renal transplant allograft biopsy tissue samples into two groups: group 1 (n = 10) with mild (<25%) renal cortical fibrosis and group 2 (n = 10) with moderate (26%–50%) renal cortical fibrosis. An unpaired two-tailed t-test was used to determine the statistical difference in strains between patients with mild and those with moderate renal cortical fibrosis. Receiver operating characteristic curve analysis was performed to assess the accuracy of developed strain and normalized strain in predicting moderate renal cortical fibrosis. The reference strain did not significantly differ between the two groups (p = 0.10). However, the developed renal cortical strain in group 1 with mild fibrosis was higher than that in group 2 with moderate fibrosis (p = 0.025). The normalized strain in group 1 was also higher than that in group 2 (p = 0.0014). The areas under receiver operating characteristic curves for developed strain and normalized strain were 0.78 and 0.95, respectively. The optimal cutoff for distinguishing moderate renal cortical fibrosis was −0.08 for developed strain (sensitivity = 0.50, specificity = 1.0) and 2.5 for normalized strain (sensitivity = 0.80, specificity = 1.0). In summary, renal cortex strain is strongly correlated with grade of renal cortical fibrosis. Normalized strain is superior to developed strain in distinguishing moderate from mild renal cortical fibrosis. We conclude that free-hand real-time strain EUI may be useful in assessing the progression of cortical fibrosis in renal transplant allografts. Further prospective study using this method is warranted.     

Liver Stiffness Measurements by Means of Supersonic Shear Imaging in Patients Without Known Liver Pathology

We used supersonic shear imaging to determine the liver stiffness (LS) values of 82 patients without known liver pathology and studied the factors that influence these measurements. Five LS measurements were made in each subject, and the median value, expressed in kilopascals, was calculated. Reliable LS measurements were obtained in 84.5% of patients. Higher body mass index and older age were associated with failure to obtain reliable measurements. The mean value of LS measurements determined by SSI in our cohort of patients without known liver pathology was 6 ± 1.4 kPa. The mean LS measurements determined by SSI for men were significantly higher than those for women; body mass index did not significantly influence SSI measurements. Thus, 6 kPa is the mean SSI value in patients without known liver pathology, with higher values being obtained in men.     

超声弹性成像技术评估肝纤维化的临床价值

超声弹性成像技术已用于临床多种疾病的诊断与鉴别诊断,针对肝纤维化的定性及定量研究也已取得一定进展。本文就三种弹性成像技术:实时弹性成像、Fibroscan仪成像及脉冲声辐射力弹性成像在肝纤维化评估中的应用及新进展综述如下。