Michael P. Andre

Magnetic resonance elastography is superior to acoustic radiation force impulse for the Diagnosis of fibrosis in patients with biopsy‐proven nonalcoholic fatty liver disease: A prospective study

Magnetic resonance elastography (MRE), an advanced magnetic resonance–based imaging technique, and acoustic radiation force impulse (ARFI), an ultrasound‐based imaging technique, are accurate for diagnosing nonalcoholic fatty liver disease (NAFLD) fibrosis. However, no head‐to‐head comparisons between MRE and ARFI for diagnosing NAFLD fibrosis have been performed. We compared MRE versus ARFI head‐to‐head for diagnosing fibrosis in well‐characterized patients with biopsy‐proven NAFLD. This cross‐sectional analysis of a prospective cohort involved 125 patients (54.4% female) who underwent MRE, ARFI, and contemporaneous liver biopsies scored using the Nonalcoholic Steatohepatitis Clinical Research Network histological scoring system. The performances of MRE versus ARFI for diagnosing fibrosis were evaluated using area under the receiver operating characteristic curves (AUROCs). The mean (± standard deviation) age and body mass index were 48.9 (±15.4) years and 31.8 (±7.0) kg/m2, respectively. For diagnosing any fibrosis (≥ stage 1), the MRE AUROC was 0.799 (95% confidence interval [CI] 0.723‐0.875), significantly (P = 0.012) higher than the ARFI AUROC of 0.664 (95% CI 0.568‐0.760). In stratified analysis by presence or absence of obesity, MRE was superior to ARFI for diagnosing any fibrosis in obese patients (P < 0.001) but not in nonobese patients (P = 0.722). The MRE AUROCs for diagnosing ≥stages 2, 3, and 4 fibrosis were 0.885 (95% CI 0.816‐0.953), 0.934 (95% CI 0.863‐1.000), and 0.882 (95% CI 0.729‐1.000); and the ARFI AUROCs were 0.848 (95% CI 0.776‐0.921), 0.896 (95% CI 0.824‐0.968), and 0.862 (95% CI 0.721‐1.000). MRE had higher AUROCs than ARFI for discriminating dichotomized fibrosis stages at all dichotomization cutoff points, but the AUROC differences decreased as the cutoff points (fibrosis stages) increased. Conclusion: MRE is more accurate than ARFI for diagnosing any fibrosis in NAFLD patients, especially those who are obese. (Hepatology 2016;63:453–461)

Noninvasive Diagnosis of Nonalcoholic Fatty Liver Disease and Quantification of Liver Fat Using a New Quantitative Ultrasound Technique

BACKGROUND & AIMS Liver biopsy analysis is the standard method used to diagnose nonalcoholic fatty liver disease (NAFLD). Advanced magnetic resonance imaging is a noninvasive procedure that can accurately diagnose and quantify steatosis, but is expensive. Conventional ultrasound is more accessible but identifies steatosis with low levels of sensitivity, specificity, and quantitative accuracy, and results vary among technicians. A new quantitative ultrasound (QUS) technique can identify steatosis in animal models. We assessed the accuracy of QUS in the diagnosis and quantification of hepatic steatosis, comparing findings with those from magnetic resonance imaging proton density fat fraction (MRI-PDFF) analysis as a reference. METHODS We performed a prospective, cross-sectional analysis of a cohort of adults (N = 204) with NAFLD (MRI-PDFF, ≥5%) and without NAFLD (controls). Subjects underwent MRI-PDFF and QUS analyses of the liver on the same day at the University of California, San Diego, from February 2012 through March 2014. QUS parameters and backscatter coefficient (BSC) values were calculated. Patients were assigned randomly to training (n = 102; mean age, 51 ± 17 y; mean body mass index, 31 ± 7 kg/m(2)) and validation (n = 102; mean age, 49 ± 17 y; body mass index, 30 ± 6 kg/m(2)) groups; 69% of patients in each group had NAFLD. RESULTS BSC (range, 0.00005-0.25 1/cm-sr) correlated with MRI-PDFF (Spearman ρ = 0.80; P < .0001). In the training group, the BSC analysis identified patients with NAFLD with an area under the curve value of 0.98 (95% confidence interval, 0.95-1.00; P < .0001). The optimal BSC cut-off value identified patients with NAFLD in the training and validation groups with 93% and 87% sensitivity, 97% and 91% specificity, 86% and 76% negative predictive values, and 99% and 95% positive predictive values, respectively. CONCLUSIONS QUS measurements of BSC can accurately diagnose and quantify hepatic steatosis, based on a cross-sectional analysis that used MRI-PDFF as the reference. With further validation, QUS could be an inexpensive, widely available method to screen the general or at-risk population for NAFLD.

MRE is superior to ARFI for the diagnosis of fibrosis in patients with biopsy‐proven NAFLD: A prospective study

Magnetic resonance elastography (MRE), an advanced magnetic resonance–based imaging technique, and acoustic radiation force impulse (ARFI), an ultrasound‐based imaging technique, are accurate for diagnosing nonalcoholic fatty liver disease (NAFLD) fibrosis. However, no head‐to‐head comparisons between MRE and ARFI for diagnosing NAFLD fibrosis have been performed. We compared MRE versus ARFI head‐to‐head for diagnosing fibrosis in well‐characterized patients with biopsy‐proven NAFLD. This cross‐sectional analysis of a prospective cohort involved 125 patients (54.4% female) who underwent MRE, ARFI, and contemporaneous liver biopsies scored using the Nonalcoholic Steatohepatitis Clinical Research Network histological scoring system. The performances of MRE versus ARFI for diagnosing fibrosis were evaluated using area under the receiver operating characteristic curves (AUROCs). The mean (± standard deviation) age and body mass index were 48.9 (±15.4) years and 31.8 (±7.0) kg/m2, respectively. For diagnosing any fibrosis (≥ stage 1), the MRE AUROC was 0.799 (95% confidence interval [CI] 0.723‐0.875), significantly (P = 0.012) higher than the ARFI AUROC of 0.664 (95% CI 0.568‐0.760). In stratified analysis by presence or absence of obesity, MRE was superior to ARFI for diagnosing any fibrosis in obese patients (P < 0.001) but not in nonobese patients (P = 0.722). The MRE AUROCs for diagnosing ≥stages 2, 3, and 4 fibrosis were 0.885 (95% CI 0.816‐0.953), 0.934 (95% CI 0.863‐1.000), and 0.882 (95% CI 0.729‐1.000); and the ARFI AUROCs were 0.848 (95% CI 0.776‐0.921), 0.896 (95% CI 0.824‐0.968), and 0.862 (95% CI 0.721‐1.000). MRE had higher AUROCs than ARFI for discriminating dichotomized fibrosis stages at all dichotomization cutoff points, but the AUROC differences decreased as the cutoff points (fibrosis stages) increased. Conclusion: MRE is more accurate than ARFI for diagnosing any fibrosis in NAFLD patients, especially those who are obese. (Hepatology 2016;63:453–461)

RSNA/QIBA: Shear wave speed as a biomarker for liver fibrosis staging

An interlaboratory study of shear wave speed (SWS) estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials were also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results.

Physical and acoustical properties of perfluorooctylbromide, an ultrasound contrast agent

Perfluorooctylbromide (PFOB: C8F17Br) has been shown to be an effective ultrasound contrast agent when incorporated in tissues. The authors have recently demonstrated that PFOB also enhances tissues and Doppler signals during its capillary phase. To help elucidate the physical basis of their observations, the authors compared physical and acoustical properties of standard PFOB-lecithin emulsion with identical lecithin emulsion minus PFOB (vehicle) for concentrations of PFOB from 0% to 50% weight per volume. Propagation velocity, attenuation, and elastic modulus were measured using a 5-MHz source, 0.6-mm hydrophone, and a waveform digitizer, whereas viscosity, density, and particle size were measured directly. Vehicle showed no significant change with increasing concentration in any of the parameters measured. Perfluoroctylbromide exhibited significant linear increase in viscosity and mass density. Increasing concentrations of PFOB emulsion produced a dramatic linear decrease in velocity (r = .99) and a linear increase in attenuation coefficient, (r = .99). Derived values for bulk modulus (reciprocal of compressibility) also showed significant linear decrease (r = .98) with concentration of PFOB. For typical human in vivo blood concentrations of 3.5% PFOB emulsion, the following values were obtained: density, 1.02 g/mL; viscosity, 10.25 cP; velocity, 1450 m/second; attenuation, 2.8 dB/cm; and bulk modulus, 2.18 GPa. Significant differences were found between PFOB and vehicle at even low concentrations, although particle number and size distributions were the same for each, indicating that the presence of PFOB strongly influences acoustic properties. This enhancement was found to be linear over a wide range of concentrations, which supports the possibility of quantitative analysis.

Ultrasonic enhancement of myocardial infarction with perfluorocarbon compounds in dogs

Fluosol-DA 20% (Fluosol) and perfluoroctylbromide (PFOB), 2 types of perfluorocarbon emulsions (PFCs), were evaluated as sound contrast agents in imaging acute myocardial infarction (MI) in dogs. Operative ligation of a coronary artery was performed in 9 dogs. PFC was administered 2 days after occlusion. One dog received Fluosol, 10 ml/kg body weight, 2 dogs received 20 ml/kg, and 2 received 25 ml/kg; 2 dogs received PFOB, 20 ml/kg, and 2 dogs received 25 ml/kg. Just before and 2 days after PFC administration, real-time, 2-dimensional ultrasound examination of the heart was performed in the short-axis view from apex to base. No enhancement was seen at the 10-ml/kg dose, but significant mild echogenic enhancement of all MIs occurred after 20 ml/kg. Moderate to marked enhancement was noted after 25 ml/kg. The enhancement was either diffuse throughout the MI or localized to the rim. Initial studies suggest that the mechanism of enhancement is related, at least in part, to the accumulation of PFC-filled macrophages within the MI.

Three-dimensional nonlinear inverse scattering: Quantitative transmission algorithms, refraction corrected reflection, scanner design and clinical results

Research in quantitative whole breast ultrasound imaging has been developing rapidly. Recently we published results from 2D transmission inverse scattering algorithms, based on optimization, incorporating diffraction, refraction, and limited multiple scattering effects, using data collected from an early prototype, which showed the feasibility of high resolution quantitative imaging of the breast tissue speed and attenuation, and concomitant refraction corrected reflection imaging. However, artifact problems in speed and attenuation result from the 2D algorithms, and the data characteristics. The reflection algorithm uses the speed map to model refractive effects of rays, so these artifacts are unacceptable. The 3D inverse scattering algorithm presented here, using data from a new prototype, overcomes most of these artifacts. We then use a 3D refraction corrected 360 degree compounded reflection algorithm for high resolution speckle free reflection images. We discuss the transmission and reflection algorithms and the advanced scanner used to collect the data, as well as initial clinical results from the Mayo Clinic, Breast Cancer Imaging Center, Orange County, and the University California, San Diego. We show examples of fibroadenomas, calcifications, cancers (IDC), in dense, fatty and average breast tissue, and compare these with hand-held ultrasound, MRI and mammography, where available.

Enhancement of the echogenicity of flowing blood by the contrast agent perflubron.

RATIONALE AND OBJECTIVES Perflubron, or perfluorooctylbromide, is an effective ultrasound and computed tomography contrast agent in a lecithin emulsion form. The authors studied acoustical properties of perflubron emulsion in static human and flowing porcine blood for concentrations from 0% to 30% weight per volume. METHODS Propagation velocity (c), the intensity attenuation coefficient (mu), density (rho), and particle size were measured directly. Because the backscatter of flowing blood is dependent on shear rate, relative echogenicity was measured as a function of perflubron concentration in whole porcine blood, in a laminar flow system, at shear rates of 16.0 to 68.5 sec-1 for realtime sector scanner images obtained at 7.5 MHz. RESULTS Neat perflubron is a colorless liquid with density of 1.93 g.mL-1 and velocity of 630 m.sec-1. The following values were obtained at 4.7 MHz in static human blood (hematocrit 44%) at expected human in vivo blood concentrations of 3.1% perflubron versus pure human blood: rho = 1.11 versus 1.05 g.mL-1, c = 1,480 versus 1,576 m.sec-1, mu = 1.00 versus 0.36 dB.cm-1. The mean echogenicity of whole porcine blood increased substantially with perflubron concentration and was inversely proportional to blood shear rate. CONCLUSION Adding 3.1% concentration of perflubron increased image echogenicity at all shear rates studied, ranging from 70% at 68.5 sec-1 (16.3 cm.sec-1) up to 180% at 16.0 sec-1 (3.8 cm.sec-1). Perflubron enhancement of blood is marked and demonstrates shear rate dependence like that of whole blood.

Effects of Transient Coronary Ischemia and Reperfusion on Myocardial Edema Formation and In Vitro Magnetic Relaxation Times

The effects of transient ischemia and reperfusion on regional myocardial function, salvage and swelling have been systematically analyzed in experimental canine preparations. The results of these interventions on myocardial in vitro measurements of magnetic relaxation times (T1 = magnetization recovery, T2 = spin echo) are of significant importance with respect to future nuclear magnetic resonance tomographic imaging. Thus, using a pulsed magnetic resonance spectrometer (10.7 MHz), myocardial tissue samples from two groups of dogs were evaluated. In group 1 (n = six dogs), the left anterior descending artery was occluded for 3 hours before sacrifice; in group 2 (six dogs), 3 hours of occlusion was followed by 1 hour of reperfusion. Multiple tissue samples from normal and ischemic (or ischemic and reperfused) myocardium were obtained for measurement of T1, T2 and % water content (wet weight--dry weight/wet weight). Water content increased with ischemia (78 +/- 4%) and reperfusion (81 +/- 4%) (both p less than 0.01 versus control values). Values for T1 increased with ischemia (598 +/- 39 versus 487 +/- 23 ms in normal tissue from the same heart, p less than 0.01). Even greater T1 changes occurred in the animals with reperfusion (654 +/- 52 ms, p less than 0.01 versus the intra-animal control values). Changes in T2 were similar but less marked (ischemic zone 43.9 +/- 1.0 versus 41.2 +/- 1.0 ms in nonischemic tissue in the corresponding heart, p less than 0.05; reperfusion zone 48.3 +/- 3.5 versus 41.9 +/- 2.3 ms in the normal zone, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease

OBJECTIVE The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed. RESULTS CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all). CONCLUSION Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD.