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Tomoelastography reveals sensitivity of tissue mechanical properties to the hydration state of multiple abdominal organs within one scan and in unprecedented resolution of anatomical details. Magn Reson Med 78:976-983, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Purpose: To demonstrate the feasibility of in vivo wideband MR elastography (wMRE) using continuous, time-harmonic shear vibrations in the frequency range of 10-50 Hz. Theory and Methods: The method was tested in a gel phantom with marked mechanical loss. The brains and livers of eight volunteers were scanned by wMRE using multislice, single-shot MRE with optimized fractional encoding and synchronization of sequence acquisition to vibration. Multifrequency three-dimensional inversion was used to reconstruct compound maps of magnitude jG*j and phase u of the complex shear modulus. A new phase estimation, u*, was developed to avoid systematic bias due to noise. Results: In the phantom, G*-dispersion measured by wMRE agreed well with oscillatory shear rheometry. jG*j and u* measured at vibrations of 10-25 HZ, 25-35 HZ, and 40-50 HZ were 0.62 6 0.08, 1.56 6 0.16, 2.18 6 0.20 kPa and 0.09 6 0.17, 0.39 6 0.16, 0.20 6 0.13 rad in brain and 0.89 6 0.11, 1.67 6 0.20, 2.27 6 0.35 kPa and 0.15 6 0.10, 0.24 6 0.05, 0.26 6 0.05 rad in liver. Elastograms including all frequencies showed the best resolution of anatomical detail with jG*j ¼ 1.38 6 0.12 kPa, u* ¼ 0.24 6 0.10 rad (brain) and jG*j ¼ 1.79 6 0.23 kPa, u* ¼ 0.24 6 0.05 rad (liver). Conclusion: wMRE reveals highly dispersive G* properties of the brain and liver, and our results suggest that the influence of large-scale structures such as fluid-filled vessels and sulci on the MRE-measured parameters increases at low vibration frequencies.

Patients with increased liver stiffness have a higher risk of developing cancer, however, the role of fluid-solid tissue interactions and their contribution to liver tumor malignancy remains elusive. Tomoelastography is a novel imaging method for mapping quantitatively the solid-fluid tissue properties of soft tissues in vivo. It provides high resolution and thus has clear clinical applications. In this work we used tomoelastography in 77 participants, with a total of 141 focal liver lesions of different etiologies, to investigate the contributions of tissue stiffness and fluidity to the malignancy of liver tumors. Shear-wave speed (c) as surrogate for tissue stiffness and phase-angle (j) of the complex shear modulus reflecting tissue fluidity were abnormally high in malignant tumors and allowed them to be distinguished from nontumorous liver tissue with high accuracy [c: AUC ¼ 0.88 with 95% confidence interval (CI) ¼ 0.83-0.94; j: AUC ¼ 0.95, 95% CI ¼ 0.92-0.98]. Benign focal nodular hyperplasia and hepatocellular adenoma could be distinguished from malignant lesions on the basis of tumor stiffness (AUC ¼ 0.85, 95% CI ¼ 0.72-0.98; sensitivity ¼ 94%, 95% CI ¼ 89-100; and specificity ¼ 85%, 95% CI ¼ 62-100), tumor fluidity (AUC ¼ 0.86, 95% CI ¼ 0.77-0.96; sensitivity ¼ 83%, 95% CI ¼ 72-93; and specificity ¼ 92%, 95% CI ¼ 77-100) and liver stiffness (AUC ¼ 0.84, 95% CI ¼ 0.74-0.94; sensitivity ¼ 72%, 95% CI ¼ 59-83; and specificity ¼ 88%, 95% CI ¼ 69-100), but not on the basis of liver fluidity. Together, hepatic malignancies are characterized by stiff, yet fluid tissue properties, whereas surrounding nontumorous tissue is dominated by solid properties. Tomoelastography can inform noninvasively on the malignancy of suspicious liver lesions by differentiating between benign and malignant lesions with high sensitivity based on stiffness and with high specificity based on fluidity.Significance: Solid-fluid tissue properties measured by tomoelastography can distinguish malignant from benign masses with high accuracy and provide quantitative noninvasive imaging biomarkers for liver tumors.

Purpose: To develop a method of compact tabletop magnetic resonance elastography (MRE) for rheological tests of tissue samples and to measure changes in viscoelastic powerlaw constants of liver and brain tissue during progressive fixation. Methods: A 10-mm bore, 0.5-T permanent-magnet-based MRI system was equipped with a gradient-amplifier-controlled piezo-actuator and motion-sensitive spin echo sequence for inducing and measuring harmonic shear vibrations in cylindrical samples. Shear modulus dispersion functions were acquired at 200-5700 Hz in animal tissues at different states of formalin fixation and fitted by the springpot powerlaw model to obtain shear modulus l and powerlaw exponent a. Results: In a frequency range of 300-1500 Hz, unfixed liver tissue was softer and less dispersive than brain tissue with l ¼ 1.68 6 0.17 kPa and a ¼ 0.51 6 0.06 versus l ¼ 2.60 6 0.68 kPa and a ¼ 0.68 6 0.03. Twenty-eight hours of formalin fixation yielded a 400-fold increase in liver l, 25-fold increase in brain l, and two-fold reduction in a of both tissues.

Objectives: Today, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adults alike. Yet, the noninvasive evaluation of disease severity remains a diagnostic challenge. In this study, we apply multifrequency magnetic resonance elastography (mMRE) for the quantification of liver steatosis and fibrosis in adolescents with NAFLD. Methods: Fifty adolescents (age range, 10-17 years; mean BMI, 33.9 kg/m 2 ; range, 21.4-42.1 kg/m 2 ) with biopsy-proven NAFLD were included in this prospective study. Multifrequency magnetic resonance elastography was performed using external multifrequency vibrations of 30 to 60 Hz and tomoelastography postprocessing, resulting in penetration rate (a) and shear wave speed (c). Hepatic fat fraction was determined using Dixon method. The diagnostic accuracy of mMRE in grading liver steatosis and staging liver fibrosis was assessed by receiver operating characteristic curve analysis. Results: Multifrequency magnetic resonance elastography parameters c and a were independently sensitive to fibrosis and steatosis, respectively, providing area under the receiver operating characteristic values of 0.79 (95% confidence interval [CI], 0.66-0.92), 0.91 (95% CI, 0.83-0.99), and 0.90 (95% CI, 0.80-0.99) for the detection of any (≥F1), moderate (≥F2), and advanced (≥F3) fibrosis, and 0.87 (95% CI, 0.76-0.97) and 0.87 (95% CI, 0.77-0.96) for the detection of moderate (≥S2) and severe (S3) steatosis. Conclusions: One mMRE measurement provides 2 independent parameters with very good diagnostic accuracy in detecting moderate and advanced fibrosis as well as moderate and severe steatosis in pediatric NAFLD.

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Purpose To measure in vivo liver stiffness by using US time-harmonic elastography in a cohort of pediatric patients who were overweight to extremely obese with nonalcoholic fatty liver disease (NAFLD) and to evaluate the diagnostic value of time-harmonic elastography for differentiating stages of fibrosis associated with progressive disease. Materials and Methods In this prospective study, 67 consecutive adolescents (age range, 10-17 years; mean body mass index, 34.7 kg/m; range, 21.4-50.4 kg/m) with biopsy-proven NAFLD were enrolled. Liver stiffness was measured by using time-harmonic elastography based on externally induced continuous vibrations of 30 Hz to 60 Hz frequency and real-time B-mode-guided wave profile analysis covering tissue depths of up to 14 cm. The diagnostic accuracy of time-harmonic elastography in staging liver fibrosis was assessed with area under the receiver operating characteristic curve (AUC) analysis. Liver stiffness cutoffs for the differentiation of fibrosis stages were identified based on the highest Youden index. Results Time-harmonic elastography was feasible in all patients (0% failure rate), including 70% (n = 47) of individuals with extreme obesity (body mass index above the 99.5th percentile). AUC analysis for the detection of any fibrosis (≥ stage F1), moderate fibrosis (≥ stage F2), and advanced fibrosis (≥ stage F3) was 0.88 (95% confidence interval [CI]: 0.80, 0.96), 0.99 (95% CI: 0.98, 1.00), and 0.88 (95% CI: 0.80, 0.96), respectively. The best liver stiffness cutoffs were 1.52 m/sec for at least stage F1, 1.62 m/sec for at least stage F2, and 1.64 m/sec for at least stage F3. Conclusion US time-harmonic elastography allows accurate detection of moderate fibrosis even in pediatric patients with extreme obesity. Larger clinical trials are warranted to confirm the accuracy of US time-harmonic elastography.