Diagnostic performance of Node Reporting and Data System (Node-RADS) for regional lymph node staging of gastric cancer by CT.

OBJECTIVES: Diagnostic performance of imaging for regional lymph node assessment in gastric cancer is still limited, and there is a lack of consensus on radiological evaluation. At the same time, there is an increasing demand for structured reporting using Reporting and Data Systems (RADS) to standardize oncological imaging. We aimed at investigating the diagnostic performance of Node-RADS compared to the use of various individual criteria for assessing regional lymph nodes in gastric cancer using histopathology as reference. METHODS: In this retrospective single-center study, consecutive 91 patients (median age, 66 years, range 33-91 years, 54 men) with CT scans and histologically proven gastric adenocarcinoma were assessed using Node-RADS assigning scores from 1 to 5 for the likelihood of regional lymph node metastases. Additionally, different Node-RADS criteria as well as subcategories of altered border contour (lobulated, spiculated, indistinct) were assessed individually. Sensitivity, specificity, and Youden's index were calculated for Node-RADS scores, and all criteria investigated. Interreader agreement was calculated using Cohen's kappa. RESULTS: Among all criteria, best performance was found for Node-RADS scores ≥ 3 and ≥ 4 with a sensitivity/specificity/Youden's index of 56.8%/90.7%/0.48 and 48.6%/98.1%/0.47, respectively, both with substantial interreader agreement (κ = 0.73 and 0.67, p < 0.01). Among individual criteria, the best performance was found for short-axis diameter of 10 mm with sensitivity/specificity/Youden's index of 56.8%/87.0%/0.44 (κ = 0.65, p < 0.01). CONCLUSION: This study shows that structured reporting of combined size and configuration criteria of regional lymph nodes in gastric cancer slightly improves overall diagnostic performance compared to individual criteria including short-axis diameter alone. The results show an increase in specificity and unchanged sensitivity. CLINICAL RELEVANCE STATEMENT: The results of this study suggest that Node-RADS may be a suitable tool for structured reporting of regional lymph nodes in gastric cancer. KEY POINTS: • Assessment of lymph nodes in gastric cancer is still limited, and there is a lack of consensus on radiological evaluation. • Node-RADS in gastric cancer improves overall diagnostic performance compared to individual criteria including short-axis diameter. • Node-RADS may be a suitable tool for structured reporting of regional lymph nodes in gastric cancer.

Feasibility of Intestinal MR Elastography in Inflammatory Bowel Disease.

BACKGROUND: While MR enterography allows detection of inflammatory bowel disease (IBD), the findings continue to be of limited use in guiding treatment-medication vs. surgery. PURPOSE: To test the feasibility of MR elastography of the gut in healthy volunteers and IBD patients. STUDY TYPE: Prospective pilot. POPULATION: Forty subjects (healthy volunteers: n = 20, 37 ± 14 years, 10 women; IBD patients: n = 20 (ulcerative colitis n = 9, Crohn's disease n = 11), 41 ± 15 years, 11 women). FIELD STRENGTH/SEQUENCE: Multifrequency MR elastography using a single-shot spin-echo echo planar imaging sequence at 1.5 T with drive frequencies of 40, 50, 60, and 70 Hz. ASSESSMENT: Maps of shear-wave speed (SWS, in m/s) and loss angle (φ, in rad), representing stiffness and solid-fluid behavior, respectively, were generated using tomoelastography data processing. Histopathological analysis of surgical specimens was used as reference standard in patients. STATISTICAL TESTS: Unpaired t-test, one-way analysis of variance followed by Tukey post hoc analysis, Pearson's correlation coefficient and area under the receiver operating characteristic curve (AUC) with 95%-confidence interval (CI). Significance level of 5%. RESULTS: MR elastography was feasible in all 40 subjects (100% technical success rate). SWS and φ were significantly increased in IBD by 21% and 20% (IBD: 1.45 ± 0.14 m/s and 0.78 ± 0.12 rad; healthy volunteers: 1.20 ± 0.14 m/s and 0.65 ± 0.06 rad), whereas no significant differences were found between ulcerative colitis and Crohn's disease (P = 0.74 and 0.90, respectively). In a preliminary assessment, a high diagnostic accuracy in detecting IBD was suggested by an AUC of 0.90 (CI: 0.81-0.96) for SWS and 0.84 (CI: 0.71-0.95) for φ. DATA CONCLUSION: In this pilot study, our results demonstrated the feasibility of MR elastography of the gut and showed an excellent diagnostic performance in predicting IBD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Prostate cancer assessment using MR elastography of fresh prostatectomy specimens at 9.4 T.

PURPOSE: Despite its success in the assessment of prostate cancer (PCa), in vivo multiparametric MRI has limitations such as interobserver variability and low specificity. Several MRI methods, among them MR elastography, are currently being discussed as candidates for supplementing conventional multiparametric MRI. This study aims to investigate the detection of PCa in fresh ex vivo human prostatectomy specimens using MR elastography. METHODS: Fourteen fresh prostate specimens from men with clinically significant PCa without formalin fixation or prior radiation therapy were examined by MR elastography at 500 Hz immediately after radical prostatectomy in a 9.4T preclinical scanner. Specimens were divided into 12 segments for both calculation of storage modulus (G' in kilopascals) and pathology (Gleason score) as reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve were calculated to assess PCa detection. RESULTS: The mean G' and SD were as follows: all segments, 8.74 ± 5.26 kPa; healthy segments, 5.44 ± 4.40 kPa; and cancerous segments, 10.84 ± 4.65 kPa. The difference between healthy and cancerous segments was significant with P ≤ .001. Diagnostic performance assessed with the Youden index was as follows: sensitivity, 69%; specificity, 79%; area under the curve, 0.81; and cutoff, 10.67 kPa. CONCLUSION: Our results suggest that prostate MR elastography has the potential to improve diagnostic performance of multiparametric MRI, especially regarding its 2 major limitations: interobserver variability and low specificity. Particularly the high value for specificity in PCa detection is a stimulating result and encourages further investigation of this method.

Diagnostic performance of tomoelastography of the liver and spleen for staging hepatic fibrosis.

OBJECTIVES: To determine the diagnostic performance, cut-off values, and optimal drive frequency range for staging hepatic fibrosis using tomoelastography by multifrequency MR elastography of the liver and spleen. METHODS: This prospective study consecutively enrolled a total of 61 subjects between June 2014 and April 2017: 45 patients with chronic liver disease and proven stage of fibrosis and 16 healthy volunteers. Tomoelastography was performed at 1.5 T using six drive frequencies from 35 to 60 Hz. Cut-off values and AUC were calculated. Shear wave speed (in m/s) of the liver and spleen was assessed separately and in combination as a surrogate of stiffness. RESULTS: For compound multifrequency processing of the liver, cut-off and AUC values by fibrosis stage were as follows: F1, 1.52 m/s and 0.89; F2, 1.55 m/s and 0.94; F3, 1.67 m/s and 0.98; and F4, 1.72 m/s and 0.98. Diagnostic performance of the best single drive frequencies (45 Hz, 55 Hz, 60 Hz) was similar (mean AUC = 0.95, respectively). Combined analysis of the liver and spleen slightly improved performance at 60 Hz in F4 patients (mean AUC = 0.97 vs. 0.95, p = 0.03). Full-field-of-view elastograms displayed not only the liver and spleen but also small anatomical structures including the pancreas and major vessels. CONCLUSION: Tomoelastography provides full-field-of-view elastograms with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. Our analysis of single-frequency tomoelastography suggests that scan time can be further reduced in future studies, making tomoelastography easier to implement in clinical routine. KEY POINTS: • Tomoelastography provides full-field-of-view elastograms of the abdomen with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. • Diagnostic performance of single-frequency tomoelastography at higher frequencies (45 Hz, 55 Hz, 60 Hz) and compound multifrequency processing are equivalent for staging hepatic fibrosis. • Combined assessment of hepatic and splenic stiffness slightly improves diagnostic performance for staging hepatic fibrosis.

Tomoelastography of the prostate using multifrequency MR elastography and externally placed pressurized-air drivers.

PURPOSE: To demonstrate the feasibility of in vivo multifrequency magnetic resonance elastography (MRE) of the prostate using externally placed drivers. METHODS: Three pressurized-air drivers were used to excite shear waves within the prostate at vibration frequencies of 60, 70, and 80 Hz. Full 3D wave fields were acquired by multislice spin-echo echo-planar imaging in conjunction with tomoelastography wave speed recovery for generating full field-of-view stiffness maps. Twelve healthy volunteers were repeatedly scanned to analyze test-retest reproducibility. Five patients with suspected prostate cancer were investigated to demonstrate the clinical feasibility of the method. RESULTS: In healthy volunteers, the shear wave speed of the entire prostate was 2.24 ± 0.20 m/s with a repeatability coefficient of 0.14 m/s and 88% intraclass correlation coefficient. No significant difference between the peripheral zone (2.27 ± 0.20 m/s) and the central gland (2.22 ± 0.23 m/s) was observed. In patients, wave-speed maps displayed stiff regions consistent with the localization of suspicious masses detected by other imaging markers. CONCLUSIONS: The proposed method provides reproducible quantitative maps of tissue stiffness throughout the pelvic region and can easily be integrated into clinical imaging protocols. Clinical stiffness maps display many details of potential interest for cancer diagnosis. Magn Reson Med 79:1325-1333, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

MR elastography of the liver and the spleen using a piezoelectric driver, single-shot wave-field acquisition, and multifrequency dual parameter reconstruction.

PURPOSE: Viscoelastic properties of the liver are sensitive to fibrosis. This study proposes several modifications to existing magnetic resonance elastography (MRE) techniques to improve the accuracy of abdominal MRE. METHODS: The proposed method comprises the following steps: (i) wave generation by a nonmagnetic, piezoelectric driver suitable for integration into the patient table, (ii) fast single-shot 3D wave-field acquisition at four drive frequencies between 30 and 60 Hz, and (iii) single-step postprocessing by a novel multifrequency dual parameter inversion of the wave equation. The method is tested in phantoms, healthy volunteers, and patients with portal hypertension and ascites. RESULTS: Spatial maps of magnitude and phase of the complex shear modulus were acquired within 6-8 min. These maps are not subject to bias from inversion-related artifacts known from classic MRE. The spatially averaged modulus for healthy liver was 1.44 ± 0.23 kPa with ϕ = 0.492 ± 0.064. Both parameters were significantly higher in the spleen (2.29 ± 0.97 kPa, P = 0.015 and 0.749 ± 0.144, P = 6.58·10(-5) , respectively). CONCLUSION: The proposed method provides abdominal images of viscoelasticity in a short time with spatial resolution comparable to conventional MR images and improved quality without being compromised by ascites. The new setup allows for the integration of abdominal MRE into the clinical workflow.

Towards compression-sensitive magnetic resonance elastography of the liver: sensitivity of harmonic volumetric strain to portal hypertension.

PURPOSE: To assess induced oscillating volumetric strain as a biomarker for intrahepatic blood pressure abnormalities. MATERIALS AND METHODS: Harmonic vibrations of 25 and 50 Hz frequency were induced in the liver and measured by fast 3D vector field magnetic resonance elastography (MRE), followed by processing of the decomposed curl (shear) and divergence (compression) fields. After an initial study on an excised sheep liver, a group of 13 patients with hepatic hypertension were examined before and after implantation of a transjugular intrahepatic portosystemic shunt (TIPS). RESULTS: In the sheep liver specimen, volumetric strain decreased with excess portal pressure, whereas shear strain was not sensitive to portal pressure. In the patient cohort, volumetric strain was significantly higher after TIPS placement (P = 1.38·10(-5) ), while neither shear strain nor the shear modulus were affected. Normalized changes in volumetric strain were significantly correlated with the hepatic venous pressure gradient (R(2) = 0.7258, P = 6.95·10(-5) ) and portal venous pressure (R(2) = 0.5028, P = 0.0016). CONCLUSION: These results indicate for the first time the sensitivity of volumetric strain to symptomatically high values of tissue pressure and motivate further developments in compression-sensitive MRE and poroelastography towards image-based and noninvasive markers of tissue pressure.

1-Norm waveform analysis for MR elastography-based quantification of inhomogeneity: Effects of the freeze-thaw cycle and Alzheimer's disease.

BACKGROUND: Despite its success in the mechanical characterization of biological tissues, magnetic resonance elastography (MRE) uses ill-posed wave inversions to estimate tissue stiffness. 1-Norm has been recently introduced as a mathematical measure for the scattering of mechanical waves due to inhomogeneities based on an analysis of the delineated contours of wave displacement. PURPOSE: To investigate 1-Norm as an MRE-based quantitative biomarker of mechanical inhomogeneities arising from microscopic structural tissue alterations caused by the freeze-thaw cycle (FTC) or Alzheimer's disease (AD). METHODS: In this proof-of-concept study, we prospectively investigated excised porcine kidney (n = 6), liver (n = 6), and muscle (n = 6) before vs. after the FTC at 500-2000 Hz and excised murine brain of healthy controls (n = 3) vs. 5xFAD species with AD (n = 3) at 1200-1800 Hz using 0.5 T tabletop MRE. 1-Norm analysis was compared with conventional wave inversion. RESULTS: While the FTC reduced both stiffness and inhomogeneity in kidney, liver, and muscle tissue, AD led to lower brain stiffness but more pronounced mechanical inhomogeneity. CONCLUSION: Our preliminary results show that 1-Norm is sensitive to tissue mechanical inhomogeneity due to FTC and AD without relying on ill-posed wave inversion techniques. 1-Norm has the potential to be used as an MRE-based diagnostic biomarker independent of stiffness to characterize abnormal conditions that involve changes in tissue mechanical inhomogeneity.

MR elastography in a murine stroke model reveals correlation of macroscopic viscoelastic properties of the brain with neuronal density.

The aim of this study was to investigate the influence of neuronal density on viscoelastic parameters of living brain tissue after ischemic infarction in the mouse using MR elastography (MRE). Transient middle cerebral artery occlusion (MCAO) in the left hemisphere was induced in 20 mice. In vivo 7-T MRE at a vibration frequency of 900 Hz was performed on days 3, 7, 14 and 28 (n = 5 per group) after MCAO, followed by the analysis of histological markers, such as neuron counts (NeuN). MCAO led to a significant reduction in the storage modulus in the left hemisphere relative to contralateral values (p = 0.03) without changes over time. A correlation between storage modulus and NeuN in both hemispheres was observed, with correlation coefficients of R = 0.648 (p = 0.002, left) and R = 0.622 (p = 0.003, right). The loss modulus was less sensitive to MCAO, but correlated with NeuN in the left hemisphere (R = 0.764, p = 0.0001). In agreement with the literature, these results suggest that the shear modulus in the brain is reduced after transient ischemic insult. Furthermore, our study provides evidence that the in vivo shear modulus of brain tissue correlates with neuronal density. In diagnostic applications, MRE may thus have diagnostic potential as a tool for image-based quantification of neurodegenerative processes.

Ex vivo magnetic resonance elastography of the small bowel in Crohn's disease.

Background: Conventional magnetic resonance enterography is limited in differentiating active inflammation and fibrosis in lesions of Crohn's disease (CD), thus providing a restricted basis for therapeutic decision making. Magnetic resonance elastography (MRE) is an emerging imaging tool that differentiates soft tissues on the basis of their viscoelastic properties. The aim of this study was to demonstrate the feasibility of MRE in assessing the viscoelastic properties of small bowel samples and quantifying differences in viscoelastic properties between healthy ileum and ileum affected by CD. Methods: Twelve patients (median age: 48 years) were prospectively enrolled in this study between September 2019 and January 2021. Patients of the study group (n=7) underwent surgery for terminal ileal CD, while patients of the control group (n=5) underwent segmental resection of healthy ileum. MRE of ileal tissue samples of surgical specimens from both groups was performed in a compact tabletop MRI scanner. Penetration rate (a in m/s) and shear wave speed (c in m/s) were determined as markers of viscosity and stiffness for vibration frequencies f of 1,000, 1,500, 2,000, 2,500, and 3,000 Hz. Additionally, damping ratio γ was deduced, and frequency-independent viscoelastic parameters were calculated using the viscoelastic spring-pot model. Results: Penetration rate a was significantly lower in CD-affected ileum compared to healthy ileum for all vibration frequencies (P<0.05). Consistently, damping ratio γ was higher in CD-affected ileum, averaged over all frequencies (healthy: 0.58±0.12, CD: 1.04±0.55, P=0.03), as well as at 1,000 and 1,500 Hz individually (P<0.05). Spring-pot-derived viscosity parameter η was also significantly reduced in CD-affected tissue (2.62±1.37 versus 10.60±12.60 Pa·s, P=0.02). No significant difference was found for shear wave speed c between healthy and diseased tissue at any frequency (P>0.05). Conclusions: MRE of surgical small bowel specimens is feasible, allowing determination of viscoelastic properties and reliable quantification of differences in viscoelastic properties between healthy and CD-affected ileum. Thus, the results presented here are an important prerequisite for future studies investigating comprehensive MRE mapping and exact histopathological correlation including characterization and quantification of inflammation and fibrosis in CD.

Feasibility of in vivo magnetic resonance elastography of mesenteric adipose tissue in Crohn's disease.

Background: Although there is growing evidence that functional involvement and structural changes of mesenteric adipose tissue (MAT) influence the course of Crohn's disease (CD), its viscoelastic properties remain elusive. Therefore, we aimed to investigate the viscoelastic properties of MAT in CD using magnetic resonance elastography (MRE), providing reference values for CD diagnosis. Methods: In this prospective proof-of-concept study, 31 subjects (CD: n=11; healthy controls: n=20) were consecutively enrolled in a specialized care center for inflammatory bowel diseases (tertiary/quaternary care). Inclusion criteria for the CD patients were a clinically and endoscopically established diagnosis of CD based on the clinical record, absence of other concurrent bowel diseases, scheduled surgery for the following day, and age of at least 18 years. Diagnoses were confirmed by histological analysis of the resected bowel the day after MRE. Subjects were investigated using MRE at 1.5-T with frequencies of 40-70 Hz. To retrieve shear wave speed (SWS), volumes of interest (VOIs) in MAT were drawn adjacent to CD lesions (MATCD) and on the opposite side without adjacent bowel lesions in patients (MATCD_Opp) and controls (MATCTRL). The presented study is not registered in the clinical trial platform. Results: A statistically significant decrease in mean SWS of 7% was found for MATCD_Opp vs. MATCTRL (0.76±0.05 vs. 0.82±0.04 m/s, P=0.012), whereas there was a nonsignificant trend with an 8% increase for MATCD vs. MATCD_Opp (0.82±0.07 vs. 0.76±0.05 m/s, P=0.098) and no difference for MATCD vs. MATCTRL. Preliminary area under the receiver operating characteristic curve (AUC) analysis showed diagnostic accuracy in detecting CD to be excellent for SWS of MATCD_Opp [AUC =0.82; 95% confidence interval (CI): 0.64-0.96] but poor for SWS of MATCD (AUC =0.52; 95% CI: 0.34-0.73). Conclusions: This study demonstrates the feasibility of MRE of MAT and presents preliminary reference values for CD patients and healthy controls. Our results motivate further studies for the biophysical characterization of MAT in inflammatory bowel disease.

Tabletop MR elastography for investigating effects of the freeze-thaw cycle on the mechanical properties of biological tissues.

PURPOSE: We aimed at characterizing the effects of the freeze-thaw cycle (FTC) on ex vivo specimens of porcine muscle, liver, kidney, and brain using tabletop magnetic resonance elastography (MRE) combined with rheological modeling. While frozen tissue banks potentially facilitate access to large amounts of well-preserved biospecimens, the impact of the FTC on their viscoelastic properties remains elusive. METHODS: In this proof-of-concept study, fresh specimens from porcine lumbar muscle (n = 6), liver (n = 6), kidney (n = 6), and brain (n = 6) were examined before and after the FTC using 0.5T tabletop MRE at 500 Hz, 1000 Hz, 1500 Hz, and 2000 Hz. Seven standard rheological models (Maxwell, Springpot, Voigt, Zener, Jeffrey, fractional Voigt, fractional Zener) were employed to calculate frequency independent viscoelastic parameters. RESULTS: The Zener rheological model showed the best fit quality for tissues before and after FTC in the investigated frequency range. Global rheological behavior after the FTC was softer for all tissues. Differences in mechanical parameters between tissues were preserved after the FTC and showed similar trends as before the FTC. Moreover, rheological fit quality improved after the FTC - a result that will be beneficial in investigating frozen tissue bank samples. CONCLUSION: Multifrequency tabletop MRE allows rheological characterization of tissue samples before and after the FTC. Our results encourage further biomechanical characterization of frozen tissue bank samples, which may provide valuable information on the diagnostic potential of elastographic methods.

Diagnostic Accuracy of Magnetic Resonance Enterography for the Evaluation of Active and Fibrotic Inflammation in Crohn's Disease.

Background: Despite the success of standard magnetic resonance enterography (MRE) in detecting Crohn's disease (CD), characterization of strictures and, thus, therapy guidance is still limited. The aim of the study was to determine diagnostic accuracy of MRE in detecting or ruling out active inflammation and identifying fibrotic lesions in patients with terminal ileal CD with histopathology as reference. Methods: Sixty-seven consecutive patients (median age 32 years, range 19-79 years) with terminal ileal CD were retrospectively enrolled between January 2015 and October 2020. The median interval between MRE and surgery was 9 days (range 0-86 days). Sensitivity, specificity, positive and negative predictive value (PPV and NPV, respectively), and area under the curve (AUC) with 95% confidence intervals (CIs) were calculated for the MRE-based AIS (acute inflammation score) using the histopathology of surgical specimens as the reference standard. Results: Sensitivity, specificity, PPV, and NPV for detecting or ruling out active inflammation were 100% (CI, 0.94-1.00; 0.44-1.00; 0.93-1.00; 0.31-1.00) using an AIS cut-off of >4.1. AUC was 1.00 (CI, 1.00-1.00; p < 0.01). In all patients with fibrotic changes only and no active inflammation, AIS was <4.1. Interobserver agreement was substantial (κ = 0.65, p < 0.01). Conclusion: Our study has shown an excellent diagnostic performance of the MRE-based AIS for determining whether active inflammation is present or lesions are due to chronic changes in ileal CD using the histopathology of surgical specimens as reference. These findings indicate that the MRE-based AIS allows a better determination of the inflammatory stage of terminal ileal CD, which facilitates the decision to perform surgery.

Investigating the heterogeneity of viscoelastic properties in prostate cancer using MR elastography at 9.4T in fresh prostatectomy specimens.

PURPOSE: To quantify the heterogeneity of viscoelastic tissue properties in prostatectomy specimens from men with prostate cancer (PC) using MR elastography (MRE) with histopathology as reference. METHODS: Twelve fresh prostatectomy specimens were examined in a preclinical 9.4T MRI scanner. Maps of the complex shear modulus (|G*| in kPa) with its real and imaginary part (G' and G" in kPa) were calculated at 500 Hz. Prostates were divided into 12 segments for segment-wise measurement of viscoelastic properties and histopathology. Coefficients of variation (CVs in %) were calculated for quantification of heterogeneity. RESULTS: Group-averaged values of cancerous vs. benign segments were significantly increased: |G*| of 12.13 kPa vs. 6.14 kPa, G' of 10.84 kPa vs. 5.44 kPa and G" of 5.45 kPa vs. 2.92 kPa, all p < 0.001. In contrast, CVs were significantly increased for benign segments: 23.59% vs. 26.32% (p = 0.014) for |G*|, 27.05% vs. 37.84% (p < 0.003) for G', and 36.51% vs. 50.37% (p = 0.008) for G". DISCUSSION: PC is characterized by a stiff yet homogeneous biomechanical signature, which may be due to the unique nondestructive growth pattern of PC with intervening stroma, providing a rigid scaffold in the affected area. In turn, increased heterogeneity in benign prostate segments may be attributable to the presence of different prostate zones with involvement by specific nonmalignant pathology.

Multifrequency magnetic resonance elastography-based tomoelastography of the parotid glands-feasibility and reference values.

OBJECTIVES: Accurate radiological differentiation of parotid tumors remains challenging despite recent technical advances in quantitative medical imaging. Multifrequency magnetic resonance elastography (MRE) could provide additional information on viscoelastic properties of normal and abnormal biological tissues. This study investigates the feasibility of MRE of the parotid glands in healthy participants and provides first reference values. METHODS: 20 healthy participants underwent multifrequency MRE of both parotid glands at 3 Tesla. Shear waves at frequencies of 25, 30, 40, and 50 Hz were introduced into the participants' heads through the occiput using pressurized-air actuators. Shear wave speed (SWS) and loss angle of the shear modulus (φ) were reconstructed by tomoelastography post-processing as surrogate parameters for tissue stiffness and viscosity or fluidity. 10 participants underwent repeated MRE to determine test-retest reliability based on intraclass correlation coefficients. RESULTS: All MRE datasets acquired could be included in the analysis. Mean SWS was 0.97 ± 0.13 m/s, and mean φ was 0.59 ± 0.05 rad, each for both sides combined and without notable lateral difference (p = 0.88/0.87). Test-retest reliability was good for SWS (ICC = 0.84 for both sides/ICC = 0.77 for the right side/ICC = 0.79 for the left side) and good to excellent for φ(ICC = 0.94/0.86/0.90). CONCLUSIONS: Multifrequency MRE of the parotid glands is feasible and reliable. This technique, therefore, is a promising method for investigating the viscoelastic properties of salivary gland tumors in future studies.

Influence of fibrosis progression on the viscous properties of in vivo liver tissue elucidated by shear wave dispersion in multifrequency MR elastography.

PURPOSE: Many elastography studies have shown that liver stiffness increases with fibrosis and thus can be used as a reliable marker for noninvasively staging fibrosis. However, the sensitivity of viscosity-related mechanical parameters, such as shear wave dispersion, to liver fibrosis is less well understood. METHODS: In this proof-of-concept study, 15 healthy volunteers and 37 patients with chronic liver disease and biopsy-proven fibrosis were prospectively investigated by MR elastography at six drive frequencies of 35-60 Hz. Maps of shear wave speed (SWS, in m/s) and loss angle (φ, in rad), as a marker of stiffness and viscous properties, respectively, were generated using tomoelastography data processing. The Child-Pugh score was used to assess cirrhosis severity. RESULTS: While SWS increased with fibrosis (F0: 1.53 ± 0.11 m/s, F1-F3: 1.71 ± 0.17 m/s, F4: 2.50 ± 0.39 m/s; P < 0.001), φ remained unchanged during mild to severe fibrosis (F0: 0.63 ± 0.05 rad, F1-F3: 0.60 ± 0.05 rad, P = 0.21) but increased in cirrhosis (F4: 0.81 ± 0.16 rad; P < 0.001). Correspondingly, the slope of SWS-dispersion within the investigated range of vibration frequencies increased from insignificant (F0-F3: 0.010 ± 0.007 m/s/Hz) to significant (F4: 0.038 ± 0.025 m/s/Hz; P = 0.005). Significant correlation with the Child-Pugh score was found for φ (R = 0.60, P = 0.01) but not for SWS. CONCLUSION: Although cirrhosis is associated with liver stiffening and, intuitively, transition towards more rigid material properties, the observed increases in φ and slope of SWS-dispersion indicate abnormally high mechanical friction in cirrhotic livers. This biophysical signature might provide a prognostic imaging marker for the detection of pathological processes associated with fibrosis independent of stiffness.

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis vs. viral hepatitis assessed by MR elastography.

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis (PSC) in comparison to viral hepatitis was assessed as a potential new biomarker using MR elastography (MRE). In this proof-of-concept study, we hypothesized a rather increased heterogeneity in PSC and a rather homogeneous distribution in viral hepatitis. Forty-six consecutive subjects (PSC: n = 20, viral hepatitis: n = 26) were prospectively enrolled between July 2014 and April 2017. Subjects underwent multifrequency MRE (1.5 T) using drive frequencies of 35-60 Hz and generating shear-wave speed (SWS in m/s) maps as a surrogate of stiffness. The coefficient of variation (CV in %) was determined to quantify fibrosis heterogeneity. Mean SWS and CV were 1.70 m/s and 21% for PSC, and 1.84 m/s and 18% for viral hepatitis. Fibrosis heterogeneity was significantly increased for PSC (P = 0.04) while no difference was found for SWS of PSC and viral hepatitis (P = 0.17). Global hepatic stiffness was similar in PSC and viral hepatitis groups, but spatial heterogeneity may reveal spatial patterns of stiffness changes towards enhanced biophysics-based diagnosis by MRI.

In Vivo Quantification of Water Diffusion, Stiffness, and Tissue Fluidity in Benign Prostatic Hyperplasia and Prostate Cancer.

OBJECTIVES: Water diffusion, tissue stiffness, and viscosity characterize the biophysical behavior of tumors. However, little is known about how these parameters correlate in prostate cancer (PCa). Therefore, we paired tomoelastography of the prostate with diffusion-sensitive magnetic resonance imaging for the quantitative mapping of biophysical parameters in benign prostatic hyperplasia (BPH) and PCa. MATERIALS AND METHODS: Multifrequency magnetic resonance imaging elastography with tomoelastography processing was performed at 60, 70, and 80 Hz using externally placed compressed-air drivers. Shear-wave speed (SWS) and loss angle (φ) were analyzed as surrogate markers of stiffness and viscosity-related fluidity in the normal peripheral zone (PZ), hyperplastic transition zone (TZ), which is consistent with BPH, and PCa lesions. The SWS and φ were correlated with the normalized apparent diffusion coefficient (nADC). RESULTS: Thirty-nine men (median age/range, 67/49-88 years), 25 with BPH and 14 with biopsy-proven PCa, were prospectively enrolled in this institutional review board-approved study. The SWS in PCa (3.1 ± 0.6 m/s) was higher than in TZ (2.8 ± 0.3 m/s, P = 0.004) or tended to be higher than in PZ (2.8 ± 0.4 m/s, P = 0.025). Similarly, φ in PCa (1.1 ± 0.1 rad) was higher than in TZ (0.9 ± 0.2 m/s, P < 0.001) and PZ (0.9 ± 0.1 rad, P < 0.001), whereas nADC in PCa (1.3 ± 0.3) was lower than in TZ (2.2 ± 0.4, P < 0.001) and PZ (3.1 ± 0.7, P < 0.001). Pooled nADC was inversely correlated with φ (R = -0.6, P < 0.001) but not with SWS. TZ and PZ only differed in nADC (P < 0.001) but not in viscoelastic properties. Diagnostic differentiation of PCa from normal prostate tissues, as assessed by area under the curve greater than 0.9, was feasible using nADC and φ but not SWS. CONCLUSIONS: Tomoelastography provides quantitative maps of tissue mechanical parameters of the prostate. Prostate cancer is characterized by stiff tissue properties and reduced water diffusion, whereas, at the same time, tissue fluidity is increased, suggesting greater mechanical friction inside the lesion. This biophysical signature correlates with known histopathological features including increased cell density and fibrous protein accumulation.

An investigation into the relationship between inhomogeneity and wave shapes in phantoms and ex vivo skeletal muscle using Magnetic Resonance Elastography and finite element analysis.

Soft biological tissues such as skeletal muscle and brain white matter can be inhomogeneous and anisotropic due to the presence of fibers. Unlike biological tissue, phantoms with known microstructure and defined mechanical properties enable a quantitative assessment and systematic investigation of the influence of inhomogeneities on the nature of shear wave propagation. This study introduces a mathematical measure for the wave shape, which the authors call as the 1-Norm, to determine the conditions under which homogenization may be a valid approach. This is achieved through experimentation using the Magnetic Resonance Elastography technique on 3D printed inhomogeneous fiber phantoms as well as on ex-vivo porcine lumbus muscle. In addition, Finite Element Analysis is used as a tool to decouple the effects of directional anisotropy from those of inhomogeneity. A correlation is then established between the values of 1-Norm derived from the wave front geometry, and the spacing (d) between neighboring inhomogeneities (spherical inclusions or fibers and fiber intersections in phantoms and muscle). Smaller values of 1-Norm indicate less wave scattering at the locations of fiber intersections, which implies that the wave propagation may be approximated to that of a homogeneous medium; homogenization may not be a valid approximation when significant scattering occurs at the locations of inhomogeneities. In conclusion, the current study proposes 1-Norm as a quantitative measure of the magnitude of wave scattering in a medium, which can potentially be used as a homogeneity index of a biological tissue.

Comparison of non-invasive assessment of liver fibrosis in patients with alpha1-antitrypsin deficiency using magnetic resonance elastography (MRE), acoustic radiation force impulse (ARFI) Quantification, and 2D-shear wave elastography (2D-SWE).

PURPOSE: Although it has been known for decades that patients with alpha1-antitrypsin deficiency (AATD) have an increased risk of cirrhosis and hepatocellular carcinoma, limited data exist on non-invasive imaging-based methods for assessing liver fibrosis such as magnetic resonance elastography (MRE) and acoustic radiation force impulse (ARFI) quantification, and no data exist on 2D-shear wave elastography (2D-SWE). Therefore, the purpose of this study is to evaluate and compare the applicability of different elastography methods for the assessment of AATD-related liver fibrosis. METHODS: Fifteen clinically asymptomatic AATD patients (11 homozygous PiZZ, 4 heterozygous PiMZ) and 16 matched healthy volunteers were examined using MRE and ARFI quantification. Additionally, patients were examined with 2D-SWE. RESULTS: A high correlation is evident for the shear wave speed (SWS) determined with different elastography methods in AATD patients: 2D-SWE/MRE, ARFI quantification/2D-SWE, and ARFI quantification/MRE (R = 0.8587, 0.7425, and 0.6914, respectively; P≤0.0089). Four AATD patients with pathologically increased SWS were consistently identified with all three methods-MRE, ARFI quantification, and 2D-SWE. CONCLUSION: The high correlation and consistent identification of patients with pathologically increased SWS using MRE, ARFI quantification, and 2D-SWE suggest that elastography has the potential to become a suitable imaging tool for the assessment of AATD-related liver fibrosis. These promising results provide motivation for further investigation of non-invasive assessment of AATD-related liver fibrosis using elastography.