Multifrequency Magnetic Resonance Elastography Detects Small Abdominal Lymph Node Metastasis by High Stiffness.

OBJECTIVES: Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is a clinical and research standard for evaluating malignant tumors and lymph node metastasis. However, quantitative analysis of nodal status is limited to measurement of short axis diameter (SAD), and metastatic lymph nodes below 10 mm in SAD are often not detected. The purpose of this study was to evaluate the value of multifrequency magnetic resonance elastography (MRE) when added to RECIST 1.1 for detection of lymph node metastasis. MATERIALS AND METHODS: Twenty-five benign and 82 metastatic lymph nodes were prospectively examined by multifrequency MRE at 1.5 T using tomoelastography postprocessing at 30, 40, 50, and 60 Hz (total scan time of 4 minutes). Shear wave speed as a surrogate of soft tissue stiffness was provided in m/s. Positron emission tomography-computed tomography was used as reference standard for identification of abdominal lymph node metastasis from histologically confirmed primary tumors. The diagnostic performance of MRE was compared with that of SAD according to RECIST 1.1 and evaluated by receiver operating characteristic curve analysis using generalized linear mixed models and binary logistic mixed models. Sensitivity, specificity, and predictive values were calculated for different cutoffs. RESULTS: Metastatic lymph nodes (1.90 ± 0.57 m/s) were stiffer than benign lymph nodes (0.98 ± 0.20 m/s, P < 0.001). An area under the curve of 0.95 for a cutoff of 1.32 m/s was calculated. Using a conservative approach with 1.0 specificity, we found sensitivity (SAD/MRE/MRE + SAD, 0.56/0.84/0.88), negative predictive values (0.41/0.66/0.71), and overall accuracy (0.66/0.88/0.91) to be improved using MRE and even higher for combined MRE and SAD. CONCLUSIONS: Multifrequency MRE improves metastatic abdominal lymph node detection by 25% based on higher tissue stiffness-even for lymph nodes with an SAD ≤10 mm. Stiffness information is quick to obtain and would be a promising supplement to RECIST.

Explorative study using ultrasound time-harmonic elastography for stiffness-based quantification of skeletal muscle function.

Time-harmonic elastography (THE) is an emerging ultrasound imaging technique that allows full-field mapping of the stiffness of deep biological tissues. THE's unique ability to rapidly capture stiffness in multiple tissues has never been applied for imaging skeletal muscle. Therefore, we addressed the lack of data on temporal changes in skeletal muscle stiffness while simultaneously covering stiffness of different muscles. Acquiring repeated THE scans every five seconds we quantified shear-wave speed (SWS) as a marker of stiffness of the long head (LHB) and short head (SHB) of biceps brachii and of the brachialis muscle (B) in ten healthy volunteers. SWS was continuously acquired during a 3-min isometric preloading phase, a 3-min loading phase with different weights (4, 8, and 12 kg), and a 9-min postloading phase. In addition, we analyzed temporal SWS standard deviation (SD) as a marker of muscle contraction regulation. Our results (median [min, max]) showed both SWS at preloading (LHB: 1.04 [0.94, 1.12] m/s, SHB: 0.86 [0.78, 0.94] m/s, B: 0.96 [0.87, 1.09] m/s, p < 0.001) and the increase in SWS with loading weight to be muscle-specific (LHB: 0.010 [0.002, 0.019] m/s/kg, SHB: 0.022 [0.017, 0.042] m/s/kg, B: 0.039 [0.019, 0.062] m/s/kg, p < 0.001). Additionally, SWS during loading increased continuously over time by 0.022 [0.004, 0.051] m/s/min (p < 0.01). Using an exponential decay model, we found an average relaxation time of 27 seconds during postloading. Analogously, SWS SD at preloading was also muscle-specific (LHB: 0.018 [0.011, 0.029] m/s, SHB: 0.021 [0.015, 0.027] m/s, B: 0.024 [0.018, 0.037] m/s, p < 0.05) and increased by 0.005 [0.003, 0.008] m/s/kg (p < 0.01) with loading. SWS SD did not change over loading time and decreased immediately in the postloading phase. Taken together, THE of skeletal muscle is a promising imaging technique for in vivo quantification of stiffness and stiffness changes in multiple muscle groups within seconds. Both the magnitude of stiffness changes and their temporal variation during isometric exercise may reflect the functional status of skeletal muscle and provide additional information to the morphological measures obtained by conventional imaging modalities.

Shear Wave Elastography for Assessing Liver Stiffness in HCV-Infected Kidney Transplant Recipients after Direct-Acting Antiviral Treatment: A Comparative Study with Magnetic Resonance Elastography.

Hepatitis C virus (HCV) infection can lead to hepatic fibrosis. The advent of direct-acting antivirals (DAAs) has substantially improved sustained virological response (SVR) rates. In this context, kidney transplant recipients (KTRs) are of particular interest due to their higher HCV infection rates and uncertain renal excretion and bioavailability of DAAs. We investigated liver stiffness after DAA treatment in 15 HCV-infected KTRs using ultrasound shear wave elastography (SWE) in comparison with magnetic resonance elastography (MRE). KTRs were treated with DAAs (daclatasvir and sofosbuvir) for three months and underwent SWE at baseline, end of therapy (EOT), and 3 (EOT+3) and 12 months (EOT+12) after EOT. Fourteen patients achieved SVR12. Shear wave speed (SWS)-as a surrogate parameter for tissue stiffness-was substantially lower at all three post-therapeutic timepoints compared with baseline (EOT: -0.42 m/s, p < 0.01; CI = -0.75--0.09, EOT+3: -0.43 m/s, p < 0.01; CI = -0.75--0.11, and EOT+12: -0.52 m/s, p < 0.001; CI = -0.84--0.19), suggesting liver regeneration after viral eradication and end of inflammation. Baseline SWS correlated positively with histopathological fibrosis scores (r = 0.48; CI = -0.11-0.85). Longitudinal results correlated moderately with APRI (r = 0.41; CI = 0.12-0.64) but not with FIB-4 scores (r = 0.12; CI = -0.19-0.41). Although higher on average, SWE-derived measurements correlated strongly with MRE (r = 0.64). In conclusion, SWE is suitable for non-invasive therapy monitoring in KTRs with HCV infection.

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.

Summary and overview of the first ISMRM workshop on magnetic resonance elastography, August 25-26, 2022, Berlin, Germany.

An ISMRM workshop on MR elastography was held at Charité-Universitätsmedizin Berlin on August 25-26, 2022. As an exclusively in-person event, 65 participants from 9 countries attended the workshop despite COVID-19-related restrictions. The topics of the workshop covered cellular and microtissue mechanical interactions, the development of MR elastography driver technology, approaches to inverse problems, clinical applications, and integration of MR elastography into multiparametric MRI protocols. The workshop was a great success by promoting direct knowledge exchange as well as for strategizing future directions for MR elastography. In this symposium review, we briefly summarized all oral presentations as well as the concluding panel discussion.

Comparison of inversion methods in MR elastography: An open-access pipeline for processing multifrequency shear-wave data and demonstration in a phantom, human kidneys, and brain.

PURPOSE: Magnetic resonance elastography (MRE) maps the viscoelastic properties of soft tissues for diagnostic purposes. However, different MRE inversion methods yield different results, which hinder comparison of values, standardization, and establishment of quantitative MRE markers. Here, we introduce an expandable, open-access, webserver-based platform that offers multiple inversion techniques for multifrequency, 3D MRE data. METHODS: The platform comprises a data repository and standard MRE inversion methods including local frequency estimation (LFE), direct-inversion based multifrequency dual elasto-visco (MDEV) inversion, and wavenumber-based (k-) MDEV. The use of the platform is demonstrated in phantom data and in vivo multifrequency MRE data of the kidneys and brains of healthy volunteers. RESULTS: Detailed maps of stiffness were generated by all inversion methods showing similar detail of anatomy. Specifically, the inner renal cortex had higher shear wave speed (SWS) than renal medulla and outer cortex without lateral differences. k-MDEV yielded higher SWS values than MDEV or LFE (full kidney/brain k-MDEV: 2.71 ± 0.19/1.45 ± 0.14 m/s, MDEV: 2.14 ± 0.16/0.99 ± 0.11 m/s, LFE: 2.12 ± 0.15/0.89 ± 0.06 m/s). CONCLUSION: The freely accessible platform supports the comparison of MRE results obtained with different inversion methods, filter thresholds, or excitation frequencies, promoting reproducibility in MRE across community-developed methods.

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.

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.

On the relationship between metabolic capacities and in vivo viscoelastic properties of the liver.

The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver's metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver's metabolic function in vivo. Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR) and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography-mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into 'stiff' and 'soft' subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange. In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients.

Outcomes of Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program with A Focus on Recipients ≥75 Years.

To evaluate the outcomes of kidney transplantations (KTs) in the Eurotransplant Senior Program (ESP) with a focus on the very old, defined as recipients ≥75 years. This retrospective clinical study included 85 patients, who under the ESP protocol underwent deceased donor kidney transplantation from January 2010 to July 2018 at the Charité-Universitätsmedizin Berlin in Germany. Recipients were divided in three age groups, i.e., Group 65-69, Group 70-74, Group ≥75, and compared. Prognostic risk factors for short and long-term outcomes of kidney transplantations were investigated. Graft survival at 1 and 5 years were respectively 90.7% and 68.0% for group 65-69, 88.9% and 76.2% for Group 70-74, and 100% and 71.4% for Group ≥75. Patient survival at 1 and 5 years were respectively 92.9% and 68.0% for Group 65-69, 85.7% and 61.5% for Group 70-74 and 100% and 62.5% for Group ≥75. Serum creatinine did not significantly differ between the three groups, with the exception of serum creatinine at 1 year. Increased recipient age and prolonged time on dialysis correlated with increased occurrence of postoperative complication. An increase in BMI, pretransplant diabetes mellitus and prolonged time on dialysis correlated with the occurrence of delayed graft function (DGF). History of smoking was identified as an independent risk factor for events of rejection. Increased human leukocyte antigen mismatches (HLA-MM) and prolonged cold ischemia time (CIT) correlated with higher rates of intensive care unit (ICU) treatment. This study supports kidney transplantations for the very old. End-stage renal disease (ESRD) patients ≥75 years of age who underwent kidney transplantation experienced comparable results to their younger counterparts. A comprehensive evaluation of ESRD patients with consideration of prognostic risk factor is the most suitable mean of identifying adequate kidney transplant candidates.

Added Value of Tomoelastography for Characterization of Pancreatic Neuroendocrine Tumor Aggressiveness Based on Stiffness.

PURPOSE: To evaluate the diagnostic performance of tomoelastography in differentiating pancreatic neuroendocrine tumors (PNETs) from healthy pancreatic tissue and to assess the prediction of tumor aggressiveness by correlating PNET stiffness with PET derived asphericity. METHODS: 13 patients with PNET were prospectively compared to 13 age-/sex-matched heathy volunteers (CTR). Multifrequency MR elastography was combined with tomoelastography-postprocessing to provide high-resolution maps of shear wave speed (SWS in m/s). SWS of pancreatic neuroendocrine tumor (PNET-T) were compared with nontumorous pancreatic tissue in patients with PNET (PNET-NT) and heathy pancreatic tissue (CTR). The diagnostic performance of tomoelastography was evaluated by ROC-AUC analysis. PNET-SWS correlations were calculated with Pearson's r. RESULTS: SWS was higher in PNET-T (2.02 ± 0.61 m/s) compared to PNET-NT (1.31 ± 0.18 m/s, p < 0.01) and CTR (1.26 ± 0.09 m/s, p < 0.01). An SWS-cutoff of 1.46 m/s distinguished PNET-T from PNET-NT (AUC = 0.89; sensitivity = 0.85; specificity = 0.92) and a cutoff of 1.49 m/s differentiated pancreatic tissue of CTR from PNET-T (AUC = 0.96; sensitivity = 0.92; specificity = 1.00). The SWS of PNET-T was positively correlated with PET derived asphericity (r = 0.81; p = 0.01). CONCLUSIONS: Tomoelastography provides quantitative imaging markers for the detection of PNET and the prediction of greater tumor aggressiveness by increased stiffness.

Tomoelastography for Longitudinal Monitoring of Viscoelasticity Changes in the Liver and in Renal Allografts after Direct-Acting Antiviral Treatment in 15 Kidney Transplant Recipients with Chronic HCV Infection.

Besides the liver, hepatitis C virus (HCV) infection also affects kidney allografts. The aim of this study was to longitudinally evaluate viscoelasticity changes in the liver and in kidney allografts in kidney transplant recipients (KTRs) with HCV infection after treatment with direct-acting antiviral agents (DAAs). Fifteen KTRs with HCV infection were treated with DAAs (daclatasvir and sofosbuvir) for 3 months and monitored at baseline, end of treatment (EOT), and 3 (FU1) and 12 (FU2) months after EOT. Shear-wave speed (SWS) and loss angle of the complex shear modulus (φ), reflecting stiffness and fluidity, respectively, were reconstructed from multifrequency magnetic resonance elastography data with tomoelastography post-processing. After virus elimination by DAAs, hepatic stiffness and fluidity decreased, while kidney allograft stiffness and fluidity increased compared with baseline (hepatic stiffness change at FU1: -0.14 m/s, p < 0.01, and at FU2: -0.11 m/s, p < 0.05; fluidity at FU1: -0.05 rad, p = 0.04 and unchanged at FU2: p = 0.20; kidney allograft stiffness change at FU1: +0.27 m/s, p = 0.01, and at FU2: +0.30 m/s, p < 0.01; fluidity at FU1 and FU2: +0.06 rad, p = 0.02). These results suggest the restoration of mechanically sensitive structures and functions in both organs. Tomoelastography can be used to monitor the therapeutic results of HCV treatment non-invasively on the basis of hepatic and renal viscoelastic parameters.

Distinguishing pancreatic cancer and autoimmune pancreatitis with in vivo tomoelastography.

OBJECTIVES: To prospectively investigate the stiffness and fluidity of pancreatic ductal adenocarcinoma (PDAC) and autoimmune pancreatitis (AIP) with tomoelastography, and to evaluate its diagnostic performance in distinguishing the two entities. METHODS: Tomoelastography provided high-resolution maps of shear wave speed (c in m/s) and phase angle (φ in rad), allowing mechanical characterization of the stiffness and fluidity properties of the pancreas. Forty patients with untreated PDAC and 33 patients with untreated AIP who underwent diagnostic pancreatic MRI at 3-T together with multifrequency MR elastography and tomoelastography data processing were prospectively enrolled. Ten healthy volunteers served as controls. Two radiologists and a technician measured pancreatic stiffness and fluidity independently. The two radiologists also independently evaluated the patients' conventional MR sequences using the following diagnostic score: 1, definitely PDAC; 2, probably PDAC; 3, indeterminate; 4, probably AIP; and 5, definitely AIP. Interobserver agreement was assessed. Stiffness and fluidity of PDAC, AIP, and healthy pancreas, as well as diagnostic performance of tomoelastography and conventional MRI, were compared. RESULTS: AIP showed significantly lower stiffness and fluidity than PDAC and significantly higher stiffness and fluidity than healthy pancreas. Pancreatic fluidity was not influenced by secondary obstructive changes. The intraclass correlation coefficient for pancreatic stiffness and fluidity by the 3 readers was near-perfect (0.951-0.979, all p < 0.001). Both stiffness and fluidity allowed distinguishing PDAC from AIP. AUCs were 0.906 for stiffness, 0.872 for fluidity, and 0.842 for conventional MRI. CONCLUSIONS: Pancreatic stiffness and fluidity both allow differentiation of PDAC and AIP with high accuracy. KEY POINTS: • AIP showed significantly lower stiffness and fluidity than PDAC and significantly higher stiffness and fluidity than healthy pancreas. • Both stiffness and fluidity allowed distinguishing PDAC from AIP. • Pancreatic fluidity could distinguish malignancy from non-malignant secondary obstructive changes.

Tomoelastography for non-invasive detection of ameloblastoma and metastatic neck lymph nodes.

Ameloblastoma is a benign epithelial tumour and the most common odontogenic tumour, accounting for about 18% of cases. We present a patient to illustrate the first use of tomoelastography for quantitatively mapping tissue stiffness (shear wave speed) and fluidity (loss angle of the complex shear modulus) in a metastasised ameloblastoma of the left mandible. Tomoelastography maps clearly depicted the extent of the tumour by abnormally high values of stiffness and fluidity (1.73±0.23 m/s, 1.18±0.08 rad) compared with normal values in the contralateral mandible (1.04±0.09 m/s, 0.93±0.12 rad). Abnormal stiffness also revealed metastatic involvement of the neck lymph nodes (1.30±0.03 m/s vs 0.86±0.01 m/s). Taken together, stiffness and fluidity measured by tomoelastography can sensitively detect the presence and extent of bone tumours and metastatic spread to cervical lymph nodes.

Tomoelastography for Measurement of Tumor Volume Related to Tissue Stiffness in Pancreatic Ductal Adenocarcinomas.

OBJECTIVES: Estimations of tumor volume and boundary in pancreatic ductal adenocarcinoma (PDAC) are crucial for surgery planning. The aim of the study is to evaluate tomoelastography for detection of PDAC and quantification of PDAC volume based on tissue stiffness. MATERIALS AND METHODS: From March 2018 to December 2019, a total of 102 participants (30 healthy participants and 72 patients with histologically proven PDAC) were prospectively enrolled in a multicenter study. Multifrequency magnetic resonance elastography was combined with tomoelastography postprocessing to generate maps of shear wave speed (SWS) depicting highly resolved anatomical details of tissue stiffness. Subregional analysis of pancreatic head, body, and tail and reproducibility tests were performed in healthy participants, whereas tumorous (PDAC-T) and nontumorous (PDAC-NT) pancreatic tissue analysis was conducted in patients. In all patients, tumor volumes measured by computed tomography (CT) were compared with SWS-derived volumes. In addition, in 32 patients, tumor sizes were evaluated by macroscopy after resection. RESULTS: Tumor volumes were quantified in 99% and 87% of all cases with tomoelastography and CT, respectively. Pancreatic SWS was highly reproducible (repeatability coefficient = 0.12) and did not vary regionally or with patient age, sex, or body mass index (all P > 0.08). Shear wave speed was higher in PDAC-T (2.08 ± 0.38 m/s) than in healthy (1.25 ± 0.09 m/s; P < 0.001) and PDAC-NT (1.28 ± 0.14 m/s; P < 0.001) participants. A threshold of 1.47 m/s separated PDAC-T from healthy volunteers (area under the curve = 1.0, sensitivity = 100%, specificity = 100%), while 1.49 m/s separated PDAC-T from PDAC-NT with high accuracy (area under the curve = 0.99, sensitivity = 90%, specificity = 100%). Tomoelastography-derived tumor volume correlated with CT volume (r = 0.91, P < 0.001) and ex vivo tumor volume (r = 0.66, P < 0.001). CONCLUSIONS: Tomoelastography provides a quantitative imaging marker for tissue stiffness depicting PDAC boundaries and separates PDAC from unaffected pancreatic tissue.

Ultrasound Time-Harmonic Elastography of the Pancreas: Reference Values and Clinical Feasibility.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a very low 5-year survival rate of 8%. The aims of this study are to determine reference values and physiologic confounders in healthy pancreas and to assess the diagnostic accuracy of ultrasound time-harmonic elastography (THE) in the detection of PDAC. MATERIALS AND METHODS: From March 2017 through May 2019, a total of 54 study participants with healthy pancreas (n = 33, CTR) or PDAC (n = 21) were prospectively enrolled. Repeatability of THE was tested in a CTR subgroup (n = 5) undergoing repeat measurement on 4 different days. Interobserver variability was analyzed in 10 healthy volunteers. Age-matched and sex-matched subgroups of CTR (n = 13) and PDAC (n = 13) were compared. In participants with histopathologically proven PDAC, measurements were performed separately in tumorous (PDAC-T) and nontumorous pancreatic tissue (PDAC-NT). Diagnostic performance of pancreatic THE was assessed by receiver operating characteristic curve analysis. RESULTS: Time-harmonic elastography was highly repeatable (intraclass correlation coefficient, 0.99), and interobserver agreement was excellent (intraclass correlation coefficient, 0.97). Shear wave speed (SWS) of PDAC-T (mean [95% confidence interval] in meters per second, 1.88 ± 0.07 [1.84-1.92]) was higher than SWS of CTR (1.63 ± 0.04 [1.60-1.66], P < 0.001) and PDAC-NT (1.59 ± 0.03 [1.57-1.61], P < 0.001). The exploratory diagnostic performance of THE in separating PDAC-T was excellent (area under the receiver operating characteristic curve, 1.0). Tumorous pancreatic ductal adenocarcinoma was distinguished from CTR and PDAC-NT with cutoff values of 1.73 m/s and 1.70 m/s, respectively. CONCLUSIONS: Pancreatic ultrasound THE has high repeatability and provides excellent imaging contrast based on SWS, allowing detection of PDAC without overlap to nontumorous pancreatic tissue.

Adherence to lumacaftor-ivacaftor therapy in patients with cystic fibrosis in France.

BACKGROUND: Lumacaftor-ivacaftor combination is a promising treatment for cystic fibrosis (CF) patients homozygous for the F508del-CFTR mutation. Optimal adherence is essential to achieve full health outcomes benefits. METHODS: This retrospective study used pharmacy refills data to calculate proportion of days covered (PDC). Adherence was defined as a PDC ≥80%. A logistic regression analysis was conducted to examine factors associated with medication adherence. RESULTS: Ninety-six patients were included in the final cohort for analysis. The mean PDC was 96%  ± 14 at 6 months, and 91% ± 17 at 12 months. The proportion of adherent patients was 89% and 83% at 6 and 12 months respectively. Age and ppFEV1 were found to affect medication adherence. CONCLUSIONS: Considering the medico-economic impact of CFTR modulator therapy, high adherence rates to lumacaftor-ivacaftor found in this study are encouraging.

Value of contrast-enhanced ultrasound (CEUS) in Focal Liver Lesions (FLL) with inconclusive findings on cross-sectional imaging.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique in order to evaluate focal liver lesions. CEUS is easy and fast to perform, overcomes the limitations of B-mode US. OBJECTIVE: To evaluate the diagnostic potential of contrast-enhanced ultrasound (CEUS) in focal liver lesions (FLL) with unclear findings on computed tomography (CT) or magnetic resonance imaging (MRI). METHODS: In this single-center retrospective study, 146 patients with at least one FLL underwent additional CEUS of the liver to clarify inconclusive cross-sectional imaging findings. Ultrasonography was performed using B-mode imaging and CEUS after injection of sulphur hexafluoride microbubbles (second-generation contrast agent) within two months after ceMRI or ceCT and interpreted by an experienced radiologist (EFSUMB level 3). Histopathological reports, long-term follow-up or clinical course served as reference standard. RESULTS: Thirty-eight of the 146 patients had malignant and 108 benign FLL. Overall, CEUS had 92% sensitivity (95% -CI, 79-97) and 98% specificity (95% -CI, 93-99) with an AUC of 0.95 in correctly characterizing the lesion as malignant or benign. Sensitivity increased to 98% (95% -CI, 96-100) for benign lesions and decreased to 92% (95% -CI, 78-98) for malignant lesions. CEUS showed the highest diagnostical accuracy in lesion <1 cm with an AUC of 1.000, while the lowest accuracy was achieved in lesions >2 cm with an AUC of 0.924 due to a decreasing specificity of 86% (95% -CI, 87-100). CONCLUSION: CEUS correctly distinguished malignant from benign FLL in cases with inconclusive cross-sectional imaging findings and achieved high levels of diagnostic accuracy. CEUS has added diagnostic value especially in small lesions ≤1 cm while specificity remains limited in larger lesions.

Tomoelastography Distinguishes Noninvasively between Benign and Malignant Liver Lesions.

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 (φ) 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 = 0.88 with 95% confidence interval (CI) = 0.83-0.94; φ: AUC = 0.95, 95% CI = 0.92-0.98]. Benign focal nodular hyperplasia and hepatocellular adenoma could be distinguished from malignant lesions on the basis of tumor stiffness (AUC = 0.85, 95% CI = 0.72-0.98; sensitivity = 94%, 95% CI = 89-100; and specificity = 85%, 95% CI = 62-100), tumor fluidity (AUC = 0.86, 95% CI = 0.77-0.96; sensitivity = 83%, 95% CI = 72-93; and specificity = 92%, 95% CI = 77-100) and liver stiffness (AUC = 0.84, 95% CI = 0.74-0.94; sensitivity = 72%, 95% CI = 59-83; and specificity = 88%, 95% CI = 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.

Tomoelastography for non-invasive detection and treatment monitoring in acute appendicitis.

Acute appendicitis is the most common cause of the acute abdomen syndrome and can be treated either surgically or conservatively with antibiotics. This case demonstrates the first time use of mechanics based MRI by tomoelastography with generation of quantitative maps of tissue stiffness (shear wave speed in m/s) and tissue fluidity (shear modulus loss angle, in rad) in a case of uncomplicated acute appendicitis with antibiotic treatment at (i) baseline, (ii) the end of treatment (EOT) and (iii) the 10 day follow-up after EOT. Baseline maps of stiffness and fluidity revealed to the naked eye the extent of intestinal inflammation by markedly increased values of stiffness and fluidity (2.56±0.12 m/s, 1.37±0.24 rad) compared with normal values, indicating the immediate response to antibiotic treatment at EOT (1.47±0.28 m/s, 0.80±0.11 rad) and persistent normalisation at follow-up (1.54±0.22 m/s, 0.92±0.22 rad). Tomoelastography is a non-invasive, quantitative imaging method for mechanics based characterisation and follow-up of acute appendicitis.