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.

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.

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.

US Time-Harmonic Elastography for the Early Detection of Glomerulonephritis.

Background Glomerulonephritis refers to renal diseases characterized by glomerular and tubulointerstitial fibrosis. Multifrequency US time-harmonic elastography enables the noninvasive quantification of tissue elasticity. Purpose To assess the diagnostic performance of US time-harmonic elastography for the early detection of glomerulonephritis. Materials and Methods From August 2016 through May 2017, study participants with biopsy-proven glomerulonephritis were prospectively examined with US time-harmonic elastography. Participants were subdivided according to chronic kidney disease (CKD) stage. All participants underwent elastography of both kidneys to generate full-field-of-view maps of renal shear wave speed (SWS). SWS was determined separately for the whole renal parenchyma, cortex, and medulla and was correlated with quantitative B-mode findings such as renal length and parenchymal thickness. Diagnostic performance of renal elastography was assessed with receiver operating characteristic curve analysis. Results Fifty-three participants with glomerulonephritis (mean age ± standard deviation, 49 years ± 14) and 30 healthy volunteers (mean age, 37 years ± 11) were evaluated. Age-adjusted renal SWS was lower in participants with glomerulonephritis than in healthy volunteers in the parenchyma, cortex, and medulla, with mean values of 1.55 m/sec (95% confidence interval [CI]: 1.51 m/sec, 1.59 m/sec) and 1.69 m/sec (95% CI: 1.64 m/sec, 1.74 m/sec; P < .001), respectively, in parenchyma, 1.80 m/sec (95% CI: 1.75 m/sec, 1.84 m/sec) and 2.08 m/sec (95% CI: 2.02 m/sec, 2.13 m/sec; P < .001) in cortex, and 1.25 m/sec (95% CI: 1.21 m/sec, 1.29 m/sec) and 1.33 (95% CI: 1.27 m/sec, 1.38 m/sec; P = .03) in medulla. Age-adjusted renal cortex SWS was lower in participants with glomerulonephritis and stage 1 CKD (preserved renal function) than in healthy volunteers (mean, 1.88 [95% CI: 1.81, 1.96] vs 2.08 [95% CI: 2.02, 2.13]; P < .001). In participants with CKD, renal cortex SWS values showed a positive association with estimated glomerular filtration rate (n = 39; r = 0.56; P < .001). Exploratory diagnostic performance of US time-harmonic elastography (area under the receiver operating characteristic curve [AUC], 0.89; 95% CI: 0.82, 0.97) outperformed that of B-mode parameters such as parenchymal thickness (AUC, 0.64; 95% CI: 0.51, 0.77; P < .001) and renal length (AUC, 0.55; 95% CI: 0.40, 0.68; P < .001) in identifying glomerulonephritis. Conclusion US time-harmonic elastography depicts abnormal renal stiffness in glomerulonephritis, particularly among patients with early disease and preserved renal function. Advanced chronic kidney disease is associated with further cortical softening. Time-harmonic elastography outperforms B-mode-based size quantification. © RSNA, 2019 Online supplemental material is available for this article.

A prospective study of daclatasvir and sofosbuvir in chronic HCV-infected kidney transplant recipients.

BACKGROUND: Only a few prospective trials exist regarding the use of novel direct-acting antiviral agents (DAAs) in kidney transplant recipients (KTR) with chronic hepatitis C virus (HCV) infection. METHODS: This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infected KTR and eGFR > 30 ml/min/1.73m2. Primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). Beside baseline liver biopsy, hepatic function and glucose metabolism were regularly assessed. RESULTS: Four of 16 study patients had previously failed interferon-based HCV treatment. Liver biopsy showed mostly moderate fibrosis score before therapy with DCV/SOF was initiated at a median of 10.3 years after transplantation. In total, 15 of 16 KTR achieved SVR12. One patient showed early viral relapse because of resistance-associated variants (RAVs) in the HCV NS5A region. Rescue treatment with SOF/velpatasvir/voxilaprevir resulted in SVR12. DAAs treatment led to significant improvement of liver metabolism and glucose tolerance accompanied with no therapy-associated major adverse events and excellent tolerability. CONCLUSIONS: Our study demonstrates safety, efficacy and functional benefit of DCV/SOF treatment in KTR with chronic HCV infection. We provide data on rescue strategies for treatment failures due to present RAVs and amelioration of hepatic function and glucose tolerance. TRIAL REGISTRATION: Registry name: European Clinical Trials Register; Trial registry number (Eudra-CT): 2014-004551-32 , Registration date: Aug 28th 2015.

Contrast-Enhanced Ultrasound (CEUS) and Quantitative Perfusion Analysis in Patients with Suspicion for Prostate Cancer.

PURPOSE: The aim of this study was to investigate contrast-enhanced ultrasound (CEUS) parameters acquired by software during magnetic resonance imaging (MRI) US fusion-guided biopsy for prostate cancer (PCa) detection and discrimination. MATERIALS AND METHODS: From 2012 to 2015, 158 out of 165 men with suspicion for PCa and with at least 1 negative biopsy of the prostate were included and underwent a multi-parametric 3 Tesla MRI and an MRI/US fusion-guided biopsy, consecutively. CEUS was conducted during biopsy with intravenous bolus application of 2.4 mL of SonoVue® (Bracco, Milan, Italy). In the latter CEUS clips were investigated using quantitative perfusion analysis software (VueBox, Bracco). The area of strongest enhancement within the MRI pre-located region was investigated and all available parameters from the quantification tool box were collected and analyzed for PCa and its further differentiation was based on the histopathological results. RESULTS: The overall detection rate was 74 (47 %) PCa cases in 158 included patients. From these 74 PCa cases, 49 (66 %) were graded Gleason ≥ 3 + 4 = 7 (ISUP ≥ 2) PCa. The best results for cancer detection over all quantitative perfusion parameters were rise time (p = 0.026) and time to peak (p = 0.037). Within the subgroup analysis (> vs ≤ 3 + 4 = 7a (ISUP 2)), peak enhancement (p = 0.012), wash-in rate (p = 0.011), wash-out rate (p = 0.007) and wash-in perfusion index (p = 0.014) also showed statistical significance. CONCLUSION: The quantification of CEUS parameters was able to discriminate PCa aggressiveness during MRI/US fusion-guided prostate biopsy.

Tomoelastography of the native kidney: Regional variation and physiological effects on in vivo renal stiffness.

PURPOSE: To measure normal renal stiffness in adults, taking into account regional variation, hydration, and urinary status. METHODS: Thirty-six healthy volunteers were examined by tomoelastography based on MR elastography at four frequencies, from 40 to 70 Hz and multifrequency shear wave speed recovery. Regional wave speeds were derived for the medulla, cortex (inner cortex and outer cortex), and renal pelvis, and examined for age-related effects. Subgroups were repeatedly examined for reproducibility, amount of prior water drinking, and urinary status. Variations in renal perfusion were simulated ex vivo using a porcine kidney subjected to venous water inflow at different pressures. RESULTS: Shear wave speed (stiffness) of renal parenchyma was 2.46 ± 0.12 m/s (inner cortex: 2.91 ± 0.17 m/s; outer cortex: 2.52 ± 0.11 m/s; medulla: 2.15 ± 0.08 m/s) without side differences and a tendency toward softening with age (P = 0.028). Corresponding intraclass correlation for reproducibility coefficients were 0.78 (inner cortex: 0.80; outer cortex: 0.81; medulla: 0.80). Water drinking resulted in slightly higher values in inner cortex and lower values in medulla (both P = 0.039), which was consistent with the results in perfused specimens. A full bladder led to higher renal pelvis stiffness (P = 0.004), whereas renal parenchyma remained uninfluenced. Stiffness of the porcine renal cortex increased with venous inflow pressure, whereas medulla stiffness decreased. CONCLUSIONS: Tomoelastography provides full field of view maps of renal stiffness with highly detailed resolution and sensitivity to physiological effects related to age and fluid-solid tissue interactions. These basic data could be used to compare pathological conditions in the future. Magn Reson Med 79:2126-2134, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Comparison of ultrasound shear wave elastography with magnetic resonance elastography and renal microvascular flow in the assessment of chronic renal allograft dysfunction.

Background Monitoring of renal allograft function is essential for early identification of dysfunction and improvement of kidney transplant (KTX) outcome. Purpose To non-invasively assess renal stiffness in KTX recipients using ultrasound shear wave elastography (USE) in correlation with multifrequency magnetic resonance elastography (MRE), renal allograft function, and renal microvascular flow determined using a novel ultrasound microvascular imaging technique. Material and Methods This prospective study investigated 25 KTXs (functional KTX [FCT], n = 14; chronic KTX insufficiency [DYS], n = 11) in 20 KTX recipients (mean age = 43 ± 14 years). USE was performed using a high-frequency broadband linear transducer and compared with MRE. Shear wave velocity (SWV) was correlated with the estimated glomerular filtration rate (eGFR). Qualitative differences in renal microvascular flow were obtained using SMI. Results FCT had higher SWV than DYS in both cortex and pyramids (cortex, FCT: 3.75 ± 0.82 m/s vs. DYS: 2.79 ± 0.73 m/s, P = 0.0002; pyramid, FCT: 2.89 ± 0.46 m/s vs. DYS: 2.39 ± 0.34 m/s, P = 0.044). Cutoff values of 3.265 m/s for cortex, 2.535 m/s for pyramids, and 2.985 m/s for combined non-hilar parenchyma provided sensitivities of 72.7%, 77.8%, and 90.9% and specificities of 71.4%, 78.6%, and 85.7% for detecting renal allograft dysfunction with area under the receiver operating characteristic curve (AUC) values of 0.831, 0.841, 0.925 (95% confidence interval [CI] = 0.67-0.99, 0.66-1.02, 0.83-1.03). USE correlated positively with eGFR ( r = 0.741, P = 0.0004) and with MRE-derived SWV ( r = 0.562, P = 0.004). Renal microvascular flow was decreased in DYS. Conclusion USE is sensitive to renal allograft dysfunction, which is characterized by reduced SWV and renal perfusion. USE has higher image resolution than MRE, while MRE has slightly better diagnostic accuracy.

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.

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.

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.

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.

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.

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.

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.

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.