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.

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.

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.

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.

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.

Multiparametric Quantitative MRI for the Detection of IgA Nephropathy Using Tomoelastography, DWI, and BOLD Imaging.

OBJECTIVES: The aim of this study was to noninvasively evaluate changes in renal stiffness, diffusion, and oxygenation in patients with chronic, advanced stage immunoglobulin A nephropathy (IgAN) by multiparametric magnetic resonance imaging using tomoelastography, diffusion-weighted imaging (DWI), and blood oxygen level-dependent (BOLD) imaging. MATERIALS AND METHODS: In this prospective study, 32 subjects (16 patients with biopsy-proven IgAN and 16 age- and sex-matched healthy controls) underwent multifrequency magnetic resonance elastography with tomoelastography postprocessing at 4 frequencies from 40 to 70 Hz to generate shear wave speed (meter per second) maps reflecting tissue stiffness. In addition, DWI and BOLD imaging were performed to determine the apparent diffusion coefficient in square millimeter per second and T2* relaxation time in milliseconds, respectively. Regions including the entire renal parenchyma of both kidneys were analyzed. Areas under the receiver operating characteristic (AUCs) curve were calculated to test diagnostic performance. Clinical parameters such as estimated glomerular filtration rate and protein-to-creatinine ratio were determined and correlated with imaging findings. RESULTS: Success rates of tomoelastography, DWI, and BOLD imaging regarding both kidneys were 100%, 91%, and 87%, respectively. Shear wave speed was decreased in IgAN (-21%, P < 0.0001), accompanied by lower apparent diffusion coefficient values (-12%, P = 0.004). BOLD imaging was not sensitive to IgAN (P = 0.12). Tomoelastography detected IgAN with higher diagnostic accuracy than DWI (area under the curve = 0.9 vs 0.8) and positively correlated with estimated glomerular filtration rate (r = 0.66, P = 0.006). CONCLUSIONS: Chronic, advanced stage IgAN is associated with renal softening and restricted water diffusion. Tomoelastography is superior to DWI and BOLD imaging in detecting IgAN.

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 Paired With T2* Magnetic Resonance Imaging Detects Lupus Nephritis With Normal Renal Function.

OBJECTIVES: The aim of this study was to test multiparametric magnetic resonance imaging including blood oxygen level-dependent (BOLD) imaging by T2* mapping, magnetic resonance elastography (MRE) by tomoelastography, and diffusion-weighted imaging (DWI) for detecting nephropathy in patients with lupus nephritis (LN). METHODS: Forty-one subjects (25 patients with LN and 16 age- and sex-matched healthy volunteers; LN: mean age, 47.3 ± 14.8 years; 22 female subjects; volunteers: mean age, 43.9 ± 11.6 years; 13 female subjects) were prospectively enrolled. The LN group was further divided into subgroups with normal (LN-nRF, GFR > 90 mL/min per 1.73 m) and compromised renal function (LN-cRF, GFR < 90 mL/min per 1.73 m). All subjects were examined by multifrequency MRE, BOLD imaging, and DWI, yielding shear wave speed (SWS; in meter per second), T2* relaxation times (in millisecond), and apparent diffusion coefficient (ADC; in millimeter square per second), respectively. Renal subregional analysis was performed for the medulla (ME), inner cortex (CoI), and outer cortex (CoO). Imaging markers were correlated to clinical parameters such as GFR and protein-to-urine creatinine ratio. Cutoffs and area under the receiver operating curve (AUROC) were computed to test diagnostic performances. RESULTS: Compared with CoI and CoO, LN-nRF predominantly affects ME tissue (SWS: -7%, P < 0.01; T2*: +9%, P < 0.05; ADC: -5%, P = 0.27). Detection of LN-nRF was better with MRE compared with BOLD imaging and DWI (AUROC = 0.81, 0.76, not significant), whereas pairing MRE with T2* further increased diagnostic power (AUROC = 0.91). Disease progression was associated with reduction of SWS also in CoI (LN-nRF, 3.04 ± 0.38 m/s; LN-cRF, 2.60 ± 0.26 m/s; p = 0.013), allowing distinction of LN-nRF from LN-cRF (AUROC = 0.83). Diffusion-weighted imaging was only sensitive to LN-cRF in ME tissue (ADC, -12%; P < 0.05). CONCLUSIONS: Lupus nephritis with normal renal function first arises in MRE and BOLD images within ME tissue, progressing to CoI tissue once renal function becomes impaired and diffusion of tissue water changes.

Full-Field-of-View Time-Harmonic Elastography of the Native Kidney.

The purpose of this study was to analyze full-field-of-view maps of renal shear wave speed (SWS) measured by time-harmonic elastography (THE) in healthy volunteers in terms of reproducibility, regional variation and physiologic effects. The kidneys of 37 healthy volunteers were investigated by multifrequency THE. The complete renal parenchyma, as well as cortex and medulla, was analyzed. A subgroup was investigated to test reproducibility (n = 3). Significant differences between SWS in cortex, medulla and full parenchyma were observed (2.10 ± 0.17, 1.35 ± 0.11 and 1.71 ± 0.16 m/s, all p values < 0.001) with mean intra-volunteer standard deviations of repeated measurements of 0.04 m/s (1.6%), 0.06 m/s (4.0%) and 0.08 m/s (4.5%), respectively. No effects of kidney anatomy, age, body mass index, blood pressure and heart rate on SWS were observed. THE allows generation of full-field-of-view SWS maps of native kidneys with high reproducibility.

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.

Time-Harmonic Elastography of the Liver is Sensitive to Intrahepatic Pressure Gradient and Liver Decompression after Transjugular Intrahepatic Portosystemic Shunt (TIPS) Implantation.

We investigated the correlation between hepatic venous pressure gradient (HVPG) and liver shear wave speed (SWS) measured by multi-frequency time-harmonic ultrasound elastography (THE) before and after transjugular intrahepatic portosystemic shunt (TIPS) implantation. Ten patients with ascites, cirrhotic liver disease and portal hypertension were prospectively examined with invasive HVPG measurement and THE before and after TIPS implantation. HVPG and SWS decreased after TIPS placement from 20.4 ± 2.2 mmHg to 9.8 ± 4.1 mmHg (mean ± standard deviation) and from 3.87 ± 0.54 m/s to 3.27 ± 0.44 m/s. Mean reduction HVPG was -10.6 ± 3.7 mmHg, p < 0.001; mean reduction SWS was -0.60 ± 0.29 m/s, p < 0.001. A linear correlation was observed between HVPG and SWS (R = 0.59, p = 0.0061). THE-measured SWS is a first potential direct ultrasound marker for liver decompression following TIPS in ascites-associated cirrhotic liver disease and therefore might be suitable to non-invasively detect portal hypertension.

Multifrequency Magnetic Resonance Elastography for the Assessment of Renal Allograft Function.

OBJECTIVE: The aim of this study was to apply multifrequency magnetic resonance elastography (MMRE) for assessment of kidney function based on renal stiffness of allografts in transplant recipients and native kidneys in controls. METHODS: In this prospective study, MMRE was used to measure stiffness in transplant kidneys in 22 recipients (age range, 23-73 years; 7 females) and in native kidneys in 11 controls (age range, 26-55 years; 4 females) after internal review board approval. The MMRE was performed on a 1.5 T magnetic resonance imaging scanner using 4 vibration frequencies from 40 to 70 Hz. Stiffness maps were computed by multifrequency reconstruction of the magnitude shear modulus (|G*|). Clinical markers such as glomerular filtration rate (GFR) and resistive index (RI) were acquired. Differences in renal stiffness among groups were compared by Mann-Whitney U test. Correlations were tested using Pearson correlation. RESULTS: Functioning transplants had higher stiffness (|G*| = 9.00 ± 1.71 kPa) than nonfunctioning transplants (|G*| = 5.88 ± 1.71 kPa, P < 0.001) and native kidneys (|G*| = 6.63 ± 1.63 kPa, P < 0.01). A cutoff value of 7.04 kPa provided sensitivity (83.33%) and specificity (86.67%) for detecting renal allograft dysfunction with an area under the receiver operating characteristic curve value of 0.9278 (95% confidence interval, 0.83-1.00). |G*| correlated positively with GFR (r = 0.52, P = 0.015) and negatively with RI (r = -0.52, P = 0.016). CONCLUSIONS: Multifrequency magnetic resonance elastography has good diagnostic accuracy in detecting renal allograft dysfunction. Renal stiffness is significantly lower in recipients with nonfunctioning transplant kidneys and correlates with clinical markers such as GFR and RI.

Time Harmonic Elastography Reveals Sensitivity of Liver Stiffness to Water Ingestion.

The aim of the study was to test the sensitivity of liver stiffness (LS) measured by time harmonic elastography in large tissue windows to water uptake and post-prandial effects. Each subject gave written informed consent to participate in this institutional review board-approved prospective study. LS was measured by time harmonic elastography in 10 healthy volunteers pre- and post-prandially, as well as before, directly after and 2 h after drinking water. The LS-time function during water intake was measured in 14 scans over 3 h in five volunteers. LS increased by 10% (p = 0.0015) post-prandially and by 11% (p = 0.0024) after pure water ingestion, and decreased to normal values after 2 h. LS was lower after overnight fasting than after 2-h fasting (3%, p = 0.04). Over the time course, LS increased to post-water peak values 15 min after drinking 0.25 L water and remained unaffected by further ingestion of water. In conclusion, our study indicates that LS measured by time harmonic elastography represents an effective-medium property sensitive to physiologic changes in vascular load of the liver.