Time-harmonic Elastography Research Articles

Time-harmonic optical flow with applications in elastography

Abstract In this paper, we propose mathematical models for reconstructing the optical flow in time-harmonic elastography. In this image acquisition technique, the object undergoes a special time-harmonic oscillation with known frequency so that only the spatially varying amplitude of the velocity field has to be determined. This allows for a simpler multi-frame optical flow analysis using Fourier analytic tools in time. We propose three variational optical flow models and show how their minimization can be tackled via Fourier transform in time. Numerical examples with synthetic as well as real-world data demonstrate the benefits of our approach.

Multimodal assessment of brain stiffness variation in healthy subjects using magnetic resonance elastography and ultrasound time-harmonic elastography

Magnetic resonance elastography (MRE) is a noninvasive brain stiffness mapping method. Ultrasound-based transtemporal time-harmonic elastography (THE) is emerging as a cost-effective, fast alternative that has potential applications for bedside monitoring of intracranial pressure. We aim to investigate the accuracy of THE in comparison to MRE performed in the brain. Ten healthy volunteers (25–40 years old) underwent multifrequency MRE (20–35 Hz) and THE (27–56 Hz). Fiducial-marker-based optical tracking of the ultrasound field of view was used to align THE to 3D MRE. THE- and MRE-derived shear wave speed (SWS) was determined as a measure of brain stiffness and averaged within regions of various depths for cross-modality correlation analysis. MRE-measured SWS ranged from 1.0 to 1.3 m/s and was negatively correlated with age (R2 = 0.44, p = 0.035). After registration of both modalities, SWS values were linearly correlated (MRE: 1.14 ± 0.08 m/s, THE: 1.13 ± 0.10 m/s; R2 = 0.62, p = 0.007). Best agreement between modalities was achieved at depths of 40–60 mm, suggesting this range provides a viable trade-off between ultrasound attenuation and near-field bias. Similar brain regions can be consistently measured with both elastography modalities, despite the regional and individual variations of stiffness. Transtemporal THE yields stiffness values in a range similar to those obtained with more expensive MRE.

Rapid wideband characterization of viscoelastic material properties by Bessel function-based time harmonic ultrasound elastography (B-THE)

Elastography is an emerging diagnostic technique that uses conventional imaging modalities such as sonography or magnetic resonance imaging to quantify tissue stiffness. However, different elastography methods provide different stiffness values, which require calibration using well-characterized phantoms or tissue samples. A comprehensive, fast, and cost-effective elastography technique for phantoms or tissue samples is still lacking.Therefore, we propose ultrasound Bessel-fit-based time harmonic elastography (B-THE) as a novel tool to provide rapid feedback on stiffness-related shear wave speed (SWS) and viscosity-related wave penetration rate (PR) over a wide range of harmonic vibration frequencies. The method relies on external induction and B-mode capture of cylindrical shear waves that satisfy the Bessel wave equation for efficient fit-based parameter recovery. B-THE was demonstrated in polyacrylamide phantoms in the frequency range of 20–200 Hz and was cross-validated by magnetic resonance elastography (MRE) using clinical 3-T MRI and compact 0.5-T tabletop MRI scanners. Frequency-independent material parameters were derived from rheological models and validated by numerical simulations.B-THE quantified frequency-resolved SWS and PR 13 to 176 times faster than more expensive clinical MRE and tabletop MRE and have a good accuracy (relative deviation to reference: 6 %, 10 % and 4 % respectively). Simulations of liver-mimicking material phantoms showed that a simultaneous fit of SWS and PR based on the fractional Maxwell rheological model outperformed a fit on PR solely.B-THE provides a comprehensive and fast elastography technique for the quantitative characterization of the viscoelastic behavior of soft tissue mimicking materials.

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.

Rapid MR elastography of the liver for subsecond stiffness sampling.

Depicting the stiffness of biological soft tissues, MR elastography (MRE) has a wide range of diagnostic applications. The purpose of this study was to improve the temporal resolution of 2D hepatic MRE in order to provide more rapid feedback on the quality of the wavefield and ensure better temporal sampling of respiration-induced stiffness changes. We developed a rapid MRE sequence that uses 2D segmented gradient-echo spiral readout to encode 40 Hz harmonic vibrations and generate stiffness maps within 625 ms. We demonstrate the use of this technique as a rapid test for shear wave amplitudes and overall MRE image quality and as a method for monitoring respiration-induced stiffness changes in the liver in comparison to 3D MRE and ultrasound-based time-harmonic elastography. Subsecond MRE allowed monitoring of increasing shear wave amplitudes in the liver with increasing levels of external stimulation within a single breath-hold. Furthermore, the technique detected respiration-induced changes in liver stiffness with peak values (1.83 ± 0.22 m/s) at end-inspiration, followed by softer values during forced abdominal pressure (1.60 ± 0.22 m/s) and end-expiration (1.49 ± 0.22 m/s). The effects of inspiration and expiration were confirmed by time-harmonic elastography. Our results suggest that subsecond MRE of the liver is useful for checking MRE driver settings and monitoring breathing-induced changes in liver stiffness in near real time.

Stiffness pulsation of the human brain detected by non-invasive time-harmonic elastography.

Introduction: Cerebral pulsation is a vital aspect of cerebral hemodynamics. Changes in arterial pressure in response to cardiac pulsation cause cerebral pulsation, which is related to cerebrovascular compliance and cerebral blood perfusion. Cerebrovascular compliance and blood perfusion influence the mechanical properties of the brain, causing pulsation-induced changes in cerebral stiffness. However, there is currently no imaging technique available that can directly quantify the pulsation of brain stiffness in real time. Methods: Therefore, we developed non-invasive ultrasound time-harmonic elastography (THE) technique for the real-time detection of brain stiffness pulsation. We used state-of-the-art plane-wave imaging for interleaved acquisitions of shear waves at a frequency of 60Hz to measure stiffness and color flow imaging to measure cerebral blood flow within the middle cerebral artery. In the second experiment, we used cost-effective lineby-line B-mode imaging to measure the same mechanical parameters without flow imaging to facilitate future translation to the clinic. Results: In 10 healthy volunteers, stiffness increased during the passage of the arterial pulse wave from 4.8% ± 1.8% in the temporal parenchyma to 11% ± 5% in the basal cisterns and 13% ± 9% in the brain stem. Brain stiffness peaked in synchrony with cerebral blood flow at approximately 180 ± 30ms after the cardiac R-wave. Line-by-line THE provided the same stiffness values with similar time resolution as high-end plane-wave THE, demonstrating the robustness of brain stiffness pulsation as an imaging marker. Discussion: Overall, this study sets the background and provides reference values for time-resolved THE in the human brain as a cost-efficient and easy-touse mechanical biomarker associated with cerebrovascular compliance.

General guidelines for the performance of viscoelastic property identification in elastography: A Monte-Carlo analysis from a closed-form solution.

Identification of the mechanical properties of a viscoelastic material depends on characteristics of the observed motion field within the object in question. For certain physical and experimental configurations and certain resolutions and variance within the measurement data, the viscoelastic properties of an object may become non-identifiable. Elastographic imaging methods seek to provide maps of these viscoelastic properties based on displacement data measured by traditional imaging techniques, such as magnetic resonance and ultrasound. Here, 1D analytic solutions of the viscoelastic wave equation are used to generate displacement fields over wave conditions representative of diverse time-harmonic elastography applications. These solutions are tested through the minimization of a least squares objective function suitable for framing the elastography inverse calculation. Analysis shows that the damping ratio and the ratio of the viscoelastic wavelength to the size of the domain play critical roles in the form of this least squares objective function. In addition, it can be shown analytically that this objective function will contain local minima, which hinder discovery of the global minima via gradient descent methods.

The effect of smoking on quantification of aortic stiffness by ultrasound time-harmonic elastography

Smoking is a significant cardiovascular risk factor that causes stiffening of the central arteries, especially the aorta. While vessel stiffness can be determined indirectly by measuring pulse wave velocity, elastography allows image-based determination of vessel stiffness while at the same time providing information on vascular morphology. This study compares abdominal aortic wall stiffness as measured by ultrasound time-harmonic elastography (THE) in fifteen smokers and fifteen age-matched non-smoking controls without a history of cardiovascular disease. Smokers had a significantly higher abdominal aortic wall stiffness with a mean shear wave speed of 2.66 m/s (95% confidence interval (CI) 2.59–2.72 m/s) compared to 2.40 m/s (95% CI 2.34–2.47 m/s) (p < 0.01) in the group of non-smokers. All other baseline characteristics including aortic diameter showed no significant differences. Inter-rater variability was excellent with an intraclass correlation coefficient of 0.99 (95% CI 0.98–0.99). Our results show that THE is sensitive to subclinical stiffening of the aorta in young and middle-aged smokers even before morphological changes occur and may therefore has the potential to serve as a screening tool for early aortic abnormalities and longitudinal risk factors for cardiovascular health.

Valsalva Maneuver Decreases Liver and Spleen Stiffness Measured by Time-Harmonic Ultrasound Elastography

Ultrasound elastography quantitatively measures tissue stiffness and is widely used in clinical practice to diagnose various diseases including liver fibrosis and portal hypertension. The stiffness of soft organs has been shown to be sensitive to blood flow and pressure-related diseases such as portal hypertension. Because of the intricate coupling between tissue stiffness of abdominal organs and perfusion-related factors such as vascular stiffness or blood volume, simple breathing maneuvers have altered the results of liver elastography, while other organs such as the spleen are understudied. Therefore, we investigated the effect of a standardized Valsalva maneuver on liver stiffness and, for the first time, on spleen stiffness using time-harmonic elastography (THE). THE acquires full-field-of-view stiffness maps based on shear wave speed (SWS), covers deep tissues, and is potentially sensitive to SWS changes induced by altered abdominal pressure in the hepatosplenic system. SWS of the liver and the spleen was measured in 17 healthy volunteers under baseline conditions and during the Valsalva maneuver. With the Valsalva maneuver, SWS in the liver decreased by 2.2% (from a median of 1.36 m/s to 1.32 m/s; p = 0.021), while SWS in the spleen decreased by 5.2% (from a median of 1.63 m/s to 1.51 m/s; p = 0.00059). Furthermore, we observed that the decrease was more pronounced the higher the baseline SWS values were. In conclusion, the results confirm our hypothesis that the Valsalva maneuver decreases liver and spleen stiffness, showing that THE is sensitive to perfusion pressure-related changes in tissue stiffness. With its extensive organ coverage and high penetration depth, THE may facilitate translation of pressure-sensitive ultrasound elastography into clinical routine.

Liquid-Liver Phantom: Mimicking the Viscoelastic Dispersion of Human Liver for Ultrasound- and MRI-Based Elastography.

Tissue stiffness can guide medical diagnoses and is exploited as an imaging contrast in elastography. However, different elastography devices show different liver stiffness values in the same subject, hindering comparison of values and establishment of system-independent thresholds for disease detection. There is a need for standardized phantoms that specifically address the viscosity-related dispersion of stiffness over frequency. To improve standardization of clinical elastography across devices and platforms including ultrasound and magnetic resonance imaging (MRI), a comprehensively characterized phantom is introduced that mimics the dispersion of stiffness of the human liver and can be generated reproducibly. The phantom was made of linear polymerized polyacrylamide (PAAm) calibrated to the viscoelastic properties of healthy human liver in vivo as reported in the literature. Stiffness dispersion was analyzed using the 2-parameter springpot model fitted to the dispersion of shear wave speed of PAAm, which was measured by shear rheometry, ultrasound-based time-harmonic elastography, clinical magnetic resonance elastography (MRE), and tabletop MRE in the frequency range of 5 to 3000 Hz. Imaging parameters for ultrasound and MRI, reproducibility, aging behavior, and temperature dependency were assessed. In addition, the frequency bandwidth of shear wave speed of clinical elastography methods (Aplio i900, Canon; Acuson Sequoia, Siemens; FibroScan, EchoSense) was characterized. Within the entire frequency range analyzed in this study, the PAAm phantom reproduced well the stiffness dispersion of human liver in vivo despite its fluid properties under static loading (springpot stiffness parameter, 2.14 [95% confidence interval, 2.08-2.19] kPa; springpot powerlaw exponent, 0.367 [95% confidence interval, 0.362-0.373]). Imaging parameters were close to those of liver in vivo with only slight variability in stiffness values of 0.5% (0.4%, 0.6%), 4.1% (3.9%, 4.5%), and -0.63% (-0.67%, -0.58%), respectively, between batches, over a 6-month period, and per °C increase in temperature. The liquid-liver phantom has useful properties for standardization and development of liver elastography. First, it can be used across clinical and experimental elastography devices in ultrasound and MRI. Second, being a liquid, it can easily be adapted in size and shape to specific technical requirements, and by adding inclusions and scatterers. Finally, because the phantom is based on noncrosslinked linear PAAm constituents, it is easy to produce, indicating potential widespread use among researchers and vendors to standardize liver stiffness measurements.

Noninvasive Detection of Intracranial Hypertension by Novel Ultrasound Time-Harmonic Elastography.

A method for measuring intracranial pressure (ICP) noninvasively has long been sought after in neurology and neurosurgery. Treatment failure in individuals presenting with unspecific symptoms such as headache, gait disturbance, or visual impairment occurring in response to increased ICP can lead to irreversible brain injury, progressive disability, and death. Guidelines for diagnostic ICP measurement recommend intracranial placement of pressure tip catheters or lumbar puncture (LP) despite their invasiveness and possible complications. As ICP fluctuations are closely associated with changes in brain stiffness, ultrasound elastography could be a valid method to detect ICP noninvasively and with short examination times. In this pilot study, we have investigated the use of time-harmonic shear waves, introduced into the brain by an external shaker, and measured in real-time by transtemporal ultrasound, for deducing a noninvasive imaging marker sensitive to elevated ICP. To this end, we developed cerebral ultrasound time-harmonic elastography for the noninvasive quantification of shear wave speed (SWS) as a surrogate marker of cerebral stiffness in a short examination time of a few minutes. We found that SWS in patients enrolled for LP with confirmed intracranial hypertension was 1.81 ± 0.10 m/s, distinguishing them from healthy volunteers with excellent diagnostic accuracy (1.55 ± 0.08 m/s; P < 0.001; area under the curve, 0.99). Interestingly, values in symptomatic patients decreased to normal stiffness immediately after LP (1.56 ± 0.06 m/s, P < 0.001). Moreover, invasively measured opening pressure correlated with SWS measured before LP and liquid volume drained through the spinal tap with the SWS difference between the 2 measurements. Collectively, our results suggest a tight link between cerebral stiffness and ICP and demonstrate that intracranial hypertension can be detected noninvasively within short examination times, opening avenues for diagnostic applications of cerebral ultrasound time-harmonic elastography in neurology and emergency medicine.

How histopathologic changes in pediatric nonalcoholic fatty liver disease influence in vivo liver stiffness

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. About 30% of patients with NAFLD progress to the more severe condition of nonalcoholic steatohepatitis (NASH), which is typically diagnosed using liver biopsy. Liver stiffness (LS) quantified by elastography is a promising imaging marker for the noninvasive assessment of NAFLD and NASH in pediatric patients. However, the link between LS and specific histopathologic features used for clinical staging of NAFLD is not well defined. Furthermore, LS data reported in the literature can vary greatly due to the use of different measurement techniques. Uniquely, time-harmonic elastography (THE) based on ultrasound and magnetic resonance elastography (MRE) use the same mechanical stimulation, allowing us to compare LS in biopsy-proven NAFLD previously determined by THE and MRE in 67 and 50 adolescents, respectively. In the present work, we analyzed the influence of seven distinct histopathologic features on LS, including septal infiltration, bridging fibrosis, pericellular fibrosis, hepatocellular ballooning, portal inflammation, lobular inflammation, and steatosis. LS was highly correlated with periportal and lobular fibrosis as well as hepatocellular ballooning while no independent association was found for inflammation and steatosis. Based on this analysis, we propose a composite elastography score (CES) which includes the four key histopathologic features identified as mechanically relevant. Interestingly, CES-relevant histopathologic features were associated with zonal distribution patterns of pediatric NAFLD.Mechano-structural changes associated with NAFLD progression can be histopathologically staged using the CES, which is easily determined noninvasively based on LS measured by time-harmonic elastography.

Cerebral Ultrasound Time-Harmonic Elastography Reveals Softening of the Human Brain Due to Dehydration.

Hydration influences blood volume, blood viscosity, and water content in soft tissues – variables that determine the biophysical properties of biological tissues including their stiffness. In the brain, the relationship between hydration and stiffness is largely unknown despite the increasing importance of stiffness as a quantitative imaging marker. In this study, we investigated cerebral stiffness (CS) in 12 healthy volunteers using ultrasound time-harmonic elastography (THE) in different hydration states: (i) during normal hydration, (ii) after overnight fasting, and (iii) within 1 h of drinking 12 ml of water per kg body weight. In addition, we correlated shear wave speed (SWS) with urine osmolality and hematocrit. SWS at normal hydration was 1.64 ± 0.02 m/s and decreased to 1.57 ± 0.04 m/s (p < 0.001) after overnight fasting. SWS increased again to 1.63 ± 0.01 m/s within 30 min of water drinking, returning to values measured during normal hydration (p = 0.85). Urine osmolality at normal hydration (324 ± 148 mOsm/kg) increased to 784 ± 107 mOsm/kg (p < 0.001) after fasting and returned to normal (288 ± 128 mOsm/kg, p = 0.83) after water drinking. SWS and urine osmolality correlated linearly (r = −0.68, p < 0.001), while SWS and hematocrit did not correlate (p = 0.31). Our results suggest that mild dehydration in the range of diurnal fluctuations is associated with significant softening of brain tissue, possibly due to reduced cerebral perfusion. To ensure consistency of results, it is important that cerebral elastography with a standardized protocol is performed during normal hydration.

Performance of a Noninvasive Time-Harmonic Elastography Technique for Liver Fibrosis Evaluation Using Vibration Controlled Transient Elastography as Reference Method.

Aim: This study aimed to evaluate the diagnosis performance of time-harmonic elastography (THE) technique in real life in assessing liver fibrosis, considering vibration-controlled transient elastography (VCTE) as a reference method. Material and Method: We prospectively evaluated outpatients from the gastroenterology department. Liver stiffness (LS) was measured by the THE system by dedicated operators, and by VCTE by experienced operators. The diagnostic accuracy of THE in staging liver fibrosis was assessed. We also performed an intra- and interobserver reproducibility sub-analysis on a sub-group of 27 subjects, where liver stiffness measurements (LSM) were performed by a novice, an elastography expert, and an ultrasound expert. Results: Of the 165 patients, using VCTE cut-off values, 49.6% were F0-F1, 15.7% were F2, 6.6% were F3, and 28.1% were F4. A direct, significant and strong correlation (r = 0.82) was observed between LSM assessed by VCTE and THE, p < 0.0001. The cut-off for ruling out liver cirrhosis (LC) by THE on our study group was <1.61 m/s (7.77 kPa)–AUROC = 0.90 [95% CI (0.82–0.93)], Se = 90.7%, Sp = 66.6%, PPV = 55.7%, NPV = 93.9%. The cut-off for ruling in LC by THE was >1.83 m/s (10 kPa)-AUROC = 0.90 [95% CI (0.82–0.93)], p < 0.0001, Se = 65.1%, Sp = 96.7%, PPV = 90.3%, NPV = 85.7%. The overall agreement between examiners was excellent: 0.94 (95% CI: 0.89–0.97); still, the ICCs were higher for the more experienced elastography examiner: 0.92 (95% CI: 0.82–0.96) vs. 0.94 (95% CI: 0.87–0.97) vs. 0.97 (95% CI: 0.95–0.99). Conclusions: THE is a feasible and reproducible elastography technique that can accurately rule in and rule out advanced liver disease.

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

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. 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. 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. Pancreatic ultrasound THE has high repeatability and provides excellent imaging contrast based on SWS, allowing detection of PDAC without overlap to nontumorous pancreatic tissue.

Quantification of Aortic Stiffness by Ultrasound Time-Harmonic Elastography: The Effect of Intravascular Pressure on Elasticity Measures in a Porcine Model.

The aim of this study was to investigate blood pressure dependency of ultrasound time-harmonic elastography (THE) for quantification of aortic stiffness. Thoracoabdominal aortas were surgically removed from 9 healthy domestic pigs and prepared for elastographic experiments. All vessels were connected to a saline-filled water column with adjustable height and pressurized over a range of 0 to 110 mm Hg in 10 mm Hg increments to simulate different levels of mean arterial pressure. In addition, 3 of the 9 aortas were soaked in 4% buffered formaldehyde for 60 minutes to simulate pathologic aortic stiffening. Ultrasound THE was performed in each vessel at each pressure level. For each pressure level, shear-wave speed (SWS) as a measure of aortic wall stiffness and luminal diameter were recorded. The pressure range between 30 and 110 mm Hg was used for statistical evaluation as it reflects a physiological mean arterial pressure range. Linear regression analysis and multivariate analysis with a general linear model were performed to evaluate the influence of increasing intravascular pressure and vessel diameter on measured SWS. Median SWS in formalin-soaked aortas was significantly higher with 3.22 m/s (interquartile range [IQR], 0.01 m/s) versus 2.14 m/s (IQR, 0.09) at 30 mm Hg and 3.38 m/s (IQR, 0.01 m/s) versus 2.28 m/s (IQR, 0.07 m/s) at 110 mm Hg (each P = 0.01). Using linear regression analysis, an increase of aortic wall SWS of 0.017 m/s per 10 mm Hg intraluminal pressure was found in untreated aortas, whereas SWS increased by 0.020 m/s per 10 mm Hg in formalin-soaked aortas (both P = 0.001). The percentage of SWS caused by intraluminal pressure was 1.89% in formalin-soaked aortas and 2.50% in untreated aortas at 30 mm Hg and 6.61% for formalin-soaked aortas and 8.60% for untreated aortas at 110 mm Hg. Multivariate analysis showed no significant interaction of luminal diameter and measured SWS (P = 0.893). In our model, aortic stiffness measurements by ultrasound time-harmonic elastography are influenced to a small extent by mean arterial pressure in a range of 1.89% to 8.60%. These findings emphasize the potential of ultrasound THE for measuring the intrinsic stiffness of the aortic wall in clinical routine.

Monitoring Liver Stiffness Changes during Controlled Hyperthermia and Microwave Ablation Using Point Shear-Wave Elastography.

HomeRadiology: Imaging CancerVol. 1, No. 2 Previous Research HighlightsFree AccessMonitoring Liver Stiffness Changes during Controlled Hyperthermia and Microwave Ablation Using Point Shear-Wave ElastographyLuke WilkinsLuke WilkinsLuke WilkinsPublished Online:Nov 29 2019https://doi.org/10.1148/rycan.2019194013MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked InEmail Take-Away Points■ Major focus: To investigate the changes in liver stiffness following controlled hyperthermia and microwave ablation in an ex vivo bovine model using point shear-wave elastography.■ Key result: Point shear-wave elastography can provide an elasticity threshold predictive of coagulative necrosis development during microwave ablation in an ex vivo liver model.■ Impact: While there are current limitations, there are opportunities for incorporation of more advanced, real-time imaging techniques to more accurately predict zones of coagulative necrosis in tumor ablation.Noninvasive monitoring of thermal ablation can greatly decrease the risk of complications while ensuring treatment efficacy. While some thermal ablation systems have the capacity to provide real-time temperature feedback, it is typically restricted to the temperature at the device level and does not provide information on tissue temperature within the remainder of the treatment cavity. Crocetti et al explore the use of elastography as a potential method to provide real-time temperature monitoring.There are several US elastographic techniques. In point shear-wave elastography (pSWE), an acoustic radiation force is induced within the tissue. The disturbance created within the tissue moves through the tissue as a shear wave. By monitoring the corresponding tissue displacements created by the shear wave under B-mode imaging, inferences can be made regarding the stiffness of the underlying tissue. This is important for thermal ablation as it is well-known that coagulation (protein denaturation and tissue dehydration) occurs at 60°C. However, the effect of thermal-induced changes in the mechanical properties of the liver tissue has not yet been fully investigated. This article sought to investigate the changes in liver stiffness in controlled hyperthermia and microwave ablation (MWA) in an ex vivo animal model.The authors used five samples of ex vivo bovine liver that were uniformly heated to temperatures ranging from 40 to 100°C. B-mode US imaging and pSWE were then performed simultaneously. In addition, MWA was performed in 11 liver samples at 60 W. Shear wave velocity (SWV) was then measured in the regions of interest (ROIs) at 10–40 mm from the antenna. Histopathologic examination was performed to correlate mean values of SWV to treatment associated changes (within, border, or outside necrotic area). The article reports that a steep transition in liver stiffness was observed at 63.0°C ± 2.4. Through this first phase of experiments, the authors determined that the mean SWV at 60°C was 2.5 m/sec (defined as Avg60). For the next set of experiments, the threshold was defined as Avg60 + 0.5 m/sec or 3 m/sec. Eight of nine experiments showed that following stoppage of ablation when the predetermined ROI reached threshold SWV of 3 m/sec, the ROI was within the necrotic area at histologic examination. While this is notable, there was no correlation between SWV values for outside, border, and within necrosis. This markedly limits current clinical applicability of this technology. Future research may allow more accurate methods for detecting changes in tissue stiffness that would be able to predict tissue still outside the necrotic zone.Highlighted ArticleCrocetti L, Calcagni F, Gherarducci G, et al. Monitoring of thermal-induced changes in liver stiffness during controlled hyperthermia and microwave ablation in an ex vivo bovine model using point shear wave elastography. Cardiovasc Interv Radiol 2019;42(5):744–750. doi: https://doi.org/10.1007/s00270-018-02152-yHighlighted ArticleCrocetti L, Calcagni F, Gherarducci G, et al. Monitoring of thermal-induced changes in liver stiffness during controlled hyperthermia and microwave ablation in an ex vivo bovine model using point shear wave elastography. Cardiovasc Interv Radiol 2019;42(5):744–750. doi: https://doi.org/10.1007/s00270-018-02152-y Crossref, Medline, Google ScholarArticle HistoryPublished online: Nov 29 2019 FiguresReferencesRelatedDetailsCited ByRecommended Articles Elastography in Chronic Liver Disease: Modalities, Techniques, Limitations, and Future DirectionsRadioGraphics2016Volume: 36Issue: 7pp. 1987-2006US Elastography in Hepatic Fibrosis—Radiology In TrainingRadiology2021Volume: 299Issue: 2pp. 264-271Quantitative Elastography Methods in Liver Disease: Current Evidence and Future DirectionsRadiology2018Volume: 286Issue: 3pp. 738-763US Time-Harmonic Elastography: Detection of Liver Fibrosis in Adolescents with Extreme Obesity with Nonalcoholic Fatty Liver DiseaseRadiology2018Volume: 288Issue: 1pp. 99-106Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus StatementRadiology2020Volume: 296Issue: 2pp. 263-274See More RSNA Education Exhibits Ultrasound Elastography Methods: Physical Principles, Techniques, and IndicationsDigital Posters2018Spleen Elastography and Portal Hypertension: An Overview and the Nitty-GrittiesDigital Posters2018Ultrasound Elastography in Children: How We Do it and What is it Helpful For?Digital Posters2019 RSNA Case Collection Hepatic AdenomatosisRSNA Case Collection2021 Cholecystitis and CholedocholithiasisRSNA Case Collection2020Radioembolization of Liver Metastasis RSNA Case Collection2020 Vol. 1, No. 2 Metrics Downloaded 178 times Altmetric Score PDF download

Ultrasound Time-Harmonic Elastography of the Aorta: Effect of Age and Hypertension on Aortic Stiffness.

The aim of this study was to investigate ultrasound time-harmonic elastography for quantifying aortic stiffness in vivo in the context of aging and arterial hypertension. Seventy-four participants (50 healthy participants and 24 participants with long-standing hypertension) were prospectively included between January 2018 and October 2018, and underwent ultrasound time-harmonic elastography of the upper abdominal aorta. Compound maps of shear-wave speed (SWS) as a surrogate of tissue stiffness were generated from multifrequency wave fields covering the full field-of-view of B-mode ultrasound. Blood pressure and pulse wave velocity were measured beforehand. Interobserver and intraobserver agreement was determined in 30 subjects. Reproducibility of time-harmonic elastography was assessed in subgroups with repeated measurements after 20 minutes and after 6 months. Linear regression analysis, with subsequent age adjustment of SWS obtained, receiver operating characteristic analysis, and intraclass correlation coefficients (ICCs) were used for statistical evaluation. Linear regression analysis revealed a significant effect of age on SWS with an increase by 0.024 m/s per year (P < 0.001). Age-adjusted SWS was significantly greater in hypertensives (0.24 m/s; interquartile range [IQR], 0.17-0.40 m/s) than in healthy participants (0.07 m/s; IQR, -0.01 to 0.06 m/s; P < 0.001). A cutoff value of 0.15 m/s was found to differentiate best between groups (area under the receiver operating characteristic curve, 0.966; 95% confidence interval, 0.93-1.0; P < 0.001; 83% sensitivity and 98% specificity). Interobserver and intraobserver variability was excellent (ICC, 0.987 and 0.937, respectively). Reproducibility was excellent in the short term (ICC, 0.968; confidence interval, 0.878-0.992) and good in the long term (ICC, 0.844; confidence interval, 0.491-0.959). Ultrasound time-harmonic elastography of the upper abdominal aorta allows quantification of aortic wall stiffness in vivo and shows significantly higher values in patients with arterial hypertension.

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.

Non-invasive structure-function assessment of the liver by 2D time-harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test.

Accurate assessment of structural and functional characteristics of the liver could improve the diagnosis and the clinical management of patients with chronic liver diseases. However, the structure-function relationship in the progression of chronic liver disease remains elusive. The aim of this study is the combined measurement of liver function by the 13 C-methacetin Liver MAximum capacity (LiMAx) test and tissue-structure related stiffness by 2D time-harmonic elastography for the assessment of liver disease progression. LiMAx test and time-harmonic elastography were applied, and the serological scores fibrosis 4 index and aspartate aminotransferase to platelet ratio index were calculated in patients with chronic liver diseases (n=75) and healthy control subjects (n=22). In 47 patients who underwent surgery, fibrosis was graded by histological examination of the resected liver tissue. LiMAx values correlated negatively with liver stiffness (r=-0.747), aminotransferase to platelet ratio index (r=-0.604), and fibrosis 4 (r=-0.573). Median (interquartile range) LiMAx values decreased with fibrosis progression from 395μg/kg/h (371-460μg/kg/h) in participants with no fibrosis to 173μg/kg/h (126-309μg/kg/h) in patients with severe fibrosis. Median liver stiffness increased progressively with the stage of fibrosis from no fibrosis (1.56m/s [1.52-1.63m/s]) to moderate fibrosis (1.60m/s [1.54-1.67m/s]) to severe fibrosis (1.85m/s [1.76-1.92m/s]). Our findings show that structural changes in the liver due to progressing liver diseases and reflected by increased tissue stiffness correlate with a functional decline of the organ as reflected by a decreased metabolic capacity of the liver.