Long-term cognitive, psychosocial, and neurovascular complications of unilateral head and neck irradiation in young to middle-aged adults.

BACKGROUND: With a growing, younger population of head and neck cancer survivors, attention to long-term side-effects of prior, often radiotherapeutic, treatment is warranted. Therefore, we studied the long-term cognitive effects in young adult patients irradiated for head and neck neoplasms (HNN). METHODS: Young to middle-aged adults with HNN (aged 18-40 years) and treated with unilateral neck irradiation ≥ 5 years before inclusion underwent cardiovascular risk and neuropsychological assessments and answered validated questionnaires regarding subjective cognitive complaints, fatigue, depression, quality of life, and cancer-specific distress. Additionally, magnetic resonance imaging (MRI) of the brain was performed to assess white matter hyperintensities (WMH), infarctions, and atrophy. RESULTS: Twenty-nine patients (aged 24-61, 13 men) median 9.2 [7.3-12.9] years post-treatment were included. HNN patients performed worse in episodic memory (Z-score = -1.16 [-1.58-0.34], p < 0.001) and reported more fatigue symptoms (Z-score = 1.75 [1.21-2.00], p < 0.001) compared to normative data. Furthermore, patients had a high level of fear of tumor recurrence (13 patients [44.8%]) and a heightened speech handicap index (13 patients [44.8%]). Only a small number of neurovascular lesions were found (3 infarctions in 2 patients and 0.11 [0.00-0.40] mL WMH), unrelated to the irradiated side. Cognitive impairment was not associated with WMH, brain atrophy, fatigue, or subjective speech problems. CONCLUSIONS: HNN patients showed impairments in episodic memory and an increased level of fatigue ≥ 5 years after radiotherapy compared to normative data. Cognitive impairments could not be explained by WMH or brain atrophy on brain MRI or psychological factors. TRIAL REGISTRATION: Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04257968 ).

Respiratory muscle imaging by ultrasound and MRI in neuromuscular disorders.

Respiratory muscle weakness is common in neuromuscular disorders (NMDs) and leads to significant respiratory difficulties. Therefore, reliable and easy assessment of respiratory muscle structure and function in NMDs is crucial. In the last decade, ultrasound and magnetic resonance imaging (MRI) have emerged as promising imaging techniques to assess respiratory muscle structure and function. Respiratory muscle imaging directly measures the respiratory muscles and, in contrast to pulmonary function testing, is independent of patient effort. This makes respiratory muscle imaging suitable to use as a tool in clinical respiratory management and as an outcome parameter in upcoming drug trials for NMDs, particularly in children. In this narrative review, we discuss the latest studies and technological developments in imaging of the respiratory muscles by ultrasound and MRI, and its clinical application and limitations. We aim to increase understanding of respiratory muscle imaging and facilitate its use as an outcome measure in daily practice and clinical trials.

Feasibility and relevance of compound strain imaging in non-stenotic arteries: comparison between individuals with cardiovascular diseases and healthy controls.

BACKGROUND: Compound strain imaging is a novel method to noninvasively evaluate arterial wall deformation which has recently shown to enable differentiation between fibrous and (fibro-)atheromatous plaques in patients with severe stenosis. We tested the hypothesis that compound strain imaging is feasible in non-stenotic arteries and provides incremental discriminative power to traditional measures of vascular health (i.e., distensibility coefficient (DC), central pulse wave velocity [cPWV], and intima-media thickness [IMT]) for differentiating between participants with and without a history of cardiovascular diseases (CVD). METHODS: Seventy two participants (60 ± 7 years) with non-stenotic arteries (IMT < 1.1 mm) were categorized in healthy participants (CON, n = 36) and CVD patients (n = 36) based on CVD history. Participants underwent standardised ultrasound-based assessment (DC, cPWV, and IMT) and compound strain imaging (radial [RS] and circumferential [CS] strain) in left common carotid artery. Area under receiver operating characteristics (AROC)-curve was used to determine the discriminatory power between CVD and CON of the various measures. RESULTS: CON had a significantly (P < 0.05) smaller carotid IMT (0.68 [0.58 to 0.76] mm) than CVD patients (0.76 [0.68 to 0.80] mm). DC, cPWV, RS, and CS did not significantly differ between groups (P > 0.05). A higher CS or RS was associated with a higher DC (CS: r = -0.32;p < 0.05 and RS: r = 0.24;p < 0.05) and lower cPWV (CS: r = 0.24;p < 0.05 and RS: r = -0.25;p < 0.05). IMT could identify CVD (AROC: 0.66, 95%-CI: 0.53 to 0.79), whilst the other measurements, alone or in combination, did not significantly increase the discriminatory power compared to IMT. CONCLUSIONS: In non-stenotic arteries, compound strain imaging is feasible, but does not seem to provide incremental discriminative power to traditional measures of vascular health for differentiation between individuals with and without a history of CVD.

Validation of Noninvasive In Vivo Compound Ultrasound Strain Imaging Using Histologic Plaque Vulnerability Features.

BACKGROUND AND PURPOSE: Carotid plaque rupture is a major cause of stroke. Key issue for risk stratification is early identification of rupture-prone plaques. A noninvasive technique, compound ultrasound strain imaging, was developed providing high-resolution radial deformation/strain images of atherosclerotic plaques. This study aims at in vivo validation of compound ultrasound strain imaging in patients by relating the measured strains to typical features of vulnerable plaques derived from histology after carotid endarterectomy. MATERIALS AND METHODS: Strains were measured in 34 severely stenotic (>70%) carotid arteries at the culprit lesion site within 48 hours before carotid endarterectomy. In all cases, the lumen-wall boundary was identifiable on B-mode ultrasound, and the imaged cross-section did not move out of the imaging plane from systole to diastole. After endarterectomy, the plaques were processed using a validated histology analysis technique. RESULTS: Locally elevated strain values were observed in regions containing predominantly components related to plaque vulnerability, whereas lower values were observed in fibrous, collagen-rich plaques. The median strain of the inner plaque layer (1 mm thickness) was significantly higher (P<0.01) for (fibro)atheromatous (n=20, strain=0.27%) than that for fibrous plaques (n=14, strain=-0.75%). Also, a significantly larger area percentage of the inner layer revealed strains above 0.5% for (fibro)atheromatous (45.30%) compared with fibrous plaques (31.59%). (Fibro)atheromatous plaques were detected with a sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 86%, 88%, and 71%, respectively. Strain did not significantly correlate with fibrous cap thickness, smooth muscle cell, or macrophage concentration. CONCLUSIONS: Compound ultrasound strain imaging allows differentiating (fibro)atheromatous from fibrous carotid artery plaques.

Automated 3-D Ultrasound Elastography of the Breast: An In Vivo Validation Study.

OBJECTIVE: Studies have indicated that adding 2-D quasi-static elastography to B-mode ultrasound imaging improved the specificity for malignant lesion detection, as malignant lesions are often stiffer (increased strain ratio) compared with benign lesions. This method is limited by its user dependency and so unsuitable for breast screening. To overcome this limitation, we implemented quasi-static elastography in an automated breast volume scanner (ABVS), which is an operator-independent 3-D ultrasound system and is especially useful for screening women with dense breasts. The study aim was to investigate if 3-D quasi-static elastography implemented in a clinically used ABVS can discriminate between benign and malignant breast lesions. METHODS: Volumetric breast ultrasound radiofrequency data sets of 82 patients were acquired before and after automated transducer lifting. Lesions were annotated and strain was calculated using an in-house-developed strain algorithm. Two strain ratio types were calculated per lesion: using axial and maximal principal strain (i.e., strain in dominant direction). RESULTS: Forty-four lesions were detected: 9 carcinomas, 23 cysts and 12 other benign lesions. A significant difference was found between malignant (median: 1.7, range: [1.0-3.2]) and benign (1.0, [0.6-1.9]) using maximal principal strain ratios. Axial strain ratio did not reveal a significant difference between benign (0.6, [-12.7 to 4.9]) and malignant lesions (0.8, [-3.5 to 5.1]). CONCLUSION: Three-dimensional strain imaging was successfully implemented on a clinically used ABVS to obtain, visualize and analyze in vivo strain images in three dimensions. Results revealed that maximal principal strain ratios are significantly increased in malignant compared with benign lesions.

Performance evaluation of commercial and non-commercial shear wave elastography implementations for vascular applications.

BACKGROUND: Shear wave elastography (SWE) is mainly used for stiffness estimation of large, homogeneous tissues, such as the liver and breasts. However, little is known about its accuracy and applicability in thin (∼0.5-2 mm) vessel walls. To identify possible performance differences among vendors, we quantified differences in measured wave velocities obtained by commercial SWE implementations of various vendors over different imaging depths in a vessel-mimicking phantom. For reference, we measured SWE values in the cylindrical inclusions and homogeneous background of a commercial SWE phantom. Additionally, we compared the accuracy between a research implementation and the commercially available clinical SWE on an Aixplorer ultrasound system in phantoms and in vivo in patients. METHODS: SWE measurements were performed over varying depths (0-35 mm) using three ultrasound machines with four ultrasound probes in the homogeneous 20 kPa background and cylindrical targets of 10, 40, and 60 kPa of a multi-purpose phantom (CIRS-040GSE) and in the anterior and posterior wall of a homogeneous polyvinyl alcohol vessel-mimicking phantom. These phantom data, along with in vivo SWE data of carotid arteries in 23 patients with a (prior) head and neck neoplasm, were also acquired in the research and clinical mode of the Aixplorer ultrasound machine. Machine-specific estimated phantom stiffness values (CIRS phantom) or wave velocities (vessel phantom) over all depths were visualized, and the relative error to the reference values and inter-frame variability (interquartile range/median) were calculated. Correlations between SWE values and target/vessel wall depth were explored in phantoms and in vivo using Spearman's correlations. Differences in wave velocities between the anterior and posterior arterial wall were assessed with Wilcoxon signed-rank tests. Intra-class correlation coefficients were calculated for a sample of ten patients as a measure of intra- and interobserver reproducibility of SWE analyses in research and clinical mode. RESULTS: There was a high variability in obtained SWE values among ultrasound machines, probes, and, in some cases, with depth. Compared to the homogeneous CIRS-background, this variation was more pronounced for the inclusions and the vessel-mimicking phantom. Furthermore, higher stiffnesses were generally underestimated. In the vessel-mimicking phantom, anterior wave velocities were (incorrectly) higher than posterior wave velocities (3.4-5.6 m/s versus 2.9-5.9 m/s, p ≤ 0.005 for 3/4 probes) and remarkably correlated with measurement depth for most machines (Spearman's ρ = -0.873-0.969, p < 0.001 for 3/4 probes). In the Aixplorer's research mode, this difference was smaller (3.3-3.9 m/s versus 3.2-3.6 m/s, p = 0.005) and values did not correlate with measurement depth (Spearman's ρ = 0.039-0.659, p ≥ 0.002). In vivo, wave velocities were higher in the posterior than the anterior vessel wall in research (left p = 0.001, right p < 0.001) but not in clinical mode (left: p = 0.114, right: p = 0.483). Yet, wave velocities correlated with vessel wall depth in clinical (Spearman's ρ = 0.574-0.698, p < 0.001) but not in research mode (Spearman's ρ = -0.080-0.466, p ≥ 0.003). CONCLUSIONS: We observed more variation in SWE values among ultrasound machines and probes in tissue with high stiffness and thin-walled geometry than in low stiffness, homogeneous tissue. Together with a depth-correlation in some machines, where carotid arteries have a fixed location, this calls for caution in interpreting SWE results in clinical practice for vascular applications.

Noninvasive vascular displacement estimation for relative elastic modulus reconstruction in transversal imaging planes.

Atherosclerotic plaque rupture can initiate stroke or myocardial infarction. Lipid-rich plaques with thin fibrous caps have a higher risk to rupture than fibrotic plaques. Elastic moduli differ for lipid-rich and fibrous tissue and can be reconstructed using tissue displacements estimated from intravascular ultrasound radiofrequency (RF) data acquisitions. This study investigated if modulus reconstruction is possible for noninvasive RF acquisitions of vessels in transverse imaging planes using an iterative 2D cross-correlation based displacement estimation algorithm. Furthermore, since it is known that displacements can be improved by compounding of displacements estimated at various beam steering angles, we compared the performance of the modulus reconstruction with and without compounding. For the comparison, simulated and experimental RF data were generated of various vessel-mimicking phantoms. Reconstruction errors were less than 10%, which seems adequate for distinguishing lipid-rich from fibrous tissue. Compounding outperformed single-angle reconstruction: the interquartile range of the reconstructed moduli for the various homogeneous phantom layers was approximately two times smaller. Additionally, the estimated lateral displacements were a factor of 2-3 better matched to the displacements corresponding to the reconstructed modulus distribution. Thus, noninvasive elastic modulus reconstruction is possible for transverse vessel cross sections using this cross-correlation method and is more accurate with compounding.

Extending arterial stiffness assessment along the circumference using beam-steered ARFI and wave-tracking: A proof-of-principle study in phantoms and ex vivo.

Background: To fully quantify arterial wall and plaque stiffness, acoustic radiation force impulse (ARFI)-induced wave-tracking along the entire vessel circumference is desired. However, attenuation and guided wave behavior in thin vessel walls limits wave-tracking to short trajectories. This study investigated the potential of beam-steered ARFI and wave-tracking to extend group velocity estimation over a larger proportion of the circumference compared to conventional 0° ARFI-induced wave-tracking. Methods: Seven vessel-mimicking polyvinyl alcohol cryogel phantoms with various dimensions and compositions and an ex vivo human carotid artery were imaged in a dedicated setup. For every 20° phantom rotation, transverse group wave velocity measurements were performed with an Aixplorer Ultimate system and SL18-5 transducer using 0°/20°/-20°-angled ultrasound pushes. Transmural angular wave velocities were derived along 60°-trajectories. A 360°-angular velocity map was composed from the top-wall 60°-trajectories 0°-data, averaged over all physical phantom rotations (reference). For each phantom rotation, 360°-angular velocity maps were composed using 0°-data (0°-approach) or data from all angles (beam-steered approach). Percentages of rotations with visible waves and relative angular velocity errors compared to the reference map as function of the circumferential angle were determined for both approaches. Results: Reference 360°-angular velocity maps could be derived for all samples, representing their stiffness. Beam-steering decreased the proportion of the circumference where waves were untraceable by 20% in phantoms and 10% ex vivo, mainly at 0° push locations. Relative errors were similar for both approaches (phantoms: 10-15%, ex vivo: 15-35%). Conclusion: Beam-steering enables wave-tracking along a higher proportion of the wall circumference than 0° ARFI-induced wave-tracking.

Ultrasound-guided breast biopsy using an adapted automated cone-based ultrasound scanner: a feasibility study.

BACKGROUND: Among available breast biopsy techniques, ultrasound (US)-guided biopsy is preferable because it is relatively inexpensive and provides live imaging feedback. The availability of magnetic resonance imaging (MRI)-3D US image fusion would facilitate US-guided biopsy even for US occult lesions to reduce the need for expensive and time-consuming MRI-guided biopsy. In this paper, we propose a novel Automated Cone-based Breast Ultrasound Scanning and Biopsy System (ACBUS-BS) to scan and biopsy breasts of women in prone position. It is based on a previously developed system, called ACBUS, that facilitates MRI-3D US image fusion imaging of the breast employing a conical container filled with coupling medium. PURPOSE: The purpose of this study was to introduce the ABCUS-BS system and demonstrate its feasibility for biopsy of US occult lesions. METHOD: The biopsy procedure with the ACBUS-BS comprises four steps: target localization, positioning, preparation, and biopsy. The biopsy outcome can be impacted by 5 types of errors: due to lesion segmentation, MRI-3D US registration, navigation, lesion tracking during repositioning, and US inaccuracy (due to sound speed difference between the sample and the one used for image reconstruction). For the quantification, we use a soft custom-made polyvinyl alcohol phantom (PVA) containing eight lesions (three US-occult and five US-visible lesions of 10 mm in diameter) and a commercial breast mimicking phantom with a median stiffness of 7.6 and 28 kPa, respectively. Errors of all types were quantified using the custom-made phantom. The error due to lesion tracking was also quantified with the commercial phantom. Finally, the technology was validated by biopsying the custom-made phantom and comparing the size of the biopsied material to the original lesion size. The average size of the 10-mm-sized lesions in the biopsy specimen was 7.00 ± 0.92 mm (6.33 ± 1.16 mm for US occult lesions, and 7.40 ± 0.55 mm for US-visible lesions). RESULTS: For the PVA phantom, the errors due to registration, navigation, lesion tracking during repositioning, and US inaccuracy were 1.33, 0.30, 2.12, and 0.55 mm. The total error was 4.01 mm. For the commercial phantom, the error due to lesion tracking was estimated at 1.10 mm, and the total error was 4.11 mm. Given these results, the system is expected to successfully biopsy lesions larger than 8.22 mm in diameter. Patient studies will have to be carried out to confirm this in vivo. CONCLUSION: The ACBUS-BS facilitates US-guided biopsy of lesions detected in pre-MRI and therefore might offer a low-cost alternative to MRI-guided biopsy. We demonstrated the feasibility of the approach by successfully taking biopsies of five US-visible and three US-occult lesions embedded in a soft breast-shaped phantom.

Dynamic Computed Tomography Angiography for capturing vessel wall motion: A phantom study for optimal image reconstruction.

BACKGROUND: Reliably capturing sub-millimeter vessel wall motion over time, using dynamic Computed Tomography Angiography (4D CTA), might provide insight in biomechanical properties of these vessels. This may improve diagnosis, prognosis, and treatment decision making in vascular pathologies. PURPOSE: The aim of this study is to determine the most suitable image reconstruction method for 4D CTA to accurately assess harmonic diameter changes of vessels. METHODS: An elastic tube (inner diameter 6 mm, wall thickness 2 mm) was exposed to sinusoidal pressure waves with a frequency of 70 beats-per-minute. Five flow amplitudes were set, resulting in increasing sinusoidal diameter changes of the elastic tube, measured during three simulated pulsation cycles, using ECG-gated 4D CTA on a 320-detector row CT system. Tomographic images were reconstructed using one of the following three reconstruction methods: hybrid iterative (Hybrid-IR), model-based iterative (MBIR) and deep-learning based (DLR) reconstruction. The three reconstruction methods where based on 180 degrees (half reconstruction mode) and 360 degrees (full reconstruction mode) raw data. The diameter change, captured by 4D CTA, was computed based on image registration. As a reference metric for diameter change measurement, a 9 MHz linear ultrasound transducer was used. The sum of relative absolute differences (SRAD) between the ultrasound and 4D CTA measurements was calculated for each reconstruction method. The standard deviation was computed across the three pulsation cycles. RESULTS: MBIR and DLR resulted in a decreased SRAD and standard deviation compared to Hybrid-IR. Full reconstruction mode resulted in a decreased SRAD and standard deviations, compared to half reconstruction mode. CONCLUSIONS: 4D CTA can capture a diameter change pattern comparable to the pattern captured by US. DLR and MBIR algorithms show more accurate results than Hybrid-IR. Reconstruction with DLR is >3 times faster, compared to reconstruction with MBIR. Full reconstruction mode is more accurate than half reconstruction mode.

Comprehensive Comparison of Image Quality Aspects Between Conventional and Plane-Wave Imaging Methods on a Commercial Scanner.

Coherent plane-wave compound imaging (CPWCI) is used as alternative for conventional focused imaging (CFI) to increase frame rates linearly with the ratio number of imaging lines to steering angles. In this study, the image quality was compared between CPWCI and CFI, and the effect of steering angles (range and number) and beamforming strategies was evaluated in CPWCI. In automated breast volume scanners (ABVSs), which suffer from reduced volume rates, CPWCI might be an excellent candidate to replace CFI. Therefore, the image quality of CFI currently in ABVS and CPWCI was also compared in an in vivo breast lesion. Images were obtained by a Siemens Sequoia ultrasound system, and two transducers (14L5 and 10L4) in a CIRS multipurpose phantom (040GSE) and a breast lesion. Phantom results showed that contrast sensitivity and resolution, axial resolution, and generalized contrast-to-noise ratio (gCNR; imaging depths <45 mm) were similar for most imaging sequences. CNR (imaging depths ≥45 mm), penetration, and lateral resolution were significantly improved for CPWCI (15 angles) compared to CFI for both transducers. In CPWCI, certain combinations of steering angles and beamforming methods yielded improved gCNR (small angles and delay-and-sum) or lateral resolution (large angles and Lu's-fk). Image quality seemed similar between CPWCI and CFI (three angles incoherent compounded as in ABVS) by visual inspection of the in vivo breast lesion images.

Assessing radiation-induced carotid vasculopathy using ultrasound after unilateral irradiation: a cross-sectional study.

BACKGROUND: Increased head and neck cancer (HNC) survival requires attention to long-term treatment sequelae. Irradiated HNC survivors have a higher ischemic stroke risk. However, the pathophysiology of radiation-induced vasculopathy is unclear. Arterial stiffness could be a biomarker. This study examined alterations in intima-media thickness (IMT) and stiffness-related parameters, shear wave (SWV) and pulse wave velocity (PWV), in irradiated compared to control carotids in unilateral irradiated patients. METHODS: Twenty-six patients, median 40.5 years, 5-15 years after unilateral irradiation for head and neck neoplasms underwent a bilateral carotid ultrasound using an Aixplorer system with SL18-5 and SL10-2 probes. IMT, SWV, and PWV were assessed in the proximal, mid, and distal common (CCA) and internal carotid artery (ICA). Plaques were characterized with magnetic resonance imaging. Measurements were compared between irradiated and control sides, and radiation dose effects were explored. RESULTS: CCA-IMT was higher in irradiated than control carotids (0.54 [0.50-0.61] vs. 0.50 [0.44-0.54] mm, p = 0.001). For stiffness, only anterior mid-CCA and posterior ICA SWV were significantly higher in the irradiated side. A radiation dose-effect was only (weakly) apparent for PWV (R2: end-systolic = 0.067, begin-systolic = 0.155). Ultrasound measurements had good-excellent intra- and interobserver reproducibility. Plaques had similar characteristics but were more diffuse in the irradiated side. CONCLUSIONS: Increased CCA-IMT and SWV in some segments were seen in irradiated carotids. These alterations, even in young patients, mark the need for surveillance of radiation-induced vasculopathy. TRIAL REGISTRATION: clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04257968 ).

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

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Multicomponent material property characterization of atherosclerotic human carotid arteries through a Bayesian Optimization based inverse finite element approach.

OBJECTIVE: Plaque rupture in atherosclerotic carotid arteries is a main cause of ischemic stroke and it is correlated with high plaque stresses. Hence, analyzing stress patterns is essential for plaque specific rupture risk assessment. However, the critical information of the multicomponent material properties of atherosclerotic carotid arteries is still lacking greatly. This work aims to characterize component-wise material properties of atherosclerotic human carotid arteries under (almost) physiological loading conditions. METHODS: An inverse finite element modeling (iFEM) framework was developed to characterize fibrous intima and vessel wall material properties of 13 cross sections from five carotids. The novel pipeline comprised ex-vivo inflation testing, pre-clinical high frequency ultrasound for deriving plaque deformations, pre-clinical high-magnetic field magnetic resonance imaging, finite element modeling, and a sample efficient machine learning based Bayesian Optimization. RESULTS: The nonlinear Yeoh constants for the fibrous intima and wall layers were successfully obtained. The optimization scheme of the iFEM reached the global minimum with a mean error of 3.8% in 133 iterations on average. The uniqueness of the results were confirmed with the inverted Gaussian Process (GP) model trained during the iFEM protocol. CONCLUSION: The developed iFEM approach combined with the inverted GP model successfully predicted component-wise material properties of intact atherosclerotic human carotids ex-vivo under physiological-like loading conditions. SIGNIFICANCE: We developed a novel iFEM framework for the nonlinear, component-wise material characterization of atherosclerotic arteries and utilized it to obtain human atherosclerotic carotid material properties. The developed iFEM framework has great potential to be advanced for patient-specific in-vivo application.

In Vivo Comparison of Pulse Wave Velocity Estimation Based on Ultrafast Plane Wave Imaging and High-Frame-Rate Focused Transmissions.

Ultrasound-based local pulse wave velocity (PWV) estimation, as a measure of arterial stiffness, can be based on fast focused imaging (FFI) or plane wave imaging (PWI). This study was aimed at comparing the accuracy of in vivo PWV estimation using FFI and PWI. Ultrasound radiofrequency data of carotid arteries were acquired in 14 healthy volunteers (25-57 y) by executing the FFI (12 lines, 7200 Hz) and PWI (128 lines, 2000 Hz) methods consecutively. PWV was derived at two time-reference points, dicrotic notch (DN) and systolic foot (SF), for multiple pressure cycles by fitting a linear function through the positions of the peaks of low-pass filtered wall acceleration curves as a function of time. The accuracy of PWV estimation was determined for various cutoff frequencies (10-200 Hz). No statistically significant difference was observed between PWVs estimated by both approaches. The PWV and R2 at DN were higher, on average, than those at SF (PWV/R2: FFI SF 5.5/0.92, FFI DN 6.1/0.92; PWI SF 5.4/0.89, PWI DN 6.3/0.95). The use of cutoff frequencies between 40 and 80 Hz provided the most accurate PWVs. Both methods seemed equally suitable for use in clinical practice, although we have a preference for the PWV at DN given the higher R2 values.

The Viability of 3-D Power Doppler Imaging Using Continuous Mechanical Translation: Simulation and Theoretical Analysis.

Although conventional Doppler ultrasound is widely used for quantifying blood flow, it is restricted by its low sensitivity to detect slow flow. The incorporation of ultrafast ultrasound and spatial-temporal clutter filters can not only extensively boost the Doppler sensitivity to low-velocity slow flow but also facilitate the development of advanced 3-D Doppler techniques. In this work, we propose a novel 3-D Doppler method which extends 2-D imaging to 3-D through the continuous mechanical translation of a linear transducer. The viability of this method is assessed by simulations with the aids of a theoretical model. The combination of simulations and the theoretical model provides unique insights into the inherent mechanisms involved in the performance of this 3-D Doppler method and the roles of factors, such as tissue vibration characteristics, blood flow velocity, elevational point-spread-function profile, probe translating speed, and signal energy ratios.

Quantitative Evaluation of an Automated Cone-Based Breast Ultrasound Scanner for MRI-3D US Image Fusion.

Breast cancer is one of the most diagnosed types of cancer worldwide. Volumetric ultrasound breast imaging, combined with MRI can improve lesion detection rate, reduce examination time, and improve lesion diagnosis. However, to our knowledge, there are no 3D US breast imaging systems available that facilitate 3D US - MRI image fusion. In this paper, a novel Automated Cone-based Breast Ultrasound System (ACBUS) is introduced. The system facilitates volumetric ultrasound acquisition of the breast in a prone position without deforming it by the US transducer. Quality of ACBUS images for reconstructions at different voxel sizes (0.25 and 0.50 mm isotropic) was compared to quality of the Automated Breast Volumetric Scanner (ABVS) (Siemens Ultrasound, Issaquah, WA, USA) in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and resolution using a custom made phantom. The ACBUS image data were registered to MRI image data utilizing surface matching and the registration accuracy was quantified using an internal marker. The technology was also evaluated in vivo. The phantom-based quantitative analysis demonstrated that ACBUS can deliver volumetric breast images with an image quality similar to the images delivered by a currently commercially available Siemens ABVS. We demonstrate on the phantom and in vivo that ACBUS enables adequate MRI-3D US fusion. To our conclusion, ACBUS might be a suitable candidate for a second-look breast US exam, patient follow-up, and US guided biopsy planning.

3D Ultrasound Strain Imaging of Puborectalis Muscle.

The female pelvic floor (PF) muscles provide support to the pelvic organs. During delivery, some of these muscles have to stretch up to three times their original length to allow passage of the baby, leading frequently to damage and consequently later-life PF dysfunction (PFD). Three-dimensional (3D) ultrasound (US) imaging can be used to image these muscles and to diagnose the damage by assessing quantitative, geometric and functional information of the muscles through strain imaging. In this study we developed 3D US strain imaging of the PF muscles and explored its application to the puborectalis muscle (PRM), which is one of the major PF muscles.

Multicomponent Mechanical Characterization of Atherosclerotic Human Coronary Arteries: An Experimental and Computational Hybrid Approach.

Atherosclerotic plaque rupture in coronary arteries, an important trigger of myocardial infarction, is shown to correlate with high levels of pressure-induced mechanical stresses in plaques. Finite element (FE) analyses are commonly used for plaque stress assessment. However, the required information of heterogenous material properties of atherosclerotic coronaries remains to be scarce. In this work, we characterized the component-wise mechanical properties of atherosclerotic human coronary arteries. To achieve this, we performed ex vivo inflation tests on post-mortem human coronary arteries and developed an inverse FE modeling (iFEM) pipeline, which combined high-frequency ultrasound deformation measurements, a high-field magnetic resonance-based artery composition characterization, and a machine learning-based Bayesian optimization (BO) with uniqueness assessment. By using the developed pipeline, 10 cross-sections from five atherosclerotic human coronary arteries were analyzed, and the Yeoh material model constants of the fibrous intima and arterial wall components were determined. This work outlines the developed pipeline and provides the knowledge of non-linear, multicomponent mechanical properties of atherosclerotic human coronary arteries.

Vascular Shear Wave Elastography in Atherosclerotic Arteries: A Systematic Review.

Ischemic stroke is a leading cause of death and disability worldwide, so adequate prevention strategies are crucial. However, current stroke risk stratification is based on epidemiologic studies and is still suboptimal for individual patients. The aim of this systematic review was to provide a literature overview on the feasibility and diagnostic value of vascular shear wave elastography (SWE) using ultrasound (US) in (mimicked) human and non-human arteries affected by different stages of atherosclerotic diseases or diseases related to atherosclerosis. An online search was conducted on Pubmed, Embase, Web of Science and IEEE databases to identify studies using US SWE for the assessment of vascular elasticity. A quality assessment was performed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) checklist, and relevant data were extracted. A total of 19 studies were included: 10 with human patients and 9 with non-human subjects (i.e., [excised] animal arteries and polyvinyl alcohol phantoms). All studies revealed the feasibility of using US SWE to assess individually stiffness of the arterial wall and plaques. Quantitative elasticity values were highly variable between studies. However, within studies, SWE could detect statistically significant elasticity differences in patient/subject characteristics and could distinguish different plaque types with good reproducibility. US SWE, with its unique ability to assess the elasticity of the vessel wall and plaque throughout the cardiac cycle, might be a good candidate to improve stroke risk stratification. However, more clinical studies have to be performed to assess this technique's exact clinical value.