US Backscatter for Liver Fat Quantification: An AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative.

Nonalcoholic fatty liver disease (NAFLD) is believed to affect one-third of American adults. Noninvasive methods that enable detection and monitoring of NAFLD have the potential for great public health benefits. Because of its low cost, portability, and noninvasiveness, US is an attractive alternative to both biopsy and MRI in the assessment of liver steatosis. NAFLD is qualitatively associated with enhanced B-mode US echogenicity, but visual measures of B-mode echogenicity are negatively affected by interobserver variability. Alternatively, quantitative backscatter parameters, including the hepatorenal index and backscatter coefficient, are being investigated with the goal of improving US-based characterization of NAFLD. The American Institute of Ultrasound in Medicine and Radiological Society of North America Quantitative Imaging Biomarkers Alliance are working to standardize US acquisition protocols and data analysis methods to improve the diagnostic performance of the backscatter coefficient in liver fat assessment. This review article explains the science and clinical evidence underlying backscatter for liver fat assessment. Recommendations for data collection are discussed, with the aim of minimizing potential confounding effects associated with technical and biologic variables.

CdTe Based Energy Resolving, X-ray Photon Counting Detector Performance Assessment: The Effects of Charge Sharing Correction Algorithm Choice.

Most modern energy resolving, photon counting detectors employ small (sub 1 mm) pixels for high spatial resolution and low per pixel count rate requirements. These small pixels can suffer from a range of charge sharing effects (CSEs) that degrade both spectral analysis and imaging metrics. A range of charge sharing correction algorithms (CSCAs) have been proposed and validated by different groups to reduce CSEs, however their performance is often compared solely to the same system when no such corrections are made. In this paper, a combination of Monte Carlo and finite element methods are used to compare six different CSCAs with the case where no CSCA is employed, with respect to four different metrics: absolute detection efficiency, photopeak detection efficiency, relative coincidence counts, and binned spectral efficiency. The performance of the various CSCAs is explored when running on systems with pixel pitches ranging from 100 µm to 600µm, in 50 µm increments, and fluxes from 106 to 108 photons mm-2 s-1 are considered. Novel mechanistic explanations for the difference in performance of the various CSCAs are proposed and supported. This work represents a subset of a larger project in which pixel pitch, thickness, flux, and CSCA are all varied systematically.

Near-infrared photoimmunotherapy targeting EGFR-Shedding new light on glioblastoma treatment.

Glioblastomas (GBMs) are high-grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12-15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signaling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR-specific affibody (ZEGFR:03115 ) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near-infrared light produces a cytotoxic response. ZEGFR:03115 -IR700DX EGFR-specific binding was confirmed by flow cytometry and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter-Glo® assay, and in vivo using subcutaneous U87-MGvIII xenografts. In addition, mice were imaged pre- and post-PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor-dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the ZEGFR:03115 -IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof-of-concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts.

Validation of the Vectra XT three-dimensional imaging system for measuring breast volume and symmetry following oncological reconstruction.

PURPOSE: Three-dimensional surface imaging (3D-SI) of the breasts enables the measurement of breast volume and shape symmetry. If these measurements were sufficiently accurate and repeatable, they could be used in planning oncological breast surgery and as an objective measure of aesthetic outcome. The aim of this study was to validate the measurements of breast volume and symmetry provided by the Vectra XT imaging system. METHODS: To validate measurements, breast phantom models of true volume between 100 and 1000 cm3 were constructed and varying amounts removed to mimic breast tissue 'resections'. The volumes of the phantoms were measured using 3D-SI by two observers and compared to a gold standard. For intra-observer repeatability and inter-observer reproducibility in vivo, 16 patients who had undergone oncological breast surgery had breast volume and symmetry measured three times by two observers. RESULTS: A mean relative difference of 2.17 and 2.28% for observer 1 and 2 respectively was seen in the phantom measurements compared to the gold standard (n = 45, Bland Altman agreement). Intra-observer variation over ten repeated measurements demonstrated mean coefficients of variation (CV) of 0.58 and 0.49%, respectively. The inter-observer variation demonstrated a mean relative difference of 0.11% between the two observers. In patients, intra-observer variation over three repeated volume measurements for each observer was 3.9 and 3.8% (mean CV); the mean relative difference between observers was 5.78%. For three repeated shape symmetry measurements using RMS projection difference between the two breasts, the intra-observer variations were 8 and 14% (mean CV), the mean relative difference between observers was 0.43 mm for average symmetry values that ranged from about 3.5 to 15.5 mm. CONCLUSION: This first validation of breast volume and shape symmetry measurements using the Vectra XT 3D-SI system suggests that these measurements have the potential to assist in pre-operative planning and also as a measure of aesthetic outcome.

High-frequency ultrasound for diagnosing skin cancer in adults.

BACKGROUND: Early, accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers with the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Ultrasound is a non-invasive imaging technique that relies on the measurement of sound wave reflections from the tissues of the body. At lower frequencies, the deeper structures of the body such as the internal organs can be visualised, while high-frequency ultrasound (HFUS) with transducer frequencies of 20 MHz or more has a much lower depth of tissue penetration but produces a higher resolution image of tissues and structures closer to the skin surface. Used in conjunction with clinical and/or dermoscopic examination of suspected skin cancer, HFUS may offer additional diagnostic information compared to other technologies. OBJECTIVES: To assess the diagnostic accuracy of HFUS to assist in the diagnosis of a) cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, b) cutaneous squamous cell carcinoma (cSCC), and c) basal cell carcinoma (BCC) in adults. SEARCH METHODS: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles. SELECTION CRITERIA: Studies evaluating HFUS (20 MHz or more) in adults with lesions suspicious for melanoma, cSCC or BCC versus a reference standard of histological confirmation or clinical follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and the poor quality of studies, we did not undertake a meta-analysis for this review. For illustrative purposes, we plot estimates of sensitivity and specificity on coupled forest plots. MAIN RESULTS: We included six studies, providing 29 datasets: 20 for diagnosis of melanoma (1125 lesions and 242 melanomas) and 9 for diagnosis of BCC (993 lesions and 119 BCCs). We did not identify any data relating to the diagnosis of cSCC.Studies were generally poorly reported, limiting judgements of methodological quality. Half the studies did not set out to establish test accuracy, and all should be considered preliminary evaluations of the potential usefulness of HFUS. There were particularly high concerns for applicability of findings due to selective study populations and data-driven thresholds for test positivity. Studies reporting qualitative assessments of HFUS images excluded up to 22% of lesions (including some melanomas) due to lack of visualisation in the test.Derived sensitivities for qualitative HFUS characteristics were at least 83% (95% CI 75% to 90%) for the detection of melanoma; the combination of three features (lesions appearing hypoechoic, homogenous and well defined) demonstrating 100% sensitivity in two studies (lower limits of the 95% CIs were 94% and 82%), with variable corresponding specificities of 33% (95% CI 20% to 48%) and 73% (95% CI 57% to 85%), respectively. Quantitative measurement of HFUS outputs in two studies enabled decision thresholds to be set to achieve 100% sensitivity; specificities were 93% (95% CI 77% to 99%) and 65% (95% CI 51% to 76%). It was not possible to make summary statements regarding HFUS accuracy for the diagnosis of BCC due to highly variable sensitivities and specificities. AUTHORS' CONCLUSIONS: Insufficient data are available on the potential value of HFUS in the diagnosis of melanoma or BCC. Given the between-study heterogeneity, unclear to low methodological quality and limited volume of evidence, we cannot draw any implications for practice. The main value of the preliminary studies included may be in providing guidance on the possible components of new diagnostic rules for diagnosis of melanoma or BCC using HFUS that will require future evaluation. A prospective evaluation of HFUS added to visual inspection and dermoscopy alone in a standard healthcare setting, with a clearly defined and representative population of participants, would be required for a full and proper evaluation of accuracy.

Computer-assisted diagnosis techniques (dermoscopy and spectroscopy-based) for diagnosing skin cancer in adults.

BACKGROUND: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and cutaneous squamous cell carcinoma (cSCC) are high-risk skin cancers which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Computer-assisted diagnosis (CAD) systems use artificial intelligence to analyse lesion data and arrive at a diagnosis of skin cancer. When used in unreferred settings ('primary care'), CAD may assist general practitioners (GPs) or other clinicians to more appropriately triage high-risk lesions to secondary care. Used alongside clinical and dermoscopic suspicion of malignancy, CAD may reduce unnecessary excisions without missing melanoma cases. OBJECTIVES: To determine the accuracy of CAD systems for diagnosing cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC in adults, and to compare its accuracy with that of dermoscopy. SEARCH METHODS: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. SELECTION CRITERIA: Studies of any design that evaluated CAD alone, or in comparison with dermoscopy, in adults with lesions suspicious for melanoma or BCC or cSCC, and compared with a reference standard of either histological confirmation or clinical follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities separately by type of CAD system, using the bivariate hierarchical model. We compared CAD with dermoscopy using (a) all available CAD data (indirect comparisons), and (b) studies providing paired data for both tests (direct comparisons). We tested the contribution of human decision-making to the accuracy of CAD diagnoses in a sensitivity analysis by removing studies that gave CAD results to clinicians to guide diagnostic decision-making. MAIN RESULTS: We included 42 studies, 24 evaluating digital dermoscopy-based CAD systems (Derm-CAD) in 23 study cohorts with 9602 lesions (1220 melanomas, at least 83 BCCs, 9 cSCCs), providing 32 datasets for Derm-CAD and seven for dermoscopy. Eighteen studies evaluated spectroscopy-based CAD (Spectro-CAD) in 16 study cohorts with 6336 lesions (934 melanomas, 163 BCC, 49 cSCCs), providing 32 datasets for Spectro-CAD and six for dermoscopy. These consisted of 15 studies using multispectral imaging (MSI), two studies using electrical impedance spectroscopy (EIS) and one study using diffuse-reflectance spectroscopy. Studies were incompletely reported and at unclear to high risk of bias across all domains. Included studies inadequately address the review question, due to an abundance of low-quality studies, poor reporting, and recruitment of highly selected groups of participants.Across all CAD systems, we found considerable variation in the hardware and software technologies used, the types of classification algorithm employed, methods used to train the algorithms, and which lesion morphological features were extracted and analysed across all CAD systems, and even between studies evaluating CAD systems. Meta-analysis found CAD systems had high sensitivity for correct identification of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in highly selected populations, but with low and very variable specificity, particularly for Spectro-CAD systems. Pooled data from 22 studies estimated the sensitivity of Derm-CAD for the detection of melanoma as 90.1% (95% confidence interval (CI) 84.0% to 94.0%) and specificity as 74.3% (95% CI 63.6% to 82.7%). Pooled data from eight studies estimated the sensitivity of multispectral imaging CAD (MSI-CAD) as 92.9% (95% CI 83.7% to 97.1%) and specificity as 43.6% (95% CI 24.8% to 64.5%). When applied to a hypothetical population of 1000 lesions at the mean observed melanoma prevalence of 20%, Derm-CAD would miss 20 melanomas and would lead to 206 false-positive results for melanoma. MSI-CAD would miss 14 melanomas and would lead to 451 false diagnoses for melanoma. Preliminary findings suggest CAD systems are at least as sensitive as assessment of dermoscopic images for the diagnosis of invasive melanoma and atypical intraepidermal melanocytic variants. We are unable to make summary statements about the use of CAD in unreferred populations, or its accuracy in detecting keratinocyte cancers, or its use in any setting as a diagnostic aid, because of the paucity of studies. AUTHORS' CONCLUSIONS: In highly selected patient populations all CAD types demonstrate high sensitivity, and could prove useful as a back-up for specialist diagnosis to assist in minimising the risk of missing melanomas. However, the evidence base is currently too poor to understand whether CAD system outputs translate to different clinical decision-making in practice. Insufficient data are available on the use of CAD in community settings, or for the detection of keratinocyte cancers. The evidence base for individual systems is too limited to draw conclusions on which might be preferred for practice. Prospective comparative studies are required that evaluate the use of already evaluated CAD systems as diagnostic aids, by comparison to face-to-face dermoscopy, and in participant populations that are representative of those in which the test would be used in practice.

Ultrasound Shear Wave Elastography of the Normal Prostate: Interobserver Reproducibility and Comparison with Functional Magnetic Resonance Tissue Characteristics.

The purpose of this study was to establish interobserver reproducibility of Young's modulus (YM) derived from ultrasound shear wave elastography (US-SWE) in the normal prostate and correlate it with multiparametric magnetic resonance imaging (mpMRI) tissue characteristics. Twenty men being screened for prostate cancer underwent same-day US-SWE (10 done by two blinded, newly-trained observers) and mpMRI followed by 12-core biopsy. Bland-Altman plots established limits of agreement for YM. Quantitative data from the peripheral zone (PZ) and the transitional zone (TZ) for YM, apparent diffusion coefficient (ADC, mm2/s from diffusion-weighted MRI), and Ktrans (volume transfer coefficient, min-1), Ve (extravascular-extracellular space, %), Kep (rate constant, /min), and initial area under the gadolinium concentration curve (IAUGC60, mmol/L/s) from dynamic contrast-enhanced MRI were obtained for slice-matched prostate sextants. Interobserver intraclass correlation coefficients were fair to good for individual regions (PZ = 0.57, TZ = 0.65) and for whole gland 0.67, (increasing to 0.81 when corrected for systematic observer bias). In the PZ, there were weak negative correlations between YM and ADC ( p = 0.008), and Ve ( p = 0.01) and a weak positive correlation with Kep ( p = 0.003). No significant intermodality correlations were seen in the TZ. Transrectal prostate US-SWE done without controlling manually applied probe pressure has fair/good interobserver reproducibility in inexperienced observers with potential to improve this to excellent by standardization of probe contact pressure. Within the PZ, increase in tissue stiffness is associated with reduced extracellular water (decreased ADC) and space (reduced Ve).

EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Short Version).

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.

EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version).

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography, focused on the assessment of diffuse liver disease. The first part (long version) of these Guidelines and Recommendations deals with the basic principles of elastography and provides an update of how the technology has changed. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided regarding optimization of scanning technique, image display, image interpretation, reporting of data and some of the known image artefacts. The second part provides clinical information about the practical use of elastography equipment and the interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.

A novel technique of detecting MRI-negative lesion in focal symptomatic epilepsy: intraoperative ShearWave elastography.

Focal symptomatic epilepsy is the most common form of epilepsy that can often be cured with surgery. A small proportion of patients with focal symptomatic epilepsy do not have identifiable lesions on magnetic resonance imaging (MRI). The most common pathology in this group is type II focal cortical dysplasia (FCD), which is a subtype of malformative brain lesion associated with medication-resistant epilepsy. We present a patient with MRI-negative focal symptomatic epilepsy who underwent invasive electrode recordings. At the time of surgery, a novel ultrasound-based technique called ShearWave Elastography (SWE) was performed. A 0.5 cc lesion was demonstrated on SWE but was absent on B-mode ultrasound and 3-T MRI. Electroencephalography (EEG), positron emission tomography (PET), and magnetoencephalography (MEG) scans demonstrated an abnormality in the right frontal region. On the basis of this finding, a depth electrode was implanted into the lesion. Surgical resection and histology confirmed the lesion to be type IIb FCD. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

An ezrin-rich, rigid uropod-like structure directs movement of amoeboid blebbing cells.

Melanoma cells can switch between an elongated mesenchymal-type and a rounded amoeboid-type migration mode. The rounded 'amoeboid' form of cell movement is driven by actomyosin contractility resulting in membrane blebbing. Unlike elongated A375 melanoma cells, rounded A375 cells do not display any obvious morphological front-back polarisation, although polarisation is thought to be a prerequisite for cell movement. We show that blebbing A375 cells are polarised, with ezrin (a linker between the plasma membrane and actin cytoskeleton), F-actin, myosin light chain, plasma membrane, phosphatidylinositol (4,5)-bisphosphate and ß1-integrin accumulating at the cell rear in a uropod-like structure. This structure does not have the typical protruding shape of classical leukocyte uropods, but, as for those structures, it is regulated by protein kinase C. We show that the ezrin-rich uropod-like structure (ERULS) is an inherent feature of polarised A375 cells and not a consequence of cell migration, and is necessary for cell invasion. Furthermore, we demonstrate that membrane blebbing is reduced at this site, leading to a model in which the rigid ezrin-containing structure determines the direction of a moving cell through localised inhibition of membrane blebbing.

Multi-directional in vivo tensile skin stiffness measurement for the design of a reproducible tensile strain elastography protocol.

BACKGROUND/AIMS: Elastography is a promising new medical imaging modality, displaying spatial distribution of biomechanical properties such as local tissue strain response to an applied stress. To develop a reproducible test protocol for skin elastography, the effect of various parameters on skin stiffness measurements was investigated. METHODS: The parameters investigated were: history of skin loading before test loading (preconditioning), direction of test loading (anisotropy) and posture (pre-stress). If a sample of skin is loaded, its stiffness will temporarily change. Finally, the reproducibility of skin stiffness and anisotropy measurements, using the developed techniques, was investigated. RESULTS: By measuring how the stiffness changed with different time delays between loading cycles, the time required for healthy skin to return to its original pre-loaded state was in the region of 125 s. A second finding, which supports and extends previous work, was that skin stiffness varied with direction, by an approximate factor of 2, and that anisotropy was less apparent with preconditioned skin than non-preconditioned skin. Study of the effect of posture showed that care needs to be taken over which stiffness measure is used. For example, measurement of the load at a given displacement was found to be highly dependent on posture, whereas measurement of the phase III stiffness was independent of posture. CONCLUSION: It was shown that when the measurement variables and methods of analysis were standardised, skin stiffness could be measured reproducibly enough to distinguish between the stiffest and softest directions, and that these methods allowed formation of skin elastograms free from confounding influences.

Ultrasound Measurement of Local Deformation in the Human Free Achilles Tendon Produced by Dynamic Muscle-Induced Loading: A Systematic Review.

Achilles tendinopathy is the most prevalent lower limb tendinopathy, yet it remains poorly understood, with mismatches between observed structure and reported function. Recent studies have hypothesised that Achilles tendon (AT) healthy function is associated with variable deformation across the tendon width during use, focusing on quantifying sub-tendon deformation. Here, the aim of this work was to synthesise recent advances exploring human free AT tissue-level deformation during use. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, Embase, Scopus and Web of Science were systematically searched. Study quality and risk of bias were assessed. Thirteen articles were retained, yielding data on free AT deformation patterns. Seven were categorised as high-quality and six as medium-quality studies. Evidence consistently reports that healthy and young tendons deform non-uniformly, with the deeper layer displacing 18%-80% more than the superficial layer. Non-uniformity decreased by 12%-85% with increasing age and by 42%-91% in the presence of injury. There is limited evidence of large effect that AT deformation patterns during dynamic loading are non-uniform and may act as a biomarker of tendon health, risk of injury and rehabilitation impact. Better considered participant recruitment and improved measurement procedures would particularly improve study quality, to explore links between tendon structure, function, aging and disease in distinct populations.

Evaluation of Performance Tradeoffs When Using Mechanically Swept 1-D Linear Arrays for 3-D DCE-US.

Dynamic contrast-enhanced ultrasound imaging (DCE-US) may be used to characterize tumor vascular perfusion using metrics derived from time-amplitude curves (TACs). The 3-D DCE-US enables generation of 3-D parametric maps of TAC metrics that may inform on how perfusion varies across the entire tumor. The aim of this work was to understand the effect of low temporal sampling (i.e., < 1 Hz) typical of 3-D imaging using a swept 1-D array transducer on the evaluation of TAC metrics and the effect of transducer motion in combination with flow on 3-D parametric maps generated using both plane wave imaging (PWI) (seven angles) and focused imaging (FI). Correlation maps were introduced to evaluate the spatial blurring of TAC metrics. A research ultrasound scanner and a pulse-inversion algorithm were used to obtain DCE-US. The 2-D (frame rate 10 Hz) and 3-D (volume rate 0.4 Hz) images were acquired of a simple wall-less vessel phantom (flow phantom) and a cartridge phantom. Volumetric imaging provided similar TACs to that of the higher 2-D sampling rate. Varying sweep speed and acceleration/deceleration had little influence on the 3-D TAC compared to 2-D for both FI and PWI. Sweeping motion and limited temporal sampling (0.4 Hz) did not change the spatial correlation of TAC metrics measured using FI, whereas a small increase in correlation across the cartridge phantom was observed for PWI. This was attributed to grating lobe artifacts, broad beam spatial blurring, and incoherent compounding caused by motion. Increased correlation will reduce the spatial resolution with which inhomogeneity of vascular perfusion can be mapped supporting the choice of FI for DCE-US.

Ultrasonic Sound Speed Estimation for Liver Fat Quantification: A Review by the AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative.

Non-alcoholic fatty liver disease (NAFLD) is a significant cause of diffuse liver disease, morbidity and mortality worldwide. Early and accurate diagnosis of NALFD is critical to identify patients at risk of disease progression. Liver biopsy is the current gold standard for diagnosis and prognosis. However, a non-invasive diagnostic tool is desired because of the high cost and risk of complications of tissue sampling. Medical ultrasound is a safe, inexpensive and widely available imaging tool for diagnosing NAFLD. Emerging sonographic tools to quantitatively estimate hepatic fat fraction, such as tissue sound speed estimation, are likely to improve diagnostic accuracy, precision and reproducibility compared with existing qualitative and semi-quantitative techniques. Various pulse-echo ultrasound speed of sound estimation methodologies have been investigated, and some have been recently commercialized. We review state-of-the-art in vivo speed of sound estimation techniques, including their advantages, limitations, technical sources of variability, biological confounders and existing commercial implementations. We report the expected range of hepatic speed of sound as a function of liver steatosis and fibrosis that may be encountered in clinical practice. Ongoing efforts seek to quantify sound speed measurement accuracy and precision to inform threshold development around meaningful differences in fat fraction and between sequential measurements.

Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography.

Hyaluronan (HA) is a key component of the dense extracellular matrix in breast cancer, and its accumulation is associated with poor prognosis and metastasis. Pegvorhyaluronidase alfa (PEGPH20) enzymatically degrades HA and can enhance drug delivery and treatment response in preclinical tumour models. Clinical development of stromal-targeted therapies would be accelerated by imaging biomarkers that inform on therapeutic efficacy in vivo. Here, PEGPH20 response was assessed by multiparametric magnetic resonance imaging (MRI) in three orthotopic breast tumour models. Treatment of 4T1/HAS3 tumours, the model with the highest HA accumulation, reduced T1 and T2 relaxation times and the apparent diffusion coefficient (ADC), and increased the magnetisation transfer ratio, consistent with lower tissue water content and collapse of the extracellular space. The transverse relaxation rate R2 * increased, consistent with greater erythrocyte accessibility following vascular decompression. Treatment of MDA-MB-231 LM2-4 tumours reduced ADC and dramatically increased tumour viscoelasticity measured by MR elastography. Correlation matrix analyses of data from all models identified ADC as having the strongest correlation with HA accumulation, suggesting that ADC is the most sensitive imaging biomarker of tumour response to PEGPH20.

Preclinical Three-Dimensional Vibrational Shear Wave Elastography for Mapping of Tumour Biomechanical Properties In Vivo.

Preclinical investigation of the biomechanical properties of tissues and their treatment-induced changes are essential to support drug-discovery, clinical translation of biomarkers of treatment response, and studies of mechanobiology. Here we describe the first use of preclinical 3D elastography to map the shear wave speed (cs), which is related to tissue stiffness, in vivo and demonstrate the ability of our novel 3D vibrational shear wave elastography (3D-VSWE) system to detect tumour response to a therapeutic challenge. We investigate the use of one or two vibrational sources at vibrational frequencies of 700, 1000 and 1200 Hz. The within-subject coefficients of variation of our system were found to be excellent for 700 and 1000 Hz and 5.4 and 6.2%, respectively. The relative change in cs measured with our 3D-VSWE upon treatment with an anti-vascular therapy ZD6126 in two tumour xenografts reflected changes in tumour necrosis. U-87 MG drug vs vehicle: Δcs = −24.7 ± 2.5 % vs 7.5 ± 7.1%, (p = 0.002) and MDA-MB-231 drug vs vehicle: Δcs = −12.3 ± 2.7 % vs 4.5 ± 4.7%, (p = 0.02). Our system enables rapid (<5 min were required for a scan length of 15 mm and three vibrational frequencies) 3D mapping of quantitative tumour viscoelastic properties in vivo, allowing exploration of regional heterogeneity within tumours and speedy recovery of animals from anaesthesia so that longitudinal studies (e.g., during tumour growth or following treatment) may be conducted frequently.

Characterisation of Prostate Lesions Using Transrectal Shear Wave Elastography (SWE) Ultrasound Imaging: A Systematic Review.

BACKGROUND: ultrasound-based shear wave elastography (SWE) can non-invasively assess prostate tissue stiffness. This systematic review aims to evaluate SWE for the detection of prostate cancer (PCa) and compare diagnostic estimates between studies reporting the detection of all PCa and clinically significant PCa (csPCa). METHODS: a literature search was performed using the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and CINAHL databases. Studies evaluating SWE for the detection of PCa using histopathology as reference standard were included. RESULTS: 16 studies including 2277 patients were included for review. Nine studies evaluated SWE for the detection of PCa using systematic biopsy as a reference standard at the per-sample level, with a pooled sensitivity and specificity of 0.85 (95% CI = 0.74-0.92) and 0.85 (95% CI = 0.75-0.91), respectively. Five studies evaluated SWE for the detection of PCa using histopathology of radical prostatectomy (RP) specimens as the reference standard, with a pooled sensitivity and specificity of 0.71 (95% CI = 0.55-0.83) and 0.74 (95% CI = 0.42-0.92), respectively. Sub-group analysis revealed a higher pooled sensitivity (0.77 vs. 0.62) and specificity (0.84 vs. 0.53) for detection of csPCa compared to all PCa among studies using RP specimens as the reference standard. CONCLUSION: SWE is an attractive imaging modality for the detection of PCa.

Clinical Application of Shear Wave Elastography for Assisting Brain Tumor Resection.

BACKGROUND: The clinical outcomes for brain tumor resection have been shown to be significantly improved with increased extent of resection. To achieve this, neurosurgeons employ different intra-operative tools to improve the extent of resection of brain tumors, including ultrasound, CT, and MRI. Young's modulus (YM) of brain tumors have been shown to be different from normal brain but the accuracy of SWE in assisting brain tumor resection has not been reported. AIMS: To determine the accuracy of SWE in detecting brain tumor residual using post-operative MRI scan as "gold standard". METHODS: Thirty-four patients (aged 1-62 years, M:F = 15:20) with brain tumors were recruited into the study. The intraoperative SWE scans were performed using Aixplorer® (SuperSonic Imagine, France) using a sector transducer (SE12-3) and a linear transducer (SL15-4) with a bandwidth of 3 to 12 MHz and 4 to 15 MHz, respectively, using the SWE mode. The scans were performed prior, during and after brain tumor resection. The presence of residual tumor was determined by the surgeon, ultrasound (US) B-mode and SWE. This was compared with the presence of residual tumor on post-operative MRI scan. RESULTS: The YM of the brain tumors correlated significantly with surgeons' findings (ρ = 0.845, p < 0.001). The sensitivities of residual tumor detection by the surgeon, US B-mode and SWE were 36%, 73%, and 94%, respectively, while their specificities were 100%, 63%, and 77%, respectively. There was no significant difference between detection of residual tumor by SWE, US B-mode, and MRI. SWE and MRI were significantly better than the surgeon's detection of residual tumor (p = 0.001 and p < 0.001, respectively). CONCLUSIONS: SWE had a higher sensitivity in detecting residual tumor than the surgeons (94% vs. 36%). However, the surgeons had a higher specificity than SWE (100% vs. 77%). Therefore, using SWE in combination with surgeon's opinion may optimize the detection of residual tumor, and hence improve the extent of brain tumor resection.