Motion correction of 3D dynamic contrast-enhanced ultrasound imaging without anatomical B-Mode images: Pilot evaluation in eight patients.

BACKGROUND: Dynamic contrast-enhanced ultrasound (DCE-US) is highly susceptible to motion artifacts arising from patient movement, respiration, and operator handling and experience. Motion artifacts can be especially problematic in the context of perfusion quantification. In conventional 2D DCE-US, motion correction (MC) algorithms take advantage of accompanying side-by-side anatomical B-Mode images that contain time-stable features. However, current commercial models of 3D DCE-US do not provide side-by-side B-Mode images, which makes MC challenging. PURPOSE: This work introduces a novel MC algorithm for 3D DCE-US and assesses its efficacy when handling clinical data sets. METHODS: In brief, the algorithm uses a pyramidal approach whereby short temporal windows consisting of three consecutive frames are created to perform local registrations, which are then registered to a master reference derived from a weighted average of all frames. We applied the algorithm to imaging studies from eight patients with metastatic lesions in the liver and assessed improvements in original versus motion corrected 3D DCE-US cine using: (i) frame-to-frame volumetric overlap of segmented lesions, (ii) normalized correlation coefficient (NCC) between frames (similarity analysis), and (iii) sum of squared errors (SSE), root-mean-squared error (RMSE), and r-squared (R2 ) quality-of-fit from fitted time-intensity curves (TIC) extracted from a segmented lesion. RESULTS: We noted improvements in frame-to-frame lesion overlap across all patients, from 68% ± 13% without correction to 83% ± 3% with MC (p = 0.023). Frame-to-frame similarity as assessed by NCC also improved on two different sets of time points from 0.694 ± 0.057 (original cine) to 0.862 ± 0.049 (corresponding MC cine) and 0.723 ± 0.066 to 0.886 ± 0.036 (p ≤ 0.001 for both). TIC analysis displayed a significant decrease in RMSE (p = 0.018) and a significant increase in R2 goodness-of-fit (p = 0.029) for the patient cohort. CONCLUSIONS: Overall, results suggest decreases in 3D DCE-US motion after applying the proposed algorithm.

Critical Advances for Democratizing Ultrasound Diagnostics in Human and Veterinary Medicine.

The democratization of ultrasound imaging refers to the process of making ultrasound technology more accessible. Traditionally, ultrasound imaging has been predominately used in specialized medical facilities by trained professionals. Advancements in technology and changes in the health-care landscape have inspired efforts to broaden the availability of ultrasound imaging to various settings such as remote and resource-limited areas. In this review, we highlight several key factors that have contributed to the ongoing democratization of ultrasound imaging, including portable and handheld devices, recent advancements in technology, and training and education. Examples of diagnostic point-of-care ultrasound (POCUS) imaging used in emergency and critical care, gastroenterology, musculoskeletal applications, and other practices are provided for both human and veterinary medicine. Open challenges and the future of POCUS imaging are presented, including the emerging role of artificial intelligence in technology development. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 26 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

In Vivo Ultrasound Molecular Imaging in the Evaluation of Complex Ovarian Masses: A Practical Guide to Correlation with Ex Vivo Immunohistochemistry.

Ovarian cancer is the fifth leading cause of cancer-related deaths in women and the most lethal gynecologic cancer. It is curable when discovered at an early stage, but usually remains asymptomatic until advanced stages. It is crucial to diagnose the disease before it metastasizes to distant organs for optimal patient management. Conventional transvaginal ultrasound imaging offers limited sensitivity and specificity in the ovarian cancer detection. With molecularly targeted ligands addressing targets, such as kinase insert domain receptor (KDR), attached to contrast microbubbles, ultrasound molecular imaging (USMI) can be used to detect, characterize and monitor ovarian cancer at a molecular level. In this article, the authors propose a standardized protocol is proposed for the accurate correlation between in- vivo transvaginal KDR-targeted USMI and ex vivo histology and immunohistochemistry in clinical translational studies. The detailed procedures of in vivo USMI and ex vivo immunohistochemistry are described for four molecular markers, CD31 and KDR with a focus on how to enable the accurate correlation between in vivo imaging findings and ex vivo expression of the molecular markers, even if not the entire tumor could can be imaged by USMI, which is not an uncommon scenario in clinical translational studies. This work aims to enhance the workflow and the accuracy of characterization of ovarian masses on transvaginal USMI using histology and immunohistochemistry as reference standards, which involves sonographers, radiologists, surgeons, and pathologists in a highly collaborative research effort of USMI in cancer.

Evaluating the effects of radiation and acoustically-stimulated microbubble therapy in an in vivo breast cancer model.

Ultrasound-stimulated microbubbles (USMB) cause localized vascular effects and sensitize tumors to radiation therapy (XRT). We investigated acoustic parameter optimization for combining USMB and XRT. We treated breast cancer xenograft tumors with 500 kHz pulsed ultrasound at varying pressures (570 or 740 kPa), durations (1 to 10 minutes), and microbubble concentrations (0.01 to 1% (v/v)). Radiation therapy (2 Gy) was administered immediately or after a 6-hour delay. Histological staining of tumors 24 hours after treatment detected changes in cell morphology, cell death, and microvascular density. Significant cell death resulted at 570 kPa after a 1-minute exposure with 1% (v/v) microbubbles with or without XRT. However, significant microvascular disruption required higher ultrasound pressure and exposure duration greater than 5 minutes. Introducing a 6-hour delay between treatments (USMB and XRT) showed a similar tumor effect with no further improvement in response as compared to when XRT was delivered immediately after USMB.

A Comprehensive Motion Compensation Method for In-Plane and Out-of-Plane Motion in Dynamic Contrast-Enhanced Ultrasound of Focal Liver Lesions.

Contrast-enhanced ultrasound (CEUS) acquisitions of focal liver lesions are affected by motion, which has an impact on contrast signal quantification. We therefore developed and tested, in a large patient cohort, a motion compensation algorithm called the Iterative Local Search Algorithm (ILSA), which can correct for both periodic and non-periodic in-plane motion and can reject frames with out-of-plane motion. CEUS cines of 183 focal liver lesions in 155 patients from three hospitals were used to develop and test ILSA. Performance was evaluated through quantitative metrics, including the root mean square error and R2 in fitting time-intensity curves and standard deviation value of B-mode intensities, computed across cine frames), and qualitative evaluation, including B-mode mean intensity projection images and parametric perfusion imaging. The median root mean square error significantly decreased from 0.032 to 0.024 (p < 0.001). Median R2 significantly increased from 0.88 to 0.93 (p < 0.001). The median standard deviation value of B-mode intensities significantly decreased from 6.2 to 5.0 (p < 0.001). B-Mode mean intensity projection images revealed improved spatial resolution. Parametric perfusion imaging also exhibited improved spatial detail and better differentiation between lesion and background liver parenchyma. ILSA can compensate for all types of motion encountered during liver CEUS, potentially improving contrast signal quantification of focal liver lesions.

Interpretable Machine Learning for Characterization of Focal Liver Lesions by Contrast-Enhanced Ultrasound.

This work proposes an interpretable radiomics approach to differentiate between malignant and benign focal liver lesions (FLLs) on contrast-enhanced ultrasound (CEUS). Although CEUS has shown promise for differential FLLs diagnosis, current clinical assessment is performed only by qualitative analysis of the contrast enhancement patterns. Quantitative analysis is often hampered by the unavoidable presence of motion artifacts and by the complex, spatiotemporal nature of liver contrast enhancement, consisting of multiple, overlapping vascular phases. To fully exploit the wealth of information in CEUS, while coping with these challenges, here we propose combining features extracted by the temporal and spatiotemporal analysis in the arterial phase enhancement with spatial features extracted by texture analysis at different time points. Using the extracted features as input, several machine learning classifiers are optimized to achieve semiautomatic FLLs characterization, for which there is no need for motion compensation and the only manual input required is the location of a suspicious lesion. Clinical validation on 87 FLLs from 72 patients at risk for hepatocellular carcinoma (HCC) showed promising performance, achieving a balanced accuracy of 0.84 in the distinction between benign and malignant lesions. Analysis of feature relevance demonstrates that a combination of spatiotemporal and texture features is needed to achieve the best performance. Interpretation of the most relevant features suggests that aspects related to microvascular perfusion and the microvascular architecture, together with the spatial enhancement characteristics at wash-in and peak enhancement, are important to aid the accurate characterization of FLLs.

Ultrasound Elastography: Review of Techniques and Clinical Applications.

Elastography-based imaging techniques have received substantial attention in recent years for non-invasive assessment of tissue mechanical properties. These techniques take advantage of changed soft tissue elasticity in various pathologies to yield qualitative and quantitative information that can be used for diagnostic purposes. Measurements are acquired in specialized imaging modes that can detect tissue stiffness in response to an applied mechanical force (compression or shear wave). Ultrasound-based methods are of particular interest due to its many inherent advantages, such as wide availability including at the bedside and relatively low cost. Several ultrasound elastography techniques using different excitation methods have been developed. In general, these can be classified into strain imaging methods that use internal or external compression stimuli, and shear wave imaging that use ultrasound-generated traveling shear wave stimuli. While ultrasound elastography has shown promising results for non-invasive assessment of liver fibrosis, new applications in breast, thyroid, prostate, kidney and lymph node imaging are emerging. Here, we review the basic principles, foundation physics, and limitations of ultrasound elastography and summarize its current clinical use and ongoing developments in various clinical applications.