The Contribution of Three-Dimensional Power Doppler Imaging in the Preoperative Assessment of Breast Tumors: A Preliminary Report

Purpose. The aim of this study was to determine the value of 3D and 3D Power Doppler sonography in the detection of tumor malignancy in breast lesions and to find new diagnostic criteria for differential diagnosis. Methods. One hundred and twenty five women with clinically or mammographically suspicious findings were referred for 3D Power Doppler ultrasound prior to surgery. Histological diagnosis was conducted after surgery and compared with ultrasound findings. Sonographic criteria used for breast cancer diagnosis were based on a system that included morphological characteristics and criteria of the vascular pattern of a breast mass by Power Doppler imaging. Results. Seventy-two lesions were histopathologically diagnosed as benign and 53 tumors as malignant. Three-dimensional ultrasound identified 49 out of 53 histologically confirmed breast cancers resulting in a sensitivity of 92.4% and a specificity of 86.1% in diagnosing breast malignancy (PPV: 0.83, NPV:0.94). Conclusions. 3D ultrasonography is a valuable tool in identifying preoperatively the possibility of a tumor to be malignant

Signal Processing Methods for Quantitative Power Doppler Microvascular Angiography

Operator-dependent instrument settings and the likelihood of image artifacts are two challenges for reliably using three-dimensional (3-D) power Doppler angiography in flow depiction and quantification applications. To address the operator-dependent settings challenge, an automated method for wall filter cut-off selection, the wall filter selection curve (WFSC) method, was developed using flow-phantom images. The flow-phantom WFSCs guided the development of a theoretical signal model relating color pixel density (CPD) and wall filter cut-off frequency. Simulations using the theoretical model were used to define criteria for the WFSC method to be applied to unprocessed power Doppler signals from 3-D vasculature. The adapted WFSC method was combined with a 3-D skeletonization and vessel network reconstruction method to present a two-stage processing method aimed at improving vascular detection, visualization and quantification. The two-stage method was evaluated using two in vivo models; a murine tumor model was used to test the performance of the method in a flow quantification application and a chick embryo chorioallantoic membrane (CAM) model was used to evaluate the method’s value for flow depiction applications. Applying the WFSC method to flow-phantom images improved vessel delineation and vascular quantification to within 3% of the vascular volume fraction of the phantom. Criteria for the WFSC method from the simulations were to assess at least 100 cut-off frequencies and that the CPD variability should be less than 5% to ensure quantification accuracy. Large variations in the cut-off frequency selected using the WFSC among images acquired at different time points and across different animals in the murine tumor model signified the relevance of spatially and temporally adjusting the cut-off frequency. The two-stage method improved visualization of the vascular network and significantly reduced artifacts in both the tumor and CAM models in comparison to images using conventional Doppler processing. In the CAM model, vessel diameters measured in two-stage processed images were more accurate than measurements in images exported from a commercial scanner. The proposed signal processing methods increase accuracy and robustness of qualitative and quantitative studies using 3-D power Doppler angiography to assess vascular networks for flow depiction and quantification

Focal Spot, Spring 1988

https://digitalcommons.wustl.edu/focal_spot_archives/1048/thumbnail.jp

Soft-tissue Tumor Differentiation Using 3D Power Doppler Ultrasonography With Echo-contrast Medium Injection

BackgroundWe aimed to evaluate the ability of 3-dimensional power Doppler ultrasonography to differentiate soft-tissue masses from blood flow and vascularization with contrast medium.MethodsTwenty-five patients (mean age, 44.1 years; range, 12-77 years) with a palpable mass were enrolled in this study. Volume data were acquired using linear and convex 3-dimensional probes and contrast medium injected manually by bolus. Data were stored and traced slice by slice for 12 slices. All patients were scanned by the same senior sonologist. The vascular index (VI), flow index (FI), and vascular-flow index (VFI) were automatically calculated after the tumor was completely traced. All tumors were later confirmed by pathology.ResultsThe study included 8 benign (mean, 36.5 mL; range, 2.4-124 mL) and 17 malignant (mean, 319.4 mL; range, 9.9-1,179.6 mL) tumors. Before contrast medium injection, mean VI, FI and VFI were, respectively, 3.22, 32.26 and 1.07 in benign tumors, and 1.97, 29.33 and 0.67 in malignant tumors. After contrast medium injection, they were, respectively, 20.85, 37.33 and 8.52 in benign tumors, and 40.12, 41.21 and 17.77 in malignant tumors. The mean differences between with and without contrast injection for VI, FI and VFI were, respectively, 17.63, 5.07 and 7.45 in benign tumors, and 38.15, 11.88 and 16.55 in malignant tumors. Tumor volume, VI, FI and VFI were not significantly different between benign and malignant tumors before and after echo-contrast medium injection. However, VI, FI and VFI under self-differentiation (differences between with and without contrast injection) were significantly different between malignant and benign tumors.ConclusionThree-dimensional power Doppler ultrasound is a valuable tool for differential diagnosis of soft-tissue tumors, especially with the injection of an echo-contrast medium

First-order statistical speckle models improve robustness and reproducibility of contrast-enhanced ultrasound perfusion estimates

Contrast-enhanced ultrasound (CEUS) permits the quantification and monitoring of adaptive tumor responses in the face of anti-angiogenic treatment, with the goal of informing targeted therapy. However, conventional CEUS image analysis relies on mean signal intensity as an estimate of tracer concentration in indicator-dilution modeling. This discounts additional information that may be available from the first-order speckle statistics in a CEUS image. Heterogeneous vascular networks, typical of tumor-induced angiogenesis, lead to heterogeneous contrast enhancement of the imaged tumor cross-section. To address this, a linear (B-mode) processing approach was developed to quantify the change in the first-order speckle statistics of B-mode cine loops due to the incursion of microbubbles. The technique, named the EDoF (effective degrees of freedom) method, was developed on tumor bearing mice (MDA-MB-231LN mammary fat pad inoculation) and evaluated using nonlinear (two-pulse amplitude modulated) contrast microbubble-specific images. To improve the potential clinical applicability of the technique, a second-generation compound probability density function for the statistics of two-pulse amplitude modulated contrast-enhanced ultrasound images was developed. The compound technique was tested in an antiangiogenic drug trial (bevacizumab) on tumor bearing mice (MDA-MB-231LN), and evaluated with gold-standard histology and contrast-enhanced X-ray computed tomography. The compound statistical model could more accurately discriminate anti-VEGF treated tumors from untreated tumors than conventional CEUS image. The technique was then applied to a rapid patient-derived xenograft (PDX) model of renal cell carcinoma (RCC) in the chorioallantoic membrane (CAM) of chicken embryos. The ultimate goal of the PDX model is to screen RCC patients for de novo sunitinib resistance. The analysis of the first-order speckle statistics of contrast-enhanced ultrasound cine loops provides more robust and reproducible estimates of tumor blood perfusion than conventional image analysis. Theoretically this form of analysis could quantify perfusion heterogeneity and provide estimates of vascular fractal dimension, but further work is required to determine what physiological features influence these measures. Treatment sensitivity matrices, which combine vascular measures from CEUS and power Doppler, may be suitable for screening of de novo sunitinib resistance in patients diagnosed with renal cell carcinoma. Further studies are required to assess whether this protocol can be predictive of patient outcome

Quantitative Assessment of Cancer Vascular Architecture by Skeletonization of High-resolution 3-D Contrast-enhanced Ultrasound Images: Role of Liposomes and Microbubbles.

The accurate characterization and description of the vascular network of a cancer lesion is of paramount importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3-D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1,2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3-D contrast-enhanced images of the tumor lesions were acquired in three conditions: pre-contrast, after the injection of micro bubbles, and after the injection of liposomes. By using a previously developed reconstruction and characterization image processing technique, we obtained the 3-D representation of the vascular architecture in these three conditions. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2-D curvature measure, the number of vascular flexes of the vessels, and the 3-D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient “theranostic” (i.e. therapeutic 1 diagnostic) ultrasound probes

Value of tissue harmonic imaging (THI) and contrast harmonic imaging (CHI) in detection and characterisation of breast tumours

The purpose of this study was to investigate the extent to which tissue harmonic imaging (THI), speckle reduction imaging (SRI), spatial compounding (SC) and contrast can improve detection and differentiation of breast tumours. We examined 38 patients (14 benign, 24 malignant tumours) with different combinations of THI, SRI and SC. The effect on delineation, margin, tissue differentiation and posttumoral phenomena was evaluated with a three-point score. Additionally, 1oo not palpable tumours (diameters: 4–15 mm) were examined by contrast harmonic imaging (CHI) with power Doppler. After bolus injection (0.5 ml Optison), vascularisation and enhancement were observed for 20 min. The best combination for detection of margin, infiltration, echo pattern and posterior lesion boundary was the combination of SRI level 2 with SC low. THI was helpful for lesions OF more than 1 cm depth. In native Power Doppler, vessels were found in 54 of 100 lesions. Within 5 min after contrast medium (CM) injection, marginal and penetrating vessels increased in benign and malignant tumours and central vessels mostly in carcinomas (p<0.05). A diffuse CM accumulation was observed up to 20 min after injection in malignant tumours only (p<0.05). THI, SRI and SC improved delineation and tissue differentiation. Second-generation contrast agent allowed detection of tumour vascularisation with prolonged enhancement

Contrast-enhanced imaging in the biological and functional assessment of breast cancer

Contrast-enhanced MRI and ultrasound have emerged as additional imaging modalities in the management of breast cancer. This thesis examines the role these modalities currently play in the surgical management of breast cancer. Ways in which MRI may contribute to staging, diagnosis, treatment and prognosis are investigated. It was demonstrated that small additional enhancing foci on MRI, away from the primary tumour, represent in-situ or invasive cancer foci. Although their resection may result in extended wide local excisions or even unnecessary mastectomies, it was demonstrated that MRI findings do not currently influence the amount of tissue removed during breast conservation surgery. Volumetric analysis of breast MRI was proposed as an accurate objective assessment of the extent of surgery required for a particular tumour. Breast MRI was shown to be useful in the assessment of extent of residual disease during primary medical therapy but not in the detection of axillary lymph node metastases. In the second section of this thesis, the clinical application of pre-operative MRI in providing prognostic as well as diagnostic information was evaluated. Contrast- enhancement with both MRI and ultrasound is believed to depend on tumour angiogenesis but only a weak correlation was demonstrated between contrast- enhancement intensity and tumour angiogenesis. The detection of angiogenesis was applied to Doppler ultrasound using a novel microbubble ultrasound contrast agent (Levovist). Within a multicentre prospective study, Doppler ultrasound was shown to be a powerful discriminator of malignancy in suspected local recurrence. A strong correlation was found between MRI and histological assessment of tumour size but there was no correlation between enhancement intensity and other pathological prognostic variables. This thesis has shown that breast MRI is useful in pre-operative planning of surgery and provides diagnostic as well as limited prognostic information. Future proposed studies to determine the effect of MRI on patient management and patient outcome in breast cancer are considered

Ultrasound Imaging

This book provides an overview of ultrafast ultrasound imaging, 3D high-quality ultrasonic imaging, correction of phase aberrations in medical ultrasound images, etc. Several interesting medical and clinical applications areas are also discussed in the book, like the use of three dimensional ultrasound imaging in evaluation of Asherman's syndrome, the role of 3D ultrasound in assessment of endometrial receptivity and follicular vascularity to predict the quality oocyte, ultrasound imaging in vascular diseases and the fetal palate, clinical application of ultrasound molecular imaging, Doppler abdominal ultrasound in small animals and so on