Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles.

This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic

Automated Method for Tracking Human Muscle Architecture on Ultrasound Scans during Dynamic Tasks

Existing approaches for automated tracking of fascicle length (FL) and pennation angle (PA) rely on the presence of a single, user-defined fascicle (feature tracking) or on the presence of a specific intensity pattern (feature detection) across all the recorded ultrasound images. These prerequisites are seldom met during large dynamic muscle movements or for deeper muscles that are difficult to image. Deep-learning approaches are not affected by these issues, but their applicability is restricted by their need for large, manually analyzed training data sets. To address these limitations, the present study proposes a novel approach that tracks changes in FL and PA based on the distortion pattern within the fascicle band. The results indicated a satisfactory level of agreement between manual and automated measurements made with the proposed method. When compared against feature tracking and feature detection methods, the proposed method achieved the lowest average root mean squared error for FL and the second lowest for PA. The strength of the proposed approach is that the quantification process does not require a training data set and it can take place even when it is not possible to track a single fascicle or observe a specific intensity pattern on the ultrasound recording.UK-India Education and Research Initiative (UKIERI)Department of Science and Technology (DST), New DelhiPeer Reviewe

Multigradient field-active contour model for multilayer boundary detection of ultrasound rectal wall image

Extraction and reconstruction of rectal wall structures from an ultrasound image is helpful for surgeons in rectal clinical diagnosis and 3-D reconstruction of rectal structures from ultrasound images. The primary task is to extract the boundary of the muscular layers on the rectal wall. However, due to the low SNR from ultrasound imaging and the thin muscular layer structure of the rectum, this boundary detection task remains a challenge. An active contour model is an effective high-level model, which has been used successfully to aid the tasks of object representation and recognition in many image-processing applications. We present a novel multigradient field active contour algorithm with an extended ability for multiple-object detection, which overcomes some limitations of ordinary active contour models—"snakes." The core part in the algorithm is the proposal of multigradient vector fields, which are used to replace image forces in kinetic function for alternative constraints on the deformation of active contour, thereby partially solving the initialization limitation of active contour for rectal wall boundary detection. An adaptive expanding force is also added to the model to help the active contour go through the homogenous region in the image. The efficacy of the model is explained and tested on the boundary detection of a ring-shaped image, a synthetic image, and an ultrasound image. The experimental results show that the proposed multigradient field-active contour is feasible for multilayer boundary detection of rectal wal

Fully automated segmentation and tracking of the intima media thickness in ultrasound video sequences of the common carotid artery

Abstract—The robust identification and measurement of the intima media thickness (IMT) has a high clinical relevance because it represents one of the most precise predictors used in the assessment of potential future cardiovascular events. To facilitate the analysis of arterial wall thickening in serial clinical investigations, in this paper we have developed a novel fully automatic algorithm for the segmentation, measurement, and tracking of the intima media complex (IMC) in B-mode ultrasound video sequences. The proposed algorithm entails a two-stage image analysis process that initially addresses the segmentation of the IMC in the first frame of the ultrasound video sequence using a model-based approach; in the second step, a novel customized tracking procedure is applied to robustly detect the IMC in the subsequent frames. For the video tracking procedure, we introduce a spatially coherent algorithm called adaptive normalized correlation that prevents the tracking process from converging to wrong arterial interfaces. This represents the main contribution of this paper and was developed to deal with inconsistencies in the appearance of the IMC over the cardiac cycle. The quantitative evaluation has been carried out on 40 ultrasound video sequences of the common carotid artery (CCA) by comparing the results returned by the developed algorithm with respect to ground truth data that has been manually annotated by clinical experts. The measured IMTmean ± standard deviation recorded by the proposed algorithm is 0.60 mm ± 0.10, with a mean coefficient of variation (CV) of 2.05%, whereas the corresponding result obtained for the manually annotated ground truth data is 0.60 mm ± 0.11 with a mean CV equal to 5.60%. The numerical results reported in this paper indicate that the proposed algorithm is able to correctly segment and track the IMC in ultrasound CCA video sequences, and we were encouraged by the stability of our technique when applied to data captured under different imaging conditions. Future clinical studies will focus on the evaluation of patients that are affected by advanced cardiovascular conditions such as focal thickening and arterial plaques

Shape-driven segmentation of the arterial wall in intravascular ultrasound images

Segmentation of arterial wall boundaries from intravascular images is an important problem for many applications in the study of plaque characteristics, mechanical properties of the arterial wall, its 3D reconstruction, and its measurements such as lumen size, lumen radius, and wall radius. We present a shape-driven approach to segmentation of the arterial wall from intravascular ultrasound images in the rectangular domain. In a properly built shape space using training data, we constrain the lumen and media-adventitia contours to a smooth, closed geometry, which increases the segmentation quality without any tradeoff with a regularizer term. In addition to a shape prior, we utilize an intensity prior through a non-parametric probability density based image energy, with global image measurements rather than pointwise measurements used in previous methods. Furthermore, a detection step is included to address the challenges introduced to the segmentation process by side branches and calcifications. All these features greatly enhance our segmentation method. The tests of our algorithm on a large dataset demonstrate the effectiveness of our approach

Automatic segmentation of the left ventricle cavity and myocardium in MRI data

A novel approach for the automatic segmentation has been developed to extract the epi-cardium and endo-cardium boundaries of the left ventricle (lv) of the heart. The developed segmentation scheme takes multi-slice and multi-phase magnetic resonance (MR) images of the heart, transversing the short-axis length from the base to the apex. Each image is taken at one instance in the heart's phase. The images are segmented using a diffusion-based filter followed by an unsupervised clustering technique and the resulting labels are checked to locate the (lv) cavity. From cardiac anatomy, the closest pool of blood to the lv cavity is the right ventricle cavity. The wall between these two blood-pools (interventricular septum) is measured to give an approximate thickness for the myocardium. This value is used when a radial search is performed on a gradient image to find appropriate robust segments of the epi-cardium boundary. The robust edge segments are then joined using a normal spline curve. Experimental results are presented with very encouraging qualitative and quantitative results and a comparison is made against the state-of-the art level-sets method

Shape-driven segmentation of the arterial wall in intravascular ultrasound images

Segmentation of arterial wall boundaries from intravascular images is an important problem for many applications in the study of plaque characteristics, mechanical properties of the arterial wall, its 3D reconstruction, and its measurements such as lumen size, lumen radius, and wall radius. We present a shape-driven approach to segmentation of the arterial wall from intravascular ultrasound images in the rectangular domain. In a properly built shape space using training data, we constrain the lumen and media-adventitia contours to a smooth, closed geometry, which increases the segmentation quality without any tradeoff with a regularizer term. In addition to a shape prior, we utilize an intensity prior through a non-parametric probability density based image energy, with global image measurements rather than pointwise measurements used in previous methods. Furthermore, a detection step is included to address the challenges introduced to the segmentation process by side branches and calcifications. All these features greatly enhance our segmentation method. The tests of our algorithm on a large dataset demonstrate the effectiveness of our approach