Vascular patterning of subcutaneous mouse fibrosarcomas expressing individual VEGF isoforms can be differentiated using angiographic optical coherence tomography

Subcutaneously implanted experimental tumors in mice are commonly used in cancer research. Despite their superficial location, they remain a challenge to image noninvasively at sufficient spatial resolution for microvascular studies. Here we evaluate the capabilities of optical coherence tomography (OCT) angiography for imaging such tumors directly through the murine skin in-vivo. Datasets were collected from mouse tumors derived from fibrosarcoma cells genetically engineered to express only single splice variant isoforms of vascular endothelial growth factor A (VEGF); either VEGF120 or VEGF188 (fs120 and fs188 tumors respectively). Measured vessel diameter was found to be significantly (p<0.001) higher for fs120 tumors (60.7±4.9μm) compared to fs188 tumors (45.0±4.0μm). The fs120 tumors also displayed significantly higher vessel tortuosity, fractal dimension and density. The ability to differentiate between tumor types with OCT suggests that the visible abnormal vasculature is representative of the tumor microcirculation, providing a robust, non-invasive method for observing the longitudinal dynamics of the subcutaneous tumor microcirculation

Quantifying Atherosclerosis: IVUS Imaging For Lumen Border Detection And Plaque Characterization

The importance of atherosclerotic disease in coronary artery has been a subject of study for many researchers in the past decade. In brief, the aim is to understand progression of such a disease, detect plaques at risks (vulnerable plaques), and treat them selectively to prevent mortality and immobility. Consequently, several imaging modalities have been developed and among them intravascular ultrasound (IVUS) has been of particular interest since it provides useful information about tissues microstructures and images with sufficient penetration as well as resolution. In general, the ultimate goal is to provide interventional cardiologists with reliable clinical tools so they can identify vulnerable plaques, make decisions confidently, choose the most appropriate drugs or implant devices (i.e. stent), and stabilize them during catheterization procedures with minimal risk. In this work, we review existing atherosclerotic tissue characterization algorithms including the state-of-the-art virtual histology (VH) framework, which has been implemented in the Volcano (Rancho Cordova, CA) IVUS clinical scanners using 64-elements 20 MHz phased-array transducer. Initially, we intended to extend this technique for data acquired with 40 MHz single-element transducers. For this reason, we started acquiring in vitro IVUS data and studied involved challenges from specimen preparation toward classification. We observed inconsistency among extracted features along with transducer's spectral parameters (i.e. bandwidth, center frequency). This, in addition to infeasibility of construction of reliable training dataset due to heterogeneity of atherosclerotic tissues motivated us to develop an unsupervised texture-based atherosclerotic tissue characterization algorithm. We proposed a two-dimensional multiscale wavelet-based algorithm to expand IVUS backscattered signals and/or grayscale images onto orthogonal symmetric quadrature mirror filters (QMF) such as Lemarie-Battle. At the bottom of decomposition tree, we employed ISODATA to cluster enveloped detected features in an unsupervised fashion and classify atherosclerotic plaque constitutes into fibrotic, lipidic, calcified, and no tissues. For the first time, we studied numbers of factors that were necessary for extension of in vitro derived classifier for in vivo applications such as reliability of classified tissues behind arc of calcified plaques and effects of pressure changes as well as flowing blood on constructed tissue color maps, called prognosis histology (PH) images. The second half of this dissertation is devoted to automatic detection of lumen borders in IVUS grayscale images acquired with high frequency (40 MHz up) transducers where more scattering exhibited within lumen area that makes the problem of interest more challenging. We established our framework on three-dimensional expansion of IVUS sub-volumes onto orthonormal brushlet basis function. The rational behind our framework was presence of incoherent (i.e. blood) versus coherent (i.e. plaque, surrounding fat) textural patterns along pullback direction, which was motivated by what an interventional cardiologist does to locate the lumen border visually by going back and forth among IVUS frames. We studied the feasibility of brushlet analysis through filtering blood speckles and supervised classification of blood versus non-blood regions. Our preliminary study confirmed that the most informative features reside in the innermost cubes, representing low-frequency components in transformed domain. Finally, we explored that tissue responses to IVUS signals are proportionally preserved in brushlet coefficients and it enabled us to classify blood regions in complex brushlet space. Subsequently, we employed surface function actives (SFA) to estimate the lumen borders after regularization. In a comparison study, we quantified our results with two of existing algorithms, employing IVUS grayscale images acquired with 40 MHz and 45 MHz single-element transducers. Overall, our proposed algorithm outperformed and the resulting automated detected borders showed good correlation with manually traced borders by an expert

Novel Algorithms for Merging Computational Fluid Dynamics and 4D Flow MRI

Time-resolved three-dimensional spatial encoding combined with three-directional velocity-encoded phase contrast magnetic resonance imaging (termed as 4D flow MRI), can provide valuable information for diagnosis, treatment, and monitoring of vascular diseases. The accuracy of this technique, however, is limited by errors in flow estimation due to acquisition noise as well as systematic errors. Furthermore, available spatial resolution is limited to 1.5mm - 3mm and temporal resolution is limited to 30-40ms. This is often grossly inadequate to resolve flow details in small arteries, such as those in cerebral circulation. Recently, there have been efforts to address the limitations of the spatial and temporal resolution of MR flow imaging through the use of computational fluid dynamics (CFD). While CFD is capable of providing essentially unlimited spatial and temporal resolution, numerical results are very sensitive to errors in estimation of the flow boundary conditions. In this work, we present three novel techniques that combine CFD with 4D flow MRI measurements in order to address the resolution and noise issues. The first technique is a variant of the Kalman Filter state estimator called the Ensemble Kalman Filter (EnKF). In this technique, an ensemble of patient-specific CFD solutions are used to compute filter gains. These gains are then used in a predictor-corrector scheme to not only denoise the data but also increase its temporal and spatial resolution. The second technique is based on proper orthogonal decomposition and ridge regression (POD-rr). The POD method is typically used to generate reduced order models (ROMs) in closed control applications of large degree of freedom systems that result from discretization of governing partial differential equations (PDE). The POD-rr process results in a set of basis functions (vectors), that capture the local space of solutions of the PDE in question. In our application, the basis functions are generated from an ensemble of patient-specific CFD solutions whose boundary conditions are estimated from 4D flow MRI data. The CFD solution that should be most closely representing the actual flow is generated by projecting 4D flow MRI data onto the basis vectors followed by reconstruction in both MRI and CFD resolution. The rr algorithm was used for between resolution mapping. Despite the accuracy of using rr as the mapping step, due to manual adjustment of a coefficient in the algorithm we developed the third algorithm. In this step, the rr algorithm was substituded with a dynamic mode decomposition algorithm to preserve the robustness. These algorithms have been implemented and tested using a numerical model of the flow in a cerebral aneurysm. Solutions at time intervals corresponding to the 4D flow MRI temporal resolution were collected and downsampled to the spatial resolution of the imaging data. A simulated acquisition noise was then added in k-space. Finally, the simulated data affected by noise were used as an input to the merging algorithms. Rigorous comparison to state-of-the-art techniques were conducted to assess the accuracy and performance of the proposed method. The results provided denoised flow fields with less than 1\% overall error for different signal-to-noise ratios. At the end, a small cohort of three patients were corrected and the data were reconstructed using different methods, the wall shear stress (WSS) was calculated using different reconstructed data and the results were compared. As it has been shown in chapter 5, the calculated WSS using different methods results in mutual high and low shear stress regions, however, the exact value and patterns are significantly different

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

LVAD Occlusion Condition Monitoring Using Boost Classification Trees

Cardiac related diseases are a serious health risk for adults. Consequently, therapies exist to treat these aliments such as heart transplant and medication. Heart transplant remains the gold standard for treating severe heart failure, however left ventricular assistive devices, a cardiac blood pump, are become a viable long term treatment. Unfortunately, with the benefits of these devices come risks of clot formation. These occlusions can cause strokes, further cardiac damage, or even death. Therefore, it is critical that these occlusions be detected as early as possible. This work presents an expanded method to non-invasively monitor the condition of a Thoratec HeartMate II ventricular assist device through the application of a boosted classification tree. In addition, both inflow and outflow blockages measured at aorta and pump locations were experimentally tested on a cardiac phantom. The proposed method presents a potential outpatient diagnostic method that may assist experienced cardiologists in their treatment of LVAD patients

Optimization and Data Analysis in Biomedical Informatics

Abstract Intravascular ultrasound (IVUS) is a catheter-based medical imaging modality that is capable of providing cross-sectional images of the interior of blood vessels. A comprehensive analysis of the IVUS data allows collecting information about the morphology and structure of the vessel and the atherosclerotic plaque, if present. Atherosclerotic plaque formation is considered to be a part of an inflammatory process. Recent evidence has suggested that the presence and proliferation of vasa vasorum (VV) in the plaque is correlated with the increase of plaque inflammation and the processes which lead to its destabilization. Hence, the detection and measurement of VV in plaque has the potential to enable the development of an index of plaque vulnerability. In this paper, we review the research at the Computational Biomedicine Lab towards the development of a complete pipeline for the detection and quantification of extra-luminal blood detection from IVUS data which may be an indication of the existence of VV

Lattice-Boltzmann interactive blood flow simulation pipeline.

PURPOSE:Cerebral aneurysms are one of the prevalent cerebrovascular disorders in adults worldwide and caused by a weakness in the brain artery. The most impressive treatment for a brain aneurysm is interventional radiology treatment, which is extremely dependent on the skill level of the radiologist. Hence, accurate detection and effective therapy for cerebral aneurysms still remain important clinical challenges. In this work, we have introduced a pipeline for cerebral blood flow simulation and real-time visualization incorporating all aspects from medical image acquisition to real-time visualization and steering. METHODS:We have developed and employed an improved version of HemeLB as the main computational core of the pipeline. HemeLB is a massive parallel lattice-Boltzmann fluid solver optimized for sparse and complex geometries. The visualization component of this pipeline is based on the ray marching method implemented on CUDA capable GPU cores. RESULTS:The proposed visualization engine is evaluated comprehensively and the reported results demonstrate that it achieves significantly higher scalability and sites updates per second, indicating higher update rate of geometry sites' values, in comparison with the original HemeLB. This proposed engine is more than two times faster and capable of 3D visualization of the results by processing more than 30 frames per second. CONCLUSION:A reliable modeling and visualizing environment for measuring and displaying blood flow patterns in vivo, which can provide insight into the hemodynamic characteristics of cerebral aneurysms, is presented in this work. This pipeline increases the speed of visualization and maximizes the performance of the processing units to do the tasks by breaking them into smaller tasks and working with GPU to render the images. Hence, the proposed pipeline can be applied as part of clinical routines to provide the clinicians with the real-time cerebral blood flow-related information

Biomedical Signal and Image Processing

Written for senior-level and first year graduate students in biomedical signal and image processing, this book describes fundamental signal and image processing techniques that are used to process biomedical information. The book also discusses application of these techniques in the processing of some of the main biomedical signals and images, such as EEG, ECG, MRI, and CT. New features of this edition include the technical updating of each chapter along with the addition of many more examples, the majority of which are MATLAB based