Análise funcional do ventrículo esquerdo em angio-TC coronária

Doutoramento em Engenharia InformáticaCoronary CT angiography is widely used in clinical practice for the assessment of coronary artery disease. Several studies have shown that the same exam can also be used to assess left ventricle (LV) function. LV function is usually evaluated using just the data from end-systolic and end-diastolic phases even though coronary CT angiography (CTA) provides data concerning multiple cardiac phases, along the cardiac cycle. This unused wealth of data, mostly due to its complexity and the lack of proper tools, has still to be explored in order to assess if further insight is possible regarding regional LV functional analysis. Furthermore, different parameters can be computed to characterize LV function and while some are well known by clinicians others still need to be evaluated concerning their value in clinical scenarios. The work presented in this thesis covers two steps towards extended use of CTA data: LV segmentation and functional analysis. A new semi-automatic segmentation method is presented to obtain LV data for all cardiac phases available in a CTA exam and a 3D editing tool was designed to allow users to fine tune the segmentations. Regarding segmentation evaluation, a methodology is proposed in order to help choose the similarity metrics to be used to compare segmentations. This methodology allows the detection of redundant measures that can be discarded. The evaluation was performed with the help of three experienced radiographers yielding low intraand inter-observer variability. In order to allow exploring the segmented data, several parameters characterizing global and regional LV function are computed for the available cardiac phases. The data thus obtained is shown using a set of visualizations allowing synchronized visual exploration. The main purpose is to provide means for clinicians to explore the data and gather insight over their meaning, as well as their correlation with each other and with diagnosis outcomes. Finally, an interactive method is proposed to help clinicians assess myocardial perfusion by providing automatic assignment of lesions, detected by clinicians, to a myocardial segment. This new approach has obtained positive feedback from clinicians and is not only an improvement over their current assessment method but also an important first step towards systematic validation of automatic myocardial perfusion assessment measures.A angiografia coronária por TC (angio-TC) é prática clínica corrente para a avaliação de doença coronária. Alguns estudos mostram que é também possível utilizar o exame de angio-TC para avaliar a função do ventrículo esquerdo (VE). A função ventricular esquerda (FVE) é normalmente avaliada considerando as fases de fim de sístole e de fim de diástole, apesar de a angio-TC proporcionar dados relativos a diferentes fases distribuídas ao longo do ciclo cardíaco. Estes dados não considerados, devido à sua complexidade e à falta de ferramentas apropriadas para o efeito, têm ainda de ser explorados para que se perceba se possibilitam uma melhor compreensão da FVE. Para além disso, podem ser calculados diferentes parâmetros para caracterizar a FVE e, enquanto alguns são bem conhecidos dos médicos, outros requerem ainda uma avaliação do seu valor clínico. No âmbito de uma utilização alargada dos dados proporcionados pelos angio- TC, este trabalho apresenta contributos ao nível da segmentação do VE e da sua análise funcional. É proposto um método semi-automático para a segmentação do VE de forma a obter dados para as diferentes fases cardíacas presentes no exame de angio- TC. Foi também desenvolvida uma ferramenta de edição 3D que permite aos utilizadores a correcção das segmentações assim obtidas. Para a avaliação do método de segmentação apresentado foi proposta uma metodologia que permite a detecção de medidas de similaridade redundantes, a usar no âmbito da avaliação para comparação entre segmentações, para que tais medidas redundantes possam ser descartadas. A avaliação foi executada com a colaboração de três técnicos de radiologia experientes, tendo-se verificado uma baixa variabilidade intra- e inter-observador. De forma a permitir explorar os dados segmentados, foram calculados vários parâmetros para caracterização global e regional da FVE, para as diversas fases cardíacas disponíveis. Os resultados assim obtidos são apresentados usando um conjunto de visualizações que permitem uma exploração visual sincronizada dos mesmos. O principal objectivo é proporcionar ao médico a exploração dos resultados obtidos para os diferentes parâmetros, de modo a que este tenha uma compreensão acrescida sobre o seu significado clínico, assim como sobre a correlação existente entre diferentes parâmetros e entre estes e o diagnóstico. Finalmente, foi proposto um método interactivo para ajudar os médicos durante a avaliação da perfusão do miocárdio, que atribui automaticamente as lesões detectadas pelo médico ao respectivo segmento do miocárdio. Este novo método obteve uma boa receptividade e constitui não só uma melhoria em relação ao método tradicional mas é também um primeiro passo para a validação sistemática de medidas automáticas da perfusão do miocárdio

Monitoring cell infiltration into the myocardial infarction site using micrometer-sized iron oxide particles-enhanced magnetic resonance imaging

The cell infiltration into the myocardial infarction (MI) site was studied using magnetic resonance imaging (MRI) with micrometer-sized iron oxide particles (MPIO) as cell labeling probes. MI is a leading cause of global death and disability. However, the roles of inflammatory cells and stem cells during the post-MI remodeling and repair processes are yet to be discovered. This study was to develop noninvasive MRI techniques to monitor and quantify the cellular infiltration into the MI site. MPIO can produce pronounced signal attenuation at regions of interest in MRI. Therefore, cells labeled with these particles can be detected after they are activated and home to the MI site. In the first project, MPIO of various doses were injected into the mouse blood stream 7 days before the MI surgery. Serial MRI was performed at various time points post-MI to monitor the inflammatory cell infiltration into the MI site. Significant signal attenuation caused by labeled cells, in particular macrophages, was observed at the MI site. The study suggests an optimal imaging window should be from 7 to 14 days post-MI, during which the MR signal was inversely proportional to the MPIO dose. The study also suggests an optimal MPIO dose should be between 9.1 and 14.5 µg Fe/g body weight. In the second project, mesenchymal stem cells labeled with MPIO were transplanted into the mouse bone marrow 14 days before the MI surgery. Serial MRI was performed at various time points post-MI to monitor the labeled cells, which mobilized from the bone marrow and homed to the MI site. All the MRI findings were further confirmed by histology. In addition to revealing the characteristics of cell infiltration during MI, this study also provides noninvasive MRI techniques to monitor and potentially quantify labeled cells at the pathological site. The technique can also be used to investigate the function of cells engaged in MI and to test the effect on cell infiltration caused by any treatment strategies.Ph.D.Committee Chair: Sang Hyun Cho; Committee Co-Chair: Tom C.-C. Hu; Committee Member: Autumn Schumacher; Committee Member: Chris C.-K. Wang; Committee Member: John N. Oshinski; Committee Member: Nathan E. Yanasa

Computational Methods for Segmentation of Multi-Modal Multi-Dimensional Cardiac Images

Segmentation of the heart structures helps compute the cardiac contractile function quantified via the systolic and diastolic volumes, ejection fraction, and myocardial mass, representing a reliable diagnostic value. Similarly, quantification of the myocardial mechanics throughout the cardiac cycle, analysis of the activation patterns in the heart via electrocardiography (ECG) signals, serve as good cardiac diagnosis indicators. Furthermore, high quality anatomical models of the heart can be used in planning and guidance of minimally invasive interventions under the assistance of image guidance. The most crucial step for the above mentioned applications is to segment the ventricles and myocardium from the acquired cardiac image data. Although the manual delineation of the heart structures is deemed as the gold-standard approach, it requires significant time and effort, and is highly susceptible to inter- and intra-observer variability. These limitations suggest a need for fast, robust, and accurate semi- or fully-automatic segmentation algorithms. However, the complex motion and anatomy of the heart, indistinct borders due to blood flow, the presence of trabeculations, intensity inhomogeneity, and various other imaging artifacts, makes the segmentation task challenging. In this work, we present and evaluate segmentation algorithms for multi-modal, multi-dimensional cardiac image datasets. Firstly, we segment the left ventricle (LV) blood-pool from a tri-plane 2D+time trans-esophageal (TEE) ultrasound acquisition using local phase based filtering and graph-cut technique, propagate the segmentation throughout the cardiac cycle using non-rigid registration-based motion extraction, and reconstruct the 3D LV geometry. Secondly, we segment the LV blood-pool and myocardium from an open-source 4D cardiac cine Magnetic Resonance Imaging (MRI) dataset by incorporating average atlas based shape constraint into the graph-cut framework and iterative segmentation refinement. The developed fast and robust framework is further extended to perform right ventricle (RV) blood-pool segmentation from a different open-source 4D cardiac cine MRI dataset. Next, we employ convolutional neural network based multi-task learning framework to segment the myocardium and regress its area, simultaneously, and show that segmentation based computation of the myocardial area is significantly better than that regressed directly from the network, while also being more interpretable. Finally, we impose a weak shape constraint via multi-task learning framework in a fully convolutional network and show improved segmentation performance for LV, RV and myocardium across healthy and pathological cases, as well as, in the challenging apical and basal slices in two open-source 4D cardiac cine MRI datasets. We demonstrate the accuracy and robustness of the proposed segmentation methods by comparing the obtained results against the provided gold-standard manual segmentations, as well as with other competing segmentation methods

Evaluating The Utility Of Spect/ct Imaging Of Angiosome Perfusion In Diabetic Patients With Critical Limb Ischemia

EVALUATING THE UTILITY OF SPECT/CT IMAGING OF ANGIOSOME PERFUSION IN DIABETIC PATIENTS WITH CRITICAL LIMB ISCHEMIA. Jessica L. Buckley, Albert J. Sinusas, Mitchel R. Stacy. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT. Impaired lower extremity perfusion is a hallmark of peripheral arterial disease (PAD) and is particularly problematic in diabetic patients, who suffer from high rates of PAD, ulceration, and lower extremity amputation. The ability to non-invasively detect deficits in microvascular perfusion within vascular territories, or angiosomes, of the feet may provide information related to tissue viability and guide therapeutic interventions. In this study, we sought to apply single photon emission computed tomography (SPECT)/CT imaging to quantify volumetric microvascular perfusion within specific angiosomes containing non-healing foot ulcers in diabetic patients with critical limb ischemia (CLI). Additionally, we sought to assess the value of SPECT/CT perfusion imaging for predicting limb salvage in CLI patients undergoing lower extremity endovascular revascularization. Forty-one diabetic patients (mean age, 66±12 yrs) with non-healing ulcers and nine healthy control subjects (mean age, 50±10 yrs) underwent SPECT/CT imaging of the feet following a resting injection of technetium-99m (99mTc)-tetrofosmin (dose, 550.6 ± 37 Mbq). CT images of diabetic feet were segmented into five angiosomes and used for quantifying relative radiotracer uptake, expressed as standardized uptake values (SUVs). SUVs were assessed for each CLI patient in the angiosome containing the non-healing ulcers, while average whole foot perfusion was assessed for healthy control subjects. Percent change in SPECT SUVs of ulcerated angiosomes was quantified following endovascular revascularization in patients, and 3-, 6-, and 12-month limb salvage outcomes were assessed. SPECT/CT imaging allowed for visualization of perfusion deficits under resting conditions. 99mTc-tetrofosmin SPECT/CT imaging of angiosome foot perfusion demonstrated a significant difference in baseline perfusion values (SUVs) between diabetic patients with CLI and healthy control subjects (p = 0.02). Analysis of baseline SPECT/CT imaging and ankle-brachial index (ABI) measurements in CLI patients and healthy control subjects demonstrated a significant and positive relationship between SPECT/CT angiosome perfusion and ABI (p = 0.01; r = 0.41). Serial evaluation of relative changes in SPECT angiosome foot perfusion following revascularization revealed significant quantitative changes in perfusion after treatment, whereas ABI measurements did not demonstrate significant changes after revascularization. Changes in SPECT/CT-derived angiosome perfusion significantly differed between patients with and patients without amputation in the 3 (p = 0.01), 6 (p = 0.03), and 12 (p = 0.03) months following revascularization. SPECT/CT imaging provides a useful non-invasive tool for evaluating microvascular perfusion within specific angiosomes of the foot under resting conditions. SPECT/CT imaging also allows for serial assessment of sensitive changes in angiosome microvascular perfusion following revascularization that are undetected by ABI. Perfusion imaging with SPECT/CT offers a novel quantitative imaging approach for assessing the efficacy of revascularization strategies targeted at restoring perfusion to non-healing wounds of the foot and may assist with predicting limb salvage outcomes in CLI patients undergoing revascularization. Future application of SPECT/CT perfusion imaging may provide additional value for detection and targeting of ischemic tissue for therapeutic interventions in the PAD patient population

Evaluation of state-of-the-art segmentation algorithms for left ventricle infarct from late Gadolinium enhancement MR images

Studies have demonstrated the feasibility of late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging for guiding the management of patients with sequelae to myocardial infarction, such as ventricular tachycardia and heart failure. Clinical implementation of these developments necessitates a reproducible and reliable segmentation of the infarcted regions. It is challenging to compare new algorithms for infarct segmentation in the left ventricle (LV) with existing algorithms. Benchmarking datasets with evaluation strategies are much needed to facilitate comparison. This manuscript presents a benchmarking evaluation framework for future algorithms that segment infarct from LGE CMR of the LV. The image database consists of 30 LGE CMR images of both humans and pigs that were acquired from two separate imaging centres. A consensus ground truth was obtained for all data using maximum likelihood estimation. Six widely-used fixed-thresholding methods and five recently developed algorithms are tested on the benchmarking framework. Results demonstrate that the algorithms have better overlap with the consensus ground truth than most of the n-SD fixed-thresholding methods, with the exception of the FullWidth-at-Half-Maximum (FWHM) fixed-thresholding method. Some of the pitfalls of fixed thresholding methods are demonstrated in this work. The benchmarking evaluation framework, which is a contribution of this work, can be used to test and benchmark future algorithms that detect and quantify infarct in LGE CMR images of the LV. The datasets, ground truth and evaluation code have been made publicly available through the website: https://www.cardiacatlas.org/web/guest/challenges