ScarGAN: Chained Generative Adversarial Networks to Simulate Pathological Tissue on Cardiovascular MR Scans

Medical images with specific pathologies are scarce, but a large amount of data is usually required for a deep convolutional neural network (DCNN) to achieve good accuracy. We consider the problem of segmenting the left ventricular (LV) myocardium on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) scans of which only some of the scans have scar tissue. We propose ScarGAN to simulate scar tissue on healthy myocardium using chained generative adversarial networks (GAN). Our novel approach factorizes the simulation process into 3 steps: 1) a mask generator to simulate the shape of the scar tissue; 2) a domain-specific heuristic to produce the initial simulated scar tissue from the simulated shape; 3) a refining generator to add details to the simulated scar tissue. Unlike other approaches that generate samples from scratch, we simulate scar tissue on normal scans resulting in highly realistic samples. We show that experienced radiologists are unable to distinguish between real and simulated scar tissue. Training a U-Net with additional scans with scar tissue simulated by ScarGAN increases the percentage of scar pixels correctly included in LV myocardium prediction from 75.9% to 80.5%.Comment: 12 pages, 5 figures. To appear in MICCAI DLMIA 201

Changes and classification in myocardial contractile function in the left ventricle following acute myocardial infarction

In this research, we hypothesized that novel biomechanical parameters are discriminative in patients following acute ST-segment elevation myocardial infarction (STEMI). To identify these biomechanical biomarkers and bring computational biomechanics ‘closer to the clinic’, we applied state-of-the-art multiphysics cardiac modelling combined with advanced machine learning and multivariate statistical inference to a clinical database of myocardial infarction. We obtained data from 11 STEMI patients (ClinicalTrials.gov NCT01717573) and 27 healthy volunteers, and developed personalized mathematical models for the left ventricle (LV) using an immersed boundary method. Subject-specific constitutive parameters were achieved by matching to clinical measurements. We have shown, for the first time, that compared with healthy controls, patients with STEMI exhibited increased LV wall active tension when normalized by systolic blood pressure, which suggests an increased demand on the contractile reserve of remote functional myocardium. The statistical analysis reveals that the required patient-specific contractility, normalized active tension and the systolic myofilament kinematics have the strongest explanatory power for identifying the myocardial function changes post-MI. We further observed a strong correlation between two biomarkers and the changes in LV ejection fraction at six months from baseline (the required contractility (r = − 0.79, p < 0.01) and the systolic myofilament kinematics (r = 0.70, p = 0.02)). The clinical and prognostic significance of these biomechanical parameters merits further scrutinization

Myocardial Infarction Quantification From Late Gadolinium Enhancement MRI Using Top-hat Transforms and Neural Networks

Significance: Late gadolinium enhanced magnetic resonance imaging (LGE-MRI) is the gold standard technique for myocardial viability assessment. Although the technique accurately reflects the damaged tissue, there is no clinical standard for quantifying myocardial infarction (MI), demanding most algorithms to be expert dependent. Objectives and Methods: In this work a new automatic method for MI quantification from LGE-MRI is proposed. Our novel segmentation approach is devised for accurately detecting not only hyper-enhanced lesions, but also microvascular-obstructed areas. Moreover, it includes a myocardial disease detection step which extends the algorithm for working under healthy scans. The method is based on a cascade approach where firstly, diseased slices are identified by a convolutional neural network (CNN). Secondly, by means of morphological operations a fast coarse scar segmentation is obtained. Thirdly, the segmentation is refined by a boundary-voxel reclassification strategy using an ensemble of CNNs. For its validation, reproducibility and further comparison against other methods, we tested the method on a big multi-field expert annotated LGE-MRI database including healthy and diseased cases. Results and Conclusion: In an exhaustive comparison against nine reference algorithms, the proposal achieved state-of-the-art segmentation performances and showed to be the only method agreeing in volumetric scar quantification with the expert delineations. Moreover, the method was able to reproduce the intra- and inter-observer variability ranges. It is concluded that the method could suitably be transferred to clinical scenarios.Comment: Submitted to IEE

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

Arrhythmias After Tetralogy of Fallot Repair

Tetralogy of Fallot is the most common cyanotic congenital heart disease, with a good outcome after total surgical correction. In spite of a low perioperative mortality and a good quality of life, late sudden death remains a significant clinical problem, mainly related to episodes of sustained ventricular tachycardia and ventricular fibrillation. Fibro-fatty substitution around infundibular resection, intraventricular septal scar, and patchy myocardial fibrosis, may provide anatomical substrates of abnormal depolarization and repolarization causing reentrant ventricular arrhythmias. Several non-invasive indices based on classical examination such as ECG, signal-averaging ECG, and echocardiography have been proposed to identify patients at high risk of sudden death, with hopeful results. In the last years other more sophisticated invasive and non-invasive tools, such as heart rate variability, electroanatomic mapping and cardiac magnetic resonance added a relevant contribution to risk stratification. Even if each method per se is affected by some limitations, a comprehensive multifactorial clinical and investigative examination can provide an accurate risk evaluation for every patien

Comparison of T1-maps and late gadolinium enhancement images in the detection of Myocardial Fibrosis in Hypertrophic Cardiomyopathy

Tese de Mestrado Integrado, Engenharia Biomédica e Biofísica, 2021, Universidade de Lisboa, Faculdade de CiênciasHypertrophic Cardiomyopathy (HCM) is characterized as an abnormal and heterogeneous thickening of the Left Ventricle (LV) wall. HCM is the leading cause of sudden cardiac death in children and young people, with an estimated prevalence of 1:500 in the general population. Myocardial fibrosis is the key histopathological hallmark in HCM and is presented in different patterns: interstitial diffuse fibrosis which, if not treated, evolves to replacement fibrosis. Cardiac Magnetic Resonance (CMR) imaging has been used for the detection and quantification of myocardial fibrosis. The Late Gadolinium Enhancement (LGE) technique is the primary tool for non-invasive tissue characterization, particularly for replacement fibrosis. Conversely, T1 mapping is commonly used for the detection of diffuse interstitial fibrosis, frequently missed using LGE. The clear disadvantage of LGE relies on the need to inject contrast agents that, despite being considered safe, may accumulate in the body for years and potentially cause nephrogenic systemic fibrosis in end-stage chronic kidney disease patients. The capability of native T1 mapping identifying not only diffuse interstitial but also replacement fibrosis would play a pivotal role in HCM diagnosis. The potential of native T1 mapping for a cheaper and non-contrast HCM assessment needs to be further studied. A database of 15 HCM patients, without and with fibrosis, was acquired at Hospital da Luz, Lisboa. In this project, (1) an extensive image preprocessing pipeline was applied to aim for the best possible spatial alignment of the myocardium between the two modalities (native T1 mapping and LGE); (2) the mean native T1 values of individuals without and with the presence of scarred tissue were examined; (3) a pixel-by-pixel analysis was performed to investigate if there is a correlation between fibrotic tissue in LGE and hyperintense regions in native T1 mapping; (4) a Texture Analysis (TA) was performed to study if texture information of native T1 mapping could provide differential diagnosis or prognostic information beyond mean T1 values. The first step was the most longstanding and challenging process. The registration of T1 and LGE images is difficult due to the different intensity profiles. The registration of the myocardial masks using a model with rigid, affine, and free-form deformation transformations revealed to be the best methodology. Mean native T1 values were not increased in patients with scarred tissue. Regarding the third aim, no clear intensity correlation between techniques was observed, which suggests the need for the TA. Seven features (in a total of 350) were selected to distinguish between cardiac segments without and with fibrotic tissue using a ML (Machine Learning) algorithm that finds the features that most contribute to distinguish the two groups. Four first-order features distinguish the cohorts due to the presence of scarred tissue - hyperintense zones - and three texture features suggest that the fibrotic remodeling in the myocardium of HCM patients might be associated with a more heterogeneous tissue texture. A Receiver Operating Characteristics (ROC) analysis was performed and revealed that the Cluster Prominence is the feature that best distinguishes sections without and with fibrotic tissue (accuracy of 70%) but with low sensitivity (65%) and low specifity (64%). A model with the 90th Percentile feature revealed an accuracy of 64%, sensitivity of 71% and specificity of 57%. Studying the Variance feature, the achieved accuracy was 63%, with 66% of sensitivity and 60% of specificity. The remaining features yielded lower accuracy values than the ones previously mentioned, but all of them higher than 50%. The low sensitivity and specificity of the best three models suggest that analysing these values considering these features may help cardiologists to identify focal fibrosis regions and avoid contrast injection methods but may not provide an accurate diagnosis of the presence of fibrotic tissue alone. Further research on the correlation of native T1 mapping and LGE cardiac images is highly recommended to develop a contrast-agent-free technology to replace LGE.A Cardiomiopatia Hipertrófica (do inglês, HCM) é descrita por um espessamento anormal e heterogéneo da parede do ventrículo esquerdo (do inglês, LV). A HCM é a principal causa de morte súbita cardíaca em crianças e jovens, com uma prevalência estimada de 1:500 na população em geral. Esta doença é, na sua maioria, hereditária, e causada por variantes nos genes da proteína do sarcómero (predominantemente MYH7 e MYBPC3). A fibrose do miocárdio é a principal marca histopatológica da HCM e apresenta-se em diferentes padrões: fibrose intersticial difusa que, se não tratada, evolui para fibrose focal. A fibrose é caracterizada por um aumento da deposição de colagénio, que afeta a viabilidade do miocárdio. A imagem de Ressonância Magnética Cardíaca (do inglês, CMR) tem sido usada para a deteção e quantificação de fibrose do miocárdio. A técnica de Realce Tardio (do inglês, LGE) é a principal ferramenta para caracterização não invasiva de tecidos, particularmente de fibrose focal. Em contrapartida, o mapeamento T1 é a técnica mais utilizada para deteção de fibrose intersticial difusa, frequentemente não detetada usando LGE. A clara desvantagem do LGE reside na necessidade de injeção de agentes de contraste. Apesar destes agentes serem considerados seguros, frequentemente causam alergias, podem-se acumular no corpo, por anos, e podem causar fibrose sistémica nefrogénica em pacientes com doença renal crónica terminal. A capacidade do mapeamento T1 nativo identificar, não só a fibrose intersticial difusa mas também a fibrose focal, desempenharia um papel fundamental no diagnóstico da HCM. Consequentemente, é de extrema importância estudar o potencial do mapeamento T1 nativo para uma avaliação desta patologia sem contraste e, desta forma, eliminar os riscos associados à injeção de contraste e reduzir os custos e tempo de preparação associados à utilização de gadolínio. Uma base de dados de 15 pacientes com HCM, com e sem fibrose, previamente adquirida no Hospital da Luz, Lisboa, foi analisada. Neste projeto, (1) aplicou-se um extenso conjunto de passos de pré-processamento de imagem para alcançar a melhor técnica possível de alinhamento espacial do miocárdio entre as duas modalidades (mapeamento T1 nativo e Realce Tardio); (2) após a divisão do miocárdio em 6 secções, como sugerido pela American Heart Association, examinaram-se os valores médios de T1, para cada secção, de indivíduos sem e com presença de tecido cicatricial; (3) realizou-se uma análise pixel a pixel para investigar se existe uma correlação entre o tecido fibrótico em LGE e as regiões hiperintensas no mapeamento T1 nativo; (4) realizou-se uma análise de textura para estudar se a informação de textura do mapeamento T1 nativo poderia fornecer um diagnóstico diferencial ou informação prognóstica além dos valores médios de T1 nativo. A primeira etapa revelou ser o processo mais demorado e desafiante. O batimento cardíaco e o ciclo respiratório representam dois desafios no registo de imagens cardíacas. Para além dos comuns desafios em alinhamento de imagens cardíacas da mesma modalidade, alinhar imagens de diferentes modalidades torna-se um processo mais complexo. Em primeiro lugar, o registo de imagens T1 e de LGE é dificultado pelos distintos perfis de intensidade das duas modalidades. Em segundo lugar, a aquisição de imagens de Realce Tardio ocorre cerca de 7 minutos após a aquisição do mapeamento T1, e o movimento dos pacientes durante este intervalo de tempo é uma fonte adicional de erro. Diferentes softwares foram utilizados, e uma imagem sintética ponderada em T1 foi criada, com o intuito de apresentar intensidades mais similares à imagem a ser alinhada (imagem de LGE). O registo das máscaras miocárdicas por meio de um modelo com transformações rígida, afim e deformações livres mostrou ser a melhor metodologia a aplicar. Os valores médios de T1 nativo não aumentaram significativamente em pacientes com tecido cicatricial, apesar de haver um aumento dos valores de T1 nativo em determinadas secções, em cortes basais e intermédios. Relativamente ao terceiro objetivo abordado, não foi observada uma clara correlação de intensidades entre as técnicas, o que reforçou a necessidade de uma análise de textura (do inglês, TA). Esta análise revelou as sete melhores características (num total de 350) que distinguem segmentos cardíacos sem e com tecido fibrótico, aplicando um método de Machine Learning (do inglês, ML) que identificou, sequencialmente, as features que adicionavam mais informação ao modelo que distinguia os dois grupos de segmentos. Quatro características de primeira ordem distinguem os segmentos devido à presença de tecido cicatricial - zonas hiperintensas - e três características de textura sugerem que a remodelação fibrótica no miocárdio de pacientes com HCM pode estar associada a uma textura mais heterogénea. Foi implementada uma análise ao desempenho de modelos com as features selecionadas, que revelou que a Cluster Prominence é a característica que melhor distingue secções sem e com tecido fibrótico, apesar de com baixa sensibilidade (65%) e baixa especificidade (64%). Um modelo que analisa o Percentil 90 revelou uma precisão de 64%, sensibilidade de 71% e especificidade de 57%. No estudo da Variância, a precisão foi de 63%, a sensibilidade 66% e a especificidade 60%. As restantes features apresentaram valores de precisão inferiores aos mencionados mas acima de 50%. Um modelo com a combinação das sete features selecionadas não melhorou a performance do modelo (precisão de 62%, sensibilidade de 75% e 49% de especificidade). A baixa sensibilidade e especificidade sugerem que a análise desses valores nessas características pode ajudar os cardiologistas a identificar regiões focais de fibrose e evitar métodos de injeção de contraste, mas pode não fornecer um diagnóstico preciso da presença de tecido fibrótico por si só. Em futuras aquisições, encontrar valores semelhantes nas features acima mencionadas, principalmente na Cluster Prominence, em novos dados, poderia ajudar os cardiologistas a identificar regiões de fibrose focal. Desta forma, não seria necessário analisar imagens de Realce Tardio, o que se traduziria na eliminação de injeção de agentes de contraste. Pesquisas adicionais focadas na correlação do mapeamento T1 nativo e imagens cardíacas de LGE são de extrema importância para desenvolver uma tecnologia independente da injeção de agentes de contraste, que substitua o Realce Tardio

Automated Method for the Volumetric Evaluation of Myocardial Scar from Cardiac Magnetic Resonance Images

In most western countries cardiovascular diseases are the leading cause of death, and for the survivors of ischemic attack an accurate quantification of the extent of the damage is required to correctly assess its impact and for risk stratification, and to select the best treatment for the patient. Moreover, a fast and reliable tool for the assessment of the cardiac function and the measurement of clinical indexes is highly desirable. The aim of this thesis is to provide computational approaches to better detect and assess the presence of myocardial fibrosis in the heart, particularly but not only in the left ventricle, by performing a fusion of the information from different magnetic resonance imaging sequences. We also developed and provided a semiautomatic tool useful for the fast evaluation and quantification of clinical indexes derived from heart chambers volumes. The thesis is composed by five chapters. The first chapter introduces the most common cardiac diseases such as ischemic cardiomyopathy and describes in detail the cellular and structural remodelling phenomena stemming from heart failure. The second chapter regards the detection of the left ventricle through the development of a semi-automated approach for both endocardial and epicardial surfaces, and myocardial mask extraction. In the third chapter the workflow for scar assessment is presented, in which the previously described approach is used to obtain the 3D left ventricle patient-specific geometry; a registration algorithm is then used to superimpose the fibrosis information derived from the late gadolinium enhancement magnetic resonance imaging to obtain a patientspecific 3D map of fibrosis extension and location on the left ventricle myocardium. Focus of the fourth chapter is on the left atrium, and fibrotic tissue detection for gaining insight on atrial fibrillation. In the fifth chapter some conclusive remarks are presented with possible future developments of the presented work

Rapid automatic segmentation of abnormal tissue in late gadolinium enhancement cardiovascular magnetic resonance images for improved management of long-standing persistent atrial fibrillation

Background: Atrial fibrillation (AF) is the most common heart rhythm disorder. In order for late Gd enhancement cardiovascular magnetic resonance (LGE CMR) to ameliorate the AF management, the ready availability of the accurate enhancement segmentation is required. However, the computer-aided segmentation of enhancement in LGE CMR of AF is still an open question. Additionally, the number of centres that have reported successful application of LGE CMR to guide clinical AF strategies remains low, while the debate on LGE CMR’s diagnostic ability for AF still holds. The aim of this study is to propose a method that reliably distinguishes enhanced (abnormal) from non-enhanced (healthy) tissue within the left atrial wall of (pre-ablation and 3 months post-ablation) LGE CMR data-sets from long-standing persistent AF patients studied at our centre. Methods: Enhancement segmentation was achieved by employing thresholds benchmarked against the statistics of the whole left atrial blood-pool (LABP). The test-set cross-validation mechanism was applied to determine the input feature representation and algorithm that best predict enhancement threshold levels. Results: Global normalized intensity threshold levels T PRE = 1 1/4 and T POST = 1 5/8 were found to segment enhancement in data-sets acquired pre-ablation and at 3 months post-ablation, respectively. The segmentation results were corroborated by using visual inspection of LGE CMR brightness levels and one endocardial bipolar voltage map. The measured extent of pre-ablation fibrosis fell within the normal range for the specific arrhythmia phenotype. 3D volume renderings of segmented post-ablation enhancement emulated the expected ablation lesion patterns. By comparing our technique with other related approaches that proposed different threshold levels (although they also relied on reference regions from within the LABP) for segmenting enhancement in LGE CMR data-sets of AF patients, we illustrated that the cut-off levels employed by other centres may not be usable for clinical studies performed in our centre. Conclusions: The proposed technique has great potential for successful employment in the AF management within our centre. It provides a highly desirable validation of the LGE CMR technique for AF studies. Inter-centre differences in the CMR acquisition protocol and image analysis strategy inevitably impede the selection of a universally optimal algorithm for segmentation of enhancement in AF studies