Will the real ventricular architecture please stand up?

Ventricular twisting, essential for cardiac function, is attributed to the contraction of myocardial helical fibers. The exact relationship between ventricular anatomy and function remains to be determined, but one commonly used explanatory model is the helical ventricular myocardial band (HVMB) model of Torrent-Guasp. This model has been successful in explaining many aspects of ventricular function, (Torrent-Guasp et al. Eur. J. Cardiothorac. Surg., 25, 376, 2004; Buckberg et al. Eur. J. Cardiothorac. Surg., 47, 587, 2015; Buckberg et al. Eur. J. Cardiothorac. Surg. 47, 778, 2015) but the model ignores important aspects of ventricular anatomy and should probably be replaced. The purpose of this review is to compare the HVMB model with a different model (nested layers). A complication when interpreting experimental observations that relate anatomy to function is that, in the myocardium, shortening does not always imply activation and lengthening does not always imply inactivation

Quantifying age-related differences in diffusion tensor imaging biomarkers for the male urethral sphincter of prostate cancer patients

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas) Universidade de Lisboa, Faculdade de Ciências, 2019For the past years, radical prostatectomy (RP) has been the treatment of choice for locally advanced prostate cancer (PC) because of its high accuracy in tumor removal. However, the surgical techniques performed tend to be invasive, with a complete removal of the proximal lisso-sphincter and partial removal of the distal rhabdosphincter. Whereas the former has been related with maintenance of continence at rest, the latter is related with active continence. Between 4 to 69 % [1] of patients undergoing RP develop urinary incontinence, with a reported decrease in quality of life. This can be a consequence, not only from the surgical technique used, but from other factors including the competence of the sphincter function, that it is expected to decrease with age [2]. It is important to find preoperative imaging biomarkers that can help predict the risk of the patient developing postoperative urinary incontinence. The TransDouglas project, approved by the Ethics Committee of Champalimaud Foundation since July 2018, aims at validating the implementation of a new surgical procedure for RP, which is an improved version of the robotic-assisted laparoscopic radical prostatectomy (RALRP) procedure. Preoperative anatomical parameters are extracted from the T2-weighted magnetic resonance imaging (MRI) that can be related with urinary incontinence after the new surgical technique, and to construct a model that can help predict the likely time until urinary continence recovery. Diffusion tensor imaging (DTI) is a MRI-based technique that allows the quantification of anisotropic movement of water molecules. It has been proven [3] that this technique can be used to visualize the microarchitecture of the urethral sphincters, and to extract relevant diffusion metrics. DTI metrics can be incorporated in the model to predict urinary incontinence recovery after RP. Considering this, an addendum to the TransDouglas project that requests the acquisition of an additional DTI sequence to the standard multiparametric (mpMRI) of the prostate has been approved this January, enabling the use of DTI to study the microarchitecture of the urethral sphincters in vivo and non-invasively. However, since parameters of sphincter function significantly change with age [2], it is important to study the influence of patient age at scan on these parameters prior to predicting the likely chance of continence recovery after RP. Therefore, the main goal of this thesis was to investigate age-related differences in DTI metrics of the male urethral sphincter complex. Furthermore, the influence of a prostate condition, including PC and benign prostatic hyperplasia (BPH), was studied. The proximal and distal sphincters, as well as the membranous urethra, were reconstructed for 95 subjects by using the deterministic tractography algorithm in DSIStudio software [4]. DTI metrics were extracted including tract length and density, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) and additional histogram parameters for each DTI metric, namely standard deviation, median, trimmed mean, median absolute deviation, minimum, maximum, range, skewness, kurtosis, standard error and the 5th, 25th, 75th and 95th percentiles. The influence of subject motion and eddy currents corrections on the extracted DTI metrics was investigated. Linear regressions and Pearson or Spearman correlations were performed between age and each of the DTI metrics. Additionally, analysis of variance (ANOVA), or the non-parametric Kruskal-Wallis test, were used to compare DTI metrics between four age groups (from 50 to 59, 60 to 69, 70 to 79 and 80 to 89 years old). For a subset of the 69 subjects with a confirmed diagnosis for PC, BPH and the absence of any of both, ANOVA testing was used to compare between disease groups, and t-tests, or the nonparametric Wilcoxon test, to compare between cancer status. For statistically significant ANOVA test results, post-hoc t-tests were used to investigate the groups between which the difference lied. No statistically significant differences were found on DTI metrics with and without motion and eddy currents corrections, so the non-corrected DTI data was used for the subsequent analysis. In this study, it was found that MD and RD distributions statistical significantly changed with age. In particular, older subjects evidenced lower RD kurtosis in the proximal sphincter, lower MD maximum in the distal sphincter and higher MD median absolute deviation in the membranous urethra. On the other hand, further investigations are needed to understand if the presence of a prostate condition affects the DTI metrics of the sphincters and membranous urethra. This project was the first to examine age related differences in the urethral sphincter complex using DTI, as well as, the first time a DTI sequence for the prostate was implemented at Champalimaud Centre for the Unknown (CCU). It was concluded that age should be used as a covariate in a model that makes use of DTI biomarkers representative of the male urethral complex microstructure to predict the likely time of post-surgical continence recovery. Ultimately, this investigation should be a starting point for helping clinicians in the prediction of the risk of complications for each patient before undergoing RP, and balance the advantages and disadvantages comparing with other available treatment options for PC.Segundo dados de 2016, no sexo masculino e em paises desenvolvidos, o cancro da prostata foi o cancro que registou maior incidencia [5]. Apos uma detecao atraves do aumento da evolucao dos niveis do antigenio especifico da prostata (PSA) no sangue e/ou de realizacao do teste do toque retal, o método de diagnostico mais comum e a biopsia, que pode ser auxiliada por ultrassons ou por ressonância magnetica multiparametrica. A escolha do tratamento adequado para cada paciente depende do estadio da doenca e das suas preferencias individuais, que geralmente pretendem equiponderar a esperanca de vida para o paciente e a qualidade de vida apos tratamento. Geralmente, as opcoes de tratamento mais adequadas para um paciente com PSA > 10 ng/mL e nodulos palpaveis sao: acompanhamento e tratamento dos sintomas a medida que estes surgem, radioterapia ou braquiterapia, e cirurgia [6]. A ultima opcao, em particular a prostatectomia radical, tem demonstrado maior precisao na remocao de tecido maligno e no aumento da esperanca media de vida para os pacientes operados [7]. Mais recentemente, tecnicas laparoscopicas convencionais tem vindo a ser substituidas por tecnicas robóticas que oferecem maiores vantagens no pos-operatorio. No entanto, a incontinencia urinaria e a disfunção eretil continuam a ser complicacoes reportadas por uma percentagem significativa de pacientes submetidos a cirurgia. Relativamente ao primeiro, afeta cerca de 4 a 69 % dos pacientes [1], e a sua ocorrencia esta intimamente ligada a remocao do esfincter proximal ou liso, que ocorre aquando da remocao da prostata, e consequente dano no esfincter distal ou rabdoesfincter. A construcao de um modelo preditivo da recuperacao da continencia pos-cirurgica com base na utilizacao de biomarcadores do esfincter, pode permitir aos prospetivos pacientes uma escolha ponderada do tipo de tratamento. No entanto, e sabido que a microestrutura do esfincter varia com a idade [2], logo e necessario conhecer o padrao de variacao dos biomarcadores do esfincter com a idade, no sentido de avaliar a recuperacao pos-cirurgica da continencia. Para estudar a microestrutura do esfincter tem sido utilizadas diversas tecnicas in vivo [8]–[13] que, no entanto, nao fornecem informacao tridimensional da estrutura e orientacao das fibras que o compoem. Contrariamente, imagem por tensor de difusao (DTI) e uma tecnica nao invasiva baseada em ressonância magnetica que permite quantificar o movimento das moleculas de agua nos tecidos, atraves da aplicação de gradientes em varias direcoes nao colineares [14]. Relacionando o gradiente aplicado com o sinal medido, obtem-se em cada voxel informacao sobre a magnitude e direcao da difusao. A partir da diagonalizacao do tensor de difusao e possivel calcular eigenvalues e eigenvectors. Enquanto que os ultimos refletem a direccionalidade, os primeiros quantificam a magnitude da difusao e combinados entre si permitem obter um conjunto de metricas – que inclui a anisotropia fracional (FA), difusibilidade axial (AD), difusibilidade media (MD) e difusibilidade radial (RD) – que permitem estudar a organizacao estrutural das fibras. Apesar das aplicacoes de DTI se focarem essencialmente em estudos de conectividade da substancia branca do cerebro, tem progressivamente sido alargadas ao estudo de outros orgaos, como o rim [15], o coracao [16] e a prostata. Relativamente ao uso de DTI para o estudo da prostata, esta tecnica tem sido utilizada para estudar este orgao em condicoes normais [17] e para definir metricas que permitam distinguir tecido saudavel de tumoral [18]. Ademais, estudos tem avaliado os feixes neuro-vasculares da prostata antes e apos a cirurgia e correlacionado com a disfunção eretil pos-prostatectomia radical [7]. Para alem de um estudo que investigou o esfincter uretral feminino usando DTI [19], que se tenha conhecimento, existe apenas um estudo que conseguiu utilizar DTI para estudo da microarquitectura do esfincter masculino em sujeitos jovens e sem patologia [3]. Assim, o principal objetivo da presente tese de mestrado e investigar variacoes derivadas da idade no complexo do esfincter uretral, que compreende os esfincteres proximais e distais e a uretra membranosa – correspondente ao segmento da uretra que se estende desde o apice da prostata ate ao bulbo peniano. No sentido de estudar o efeito da presenca de uma condicao da prostata, incluindo cancro da prostata e hiperplasia benigna da prostata (HBP), a variacao das metricas de DTI do esfincter para o grupo de pacientes diagnosticados foi tambem avaliada. Como objetivo secundario, que teve importancia na etapa de processamento dos dados de DTI, foi investigado se a correcao de movimento durante a aquisicao e correcao de correntes de Foucault afetava significativamente as metricas de DTI em estudo, para cada uma das estruturas. Para tal, os esfincteres proximal e distal, bem como a uretra membranosa, foram reconstruidos para 95 individuos usando o algoritmo deterministico de tractografia no software DSIStudio [4]. Previamente foram definidas manualmente um conjunto de regioes de interesse nos mapas coloridos de FA para os esfincteres proximal e distal, e na imagem anatomica em T2 para a uretra membranosa. Para a tractografia, foram otimizados alguns parametros segundo uma abordagem de tentativa e erro, que acabou por estabelecer um valor limite de anisotropia fracional de 0.15, e um limite angular de 75o e 45o, respetivamente para os esfincteres e para a uretra. As metricas de DTI foram extraidas para cada uma das estruturas reconstruidas, incluindo o comprimento e densidade das fibras, FA, AD, MD e RD e parametros adicionais do histograma para cada metrica de DTI, ou seja, desvio padrao, mediana, media aparada, desvio absoluto mediano, minimo, maximo, amplitude, assimetria, curtose, erro padrao e os percentis 5, 25, 75 e 95. A influencia do movimento e da presenca de correntes de Foucault nas métricas de DTI extraidas foram investigadas. Regressoes lineares e correlacoes de Pearson ou Spearman foram realizadas entre a idade e cada uma das metricas de DTI. Alem disso, uma analise de variância (ANOVA) – ou o equivalente teste nao parametrico de Kruskal-Wallis –, foram realizados para comparar metricas de DTI entre quatro faixas etarias (de 50 a 59, 60 a 69, 70 a 79 e 80 a 89 anos). Para um subconjunto dos 69 individuos com diagnostico confirmado de cancro de prostata, HBP ou da ausencia de qualquer um dos dois, o teste ANOVA foi usado para comparar entre grupos de doenca. Adicionalmente, testes t-student – ou o teste nao parametrico de Wilcoxon – foram utilizados para comparar a presenca vs. ausencia de cancro. Para resultados estatisticamente significativos do teste ANOVA, foram posteriormente empregues testes t-student para investigar entre que grupos se encontrava a diferenca. Nao foram encontradas diferencas estatisticamente significativas nas metricas de DTI com e sem correcao de movimento e correntes de Foucault, logo, os dados de DTI sem correcao foram utilizados para a analise subsequente. Neste estudo, verificou-se que as distribuicoes de MD e RD variaram significativamente com a idade. Em particular, individuos mais velhos evidenciaram menor curtose da RD no esfincter proximal, menor valor maximo de MD no esfincter distal e maior desvio absoluto mediano de MD na uretra membranosa. Por outro lado, sao necessarias investigacoes adicionais para entender se a presenca de uma condicao da prostata pode afetar as metricas de DTI dos esfincteres e da uretra membranosa. Tal acontece, pois os resultados obtidos neste estudo para a presenca de doença estao limitados pela heterogeneidade da amostra em termos das diferentes condicoes que cada individuo pode apresentar. Julga-se que este estudo foi o primeiro a identificar variacoes com a idade nas metricas de DTI do esfincter. Alem disso, definiu a inclusao de uma sequencia de DTI a ressonancia magnética multiparametrica da pratica clinica da Fundacao Champalimaud. Por se tratar de um estudo prospetivo, foi possivel definir os parametros de aquisicao – nomeadamente o valor de b (em s/mm2), o numero de direcoes da aplicacao do gradiente, o numero de cortes adquiridos e a extensao da aquisicao - otimospara a visualizacao das estruturas do complexo uretral masculino, com o melhor compromisso entre duracao da aquisicao (em minutos) e a resolucao espacial (em milimetros). Esta nova sequencia so comecou a ser incluida na clinica desde Janeiro 2019, o que representa cerca de 14 pacientes operados, dos 45 diagnosticados com cancro da prostata. Assim que for possivel aumentar a amostra de pacientes operados com um intervalo de tempo pos-cirurgico de 3 a 6 meses, sera possivel utilizar os resultados dos testes de incontinencia, os dados de DTI do esfincter corrigidos da idade e as medidas do comprimento da uretra em T2, para prever o tempo de recuperacao de continencia pos-cirurgica. No futuro, esperamos poder extrair os biomarcadores de DTI para o complexo do esfincter uretral de cada paciente e usa-los como um preditor da taxa de incontinencia pos-cirurgica. No entanto, e importante que este modelo tenha em conta alteracoes nas metricas de DTI do complexo uretral masculino que são influenciadas pelo envelhecimento. Esse modelo preditivo pode orientar os pacientes na escolha informada da melhor opcao de tratamento personalizado para tratar o tumor da prostata e, simultaneamente, proporcionar uma qualidade de vida satisfatoria

Reconstruction et description des fonctions de distribution d'orientation en imagerie de diffusion à haute résolution angulaire

This thesis concerns the reconstruction and description of orientation distribution functions (ODFs) in high angular resolution diffusion imaging (HARDI) such as q-ball imaging (QBI). QBI is used to analyze more accurately fiber structures (crossing, bending, fanning, etc.) in a voxel. In this field, the ODF reconstructed from QBI is widely used for resolving complex intravoxel fiber configuration problem. However, until now, the assessment of the characteristics or quality of ODFs remains mainly visual and qualitative, although the use of a few objective quality metrics is also reported that are directly borrowed from classical signal and image processing theory. At the same time, although some metrics such as generalized anisotropy (GA) and generalized fractional anisotropy (GFA) have been proposed for classifying intravoxel fiber configurations, the classification of the latters is still a problem. On the other hand, QBI often needs an important number of acquisitions (usually more than 60 directions) to compute accurately ODFs. So, reducing the quantity of QBI data (i.e. shortening acquisition time) while maintaining ODF quality is a real challenge. In this context, we have addressed the problems of how to reconstruct high-quality ODFs and assess their characteristics. We have proposed a new paradigm allowing describing the characteristics of ODFs more quantitatively. It consists of regarding an ODF as a general three-dimensional (3D) point cloud, projecting a 3D point cloud onto an angle-distance map (ADM), constructing an angle-distance matrix (ADMAT), and calculating morphological characteristics of the ODF such as length ratio, separability and uncertainty. In particular, a new metric, called PEAM (PEAnut Metric), which is based on computing the deviation of ODFs from a single fiber ODF represented by a peanut, was proposed and used to classify intravoxel fiber configurations. Several ODF reconstruction methods have also been compared using the proposed metrics. The results showed that the characteristics of 3D point clouds can be well assessed in a relatively complete and quantitative manner. Concerning the reconstruction of high-quality ODFs with reduced data, we have proposed two methods. The first method is based on interpolation by Delaunay triangulation and imposing constraints in both q-space and spatial space. The second method combines random gradient diffusion direction sampling, compressed sensing, resampling density increasing, and missing diffusion signal recovering. The results showed that the proposed missing diffusion signal recovering approaches enable us to obtain accurate ODFs with relatively fewer number of diffusion signals.Ce travail de thèse porte sur la reconstruction et la description des fonctions de distribution d'orientation (ODF) en imagerie de diffusion à haute résolution angulaire (HARDI) telle que l’imagerie par q-ball (QBI). Dans ce domaine, la fonction de distribution d’orientation (ODF) en QBI est largement utilisée pour étudier le problème de configuration complexe des fibres. Toutefois, jusqu’à présent, l’évaluation des caractéristiques ou de la qualité des ODFs reste essentiellement visuelle et qualitative, bien que l’utilisation de quelques mesures objectives de qualité ait également été reportée dans la littérature, qui sont directement empruntées de la théorie classique de traitement du signal et de l’image. En même temps, l’utilisation appropriée de ces mesures pour la classification des configurations des fibres reste toujours un problème. D'autre part, le QBI a souvent besoin d'un nombre important d’acquisitions pour calculer avec précision les ODFs. Ainsi, la réduction du temps d’acquisition des données QBI est un véritable défi. Dans ce contexte, nous avons abordé les problèmes de comment reconstruire des ODFs de haute qualité et évaluer leurs caractéristiques. Nous avons proposé un nouveau paradigme permettant de décrire les caractéristiques des ODFs de manière plus quantitative. Il consiste à regarder un ODF comme un nuage général de points tridimensionnels (3D), projeter ce nuage de points 3D sur un plan angle-distance (ADM), construire une matrice angle-distance (ADMAT), et calculer des caractéristiques morphologiques de l'ODF telles que le rapport de longueurs, la séparabilité et l'incertitude. En particulier, une nouvelle métrique, appelé PEAM (PEAnut Metric) et qui est basée sur le calcul de l'écart des ODFs par rapport à l’ODF (représenté par une forme arachide) d’une seule fibre, a été proposée et utilisée pour classifier des configurations intravoxel des fibres. Plusieurs méthodes de reconstruction des ODFs ont également été comparées en utilisant les paramètres proposés. Les résultats ont montré que les caractéristiques du nuage de points 3D peuvent être évaluées d'une manière relativement complète et quantitative. En ce qui concerne la reconstruction de l'ODF de haute qualité avec des données réduites, nous avons proposé deux méthodes. La première est basée sur une interpolation par triangulation de Delaunay et sur des contraintes imposées à la fois dans l’espace-q et dans l'espace spatial. La deuxième méthode combine l’échantillonnage aléatoire des directions de gradient de diffusion, le compressed sensing, l’augmentation de la densité de ré-échantillonnage, et la reconstruction des signaux de diffusion manquants. Les résultats ont montré que les approches de reconstruction des signaux de diffusion manquants proposées nous permettent d'obtenir des ODFs précis à partir d’un nombre relativement faible de signaux de diffusion

Assessment of cardiac motion effects on the fiber architecture of the human heart in vivo.

International audienceThe use of diffusion tensor imaging (DTI) for studying the human heart in vivo is very challenging due to cardiac motion. This paper assesses the effects of cardiac motion on the human myocardial fiber architecture. To this end, a model for analyzing the effects of cardiac motion on signal intensity is presented. A Monte-Carlo simulation based on polarized light imaging data is then performed to calculate the diffusion signals obtained by the displacement of water molecules, which generate diffusion weighted (DW) images. Rician noise and in vivo motion data obtained from DENSE acquisition are added to the simulated cardiac DW images to produce motion-induced datasets. An algorithm based on principal components analysis filtering and temporal maximum intensity projection (PCATMIP) is used to compensate for motion-induced signal loss. Diffusion tensor parameters derived from motion-reduced DW images are compared to those derived from the original simulated DW images. Finally, to assess cardiac motion effects on in vivo fiber architecture, in vivo cardiac DTI data processed by PCATMIP are compared to those obtained from one trigger delay (TD) or one single phase acquisition. The results showed that cardiac motion produced overestimated fractional anisotropy (FA) and mean diffusivity (MD) as well as a narrower range of fiber angles. The combined use of shifted TD acquisitions and post-processing based on image registration and PCATMIP effectively improved the quality of in vivo DW images and subsequently, the measurement accuracy of fiber architecture properties. This suggests new solutions to the problems associated with obtaining in vivo human myocardial fiber architecture properties in clinical conditions