[en] Introduction Congenital diaphragmatic hernia (CDH) is seen at 1 in every 2500 live births. Its overall mortality is still as high as 50%. Pulmonary hypertension and underdevelopment are the primary causes of death in CDH. Per our current knowledge, the severity of the CDH could be predicted by the ratio of ipsilateral lung area to head circumference, total lung volume, left/right ventricle ratio, modified McGoon index, location of the stomach with the existence of polyhydramnios, and the location of the liver. When the blood pressure in the pulmonary system exceeds 2/3 of the pressure in the systemic circulation, it is said to be pulmonary hypertension. Although the main pathology emerged in utero, this could only be documented by echocardiography in the early neonatal period. This is mostly because the blood flow into the lungs is limited in utero for the sake of fetal blood circulation. This is a significant barrier for treating CDH patients in-utero. Nonetheless, the aberrant organization of the pulmonary vascular network in pulmonary hypertension can only be shown in postmortem subjects by histopathological analyses. Hypothesis Since pulmonary hypertension is one of the predictors of the survival of these patients, this proposal seeks to test the general hypothesis that a prenatal pulmonary vascular branching index correlates with the severity of postnatal pulmonary hypertension. Materials and Methods Sprague Dawley rat fetuses that were both healthy and nitrofen-induced were used. The fetuses underwent micro-computed tomography scanning. Using artificial intelligence techniques, the pulmonary artery tree was 3D reconstructed. Moreover, a framework is developed to generate 3D pulmonary vascular tree structures by using Computed Tomography (CT) scans. Then, the developed framework is used to compare pulmonary vascular trees of CDH samples and healthy controls to determine the characterization of the CDH disease. Finally, by using pulmonary vascular trees, morphological features are obtained, and characterization of the disease is achieved. Results There were 70 fetuses examined throughout the study, 40 of which were used in the first part to demonstrate the feasibility of the Lugol application while the rest were used in the second part. Lugol diffused uniformly throughout the capillaries in the pups with partially removed skin, allowing fine-grained imaging of the lung vasculature. The segmentation part of this project had 86% precision, 82% sensitivity, and 84% F1 score. For the characterization of the CDH, the required features are obtained from the segmented output, and they were prioritized by their impact on the classification. The number of segments in CDH was significantly lower than the control group on the left (U=2.5, p=0.004) and right (U=0, p=0.001) sides for order 1(O1), whereas there was a significant difference only on the right side for O2 and O3. The pooled element numbers in the control group obeyed Horton's Law (R2=0.996 left and R2=0.811 right lungs), while the CDH group broke it. Connectivity matrices showed that the average number of elements of O1 springing from elements of O1 on the left side and the number of elements of O1 springing from elements of O3 on the right side were significantly lower in CDH samples. Conclusion Lung vasculature in CDH is of particular interest for pulmonary development and is the main underlying factor that determines the disease severity. We observed that, besides the known reduced airway branching of the hypoplastic lungs, arterial branching was decreased in fetuses with CDH as well. Herein, we have demonstrated that the radiological imaging techniques were able to define the prenatal lung vascular tree, which could potentially estimate the degree of pulmonary hypertension and enable physicians to determine the severity of the disease prenatally and promote prenatal therapy.

[es] Introducción La hernia diafragmática congénita (HDC) afecta a 1 de cada 2500 nacimientos vivos, con una mortalidad del 50%. La principal causa de muerte es la hipertensión pulmonar y el subdesarrollo pulmonar. La severidad de la HDC puede predecirse por varios indicadores, incluyendo la relación entre el área pulmonar ipsilateral y la circunferencia cefálica, el volumen pulmonar total, y la posición del estómago y el hígado. La hipertensión pulmonar, definida cuando la presión pulmonar excede 2/3 de la sistémica, es crucial, siendo diagnósticable por ecocardiografía neonatal temprana debido a la limitada circulación fetal hacia los pulmones. Esta condición complica el tratamiento prenatal de HDC. La organización anormal de la red vascular pulmonar se evidencia post mortem. Hipótesis Proponemos que un índice de ramificación vascular pulmonar prenatal correlaciona con la severidad de la hipertensión pulmonar postnatal, siendo un predictor clave de supervivencia. Materiales y Métodos Se utilizaron fetos de ratas Sprague Dawley sanos y tratados con nitrofeno. Mediante tomografía computarizada micro y técnicas de inteligencia artificial, se reconstruyeron en 3D los árboles arteriales pulmonares. Este marco permitió comparar las estructuras vasculares pulmonares de muestras de HDC y controles sanos, obteniendo características morfológicas para la caracterización de la HDC. Resultados De 70 fetos examinados, 40 demostraron la viabilidad del uso de Lugol para la imagenología detallada de la vasculatura pulmonar. La segmentación alcanzó un 86% de precisión, 82% de sensibilidad y 84% de puntuación F1. La caracterización de la HDC reveló un número significativamente menor de segmentos vasculares en los fetos afectados, especialmente en el primer orden de ramificación, desviándose de la Ley de Horton, lo que indica una disminución en la ramificación arterial. Conclusión La reducción en la ramificación de las arterias, además de la conocida disminución en la ramificación de las vías aéreas en pulmones hipoplásicos, fue notable en fetos con HDC. Las técnicas de imagenología radiológica permitieron definir el árbol vascular pulmonar prenatal, estimar el grado de hipertensión pulmonar y, potencialmente, facilitar la determinación prenatal de la severidad de la enfermedad para orientar terapias prenatales.