Magnetic resonance imaging nowadays supplies a noninvasive method in clinical applications. For tetralogy of Fallot (TOF) patients, after undergoing clinical operation, their cardiac anatomy still cannot supply sufficient blood flow in the pulmonary arteries with respect to the normal. In this study, we use phase contrast MR imaging to evaluate of regurgitation and turbulence of flow in pulmonary arteries after repair of TOF. We use parameters such as coefficient of variance (CV), regurgitant fraction (RF), and normalized area variation (NAV) to analyze the difference between repaired patients and normal controls. Our result also shows that CV and regurgitant fraction have loose relation. This study may provide more information to help doctors in clinical diagnosis. In the meanwhile, another three parameters were used to evaluate patients and normal persons. We use windkessel volume to see the difference of flow volume between inlet and outlet in the pulmonary arteries. We use pulse wave velocity (PWV) to discuss the propagating velocity of pressure wave on the vascular wall. We use pulmonary vascular resistance (PVR) to analyze the resistance of blood wall. PWV and PVR may lose information by means of insufficient points in a cardiac cycle, but the result may still be a kind of reference.

Magnetic Resonance Imaging (MRI) provides noninvasive method in clinical application. For the patients of Tetralogy of Fallot underwent surgical correction,regurgitation and turbulence in blood flow may still present in pulmonary arteries.In this study,Phase Contrast MR Imaging will be used to quantitate,and to observe blood flow in after repair Tetralogy of Fallot (TOF) patients.We use 3 parameters,which are Coefficient of Variance (CV),Regurgitant Fraction (RF) and Net Flow analysis to analyze two situations of blood flow in patients¡¦ left pulmonary artery ¡Bright pulmonary artery and main pulmonary artery.We also compare normal subjects to patients in this experiment. The pulmonary circulation is the action of blood flow from right ventricular to main pulmonary artery then to left pulmonary artery and right pulmonary artery. We use three additional parameters: rPA / lPA flow ratio¡BPeak Velocities and Total Flow to observe the pulmonary blood flow. We use rPA / lPA flow ratio to identify the tendency of blood flow, with Peak Velocities to find out Peak Velocity in normal difference between patient.Meanwhile, the measurement of Total Flow is applied to observe the flow from main pulmonary artery to left and right pulmonary artery. We hope to use these parameters that can help doctors on clinical diagnosis.

Recently magnetic resonance imaging has become more and more popular in clinical applications. In clinical studies, the heart of the TOF patient has some congenital defects. These defects lead to insufficient blood flowing into the pulmonary arteries, rendering the necessary of repair for TOF patients. However, even after repair, the blood in pulmonary arteries still cannot flow in the same way with those of normal people. For this reason, studies on the flow behavior of pulmonary arteries in TOF patients would be valuable in clinical applications. In this study, we focus on the quantitative analysis of in-plane flow in branch pulmonary arteries (left and right pulmonary arteries) after repair of tetralogy of Fallot (TOF) by means of phase-contrast MR imaging. The regurgitation and turbulence were evaluated by coefficient of variance (CV) and regurgitant fraction. Vector map of in-plane flow was also included in order to facilitate the observation of flow patterns. Our result shows a positive correlation of CV and regurgitant fraction in terms of turbulence and regurgitation. Therefore, we conclude that CV and regurgitant fraction as well as vector maps may be helpful to quantitate in-plane flow for after repair of TOF patients, providing a more accurate analysis in clinical diagnosis.

Magnetic resonance imaging (MRI) is an useful technique that provides a noninvasive method in clinical applications. For the patient of tetralogy of Fallot (TOF) after repaired, turbulence and regurgitation in blood flow may appear in pulmonary arteries. In this study, phase contrast MR imaging was applied and vortical flow patterns in the pulmonary arteries of patients after repair of TOF has been investigated. There are two major part of this study. Firstly we simulated vortical flow patterns of star, focus, and saddle which are most frequently appeared in blood flow. Quadrant index has been proposed for pattern analysis. In the second part we applied these parameters to in vivo data of repaired TOF patients, and compared with other parameters such as vorticity, coefficient of variance (CV), and regurgitant fraction (RF). Our result shows that the linear correlation between the mean of CV of velocity and mean of CV of vorticity in right pulmonary artery (RPA) as well as pulmonary trunk (PT) is larger than that in left pulmonary artery (LPA). This study shows that vorticity may provide some useful information of flow patterns and therefore helps doctors in clinical diagnosis

Le terme d’« hypertension artérielle pulmonaire » (HTAP) décrit une maladie vasculaire pulmonaire caractérisée par une augmentation progressive des pressions artérielles pulmonaires (PAP), définie par une PAP moyenne supérieure ou égale à 25 mmHg au repos et dont le principal symptôme est un essoufflement à l’effort. Un remodelage artériel pulmonaire intense conduisant à une obstruction des petits vaisseaux pulmonaires est responsable de la maladie. C’est une maladie rare mais néanmoins grave car pouvant aboutir à une insuffisance ventriculaire droite et entraîner le décès du patient.Le cadre général de notre étude est l’amélioration de la compréhension des mécanismes physiopathologiques de l’HTAP afin d’identifier de nouvelles cibles thérapeutiques potentielles. Nous nous sommes intéressés plus particulièrement au phénotype « pseudo-tumoral » des cellules musculaires lisses des artères pulmonaires (CML-AP) des patients atteints d’HTAP qui jouent un rôle primordial dans le remodelage vasculaire pulmonaire de l’HTAP et qui présentent des caractéristiques communes avec les cellules cancéreuses, notamment une hyper-prolifération, une résistance à l’apoptose, des désordres métaboliques et une instabilité génomique. Etant donné que la protéine p53, un des plus importants suppresseurs de tumeur, est largement décrite comme inactivée dans la plupart des cancers, nous avons émis l’hypothèse qu’elle pourrait également jouer un rôle important dans le développement de l’HTAP. Les résultats des études in vitro menées sur des CML-AP de patients atteints d'HTAP idiopathiques (HTAPi) versus des sujets contrôles semblent indiquer que la protéine p53 n’est pas altérée dans les CML-AP HTAPi. En effet, la séquence codante du gène TP53 ne présente pas de mutation dans les CML-AP HTAPi, les expressions génique et protéique de p53 (et de certaines de ses protéines cibles) ne semblent pas être différentes entre contrôles et HTAPi, ni à l’état basal ni en réponse à différents stress cellulaires inducteurs de p53 (étoposide et H2O2). Cependant, la régulation de p53 semble altérée puisque nous avons observé une augmentation du taux protéique de MDM2, principal régulateur de p53, dans les CML-AP HTAPi. Ce résultat peut être considéré comme une des caractéristiques « pseudo-tumorales » des CML-AP HTAPi mais également être un élément déterminant du mécanisme d’action de la Nutlin-3a, qui a montré des effets anti-prolifératifs accrus dans les CML-AP HTAPi.Dans des études in vivo menées chez le rat, la protéine p53 semble jouer un rôle dans l’initiation de la pathogénèse d’une HTAP. En effet, les taux protéiques pulmonaires de p53, de sa cible p21 et de son régulateur (mais également cible transcriptionnelle) MDM2 sont diminués lors de la première semaine dans un modèle d’induction d’HTAP par mono-injection de monocrotaline (MCT) chez le rat, au cours duquel la pathologie se développe à partir de la 2ème semaine. De plus, l’administration quotidienne à des rats d’un inhibiteur de l’activité transcriptionnelle de p53, le pifithrin-α (PFT), conduit au développement d’une HTAP en 14 jours, au même titre qu’une mono-injection de MCT, et aggrave l’HTAP induite par la MCT. Des effets pro-prolifératifs et anti-apoptotiques du PFT révélés sur des CML-AP indiquent que l’inhibition de l’activité transcriptionnelle de p53 est à l'origine d'une prolifération exagéree et une résistance à l'apoptose, deux composantes clés dans le remaniement vasculaire pulmonaire et le développement de l'HTAP.En conclusion, ces résultats mettent en évidence l’implication de l’inactivation de la voie de p53 lors de la phase initiatrice du développement de l’HTAP, alors qu’aux stades tardifs et sévères de la maladie, il semble il y avoir une normalisation de p53. En revanche, l’augmentation de l’expression de son principal régulateur MDM2 observée dans les CML-AP de patients HTAP semble être une cible thérapeutique potentiellement intéressante. / Pulmonary artery hypertension (PAH) is a severe pulmonary vascular disease characterized by a progressive increase of the pulmonary arterial pressure (PAP), defined by a mean PAP greater than or equal to 25 mmHg at rest. The main symptom is a shortness of breath. An intense pulmonary arterial remodeling that leads to an obstruction of the small pulmonary vessels is responsible of the disease. PAH is a rare but severe disease that develops into right ventricular cardiac failure leading to the patient's death.The general framework of our study was to improve the understanding of the pathophysiology of PAH in order to identify new potential therapeutic targets and improve the clinical management of patients. In particular, we were interested in the “cancer-like phenotype” of PAH patient pulmonary arterial smooth muscle cells (PA-SMCs). PA-SMCs play a key role in the pulmonary vascular remodeling of PAH. These cells share characteristics with cancerous cells, such as: exaggerated proliferation, apoptosis resistance, metabolic disorders and genomic instability. Owing to the growth-suppressive and pro-apoptotic functions of p53 protein and its inactivation largely described in cancer, we hypothesized that the p53 pathway could also be altered during PAH development in PA-SMCs.The results of in vitro studies on PA-SMCs of late stage patients with idiopathic PAH (iPAH) versus control patients suggest that the p53 protein nor pathway is not altered in iPAH PA-SMCs. Indeed, the coding sequence of the TP53 gene presented no mutations in iPAH PA-SMCs. Analysis of mRNA and protein levels of p53 and its target proteins showed no difference between controls and iPAH PA-SMCs, neither in a basal state or in response to various cellular stresses such as etoposide and H2O2. However, regulation of p53 may be altered in iPAH PA-SMCs as we observed an increase of the MDM2 (the main p53 regulator) protein level compared to control. This last result may be considered as a “cancer-like” characteristic of iPAH PA-SMCs and also be a determining factor in the mechanism of action of Nutlin-3a, which had more important anti-proliferative effects in iPAH PA-SMCs than in control cells.In vivo studies in rats revealed, however, that the p53 pathway may play a role in the initiation stage of PAH pathogenesis. Indeed, kinetics evaluation of p53 lung expression in the PAH model, induced by a single injection of monocrotaline (MCT), revealed a decrease in the p53 protein level during the first week, followed by a normalization by the second week. PAH symptoms are developed in MCT rats after two weeks. Similarly, the protein levels of p21, a p53 target, and MDM2, the major p53 regulator, and also a transcriptional target of p53, decreased during the first week in the MCT-PAH model. In addition, daily treatment in rats with an inhibitor of p53 transcriptional activity, pifithrin-α (PFT), led to the development of PAH in 14 days, similarly to MCT, and worsened the PAH induced by MCT. Pro-apoptotic and anti-proliferative effects of PFT on PA-SMCs indicate that inhibition of p53 transcriptional activity causes an excessive proliferation and an apoptosis resistance, which are two key components of the pulmonary vascular remodeling and development of human and experimental PAH.In conclusion, these results demonstrate the involvement of the p53 pathway inactivation in the initiation stage of PAH development, whereas in late and severe stages of disease, its role seems to be less implicated. In contrast, the increased expression of MDM2 observed in PA-SMCs of PAH patients may be a potential therapeutic target.

Hintergrund und Fragestellung Um den Zeitpunkt des Beginns der Datenakquisition bei der CT-Koronarangiographie festzulegen, bietet die Methode des Bolus-Trackings eine weit verbreitete Möglichkeit. Hierfür muss eine sogenannte Region of Interest (ROI) festgelegt werden, in der die Kontrastmittelanflutung gemessen wird. Bisher wurden die Auswirkungen unterschiedlicher Positionierungen dieser ROI auf die Bildqualität der Koronararterien (Hauptstamm der linken Koro-nararterie: LM; rechte Koronararterie: RCA) noch nicht systematisch untersucht. Zwei häufig verwendete Positionen sind der linke Herzvorhof (LV) und die Aorta ascendens (AA). Diese Positionierungen sollten in dieser Studie verglichen werden. Auch bei der Triple-Rule-Out-CT-Angiographie (TRO-CTA), in der zusätzlich zu den Koronararterien auch die Pulmonalarterien sowie die thorakale Aorta beurteilt werden sollen, kommt das Bolus-Tracking zur Anwendung. Die ROI wird hierbei meist im linken Herzvorhof positioniert. Da bisher nicht gezeigt wurde, ob die Pulmonalarterien (rechte Pulmonalarterie: RPA; linke Pulmonalarterie: LPA) dadurch tatsächlich in besserer Qualität dargestellt werden, sollte auch diese Frage in der Studie beantwortet werden. Methode Alle Patienten der vorliegenden monozentrischen, retrospektiven Studie erhielten eine CT-Koronarangiographie im Step-and-Shoot-Modus zum Ausschluss einer koronaren Herzkrankheit bei intermediärem Risiko. Mittels Propensity-Score-Matching wurden insgesamt 192 Patienten für die Studie ausgewählt: je 96 mit Positionierung der ROI im linken Vorhof bzw. in der Aorta ascendens (122 männliche und 70 weibliche Patienten, Alter 21 bis 87 Jahre, Durchschnittsalter 61 Jahre). Um möglichst ähnliche Patientencharakteristika in beiden Gruppen zu erreichen, wurden beim Propensity-Score-Matching folgende Faktoren berücksichtigt: Geschlecht, Körpergröße, Körpergewicht und Herzfrequenz. Für die Beurteilung der Bildqualität wurden sowohl ein quantitativer als auch ein qualitativer Score verwendet. Bei der quantitativen Analyse wurden die Signalintensitäten sowie deren Standardabweichungen in den zu beurteilenden Strukturen gemessen und daraus die Signal-Rausch-Verhältnisse (SNR) errechnet. Die qualitative Auswertung wurde von zwei Fachärzten für Radiologie mit 10 bzw. 6 Jahren Erfahrung in der CT-Koronarangiographie unabhängig voneinander mit Hilfe einer 5-Punkte-Likert-Skala durchgeführt. So wurde zum einen die Qualität der Darstellung der Koronararterien verglichen, zum anderen die der Pulmonalarterien. Für die statistische Auswertung wurde der Wilcoxon-Test verwendet, um die quantitativen sowie qualitativen Scores beider Patientengruppen miteinander zu vergleichen. Außerdem wurde bezüglich der qualitativen Analyse die Interrater-Reliabilität mittels gewichtetem Cohens Kappa (κ) bestimmt. Zusätzlich wurde die Strahlenbelastung beider Gruppen durch die Betrachtung der Dosis-Längen-Produkte sowie die Berechnung der effektiven Dosen verglichen. Ergebnisse Bezüglich der Koronararterien fanden sich sowohl beim Vergleich der quantitativen (SNR AA 14.92 vs. 15.46; p = 0.619 | SNR LM 19.80 vs. 20.30; p = 0.661 | SNR RCA 24.34 vs. 24.30; p = 0.767) als auch der qualitativen Scores (4.25 vs. 4.29; p = 0.672) keine signifikanten Unterschiede in beiden Gruppen. Für die Darstellung der Pulmonalarterien hat die Position der ROI allerdings eine entscheidende Bedeutung. Bei einer Positionierung im linken Vorhof ergeben sich signifikant höhere quantitative (SNR RPA 8.70 vs. 5.89; p < 0.001 | SNR LPA 9.06 vs. 6.25; p < 0.001) und auch qualitative Scores (3.97 vs. 2.24; p < 0.001) als bei einer Positionierung in der Aorta ascendens. Bezüglich der Interrater-Reliabilität konnte in dieser Studie eine beachtliche Konkordanz bei der Analyse der Koronararterien (κ = 0.654) bzw. eine nahezu vollkommene Konkordanz bei der Analyse der Pulmonalarterien (κ = 0.846) festgestellt werden. Die Strahlenbelastung war in beiden Gruppen nahezu identisch (4.13 mSv vs. 4.13 mSv; p = 0.501). Schlussfolgerung Für CT-Angiographien mit ausschließlich koronarer Indikation bedeutet dieses Ergebnis, dass die Positionierung der ROI für das Bolus-Tracking in der Aorta ascendens bzw. im linken Herzvorhof zu gleichwertigen Ergebnissen bezüglich der Bildqualität führen und somit die aktuell von vielen Untersuchern bevorzugte Positionierung der ROI in der Aorta ascendens weiterhin angewendet werden kann. Außerdem wurde in dieser Studie nachgewiesen, dass eine Positionierung der ROI im linken Herzvorhof zu einer besseren Beurteilbarkeit der Pulmonalarterien führt und deshalb bei der TRO-CTA angewendet werden sollte. Das Ergebnis zeigt aber auch, dass diese bei der TRO-CTA übliche Positionierung im linken Herzvorhof die Abbildung der Koronararterien nicht beeinträchtigt und der Einsatzbereich der TRO-CTA somit weiter ausgedehnt werden kann. / Background, aims and objectives The bolus tracking technique is widely used for choosing the optimal starting point of data acquisition in coronary computed tomography angiography (CCTA) scans. It utilizes repeated scans at a predefined position in order to determine the concentration of contrast media in a region of interest (ROI). The scan starts automatically when a trigger threshold is reached. The effect by different ROI positioning on image quality in CCTA has not been systematically evaluated yet. In CCTA, the ROI may be positioned in the left atrium (LV) or the ascending aorta (AA). In triple-rule-out-CTA (TRO-CTA), which allows for the evaluation of the pulmonary arteries and the thoracic aorta in addition to the coronary arteries, the ROI is mostly positioned in the left atrium. This choice of ROI positioning is empirical and its effect on the contrast filling of the pulmonary arteries has not been studied systematically. In the current study we evaluated the effect of ROI positioning on image quality of the coronary arteries (left main coronary artery: LM; right coronary artery: RCA) and the pulmonary arteries (right pulmonary artery: RPA; left pulmonary artery: LPA), respectively. Method In the current monocentric retrospective study all patients underwent CCTA by step-and-shoot mode to rule out coronary artery disease at intermediate risk. We compared two groups of patients with ROI in the left atrium or the ascending aorta. Each group contained 96 patients, so overall 192 patients were included (122 male, 70 female, age 21 to 87 years, 61 years on average). To select pairs of patients with similar characteristics, propensity score matching was used. Matching criteria were height, body weight, sex and heart rate. To evaluate the image quality, we used quantitative and qualitative scores. Signal-to-noise ratio (SNR), defined as the quotient of the mean signal intensity and the standard deviation of signal intensity, represented the quantitative score. For generating the qualitative score, overall image quality was assessed independently by two radiologists with ten and six years of experience with CCTA, respectively, using a five point Likert scale. This way, we compared the quality of the depiction of the coronary arteries on the one hand and of the pulmonary arteries on the other hand. For statistical evaluation the Wilcoxon test was used to compare the quantitative and qualitative scores of the two groups. Regarding the qualitative analysis, interrater agreement was evaluated using weighted Cohens kappa. Furthermore the radiation exposure was compared by viewing the dose-length products provided by the scanner and calculating the effective doses from these. Results In terms of the coronary arteries, there was no significant difference between both groups regarding quantitative (SNR AA 14.92 vs. 15.46; p = 0.619 | SNR LM 19.80 vs. 20.30; p = 0.661 | SNR RCA 24.34 vs. 24.30; p = 0.767) or qualitative scores (4.25 vs. 4.29; p = 0.672), respectively. In terms of the pulmonary arteries, we can see significant higher quantitative (SNR RPA 8.70 vs. 5.89; p < 0.001 | SNR LPA 9.06 vs. 6.25; p < 0.001) and qualitative scores (3.97 vs. 2.24; p < 0.001) for bolus tracking positioning in the left atrium than for bolus tracking positioning in the ascending aorta. The calculation of the interrater reliability showed substantial agreement for the analysis of the coronary arteries (κ = 0.654) and almost perfect agreement for the analysis of the pulmonary arteries (κ = 0.846). The radiation exposure was almost identical in both groups of patients (4.13 mSv vs. 4.13 mSv; p = 0.501). Conclusion Bolus tracking positioning in the left atrium or the ascending aorta causes equivalent image quality of the coronary arteries, so that the current mostly preferred position for the exclusively consideration of the coronary arteries in the ascending aorta can be maintained. Positioning in the left atrium causes a significant higher image quality of the pulmonary arteries, therefore it should be used for TRO-CTA. In addition, the study shows that this for TRO-CTA mostly used position in the left atrium does not adversely affect depiction of the coronary arteries, if compared to conventional bolus tracking positioning in the ascending aorta. This implies that despite the improved depiction of the pulmonary arteries and the aorta in TRO-CTA, the depiction of the coronary arteries is not restricted. Consequently these results are a further argument for an extension of the indication for TRO-CTA in place of conventional CCTA in patients with acute thoracic pain.