京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20986号 / 医博第4332号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 富樫 かおり, 教授 羽賀 博典, 教授 別所 和久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

INTRODUCTION Les anévrismes cérébraux représentent une condition potentiellement mortelle. Ils sont traités par voie chirurgicale (« clipping ») ou endovasculaire (dont le « coiling »), et plusieurs essais cliniques randomisés comparant ces traitements utilisent les résultats angiographiques comme mesure du succès du traitement. Le développement d'une classification standardisée et applicable aux deux traitements et aux trois modalités angiographiques (conventionnelle, angioscan et angio-IRM) est nécessaire. Nos objectifs furent de revoir systématiquement les classifications existantes, d’évaluer la fiabilité inter/intra-observateur d’une nouvelle classification angiographique commune, et d’en vérifier la pertinence clinique. MÉTHODES Deux revues systématiques furent effectuées dans 5 bases de données pour recenser les classifications (et leur fiabilité, lorsque rapportée) pour chaque traitement. Les résultats d’angiographie conventionnelle post-clipping (n=30) ou coiling (n=30) de 60 patients furent évalués de manière indépendante, à l’aide d’une nouvelle classification à 3 catégories, par 19 cliniciens ayant diverses pratiques et expériences. Les observateurs devaient également indiquer la prise en charge clinique appropriée pour chaque cas: un suivi espacé, étroit, ou un retraitement. Quinze lecteurs ont procédé à une 2e évaluation des cas (présentée selon un ordre permuté) à 1 mois d’écart. Le même travail fut reconduit, dans un deuxième temps, par 24 observateurs avec 60 cas évalués par angioscan (n=30) ou angio-IRM (n=30). Les accords inter/intra-observateurs furent estimés avec la statistique Alpha de Krippendorff (aK); la corrélation entre le choix de classe et la prise en charge fut calculée avec un test V de Cramer. RÉSULTATS Soixante-dix classifications (44 post-clipping, 26 post-coiling) furent recensées dans la littérature. La fiabilité variait de 0.12 à 1.00, avec une hétérogénéité significative en termes d’observateurs et de patients. L’accord inter-observateur pour la classification retenue était substantiel pour les résultats d’angiographie conventionnelle (aK=0.76; 0.67–0.83) et des autres modalités (aK=0.63; 0.55–0.70); peu importe le traitement, la spécialité ou l’expérience des évaluateurs. La classe est fortement corrélée à la prise en charge (V de Cramer de 0,77 à 0,80 selon la modalité angiographique; p<0,001). CONCLUSION La classification proposée est fiable et pertinente cliniquement. Elle servira d’outil valide pour évaluer les résultats angiographiques d’anévrismes dans les futurs essais cliniques comparant les deux traitements, peu importe la modalité d’imagerie utilisée. / INTRODUCTION Intracranial aneurysms are a medical condition associated with serious morbidity and mortality when ruptured. They are mainly treated with surgical clipping or endovascular coiling, and randomized clinical trials comparing both treatments often use angiographic results as a surrogate outcome of treatment success. The development of a standardized, reliable method to report angiographic results, applicable to both treatments using any angiographic modality (Conventional [CA], Computed tomography [CTA], or magnetic resonance [MRA] angiography) is needed. We sought to systematically review existing methods of classifying treated aneurysms and to assess the inter-/intra-rater reliability of a new angiographic grading scale, as well as its clinical relevance. METHODS We conducted two separate systematic reviews in 5 databases to collect post-clipping and post-coiling grading scales, along with their reliability when reported. The CA of 60 cases of clipped (n=30) and coiled (n=30) aneurysms were independently evaluated by 19 raters of various backgrounds and experiences using a new 3-grade scale. Raters were also asked how they would manage each case (delayed, close follow-up, or retreatment). Fifteen raters performed a 2nd evaluation of the same cases (in a permuted order) at least one month apart. The same methodology was used to study the reliability of the scale when 60 noninvasive angiography cases of clipped (30 CTA) or coiled (30 MRA) aneurysms were evaluated by 24 raters. Inter and intra-rater agreements were assessed using Krippendorff’s Alpha statistics (aK), and the relationship between occlusion grade and clinical management using Cramer’s V test. RESULTS The systematic reviews found 70 grading scales (44 post-clipping, 26 post-coiling) with significant heterogeneity in terms of reliability (kappa values from 0.12 to 1.00), raters, and patients. Overall inter-rater agreement for the grading scale was substantial for CA results (aK=0.76; 0.67–0.83) as well as for noninvasive results (aK=0.63; 0.55–0.70); regardless of background, experience, or treatment used. A strong relationship was found between angiographic grades and management decisions (V=0.80±0.12 for CA; V=0.77±0.14 for CTA/MRA [p<0.001]). CONCLUSION A standardized 3-grade scale was found to be a reliable and clinically meaningful tool to compare the results of clipping and coiling of aneurysms using any angiographic modality. It could be used as a valid tool to adjudicate results of comparative randomized trials, and to standardize the reporting of aneurysm treatments.

Das Ziel: der Arbeit war die Überprüfung der Aussagekraft der MRA in time-of-flight-technique der Arteria caroits bei 1,0 Tesla im Vergleich zur intaarteriellen DSA und der Wertigkeit in der Einsatzfähigkeit in der klinischen Routine bei der Diagnostik von Carotisstenosen. 101 Patienten wurden zur Abklärung einer Stenose der Arteria carotis vergleichend mittels TOF-MRA und i.a. DSA der Arteriae carotis untersucht. Morphologische Veränderungen wurden für sämliche Gefässe erfasst, wobei die Stenosen der Arteriae carotis entsprechend den NASCET-Kriterien graduiert wurden (geringgrade, mittelgradige,hochgradige Stenose oder Verschluss).Die Ergebnisse wurden mit folgenden drei verschiedenen statistischen Tests ausgewertet: Kappa Test, gewichteter Kappa Test und Intraklassenkorrelationskoeffizient. Von den 84 in die Auswertung eingebezogenen Gefässen wurden 66 Stenosen in der DSA als geringgradig klassifiziert. In dieser Kategorie wurden 60 dieser Stenosen von der MRA korrekt als geringgradig klassifiziert. In der DSA wurden 60 Stenosen der Arteria carotis als mittelgradig klassifiziert. 29 dieser Stenosen wurden von der MRA korrekt als mittelgradig eingeschätzt. 21 Stenosen wurden von der DSA als hochgradig klassifiziert. 20 dieser Stenosen wurden von der MRA korrekt als hochgradige Stenosen eingeschätzt. Die 16 kompletten Gefäsverschlüsse wurden alle von der MRA detektiert. Der Kappa Test ergab eine starke Korrelation der Ergebnisse. Insgesamt zeigte sich eine gute Überstimmung zwischen MRA und DSA. Aber gerade im Bereich der mittelgradigen Stenosen neigte die MRA dazu den Stenosegrad zu überschätzen. Das Ziel der Gefässdiagnostik ist eine präzise und reproduzierbare Bestimmung des Stenosegrades. Die Magnetresonanzangiographie kann als eine akkurate und zuverlässige Methode zur Bestimmung von Carotisstenosen angesehen werden / The purpose was to evaluate the efficiacy of the time-of-flight MRA of the carotid artery with a 1.0 Tesla system in comparison to intraarterial digital subtraction angiography for the assessment of carotid artery disease. 101 patients with suspected stenosis of the carotid artery were examined with a 1.0 Tesla scanner in time-of-flight-technique and with the selective i.a. DSA in parallel. Morphological pathologies were registered for all arteries, stenosis of the internal carotid artery of both examinations were blindly graded by applying the NASCET criteria (mild, moderately, severely or occluded). Three different assessment methods were conducted for the MRA data. Kappa, weighted kappa, intraclass correlation were calculated for MRA results compared to DSA. Of the 84 common carotid bifurcation, 66 were classified as mild stenosis by DSA. In this category, MRA correctly identified 60 of these as mild stenosis. Among 60 common carotid artery bifurcation graded as moderate by DSA, 29 were correctly graded as moderate by MRA. Among 21 common carotid artery bifurcation graded as severe by DSA, 20 of these were correctly graded by the MRA. There were 16 complete occlusions which were all correctly graded by MRA. A good kappa value was calculated for the data. In general the MRA were considered to find a good agreement with the DSA, but tended to overestimate stenosis, especially in the range of moderate stenosis. The aim of diagnosis is exact grading of carotid stenosis. MRA with its high agreement with DSA can be regarded as an accurate screening method of the common carotid bifurcation.

INTRODUÇÃO: Em pacientes hipertensos com suspeita de doença arterial coronária (DAC), indicações para a realização de arteriografia renal no mesmo procedimento da cinecoronariografia estão bem estabelecidas. Entretanto, em hipertensos com suspeita de estenose de artéria renal (EAR) com indicação de arteriografia renal, não estão bem definidos os determinantes da presença de DAC grave. OBJETIVOS: Avaliar a prevalência e os determinantes de DAC grave em pacientes hipertensos com indicação de arteriografia renal por suspeita de EAR. METODOLOGIA: Oitenta e dois pacientes com suspeita clínica de EAR foram submetidos à cinecoronariografia e arteriografia renal no mesmo procedimento. Lesão arterial significativa em artérias renal e/ou coronária foi definida por obstrução luminal maior ou igual a 70%. RESULTADOS: Obstrução luminal significativa, tanto em artéria coronária quanto em renal, foi encontrada em 39% dos pacientes. Os pacientes com DAC grave apresentaram idade mais avançada (63±12 vs. 56±13 anos; p=0,03), maior prevalência de angina (41 vs. 16%; p=0,013), maior diâmetro do átrio esquerdo (44,7 vs. 40,6mm; p=0,005) e maior velocidade de onda de pulso (12,6 vs. 10,7 m/s, p=0,02), comparados com os pacientes sem DAC grave. A presença de EAR significativa esteve associada a uma maior prevalência de DAC grave comparada a pacientes sem a lesão (66% vs. 22%; p<0,001). A análise multivariada demonstrou que EAR70% esteve associada com DAC grave de maneira independente (OR: 11,48; 95%CI 3,2-40,2; p<0,001), mesmo em pacientes sem angina (OR: 13,48; 95%CI 2,6-12,1; p<0,001). CONCLUSÃO: Há elevada prevalência de doença coronária grave em pacientes hipertensos com estenose de artéria renal significativa. A presença de estenose maior ou igual a 70%, verificada em arteriografia renal, é preditor forte e independente para a presença de DAC grave, mesmo na ausência de angina / INTRODUCTION: In patients with suspected coronary artery disease (CAD), indications for performing coronary and renal angiography at the same setting are well established. However, in hypertensive patients with suspected renal artery stenosis (RAS) with indication for renal angiography, it is not well defined the determinants of the presence of severe CAD. OBJECTIVES: We aimed to evaluate the prevalence and determinants of severe CAD in hypertensive patients referred to renal angiography for the diagnosis of RAS. METHODS: Eighty-two consecutive patients with high clinical risk for RAS systematically underwent renal angiography and coronary angiography at the same procedure. Significant RAS and CAD were defined as arterial luminal obstruction 70%. RESULTS: Either significant RAS or significant CAD were present in 32/82 patients (39%). Patients with severe CAD were older (63±12 vs. 56±13 years, p=0.03), had more angina (41 vs. 16%; p=0.013), higher left atrial diameter (44.7 vs. 40,6mm; p=0.005), and higher pulse wave velocity (12.6 vs. 10.7 m/s); p=0.02) compared to patients without significant CAD. Significant RAS was associated with an increased prevalence of severe CAD compared to patients without the lesion (66% vs. 22%, respectively; p<0.001). Binary logistic regression analysis showed that RAS 70% was independently associated with severe CAD (OR: 11.48; 95%CI 3.2-40.2; p<0.001), even in patients without angina (OR: 13.48; 95%CI 2.6-12.1; p<0.001). CONCLUSION: The prevalence of severe CAD in hypertensive patients with significant RAS is high. The presence of RAS 70%, diagnosed by renal angiography, is a strong and useful predictor to identify severe CAD, independently of the presence of angina

Η CT αγγειογραφία εγκεφάλου (CTA) είναι μέθοδος καθιερωμένη για την διερεύνηση και την θεραπεία των ενδοκρανιακών ανευρυσμάτων. Σκοπός της μελέτης μας ήταν η σύγκριση των ευρημάτων της ψηφιακής αγγειογραφίας (DSA) με αυτά της CTA και με τα χειρουργικά ευρήματα σε ασθενείς με οξεία υπαραχνοειδή αιμορραγία, καθώς επίσης και η αξιολόγηση της κλινικής χρησιμότητας της μεθόδου. Κατά την διάρκεια τριών ετών, 82 ασθενείς προσήλθαν με κλινική εικόνα και σημειολογία συμβατή με υπαραχνοειδή αιμορραγία. Η CTA έγινε αμέσως μετά την απλή CT, ενώ η DSA εντός των πρώτων 48 ωρών από την εισαγωγή. Όλα τα ανευρύσματα που ευρέθησαν με τις δύο μεθόδους υπεβλήθησαν σε χειρουργική αποκατάσταση ή ενδαγγειακό εμβολισμό. Σε όσους ασθενείς βρέθηκε αρνητικό αποτέλεσμα και με τις δύο μεθόδους, έγινε επαναληπτική DSA 15 ημέρες μετά το επεισόδιο με σκοπό την επιβεβαίωση της απουσίας ανευρύσματος. Οι CTA εξετάσεις καθώς και οι κλασσικές αγγειογραφίες μελετήθηκαν από μια ομάδα δύο ακτινολόγων για κάθε τεχνική, οι οποίοι έπρεπε να καταγράψουν την ύπαρξη ή μη ανευρύσματος, να περιγράψουν τα χαρακτηριστικά του και να αξιολογήσουν την μέθοδο. Χειρουργική ή και ενδαγγειακή θεραπεία έγινε σε 45 ασθενείς και ανευρέθησαν 53 ανευρύσματα. Χρησιμοποιώντας την CTA, ευρέθησαν 47 ανευρύσματα σε 42 ασθενείς. Η DSA ανίχνευσε 43 ανευρύσματα σε 39 ασθενείς. Η ευαισθησία της CTA για τον εντοπισμό όλων των ανευρυσμάτων με βάση το χειρουργικό/θεραπευτικό αποτέλεσμα ήταν 88,7%, η ειδικότητα 100%, η θετική προβλεπτική αξία (PPV) 100%, η αρνητική προβλεπτική αξία (NPV) 80,7% και η ακρίβεια 92,3%. Αντίστοιχα, η ευαισθησία της DSA ήταν 87,8%, η ειδικότητα 98%, η PPV 97,7%, η NPV 89,1% και η ακρίβεια 92,9%. Όσον αφορά στα ανευρύσματα ≥3 mm, η CTA είχε ευαισθησία που κυμαινόταν μεταξύ 93,3 έως 100%, ίση με αυτή της DSA. Η CTA εμφάνισε τα ίδια ποσοστά ευαισθησίας με αυτά της DSA σε ανευρύσματα ≥3 mm. Εμφάνισε επίσης 100% ποσοστό ανίχνευσης σε ανευρύσματα της πρόσθιας αναστομωτικής και του διχασμού της μέσης εγκεφαλικής αρτηρίας, ενώ μερικές εντοπίσεις όπως η οπίσθια αναστομωτική αρτηρία παραμένουν προβληματικές. 80 Κατά την διάρκεια της παρούσας μελέτης προσπαθήσαμε να δημιουργήσουμε μια τεχνική προσομοίωσης της διεγχειρητικής εικόνας των ραγέντων ενδοκρανιακών ανευρυσμάτων, με τη χρήση volume rendering techniques σε εικόνες που προκύπτουν από CT αγγειογραφία. Η τρισδιάστατη κατασκευή των εικόνων προέκυψε από την συνεργασία μιας ομάδας αποτελούμενης από τέσσερις ακτινολόγους, έναν νευροχειρουργό και έναν ιατρικό φυσικό. Το αποτέλεσμα αυτής της συνεργασίας ήταν η παραγωγή μιας εικόνας οριοθετημένης στο χώρο, με οδηγά σημεία που εύκολα μπορούσαν να αναπαραχθούν κατά την διάρκεια του χειρουργείου. Οι εικόνες χειρουργικής προσομοίωσης ενός ανευρύσματος είναι πιθανώς χρήσιμο εργαλείο για τον προεγχειρητικό σχεδιασμό των ενδοκρανιακών ανευρυσμάτων. / Cerebral CT angiography is an established method applied to both the detection and treatment planning of intracranial aneurysms. The aim of our study was to compare DSA to CTA findings and with the surgical results mainly in patients with acute SAH and to evaluate the clinical usefulness of CTA. During the last three years, 82 consecutive patients were admitted under clinical symptoms and signs suggestive of harbouring an intracranial aneurysm. CT angiography performed immediately afterwards the plain CT, while DSA was performed within the first 48 hours of admission. All aneurysms detected, were confirmed during surgery or endovascular embolization. Repeat DSA was performed in all patients having both the initial CTA and the DSA 15 days after the onset of symptoms negative. CT angiograms and conventional angiographies were studied by a consensus of two radiologists for each technique, who performed aneurysm detection, morphological features characterization and evaluation of the technique. Surgical or/and endovascular treatment was performed in 45 patients and 53 aneurysms were confirmed. Using 3D-CT angiography we detected 47 aneurysms in 42 patients. Conventional angiography depicted 43 aneurysms in 39 patients. The sensitivity of CTA for the detection of all aneurysms versus surgery was 88.7%, the specificity 100%, the positive predictive value (PPV) 100%, the negative predictive value (NPV) 80.7% and the accuracy 92.3%. Consequently, the sensitivity of DSA was 87.8%, the specificity 98%, the PPV 97.7%, the NPV 89.1% and the accuracy 92.9%. Considering the aneurysms ≥ 3 mm, CTA showed a sensitivity ranging from 93.3% to 100%, equal to that of DSA. Cerebral CT angiography has an equal sensitivity to DSA in the detection of intracranial aneurysms greater than 3 mm. It has also 100% detection rate in AcoA and MCA bifurcation aneurysms, while some locations like posterior communicating artery aneurysms remain problematic. The delineating features of each aneurysm are better depicted with CTA due to 3D visualization. The use of Digital Subtraction Angiography as a diagnostic tool can be limited in equivocal cases. A supplement to the above work is our effort to describe a technique for simulating the surgical view of ruptured intracranial aneurysms, using volume 82 rendering techniques in spiral CT angiography data. The 3D rendered images were assessed by a team consisted of four radiologists, one neurosurgeon and one medical physicist. The resultant ‘surgical view’ image was standardized in space using a three-dimensional coordinate system, which allowed for its reproduction in the operating theatre. The surgical views are easily reproducible and αποτελούν a useful tool for the surgical planning of intracranial aneurysms.

This thesis explores two possible ways of detecting soft plaque present in the coronary arteries, using CTA imagery. The coronary arteries are vessels that supply oxidized blood to the cardiac muscle and are thus important for the proper functioning of heart. Cholesterol or reactive oxygen species from cigarette smoke and other toxins may get adhered to the walls of coronary arteries and trigger chronic inflammation that leads to formation of the soft plaque. When the soft plaque grows bigger in volume, it occludes the blood flow to the cardiac muscle and finally results in ischemic heart attack. Moreover, smaller plaque can easily rupture due to the blood flow in arteries and can result in complications such as stroke. Hence there is a need to detect the soft plaque using non-invasive or minimally invasive techniques. In CTA imagery, the cardiac muscle appears as a dark gray color, while the blood appears as dull white color and the the calcified plaque appears as bright white. The soft plaque has an intensity which falls between the intensity level of the blood and cardiac muscle, making it difficult to directly segment the soft plaque using standard segmentation methods. Soft plaque in its advanced stages forms a concavity in the blood lumen. A watershed based segmentation method was used to detect the presence of this concavity which in turn identifies the location of the soft plaque. For segmenting the soft plaque at its earlier stages, a novel segmentation technique was used. In this technique the surface is evolved based on a region-based energy calculated in the local neighborhood around each point on the evolving surface. This method seems to be superior to the watershed based segmentation method in detecting smaller plaque deposits.

INTRODUÇÃO: Em pacientes hipertensos com suspeita de doença arterial coronária (DAC), indicações para a realização de arteriografia renal no mesmo procedimento da cinecoronariografia estão bem estabelecidas. Entretanto, em hipertensos com suspeita de estenose de artéria renal (EAR) com indicação de arteriografia renal, não estão bem definidos os determinantes da presença de DAC grave. OBJETIVOS: Avaliar a prevalência e os determinantes de DAC grave em pacientes hipertensos com indicação de arteriografia renal por suspeita de EAR. METODOLOGIA: Oitenta e dois pacientes com suspeita clínica de EAR foram submetidos à cinecoronariografia e arteriografia renal no mesmo procedimento. Lesão arterial significativa em artérias renal e/ou coronária foi definida por obstrução luminal maior ou igual a 70%. RESULTADOS: Obstrução luminal significativa, tanto em artéria coronária quanto em renal, foi encontrada em 39% dos pacientes. Os pacientes com DAC grave apresentaram idade mais avançada (63±12 vs. 56±13 anos; p=0,03), maior prevalência de angina (41 vs. 16%; p=0,013), maior diâmetro do átrio esquerdo (44,7 vs. 40,6mm; p=0,005) e maior velocidade de onda de pulso (12,6 vs. 10,7 m/s, p=0,02), comparados com os pacientes sem DAC grave. A presença de EAR significativa esteve associada a uma maior prevalência de DAC grave comparada a pacientes sem a lesão (66% vs. 22%; p<0,001). A análise multivariada demonstrou que EAR70% esteve associada com DAC grave de maneira independente (OR: 11,48; 95%CI 3,2-40,2; p<0,001), mesmo em pacientes sem angina (OR: 13,48; 95%CI 2,6-12,1; p<0,001). CONCLUSÃO: Há elevada prevalência de doença coronária grave em pacientes hipertensos com estenose de artéria renal significativa. A presença de estenose maior ou igual a 70%, verificada em arteriografia renal, é preditor forte e independente para a presença de DAC grave, mesmo na ausência de angina / INTRODUCTION: In patients with suspected coronary artery disease (CAD), indications for performing coronary and renal angiography at the same setting are well established. However, in hypertensive patients with suspected renal artery stenosis (RAS) with indication for renal angiography, it is not well defined the determinants of the presence of severe CAD. OBJECTIVES: We aimed to evaluate the prevalence and determinants of severe CAD in hypertensive patients referred to renal angiography for the diagnosis of RAS. METHODS: Eighty-two consecutive patients with high clinical risk for RAS systematically underwent renal angiography and coronary angiography at the same procedure. Significant RAS and CAD were defined as arterial luminal obstruction 70%. RESULTS: Either significant RAS or significant CAD were present in 32/82 patients (39%). Patients with severe CAD were older (63±12 vs. 56±13 years, p=0.03), had more angina (41 vs. 16%; p=0.013), higher left atrial diameter (44.7 vs. 40,6mm; p=0.005), and higher pulse wave velocity (12.6 vs. 10.7 m/s); p=0.02) compared to patients without significant CAD. Significant RAS was associated with an increased prevalence of severe CAD compared to patients without the lesion (66% vs. 22%, respectively; p<0.001). Binary logistic regression analysis showed that RAS 70% was independently associated with severe CAD (OR: 11.48; 95%CI 3.2-40.2; p<0.001), even in patients without angina (OR: 13.48; 95%CI 2.6-12.1; p<0.001). CONCLUSION: The prevalence of severe CAD in hypertensive patients with significant RAS is high. The presence of RAS 70%, diagnosed by renal angiography, is a strong and useful predictor to identify severe CAD, independently of the presence of angina

Background: Coronary artery disease (CAD) is a frequent comorbidity in patients undergoing transcatheter aortic valve implantation (TAVI). If significant CAD can be excluded on coronary CT-angiography (cCTA), invasive coronary angiography (ICA) may be avoided. However, a high plaque burden may make the exclusion of CAD challenging, particularly for less experienced readers. The objective was to analyze the ability of machine learning (ML)-based CT-derived fractional flow reserve (CT-FFR) to correctly categorize cCTA studies without obstructive CAD acquired during pre-TAVI evaluation and to correlate recategorization to image quality and coronary artery calcium score (CAC). Methods: In total, 116 patients without significant stenosis (≥50% diameter) on cCTA as part of pre-TAVI CT were included. Patients were examined with an electrocardiogram-gated CT scan of the heart and high-pitch scan of the torso. Patients were re-evaluated with ML-based CT-FFR (threshold = 0.80). The standard of reference was ICA. Image quality was assessed quantitatively and qualitatively. Results: ML-based CT-FFR was successfully performed in 94.0% (109/116) of patients, including 436 vessels. With CT-FFR, 76/109 patients and 126/436 vessels were falsely categorized as having significant CAD. With CT-FFR 2/2 patients but no vessels initially falsely classified by cCTA were correctly recategorized as having significant CAD. Reclassification occurred predominantly in distal segments. Virtually no correlation was found between image quality or CAC. Conclusions: Unselectively applied, CT-FFR may vastly increase the number of false positive ratings of CAD compared to morphological scoring. Recategorization was virtually independently from image quality or CAC and occurred predominantly in distal segments. It is unclear whether or not the reduced CT-FFR represent true pressure ratios and potentially signifies pathophysiology in patients with severe aortic stenosis.

Background: Significant coronary artery disease (CAD) is a common finding in patients undergoing transcatheter aortic valve implantation (TAVI). Assessment of CAD prior to TAVI is recommended by current guidelines and is mainly performed via invasive coronary angiography (ICA). In this study we analyzed the ability of coronary CT-angiography (cCTA) to rule out significant CAD (stenosis ≥ 50%) during routine pre-TAVI evaluation in patients with high pre-test probability for CAD. Methods: In total, 460 consecutive patients undergoing pre-TAVI CT (mean age 79.6 ± 7.4 years) were included. All patients were examined with a retrospectively ECG-gated CT-scan of the heart, followed by a high-pitch-scan of the vascular access route utilizing a single intravenous bolus of 70 mL iodinated contrast medium. Images were evaluated for image quality, calcifications, and significant CAD; CT-examinations in which CAD could not be ruled out were defined as positive (CAD+). Routinely, patients received ICA (388/460; 84.3%; Group A), which was omitted if renal function was impaired and CAD was ruled out on cCTA (Group B). Following TAVI, clinical events were documented during the hospital stay. Results: cCTA was negative for CAD in 40.2% (188/460). Sensitivity, specificity, PPV, and NPV in Group A were 97.8%, 45.2%, 49.6%, and 97.4%, respectively. Median coronary artery calcium score (CAC) was higher in CAD+-patients but did not have predictive value for correct classification of patients with cCTA. There were no significant differences in clinical events between Group A and B. Conclusion: cCTA can be incorporated into pre-TAVI CT-evaluation with no need for additional contrast medium. cCTA may exclude significant CAD in a relatively high percentage of these high-risk patients. Thereby, cCTA may have the potential to reduce the need for ICA and total amount of contrast medium applied, possibly making pre-procedural evaluation for TAVI safer and faster.

Medical imaging is an important part of the clinical workflow. With the increasing amount and complexity of image data comes the need for automatic (or semi-automatic) analysis methods which aid the physician in the exploration of the data. One specific imaging technique is angiography, in which the blood vessels are imaged using an injected contrast agent which increases the contrast between blood and surrounding tissue. In these images, the blood vessels can be viewed as tubular structures with varying diameters. Deviations from this structure are signs of disease, such as stenoses introducing reduced blood flow, or aneurysms with a risk of rupture. This thesis focuses on segmentation and visualization of blood vessels, consituting the vascular tree, in angiography images. Segmentation is the problem of partitioning an image into separate regions. There is no general segmentation method which achieves good results for all possible applications. Instead, algorithms use prior knowledge and data models adapted to the problem at hand for good performance. We study blood vessel segmentation based on a two-step approach. First, we model the vessels as a collection of linear structures which are detected using multi-scale filtering techniques. Second, we develop machine-learning based level set segmentation methods to separate the vessels from the background, based on the output of the filtering. In many applications the three-dimensional structure of the vascular tree has to be presented to a radiologist or a member of the medical staff. For this, a visualization technique such as direct volume rendering is often used. In the case of computed tomography angiography one has to take into account that the image depends on both the geometrical structure of the vascular tree and the varying concentration of the injected contrast agent. The visualization should have an easy to understand interpretation for the user, to make diagnostical interpretations reliable. The mapping from the image data to the visualization should therefore closely follow routines that are commonly used by the radiologist. We developed an automatic method which adapts the visualization locally to the contrast agent, revealing a larger portion of the vascular tree while minimizing the manual intervention required from the radiologist. The effectiveness of this method is evaluated in a user study involving radiologists as domain experts.