Dual Energy Computed Tomography (DECT) is an emerging technique that offers new possibilities to determine composition of tissues in clinical applications. Accurate knowledge of tissue composition is important for instance for brachytherapy (BT) treatment planning. However, the accuracy of CT numbers measured with contemporary clinical CT scanners is relatively low since CT numbers are affected by image artifacts. The aim of this work was to estimate the accuracy of CT numbers measured with the Siemens SOMATOM Definition Flash DECT scanner and the accuracy of the resulting volume or mass fractions calculated via the three material decomposition method. CT numbers of water, gelatin and a 3rd component (salt, hydroxyapatite or protein powder) mixtures were measured using Siemens SOMATOM Definition Flash DECT scanner. The accuracy of CT numbers was determined by (i) a comparison with theoretical (true) values and (ii) using different measurement conditions (configurations) and assessing the resulting variations in CT numbers. The accuracy of mass fractions determined via the three material decomposition method was estimated by a comparison with mass fractions measured with calibrated scales. The latter method was assumed to provide highly accurate results. It was found that (i) axial scanning biased CT numbers for some detector rows. (ii) large volume of air surrounding the measured region shifted CT numbers compared to a configuration where the region was surrounded by water. (iii) highly attenuating object shifted CT numbers of surrounding voxels. (iv) some image kernels caused overshooting and undershooting of CT numbers close to edges. The three material decomposition method produced mass fractions differing from true values by 8% and 15% for the salt and hydroxyapatite mixtures respectively. In this case, the analyzed CT numbers were averaged over a volumetric region. For individual voxels, the volume fractions were affected by statistical noise. The method failed when statistical noise was high or CT numbers of the decomposition triplet were similar. Contemporary clinical DECT scanners produced image artifacts that strongly affected the accuracy of the three material decomposition method; the Siemens’ image reconstruction algorithm is not well suited for quantitative CT. The three material decomposition method worked relatively well for averages of CT numbers taken from volumetric regions as these averages lowered statistical noise in the analyzed data.

Η υπολογιστική τομογραφία διπλής ενέργειας είναι μια σύγχρονη και συνεχώς εξελισσόμενη τεχνική, η οποία ενισχύει την διαφοροποίηση υλικών, βασιζόμενη στις φασματικές τους ιδιότητες. Φασματική απεικόνιση στην υπολογιστική τομογραφία απαιτεί τη χρήση δυο διαφορετικών ενεργειακών φασμάτων, και μπορεί να διαχωρίσει υλικά τα οποία διαφέρουν σημαντικά στον ατομικό τους αριθμό. Για το λόγο αυτό το ιώδιο (Ζ=53), το οποίο χρησιμοποιείται ως σκιαγραφική ουσία, καθώς και το οστό και οι ασβεστώσεις, τα οποία περιέχουν ασβέστιο (Ζ=20) σε μεγάλο ποσοστό, μπορούν να είναι διακριτά από τα υπόλοιπα στοιχεία τα οποία αποτελούν το ανθρώπινο σώμα, όπως υδρογόνο (Ζ=1), οξυγόνο (Ζ=8), άνθρακα (Ζ=6) και άζωτο (Ζ=7), τα οποία είναι υλικά χαμηλού ατομικού αριθμού. Αυτή τη στιγμή υπάρχουν τρεις διαφορετικές τεχνολογίες υπολογιστικής τομογραφίας διπλής ενεργείας. Ο τομογράφος με ανιχνευτή δυο στρωμάτων, ο οποίος χρησιμοποίει μια λυχνία ακτίνων Χ και ένα ανιχνευτή με δύο στρώματα σπινθηρισμού τοποθετημένα το ένα πάνω στο άλλο. Το πάνω στρώμα απορροφά τα μεγαλύτερο μέρος φωτονίων χαμηλής ενέργειας, ενώ το κάτω τα εναπομείναντα φωτόνια υψηλής ενέργειας, κάνοντας λήψη δυο σειρών δεδομένων διαφορετικών ενεργειών ταυτόχρονα. Η δεύτερη τεχνολογική προσέγγιση είναι μέσω ταχύτατης εναλλαγής της τάσης της λυχνίας. Με αυτό τον τρόπο γίνεται λήψη δυο σειρών δεδομένων διαφορετικών ενεργειών, μεταβάλλοντας τη τάση της λυχνίας από χαμηλή σε υψηλή μέσα σε μια μόνο περιστροφή. Τέλος ο τρίτος υπολογιστικός τομογράφος διπλής ενεργείας, ο οποίος χρησιμοποιείται και σε αυτή τη μελέτη, είναι ο τομογράφος δύο λυχνιών, οποίος αποτελείται από δυο λυχνίες ακτίνων Χ και δυο ανιχνευτές. Οι δύο λυχνίες μπορούν να λειτουργήσουν σε διαφορετικά kV ανεξάρτητα η μία από την άλλη, λαμβάνοντας δύο σειρές δεδομένων διαφορετικών ενεργειών ταυτόχρονα. Όταν ο υπολογιστικός τομογράφος δυο λυχνιών χρησιμοποιείται για λήψη εικόνων διπλής ενέργειας, η μια λυχνία λειτουργεί στα 80 kV και η άλλη στα 140 kV. Σε αυτή τη μελέτη εξετάστηκε η συμπεριφορά σε δύο ενέργειες μέσω μια σειράς πειραμάτων, υλικών όπως, πολυμερών ισοδύναμων με μαλακούς ιστούς και οστό, καθώς επίσης, συγκεντρώσεων ιωδίου και ασβεστίου. Χρησιμοποιήθηκαν δυο πρωτόκολλα λήψεων, ένα μιας ενέργειας με λήψεις στα 80, 100, 120, και 140 kV, καθώς και ένα πρωτόκολλο διπλής ενέργειας. Στα πειράματα που πραγματοποιήθηκαν μετρήθηκαν οι αριθμοί CT των υλικών, ο θόρυβος, η αντίθεση και ο λόγος αντίθεσης προς θόρυβο. Επίσης έγινε σύγκριση ως προς τα παραπάνω χαρακτηριστικά ποιότητα εικόνας με βάση τους παραπάνω δείκτες μεταξύ της συμβατικής 120 kV εικόνας και της ανακατασκευασμένης διπλής ενέργειας “virtual 120” kV. Η λεγόμενη “virtual 120” kV, μια αναμεμιγμένη εικόνα, κατασκευασμένη από δυο σειρές δεδομένων διαφορετικών ενεργειών, με γραμμικό συνδυασμό . Επιπλέον διερευνήθηκαν και συγκρίθηκαν ως προς τη ποιότητα εικόνας όλοι οι πιθανοί συνδυασμοί των δυο σειρών δεδομένων ενέργειας. Τα αποτελέσματα έδειξαν ότι μόνο υλικά υψηλού ενεργού ατομικού αριθμού, όπως το οστό και οι υψηλές συγκεντρώσεις ιωδίου 17, 25 και 35 mg/ml, καθώς και ασβεστίου 200, 250 και 300 mg/ml, είχαν ενισχυμένη αντίθεση στα 80 kV. Αξίζει να σημειωθεί ότι για μικρές συγκεντρώσεις ,όπως 1.25, 2.5, 3.5 mg/ml και 45, 83 mg/ml ιωδίου και ασβεστίου αντιστοίχως, η αντίθεση έχει συμπεριφορά μαλακού ιστού. Αντίθετα η τιμή του λόγου αντίθεσης προς θόρυβο δεν είναι όσο υψηλή είναι η τιμή της αντίθεσης. Τα επίπεδα θορύβου της εικόνας στα 80 kV είναι τόσο υψηλά, με αποτέλεσμα οι τιμές του λόγου αντίθεσης προς θόρυβο για όλα τα υλικά υψηλού ατομικού αριθμού να είναι χαμηλότερες στα 80 kV, συγκρινόμενες με τις αντίστοιχες τιμές στις υπόλοιπες τάσεις, παρά το γεγονός ότι η τιμή της αντίθεσης είναι πολύ υψηλή στα 80 kV. Όσο αναφορά τη σύγκριση της 120 kV εικόνας με την λεγόμενη “virtual 120” kV, τα αποτελέσματα των πειραμάτων έδειξαν ότι οι τιμές αντίθεσης του οστού, καθώς επίσης και των συγκεντρώσεων ιωδίου και ασβεστίου, ήταν ισοδύναμες, αλλά η τιμή του λόγου αντίθεσης προς θόρυβο της “virtual 120” kV εικόνας ήταν αρκετά χαμηλότερη σε σχέση με την 120 kV εικόνα. Τέλος το τρίτο πείραμα έδειξε ότι η τιμή της αντίθεσης αυξάνεται όσο αυξάνεται το ποσοστό της 80 kV πληροφορίας στη μεικτή εικόνα, ενώ ο λόγος αντίθεσης προς θόρυβο έχει ένα εύρος συνδυασμών που είναι υψηλός. Συγκεκραμένα οι γραμμικοί συνδυασμοί οι όποιοι είχαν τη μεγαλύτερη τιμή αντιθέσεις προς θόρυβο ήταν οι συντελεστές της 80 kV πληροφορίας από 0.4 έως 0.7. / Dual Energy Computed Tomography (DECT) is an evolving technique, which enhances material differentiation benefiting from the spectral properties of the materials. Spectral CT imaging requires the use of two different energy spectra, and it can distinguish elements, which differ considerably in atomic number. Therefore iodine (Z=53) which is used as contrast agent in CT scans, bone and plaque calcifications which contain calcium (Z=20), can be distinguished from other elements of which the human body consists, such as hydrogen (Z=1), oxygen (Z=8), carbon (Z=6) and nitrogen (Z=7), which are low atomic number elements. Currently there are three technical approaches of dual energy computed tomography. The dual layer detector system, which uses a single x-ray source and a detector with two scintillation layers one on top of one another. The top layer absorbs most of the low energy photons, while the bottom one the remaining high energy photons, acquiring two energy datasets simultaneously. The second technology of dual energy imaging is via fast kVp switching, which acquires two different energy spectra, alternating on a view by view basis between low and high kVp in a single rotation. Finally the third dual energy imaging technique, used in this study, is via the dual source CT system, which contains two x-ray tubes and two detectors. The two tubes can be operated independently at different kV. The dual source CT when it is used for dual energy scan is operated 80 kV/140 kV. Thus two dual energy datasets are acquired simultaneously. In this study the dual energy behavior of soft tissue equivalent materials, bone, iodine and calcium water solutions are examined through a series of experiments. Two acquisition protocols are used, a single energy at 80, 100, 120 and 140 kV, and a dual energy protocol. The CT numbers of these materials, as well as image noise, contrast and contrast to noise ratio are measured. Moreover comparison of these image quality features for standard single energy 120 kV image, which is the convention CT scan, and the “virtual 120” kV image is presented. The “virtual 120” kV is a blended image, reconstructed by the two dual energy datasets in a linear combination of In addition examination of all the possible linear combinations of the two dual energy datasets, and comparison in image quality, is presented. The results showed that only high Zeff materials had enhanced contrast at 80 kV, like bone, and the high iodine and calcium concentrations, such as 17, 25, and 35 mg/ml and 200, 250, and 300 mg/ml respectively. It is noteworthy that for small concentrations, such as 1.25, 2.5, 3.5 mg/ml and 45, 83 mg/ml of iodine and calcium respectively, contrast behavior is like the one of a soft tissue. Contrarily contrast to noise ratio is not as high as contrast at 80 kV. Image noise values at 80 kV are so high that CNR values for all high atomic number materials are lower at 80 kV compared to the ones of other voltages, despite the fact that contrast is very high at 80 kV. As it concerns the comparison of the single energy 120 kV image and the “virtual 120” kV, the results of the experiments showed that contrast values of bone, iodine and calcium concentrations, were equal, but contrast to noise ratio of the “virtual 120” was quite lower compared to the single energy 120 kV. Finally the third experiment showed that contrast values increase as the percentage of the 80 kV datasets increases in the blended image, while contrast to noise ratio has a range in which is higher. Specifically the linear combinations which had the highest CNR values were the ones with weighting factor of the 80 kV starting from 0.4 to 0.7.

The current thesis concerns Dual Energy Computed Tomography and specifically the physical principles and methods it is based on. Dual Energy CT offers the potential of not only anatomical, but also functional information from Computed Tomography (CT) exams. This is achieved by utilizing the energy dependence of X-rays’ attenuation within matter. In this way, materials are divided into those that are characterized by energy-dependent attenuation (strong spectral behavior), due to strong photoelectric effect contribution to total attenuation, and those that do not exhibit important photoelectric attenuation at radiological energies and therefore they attenuate X-rays in a much less energy dependent way. This information is useful for the identification of materials that, despite the fact that they are completely different as far as their chemical composition is concerned, they have the same or similar CT number values at a particular kVp level. The energy dependence of attenuation leads to the determination of a polychromatic linear attenuation coefficient. This coefficient may be approximated either by considering an equivalent monoenergetic attenuation coefficient that is characterized by the same half value layer as the the polyenergetic beam, or by a local linear attenuation coefficient that is determined by knowledge of the local x-ray spectrum. The energy dependence of attenuation is the cause of beam hardening effects. The basic fields where dual energy CT has become feasible and its current clinical applications are described in the thesis. The utility of DECT ranges from artifact elimination (beam hardening, metal artifacts) to tissue discrimination, material selective images and “conventional CT acquisition” equivalent images. The implementations of dual energy CT are also presented in the thesis and include consecutive scans at two different kVp values, fast kV-switching, dual source CT and dual layer CT. / Η παρούσα διπλωματική εργασία αφορά στην τομογραφία διπλής ενέργειας και ειδικότερα τις φυσικές αρχές και μεθόδους στις οποίες βασίζεται. H τομογραφία διπλής ενέργειας δίνει την προοπτική της απόκτησης όχι μόνο ανατομικής, αλλά και λειτουργικής πληροφορίας από τις εξετάσεις αξονικής τομογραφίας. Αυτό το επιτυγχάνει χρησιμοποιώντας την εξάρτηση της εξασθένησης των ακτίνων X μέσα στην ύλη από την ενέργεια των φωτονίων. Με αυτό τον τρόπο, τα υλικά διαχωρίζονται σε αυτά που εξασθενούν τα φωτόνια με πολύ διαφορετικό τρόπο σε διαφορετικές ενέργειες λόγω έντονου φωτοηλεκτρικού φαινομένου και σε αυτά που η ενεργειακή εξάρτηση του συντελεστή εξασθένησης τους είναι λιγότερο έντονη (λιγότερη συμμετοχή του φωτοηλεκτρικού φαινομένου στη συνολική εξασθένηση). Η πληροφορία αυτή είναι χρήσιμη για την ταυτοποίηση της σύστασης υλικών, που ενώ είναι εντελώς διαφορετικά σε χημική σύσταση, έχουν τον ίδιο αριθμό CT (CT number) σε συγκεκριμένη τάση λειτουργίας της πηγής ακτίνων X. Στην εκτεταμένη περίληψη αυτής της εργασίας, αρχικά γίνεται σύντομη αναφορά στην εξάρτηση του συντελεστή εξασθένησης από την ενέργεια και πώς αυτή επηρεάζει τον ορισμό του συντελεστή γραμμικής εξασθένησης για πολυχρωματικές ακτινοβολίες. Στη συνέχεια ακολουθεί μια συνοπτική περιγραφή υλοποιήσεων της τομογραφίας διπλής ενέργειας καθώς επίσης και των αλγορίθμων και των κλινικών εφαρμογών που είναι διαθέσιμες σήμερα. Τέλος, περνώντας στην περιγραφή του κυρίως μέρους της διπλωματικής, ακολουθεί συνοπτική περιγραφή της θεωρητικής και πειραματικής μελέτης της συμπεριφοράς διπλής ενέργειας του ιωδίου, του ασβεστίου, του οστού και υλικών που προσομοιάζουν το μαλακό και λιπώδη ιστό. Στη θεωρητική περιγραφή, η διπλωματική εστιάζει στις εξαρτήσεις του συντελεστή γραμμικής εξασθένησης, πρώτα από τα χαρακτηριστικά του ίδιου του υλικού (πυκνότητα, χημική σύσταση) και έπειτα από την ενέργεια των φωτονίων. Ο προβληματισμός σχετικά με την εξάρτηση του συντελεστή εξασθένησης με την ενέργεια έχει οδηγήσει συχνά σε τρόπους προσέγγισης και ορισμού ενός συντελεστή γραμμικής εξασθένησης που να ανταποκρίνεται σε πολυενεργειακές δέσμες, όπως αυτές που χρησιμοποιεί ο αξονικός τομογράφος. Ο συντελεστής γραμμικής εξασθένησης μιας πολυενεργειακής δέσμης από ένα συγκεκριμένο υλικό, προσδιορίζεται είτε μέσω ενός ισοδύναμου μονοενεργειακού συντελεστή εξασθένησης που να χαρακτηρίζεται από το ίδιο half value layer (HVL) με την πολυενεργειακή δέσμη είτε μέσω ενός «τοπικού» συντελεστή εξασθένησης. που για να προσδιοριστεί απαιτείται γνώση του φάσματος στην συγκεκριμένη θέση και στο συγκεκριμένο υλικό. Η εξάρτηση του συντελεστή εξασθένησης από την ενέργεια των φωτονίων ευθύνεται για τεχνήματα σκλήρυνσης δέσμης (beam hardening artifacts).

abstract: Computed tomography (CT) is one of the essential imaging modalities for medical diagnosis. Since its introduction in 1972, CT technology has been improved dramatically, especially in terms of its acquisition speed. However, the main principle of CT which consists in acquiring only density information has not changed at all until recently. Different materials may have the same CT number, which may lead to uncertainty or misdiagnosis. Dual-energy CT (DECT) was reintroduced recently to solve this problem by using the additional spectral information of X-ray attenuation and aims for accurate density measurement and material differentiation. However, the spectral information lies in the difference between two low and high energy images or measurements, so that it is difficult to acquire the accurate spectral information due to amplification of high pixel noise in the resulting difference image. In this work, a new model and an image enhancement technique for DECT are proposed, based on the fact that the attenuation of a high density material decreases more rapidly as X-ray energy increases. This fact has been previously ignored in most of DECT image enhancement techniques. The proposed technique consists of offset correction, spectral error correction, and adaptive noise suppression. It reduced noise, improved contrast effectively and showed better material differentiation in real patient images as well as phantom studies. / Dissertation/Thesis / Ph.D. Bioengineering 2011

abstract: Coronary heart disease (CHD) is the most prevalent cause of death worldwide. Atherosclerosis which is the condition of plaque buildup on the inside of the coronary artery wall is the main cause of CHD. Rupture of unstable atherosclerotic coronary plaque is known to be the cause of acute coronary syndrome. The composition of plaque is important for detection of plaque vulnerability. Due to prognostic importance of early stage identification, non-invasive assessment of plaque characterization is necessary. Computed tomography (CT) has emerged as a non-invasive alternative to coronary angiography. Recently, dual energy CT (DECT) coronary angiography has been performed clinically. DECT scanners use two different X-ray energies in order to determine the energy dependency of tissue attenuation values for each voxel. They generate virtual monochromatic energy images, as well as material basis pair images. The characterization of plaque components by DECT is still an active research topic since overlap between the CT attenuations measured in plaque components and contrast material shows that the single mean density might not be an appropriate measure for characterization. This dissertation proposes feature extraction, feature selection and learning strategies for supervised characterization of coronary atherosclerotic plaques. In my first study, I proposed an approach for calcium quantification in contrast-enhanced examinations of the coronary arteries, potentially eliminating the need for an extra non-contrast X-ray acquisition. The ambiguity of separation of calcium from contrast material was solved by using virtual non-contrast images. Additional attenuation data provided by DECT provides valuable information for separation of lipid from fibrous plaque since the change of their attenuation as the energy level changes is different. My second study proposed these as the input to supervised learners for a more precise classification of lipid and fibrous plaques. My last study aimed at automatic segmentation of coronary arteries characterizing plaque components and lumen on contrast enhanced monochromatic X-ray images. This required extraction of features from regions of interests. This study proposed feature extraction strategies and selection of important ones. The results show that supervised learning on the proposed features provides promising results for automatic characterization of coronary atherosclerotic plaques by DECT. / Dissertation/Thesis / Ph.D. Bioengineering 2013

no / Rationale and Objectives: To determine whether a single source computed tomography (CT) system utilizing fast kV switching and low dose settings can characterize (diameter and chemical composition) renal stones accurately when compared infrared spectroscopy. Materials and Methods: The chemical composition of 15 renal stones was determined using Fourier transform infrared spectroscopy. The stones were inserted into a porcine kidney and placed within a water tank for CT scanning using both fast kV switching dual energy and standard protocols. Effective atomic number of each stone was measured using scanner software. Stone diameter measurements were repeated twice to determine intra-rater variation and compared to actual stone diameter as measured by micro CT. Results: The chemical composition of three stones (one calcium phosphate and two carbonite apatite) could not be determined using the scanner software. The composition of 10/12 remaining stones was correctly identified using dual energy computed tomography (83% absolute agreement; k = 0.69). No statistical difference (p = 0.051) was noted in the mean stone diameter as measured by clinical CT and micro CT. Conclusion: Dual energy computed tomography using fast kV switching may potentially be developed as a low dose clinical tool for identifying and classifying renal stones in vivo supporting clinical decision-making.

No description available.

Introdução: A hipertensão arterial pulmonar (HAP) é uma doença grave da circulação pulmonar, cujo diagnóstico e cuja avaliação funcional dependem do cateterismo cardíaco direito. A tomografia de dupla energia (TCDE), por meio da técnica de decomposição de materiais, permite obter um mapa de Iodo do parênquima pulmonar, que pode ser avaliado de forma qualitativa e quantitativa, e pode ser útil na avaliação da HAP. Objetivos: Avaliar a distribuição de Iodo no parênquima pulmonar, comparando com marcadores hemodinâmicos, marcadores de gravidade e com grupo-controle normopressórico. Métodos: Pacientes com HAP, acompanhados na Unidade de Circulação Pulmonar (InCor-HCFMUSP), foram avaliados por angiotomografia das artérias pulmonares (angioTC) como parte de sua rotina diagnóstica, em modo de dupla energia. O grupo-controle foi composto por pacientes com suspeita clínica de tromboembolismo pulmonar (TEP), com angioTC negativa para TEP e com ecocardiograma normal. Foram avaliadas as concentrações de Iodo no pulmão (mg/mL) por meio de 8 regiões de interesse redondas com 1 cm2 de área, distribuídas ao longo do eixo ântero-posterior do pulmão direito, em 3 níveis predeterminados. Foram obtidas, também, as medidas do ventrículo direito (VD), ventrículo esquerdo (VE), razão VD/VE, diâmetros da aorta (AO) e artéria pulmonar (AP). O realce da artéria pulmonar por meio da TCDE (PAenh) também foi obtido. Os resultados foram comparados entre os grupos, e correlacionados no grupo HAP com parâmetros hemodinâmicos invasivos e marcadores de gravidade. Resultados: O grupo HAP foi composto por 21 pacientes, com idade média de 42 anos, 47,6% em classe funcional I/II. Houve diferença significativa nos diâmetros da AP (p<0,01), VD (p<0,01), e VE (p=0,01), entre os grupos HAP e controle. Também demonstraram diferenças significativas às relações entre os diâmetros AP/AO (p < 0,01) e VD/VE (p < 0,01), entre os grupos. Calibre da artéria pulmonar maior do que 2,9 cm e relação AP/AO maior do que 1,1 cm demonstraram sensibilidade de 90,5% e 87,5%, e especificidade de 100% para o diagnóstico de HP. A PAenh não demonstrou diferenças significativas entre os grupos HAP e controle, contudo se correlacionou significativamente com a medida do débito cardíaco no grupo HAP (r=-0,661, p=0,01). A PAPm demonstrou correlação com a relação AP/AO (r=0,676) e, também, com a relação VD/VE (r=0,679), ambas com p < 0,01. A concentração de Iodo no parênquima foi significativamente menor no grupo HAP em todos os segmentos analisados. O mapa de Iodo demonstrou gradiente progressivo da concentração de Iodo no parênquima pulmonar, de caráter ântero-posterior, em ambos os grupos, de magnitude significativamente menor no grupo HAP. Usando-se o valor de PAenh para correção das medidas de concentração de Iodo, deixa de haver diferença entre os grupos HAP e controle. Conclusões: A TCDE, além das medidas anatômicas obtidas pela técnica convencional, permitiu demonstrar a manutenção do gradiente ântero-posterior da concentração de Iodo em pacientes com HAP, sugerindo que sua menor magnitude seja determinada pelo baixo débito cardíaco / Background: Pulmonary arterial hypertension (PAH) is a severe disease of the pulmonary circulation. Right heart catheterization (RHC) is crucial for diagnosis and management of these patients. High-resolution computed tomography (CT) and CT angiography play a crucial role in the diagnostic work-up of pulmonary hypertension. Dual energy computed tomography (DECT) is a technique of acquisition of modern CT scanners that allows obtaining a computed tomography of the pulmonary arteries with low iodine dose, and providing an estimation of iodine distribution in the lungs. Although the search for non-invasive methods for evaluation of PAH is developing, data concerning application of DECT on PAH patients remain scarce. Objectives: To evaluate the iodine distribution in the lungs obtained by DECT in PAH patients and a control group and compare to the hemodynamic profile, and prognostic markers of PAH patients. Methods: 21 patients followed at the Pulmonary Circulation Unit (InCor-HCFMUSP) and submitted to CT angiography were evaluated by DECT. A matched control group was composed by patients routinely referred to CT angiography to rule out pulmonary embolism with negative results and also a normal echocardiogram obtained at the same day. Eight circular 1cm2 ROIs were placed along the anteroposterior axis, at the middle of the right lung and at predetermined levels to measure the Iodine concentration in the lungs. Measurements of the pulmonary artery (PA), ascending aorta (AO), right ventricle (RV) and left ventricles (LV) were obtained, as well as enhancement of the PA (PAenh). Results were compared to the control group, and correlated with hemodynamic parameters in the PAH group. Results: PAH patients averaged 42 y/o, female/male ratio of 7/1, NYA functional classes I/II. Statistically significant differences between PAH patients and controls were found regarding measurements of PA (p < 0,01), RV (p < 0,01), LV (p=0,01), PA/AO (p < 0,01) and RV/LV (p < 0,01). PA diameter greater than 2,9 cm and PA/AO ratio greater 1,1 were diagnostic for pulmonary hypertension with sensitivity/specifity of 90,5%/100% and 87,5%/100%. PAenh showed no statistical difference between PAH patients and controls . A characteristic anteroposterior Iodine concentration gradient was found in all subjects, both PAH patients showed lower Iodine concentration diffusely (p < 0,01). When corrected by PAenh, Iodine gradients showed no statistical difference between PAH patients and controls. PAenh correlates with cardiac output (r=-0,661), and mPaP correlates with PA/AO ratio (r=0,676), RV/LV ratio VD/VE ratio (r=0,679), and p<0,01. Conclusion: Anteroposterior Iodine concentration gradient is preserved in PAH in comparison with controls, but with lower magnitude. This difference was corrected through the multiplication of individual Iodine measurements by PAenh, suggesting that this could be explained by lower blood flow to the lungs of PAH patients. PAenh correlates with cardiac output, mean pulmonary arterial pressure correlates with PA/AO and RV/LV in PAH patients. DECT provided conventional anatomic measurements and allowed the characterization of preserved anteroposterior Iodine gradients in PAH patients, with decreased magnitude in comparison with controls, that could be atributed to a lower CO of these patients

Introdução: A hipertensão arterial pulmonar (HAP) é uma doença grave da circulação pulmonar, cujo diagnóstico e cuja avaliação funcional dependem do cateterismo cardíaco direito. A tomografia de dupla energia (TCDE), por meio da técnica de decomposição de materiais, permite obter um mapa de Iodo do parênquima pulmonar, que pode ser avaliado de forma qualitativa e quantitativa, e pode ser útil na avaliação da HAP. Objetivos: Avaliar a distribuição de Iodo no parênquima pulmonar, comparando com marcadores hemodinâmicos, marcadores de gravidade e com grupo-controle normopressórico. Métodos: Pacientes com HAP, acompanhados na Unidade de Circulação Pulmonar (InCor-HCFMUSP), foram avaliados por angiotomografia das artérias pulmonares (angioTC) como parte de sua rotina diagnóstica, em modo de dupla energia. O grupo-controle foi composto por pacientes com suspeita clínica de tromboembolismo pulmonar (TEP), com angioTC negativa para TEP e com ecocardiograma normal. Foram avaliadas as concentrações de Iodo no pulmão (mg/mL) por meio de 8 regiões de interesse redondas com 1 cm2 de área, distribuídas ao longo do eixo ântero-posterior do pulmão direito, em 3 níveis predeterminados. Foram obtidas, também, as medidas do ventrículo direito (VD), ventrículo esquerdo (VE), razão VD/VE, diâmetros da aorta (AO) e artéria pulmonar (AP). O realce da artéria pulmonar por meio da TCDE (PAenh) também foi obtido. Os resultados foram comparados entre os grupos, e correlacionados no grupo HAP com parâmetros hemodinâmicos invasivos e marcadores de gravidade. Resultados: O grupo HAP foi composto por 21 pacientes, com idade média de 42 anos, 47,6% em classe funcional I/II. Houve diferença significativa nos diâmetros da AP (p<0,01), VD (p<0,01), e VE (p=0,01), entre os grupos HAP e controle. Também demonstraram diferenças significativas às relações entre os diâmetros AP/AO (p < 0,01) e VD/VE (p < 0,01), entre os grupos. Calibre da artéria pulmonar maior do que 2,9 cm e relação AP/AO maior do que 1,1 cm demonstraram sensibilidade de 90,5% e 87,5%, e especificidade de 100% para o diagnóstico de HP. A PAenh não demonstrou diferenças significativas entre os grupos HAP e controle, contudo se correlacionou significativamente com a medida do débito cardíaco no grupo HAP (r=-0,661, p=0,01). A PAPm demonstrou correlação com a relação AP/AO (r=0,676) e, também, com a relação VD/VE (r=0,679), ambas com p < 0,01. A concentração de Iodo no parênquima foi significativamente menor no grupo HAP em todos os segmentos analisados. O mapa de Iodo demonstrou gradiente progressivo da concentração de Iodo no parênquima pulmonar, de caráter ântero-posterior, em ambos os grupos, de magnitude significativamente menor no grupo HAP. Usando-se o valor de PAenh para correção das medidas de concentração de Iodo, deixa de haver diferença entre os grupos HAP e controle. Conclusões: A TCDE, além das medidas anatômicas obtidas pela técnica convencional, permitiu demonstrar a manutenção do gradiente ântero-posterior da concentração de Iodo em pacientes com HAP, sugerindo que sua menor magnitude seja determinada pelo baixo débito cardíaco / Background: Pulmonary arterial hypertension (PAH) is a severe disease of the pulmonary circulation. Right heart catheterization (RHC) is crucial for diagnosis and management of these patients. High-resolution computed tomography (CT) and CT angiography play a crucial role in the diagnostic work-up of pulmonary hypertension. Dual energy computed tomography (DECT) is a technique of acquisition of modern CT scanners that allows obtaining a computed tomography of the pulmonary arteries with low iodine dose, and providing an estimation of iodine distribution in the lungs. Although the search for non-invasive methods for evaluation of PAH is developing, data concerning application of DECT on PAH patients remain scarce. Objectives: To evaluate the iodine distribution in the lungs obtained by DECT in PAH patients and a control group and compare to the hemodynamic profile, and prognostic markers of PAH patients. Methods: 21 patients followed at the Pulmonary Circulation Unit (InCor-HCFMUSP) and submitted to CT angiography were evaluated by DECT. A matched control group was composed by patients routinely referred to CT angiography to rule out pulmonary embolism with negative results and also a normal echocardiogram obtained at the same day. Eight circular 1cm2 ROIs were placed along the anteroposterior axis, at the middle of the right lung and at predetermined levels to measure the Iodine concentration in the lungs. Measurements of the pulmonary artery (PA), ascending aorta (AO), right ventricle (RV) and left ventricles (LV) were obtained, as well as enhancement of the PA (PAenh). Results were compared to the control group, and correlated with hemodynamic parameters in the PAH group. Results: PAH patients averaged 42 y/o, female/male ratio of 7/1, NYA functional classes I/II. Statistically significant differences between PAH patients and controls were found regarding measurements of PA (p < 0,01), RV (p < 0,01), LV (p=0,01), PA/AO (p < 0,01) and RV/LV (p < 0,01). PA diameter greater than 2,9 cm and PA/AO ratio greater 1,1 were diagnostic for pulmonary hypertension with sensitivity/specifity of 90,5%/100% and 87,5%/100%. PAenh showed no statistical difference between PAH patients and controls . A characteristic anteroposterior Iodine concentration gradient was found in all subjects, both PAH patients showed lower Iodine concentration diffusely (p < 0,01). When corrected by PAenh, Iodine gradients showed no statistical difference between PAH patients and controls. PAenh correlates with cardiac output (r=-0,661), and mPaP correlates with PA/AO ratio (r=0,676), RV/LV ratio VD/VE ratio (r=0,679), and p<0,01. Conclusion: Anteroposterior Iodine concentration gradient is preserved in PAH in comparison with controls, but with lower magnitude. This difference was corrected through the multiplication of individual Iodine measurements by PAenh, suggesting that this could be explained by lower blood flow to the lungs of PAH patients. PAenh correlates with cardiac output, mean pulmonary arterial pressure correlates with PA/AO and RV/LV in PAH patients. DECT provided conventional anatomic measurements and allowed the characterization of preserved anteroposterior Iodine gradients in PAH patients, with decreased magnitude in comparison with controls, that could be atributed to a lower CO of these patients

Unsicherheiten in der Reichweitevorhersage limitieren wesentlich das Ausnutzen der Vorteile von Protonentherapie gegenüber konventioneller Strahlentherapie. Die Verwendung von Zwei-Spektren-Computertomographie (DECT) zur direkten Vorhersage des Bremsvermögen (DirectSPR) ermöglicht eine relevante Verbesserung der Reichweitevorhersage gegenüber der üblicherweise verwendeten Ein-Spektren-Computertomographie (SECT). Im Rahmen dieser Dissertation wurde die Variation in der Reichweitevorhersage zwischen 17 europäischen Partikeltherapiezentren experimentell verglichen. Die Genauigkeit der Reichweitevorhersage bei Verwendung einer DirectSPR-Implementierung wurde umfassend quantifiziert und die Implementierung in die klinische Routine integriert. Dies führte zu einer Reduzierung des klinischen Sicherheitssaum um ca. 35% für die Behandlung von quasistatischen Tumoren in Kopf und Becken und damit einer Schonung des Normalgewebes sowie der das Zielgebiet umgebenden Risikoorgane. Darüber hinaus wurde die DirectSPR-Implementierung zur Bestimmung von Gewebeparametern sowie deren Variabilität für zehn Organe im Kopf und Becken in einer Patienkohorte genutzt. Die vorgestellten Ergebnisse etablieren DECT weiter als zukünftiges Standard-Bildgebungsverfahren in der Partikeltherapie.:1. Introduction 2. Proton therapy 2.1. Physical principles of proton therapy 2.2. Treatment with protons 2.3. Accuracy in proton therapy 3. CT Imaging for proton therapy 3.1. Principles of CT imaging 3.2. CT-based range prediction 3.3. Investigated phantoms and materials 3.4. DECT scan acquisition 3.5. Determination of proton stopping power for reference materials 4. Accuracy of stopping-power prediction in European proton centres 4.1. Study design 4.2. Experimental setup and analysis 4.3. Results 4.4. Discussion of determined deviations 4.5. Conclusion and outlook 4.6. Establishment of guidelines for HLUT calibration 5. Range uncertainties in DirectSPR-based treatment planning 5.1. Clinical implementation of DirectSPR 5.2. Uncertainty quantification 5.3. Resulting uncertainties in SPR prediction 5.4. Experimental validation 5.5. Dosimetric effect of range uncertainty reduction 5.6. Discussion 6. In-vivo tissue characterisation using DirectSPR 6.1. Tissue parameter determination by Woodard and White 6.2. Data preparation and analysis 6.3. Determined tissue parameters and variations 6.4. Discussion 7. The future of image-based range prediction 7.1. Particle imaging 7.2. Creation of synthetic CT images 7.3. Photon-counting computed tomography 8. Summary 9. Zusammenfassung A. Supplement A.1. Investigated materials A.2. EPTN study: Individual results A.3. DirectSPR validation results / Imaging-related range uncertainties effectively limit the full exploitation of the benefits proton therapy offers with respect to conventional photon radiotherapy. The use of dual-energy computed tomography (DECT) for direct stopping-power prediction (DirectSPR) was determined to provide relevant improvements in range prediction over commonly used singleenergy CT (SECT). Within this thesis, the variation in range prediction accuracy between 17 European particle treatment centres were experimentally quantified to determine the current status quo in the community. The overall range uncertainty when using a DirectSPR implementation in treatment planning was comprehensively quantified and the implementation integrated into the clinical workflow. This led to a reduction of clinical safety margins by about 35% for the treatment of quasi-static tumours in the head and pelvis, effectively reducing the dose to surrounding healthy tissue and organs at risk. The DirectSPR implementation was furthermore utilised to assess tissue parameters and their inter- and intra-patient variability for ten organs in the head and pelvis from a cohort of patients. The presented results further establish DirectSPR as the future standard imaging modality in particle therapy.:1. Introduction 2. Proton therapy 2.1. Physical principles of proton therapy 2.2. Treatment with protons 2.3. Accuracy in proton therapy 3. CT Imaging for proton therapy 3.1. Principles of CT imaging 3.2. CT-based range prediction 3.3. Investigated phantoms and materials 3.4. DECT scan acquisition 3.5. Determination of proton stopping power for reference materials 4. Accuracy of stopping-power prediction in European proton centres 4.1. Study design 4.2. Experimental setup and analysis 4.3. Results 4.4. Discussion of determined deviations 4.5. Conclusion and outlook 4.6. Establishment of guidelines for HLUT calibration 5. Range uncertainties in DirectSPR-based treatment planning 5.1. Clinical implementation of DirectSPR 5.2. Uncertainty quantification 5.3. Resulting uncertainties in SPR prediction 5.4. Experimental validation 5.5. Dosimetric effect of range uncertainty reduction 5.6. Discussion 6. In-vivo tissue characterisation using DirectSPR 6.1. Tissue parameter determination by Woodard and White 6.2. Data preparation and analysis 6.3. Determined tissue parameters and variations 6.4. Discussion 7. The future of image-based range prediction 7.1. Particle imaging 7.2. Creation of synthetic CT images 7.3. Photon-counting computed tomography 8. Summary 9. Zusammenfassung A. Supplement A.1. Investigated materials A.2. EPTN study: Individual results A.3. DirectSPR validation results