No description available.

No description available.

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.

Osteoporosis is a disease of the bones. It is often called the “silent disease," because someone could have it now or be at-risk without even realizing it. As a result, bones become weak and can break from a minor fall or, in serious cases, even from simple actions, like sneezing or bumping into furniture. Breaking a bone is often the first clue that someone suffers from osteoporosis. The diagnosis of osteoporosis can be made using conventional radiography and by measuring the Bone Mineral Density (BMD). The most popular method of measuring BMD is Dual-Energy X-ray Absorptiometry (DXA). In conventional methods the measurement of bone does not give information about the bone quality but for the bone quantity. A non-invasive method that will have the ability to determine the bone quality is of interest. Such a method will contribute to the prediction or even the prevention of bone malfunction. In this study, two quality parameters, that are designed to contribute to improved diagnostic methods of osteoporosis, are determined. Those bone quality parameters are the Calcium/Phosphate (Ca/P) and Hydroxyapatite/Collagen (HAp/Col) ratios. The algorithm developed allows us to trace the spectral changes which take place when an x-ray beam passes through filters based on the Lambert and Beer’s law. A large number of filters were applied to spectra so as to obtain pseudo-monoenergetic spectra. The optimum energy pair would derive from two quasi-monoenergetic spectra with sufficient number of photons which will result in the minimization of the Coefficient of Variation (CV) of the aforementioned ratios. Dual Energy x-ray method is used in order to obtain this energy pair. Both Single and Double exposure techniques are used. / Η οστεοπόρωση είναι μια ασθένεια των οστών. Συχνά αποκαλείται ως η «αθόρυβη ασθένεια», καθώς κάποιος δεν αντιλαμβάνεται ότι νοσεί από αυτή. Σαν αποτέλεσμα της ασθένειας αυτής, τα οστά αδυνατίζουν και μπορεί να σπάσουν ακόμα και με ένα πολύ μικρό πέσιμο, ή ακόμα στις πιο σοβαρές περιπτώσεις, ακόμα και με ένα φτέρνισμα ή ένα χτύπημα στα έπιπλα. Η θραύση ενός οστού είναι το πρώτο σύμπτωμα της εμφάνισης της οστεοπόρωσης. Η διάγνωση της οστεοπόρωσης μπορεί να γίνει με τη συμβατική ακτινογραφία και μετρώντας την πυκνότητα των οστικών αλάτων (BMD). Η πιο διαδεδομένη μέθοδος μέτρησης του BMD είναι η DXA. Στην παρούσα μελέτη, υπολογίστηκαν δύο ποιοτικοί παράμετροι , ο λόγος ασβεστίου-φωσφόρου (Ca/P) και ο λόγος υδροξυαπατίτη- κολλαγόνου (HAp/Col). Πραγματοποιήθηκε αλγόριθμος στον οποίο έγινε χρήση διαφόρων φίλτρων έτσι ώστε να τροποποιηθούν τα φάσματα ακτίνων-Χ και να αποκτηθούν σχεδόν μονοενεργειακά φάσματα. Επιπλέον χρησιμοποιήθηκαν οι τεχνικές μονής και η διπλής έκθεσης.

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

Contrast-enhanced mammography (CEM) relies on visualizing the growth of new blood vessels (i.e. tumor angiogenesis) to provide sufficient materials for cell proliferation during the development of cancer. Since cancers will accumulate an injected contrast agent more than other tissues, it is possible to use one of several methods to enhance the area of lesions in the x-ray image and remove the contrast of normal tissue. Large area flat panel detectors may be used for CEM wherein the subtraction of two acquired images is used to create the resulting enhanced image. There exist several methods to acquire the images to be subtracted, which include temporal subtraction (pre- and post-contrast images) and dual-energy subtraction (low- and high-energy images), however these methods suffer from artifacts due to patient motion between image acquisitions. In this research the use of a multilayer flat panel detector is examined for CEM that is designed to acquire both (low- and high-energy) images simultaneously, thus avoiding motion artifacts in the resulting subtracted image. For comparison, a dual-energy technique prone to motion artifacts that uses a single-layer detector is also investigated. Both detectors are evaluated and optimized using amorphous selenium as the x-ray to charge conversion material, however the theoretical analysis could be extended to other conversion materials. Experimental results of single pixel prototypes of both multilayer and single-layer detectors are also discussed and compared to theoretical results. For a more comprehensive analysis, the motion artifacts present in dual-exposure techniques are modeled and the performance degradation due to motion artifacts is estimated. The effects of noise reduction techniques are also evaluated to determine potential image quality improvements in CEM images.

<p>A bench-top dual cone-beam computed tomography (CBCT) system was developed consisting of two orthogonally placed 40x30 cm<super>2</super> flat-panel detectors and two conventional X-ray tubes with two individual high-voltage generators sharing the same rotational axis. The X-ray source to detector distance is 150 cm and X-ray source to rotational axis distance is 100 cm for both subsystems. The objects are scanned through 200° of rotation. The dual CBCT (DCBCT) system utilized 110° of projection data from one detector and 90° from the other while the two individual single CBCTs utilized 200° data from each detector. The system performance was characterized in terms of uniformity, contrast, spatial resolution, noise power spectrum and CT number linearity. The uniformity, within the axial slice and along the longitudinal direction, and noise power spectrum were assessed by scanning a water bucket; the contrast and CT number linearity were measured using the Catphan phantom; and the spatial resolution was evaluated using a tungsten wire phantom. A skull phantom and a ham were also scanned to provide qualitative evaluation of high- and low-contrast resolution. Each measurement was compared between dual and single CBCT systems.</p><p>Compared with single CBCT, the DCBCT presented: 1) a decrease in uniformity by 1.9% in axial view and 1.1% in the longitudinal view, as averaged for four energies (80, 100, 125 and 150 kVp); 2) comparable or slightly better contrast to noise ratio (CNR) for low-contrast objects and comparable contrast for high-contrast objects; 3) comparable spatial resolution; 4) comparable CT number linearity with R<super>2</super> &#8805; 0.99 for all four tested energies; 5) lower noise power spectrum in magnitude. DCBCT images of the skull phantom and the ham demonstrated both high-contrast resolution and good soft-tissue contrast.</p><p>One of the major challenges for clinical implementation of four-dimensional (4D) CBCT is the long scan time. To investigate the 4D imaging capabilities of the DCBCT system, motion phantom studies were conducted to validate the efficiency by comparing 4D images generated from 4D-DCBCT and 4D-CBCT. First, a simple sinusoidal profile was used to confirm the scan time reduction. Next, both irregular sinusoidal and patient-derived profiles were used to investigate the advantage of temporally correlated orthogonal projections due to a reduced scan time. Normalized mutual information (NMI) between 4D-DCBCT and 4D-CBCT was used for quantitative evaluation.</p><p>For the simple sinusoidal profile, the average NMI for ten phases between two single 4D-CBCTs was 0.336, indicating the maximum NMI that can be achieved for this study. The average NMIs between 4D-DCBCT and each single 4D-CBCT were 0.331 and 0.320. For both irregular sinusoidal and patient-derived profiles, 4D-DCBCT generated phase images with less motion blurring when compared with single 4D-CBCT.</p><p>For dual kV energy imaging, we acquired 80kVp projections and 150 kVp projections, with an additional 0.8 mm tin filtration. The virtual monochromatic (VM) technique was implemented, by first decomposing these projections into acrylic and aluminum basis material projections to synthesize VM projections, which were then used to reconstruct VM CBCTs. The effect of the VM CBCT on metal artifact reduction was evaluated with an in-house titanium-BB phantom. The optimal VM energy to maximize CNR for iodine contrast and minimize beam hardening in VM CBCT was determined using a water phantom containing two iodine concentrations. The linearly-mixed (LM) technique was implemented by linearly combining the low- (80kVp) and high-energy (150kVp) CBCTs. The dose partitioning between low- and high-energy CBCTs was varied (20%, 40%, 60% and 80% for low-energy) while keeping total dose approximately equal to single-energy CBCTs, measured using an ion chamber. Noise levels and CNRs for four tissue types were investigated for dual-energy LM CBCTs in comparison with single-energy CBCTs at 80, 100, 125 and 150kVp.</p><p>The VM technique showed a substantial reduction of metal artifacts at 100 keV with a 40% reduction in the background standard deviation compared with a 125 kVp single-energy scan of equal dose. The VM energy to maximize CNR for both iodine concentrations and minimize beam hardening in the metal-free object was 50 keV and 60 keV, respectively. The difference in average noise levels measured in the phantom background was 1.2% for dual-energy LM CBCTs and equivalent-dose single-energy CBCTs. CNR values in the LM CBCTs of any dose partitioning were better than those of 150 kVp single-energy CBCTs. The average CNRs for four tissue types with 80% dose fraction at low-energy showed 9.0% and 4.1% improvement relative to 100 kVp and 125 kVp single-energy CBCTs, respectively. CNRs for low contrast objects improved as dose partitioning was more heavily weighted towards low-energy (80kVp) for LM CBCTs.</p><p>For application of the dual-energy technique in the kilovoltage (kV) and megavoltage (MV) range, we acquired both MV projections (from gantry angle of 0° to 100°) and kV projections (90° to 200°) with the current orthogonal kV/MV imaging hardware equipped in modern linear accelerators, as gantry rotated a total of 110°. A selected range of overlap projections between 90° to 100° were then decomposed into two material projections using experimentally determined parameters from orthogonally stacked aluminum and acrylic step-wedges. Given attenuation coefficients of aluminum and acrylic at a predetermined energy, one set of VM projections could be synthesized from two corresponding sets of decomposed projections. Two linear functions were generated using projection information at overlap angles to convert kV and MV projections at non-overlap angles to approximate VM projections for CBCT reconstruction. The CNRs were calculated for different inserts in VM CBCTs of a CatPhan phantom with various selected energies and compared with those in kV and MV CBCTs. The effect of overlap projection number on CNR was evaluated. Additionally, the effect of beam orientation was studied by scanning the CatPhan sandwiched with two 5 cm solid-water phantoms on both lateral sides and an electronic density phantom with two metal bolt inserts.</p><p>Proper selection of VM energy (30keV and 40keV for low-density polyethylene (LDPE), polymethylpentene (PMP), 2MeV for Delrin) provided comparable or even better CNR results as compared with kV or MV CBCT. An increased number of overlap between kV and MV projections demonstrated only marginal improvements of CNR for different inserts (with the exception of LDPE) and therefore one projection overlap was found to be sufficient for the CatPhan study. It was also evident that the optimal CBCT image quality was achieved when MV beams penetrated through the heavy attenuation direction of the object. </p><p>In conclusion, the performance of a bench-top DCBCT imaging system has been characterized and is comparable to that of a single CBCT. The 4D-DCBCT provides an efficient 4D imaging technique for motion management. The scan time is reduced by approximately a factor of two. The temporally correlated orthogonal projections improved the image blur across 4D phase images. Dual-energy CBCT imaging techniques were implemented to synthesize VM CBCT and LM CBCTs. VM CBCT was effective at achieving metal artifact reduction. Depending on the dose-partitioning scheme, LM CBCT demonstrated the potential to improve CNR for low contrast objects compared with single-energy CBCT acquired with equivalent dose. A novel technique was developed to generate VM CBCTs from kV/MV projections. This technique has the potential to improve CNR at selected VM energies and to suppress artifacts at appropriate beam orientations.</p> / Dissertation

Contrast-enhanced mammography (CEM) relies on visualizing the growth of new blood vessels (i.e. tumor angiogenesis) to provide sufficient materials for cell proliferation during the development of cancer. Since cancers will accumulate an injected contrast agent more than other tissues, it is possible to use one of several methods to enhance the area of lesions in the x-ray image and remove the contrast of normal tissue. Large area flat panel detectors may be used for CEM wherein the subtraction of two acquired images is used to create the resulting enhanced image. There exist several methods to acquire the images to be subtracted, which include temporal subtraction (pre- and post-contrast images) and dual-energy subtraction (low- and high-energy images), however these methods suffer from artifacts due to patient motion between image acquisitions. In this research the use of a multilayer flat panel detector is examined for CEM that is designed to acquire both (low- and high-energy) images simultaneously, thus avoiding motion artifacts in the resulting subtracted image. For comparison, a dual-energy technique prone to motion artifacts that uses a single-layer detector is also investigated. Both detectors are evaluated and optimized using amorphous selenium as the x-ray to charge conversion material, however the theoretical analysis could be extended to other conversion materials. Experimental results of single pixel prototypes of both multilayer and single-layer detectors are also discussed and compared to theoretical results. For a more comprehensive analysis, the motion artifacts present in dual-exposure techniques are modeled and the performance degradation due to motion artifacts is estimated. The effects of noise reduction techniques are also evaluated to determine potential image quality improvements in CEM images.

Le traitement des gliomes de haut grade constitue aujourd'hui encore un réel enjeu médical. Les techniques actuellement disponibles sont principalement palliatives et permettent d'augmenter la survie des patients de quelques mois seulement. Une technique innovante de radiothérapie consiste à renforcer la dose déposée dans la tumeur grâce à l'injection d'atomes lourds de manière spécifique dans celle-ci au préalable d'une irradiation de photons de basse énergie (50-100 keV). Cette technique a fait l'objet d'essais précliniques et maintenant d'essais cliniques de phases I et II sur la ligne médicale du synchrotron Européen dont le rayonnement monochromatique et intense est particulièrement adapté pour l'application. L'utilisation d'un agent de contraste (AC) iodé (Z=53) injecté par voie veineuse permet d'améliorer le bénéfice de la radiothérapie mais n'est cependant pas suffisante pour l'élimination complète de la tumeur. En effet, l'accumulation passive d'atomes lourds dans la tumeur n'est pas assez importante et le caractère extracellulaire d'un AC ne maximise pas l'efficacité biologique de l'irradiation. Les nanoparticules (NPs) métalliques apparaissent comme un moyen efficace pour repousser ces limites. Dans le cadre de cette thèse, des études ont été conduites sur la lignée cellulaire de gliome F98 afin de caractériser la toxicité et l'internalisation de trois types de nanoparticules différents : nanoparticules de gadolinium (GdNPs 3 nm), d'or (AuNPs 13 nm) et de platine (PtNPs 6 nm). La survie cellulaire a également été évaluée après différentes conditions d'irradiation de photons monochromatiques en présence de ces nano-objets. La dépendance de la réponse cellulaire à l'énergie du rayonnement incident ainsi qu'à la distribution subcellulaire des NPs a permis de mettre en évidence plusieurs mécanismes mis en jeu dans ce traitement. A concentration identique, les NPs diminuent la survie cellulaire de manière plus importante qu'un AC, validant ainsi l'intérêt microdosimétrique des NPs. L'effet est préférentiel à basse énergie (keV) indiquant que la photoactivation des atomes lourds est en partie responsable la réponse cellulaire. Par ailleurs, les GdNPs et les PtNPs se sont aussi montrées efficaces pour diminuer la survie cellulaire en combinaison à une irradiation à haute énergie (1.25 MeV) indiquant qu'un mécanisme de radiosensibilisation différent de la photoactivation intervient également. Les études précliniques, ont montré que le recouvrement complet de la tumeur par les NPs constitue un point clé pour garantir le bénéfice thérapeutique du traitement. Dans cette optique, une méthode de tomographie à deux énergies développée au synchrotron, a été caractérisée dans le cadre de ce travail. L'étude a permis d'imager de manière quantitative et simultanée la tumeur (mise en évidence par un AC iodé) et son recouvrement par des GdNPs (injectées par voie directe) chez le rongeur porteur d'un gliome. La correspondance entre la distribution de l'AC et la tumeur a également été étudiée à l'aide de techniques d'imagerie à haute résolution (IRM, tomographie X par contraste de phase et histologie). / Gliomas treatment is still a serious challenge in medicine. Available treatments are mainly palliative and patients' survival is increased by a few months only. An original radiotherapy technique consists in increasing the dose delivered to the tumor by loading it with high Z atoms before an irradiation with low energy X-rays (50-100 keV). Preclinical studies have been conducted using iodine contrast agent (CA) (Z=53) and 50 keV X-rays. The increase of the animals' survival leads today to the beginning of clinical trials (phases I and II) at the medical beamline of the European synchrotron, where the available monochromatic and intense photons beam is well suited for this treatment. The use of intravenously injected CA is however insufficient for curing rat's bearing glioma. Indeed, the contrast agent's accumulation is limited by the presence of the BBB and it remains extracellular. Metallic nanoparticles (NPs) appear interesting for improving the treatment efficacy. During this work, three different types of NPs have been studied: GdNPs (3 nm), AuNPs (13 nm) and PtNPs (6 nm). Their toxicity and internalization have been evaluated in vitro on F98 rodent glioma cells. Cells' survival has also been measured after different irradiation conditions in presence of these NPs and with monochromatic photons beams. Several mechanisms implicated in the treatment have been highlighted by the study of the cells' response dependence to the incident particles energy and to the sub cellular NPs distribution during irradiation. For identical concentrations, NPs were more efficient in cells killing than CA, illustrating their microdosimetric potential. The effect was also preferential for low energy X-rays, indicating that photoactivation of heavy atoms plays a role in the cells' death. GdNPs and PtNPs have also lead to an effect in combination to high energy photons (1.25 MeV), indicating that another mechanism may also increase the cell sensitivity to radiations with such NPs. Preclinical trials, performed on rats bearing F98 glioma, have shown that the complete tumor's overlap with NPs is a key point for the success of this treatment. Dual energy computed tomography (CT) has been developed at the synchrotron medical beamline and evaluated during this PhD thesis. The study has allowed quantitatively and simultaneously imaging the tumor (highlighted by iodinated CA) and the GdNPs distribution injected intracerebrally in rodents bearing glioma. The comparison between the CA distribution and the tumor's volume has also been performed using high spatial resolutions imaging methods (MRI, X-rays phase contrast tomography and histology).