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Les maladies cardio-vasculaires demeurent une cause majeure de mortalité et morbidité dans les sociétés développées. La recherche de déterminants prédictifs d’évènements vasculaires représente toujours un enjeu d’actualité face aux coûts croissants des dépenses reliées aux soins médicaux et à l’élargissement des populations concernées, notamment face à l’occidentalisation des pays émergeants comme l’Inde, le Brésil et la Chine. La cardiologie nucléaire occupe depuis trente ans, une place essentielle dans l’arsenal des méthodes diagnostiques et pronostiques des cardiopathies. De plus, de nouvelles percées permettront de dépister d’une façon plus précoce et précise, la maladie athérosclérotique cardiaque et périphérique chez les populations atteintes ainsi qu’en prévention primaire. Nous présenterons dans cette thèse, deux approches nouvelles de la cardiologie nucléaire. La dysfonction endothéliale est considérée comme le signal pathologique le plus précoce de l’athérosclérose. Les facteurs de risques cardiovasculaires traditionnels atteignent la fonction endothéliale et peuvent initier le processus d’athérosclérose même en l’absence de lésion endothéliale physique. La quantification de la fonction endothéliale coronarienne comporte donc un intérêt certain comme biomarqueur précoce de la maladie coronarienne. La pléthysmographie isotopique, méthodologie développée lors de ce cycle d’étude, permet de quantifier la fonction endothéliale périphérique, cette dernière étant corrélée à la fonction endothéliale coronarienne. Cette méthodologie est démontrée dans le premier manuscrit (Harel et. al., Physiol Meas., 2007). L’utilisation d’un radiomarquage des érythrocytes permet la mesure du flot artériel au niveau du membre supérieur pendant la réalisation d’une hyperémie réactive locale. Cette nouvelle procédure a été validée en comparaison à la pléthysmographie par jauge de contrainte sur une cohorte de 26 patients. Elle a démontré une excellente reproductibilité (coefficient de corrélation intra-classe = 0.89). De plus, la mesure du flot artérielle pendant la réaction hyperémique corrélait avec les mesure réalisées par la méthode de référence (r=0.87). Le deuxième manuscrit expose les bases de la spectroscopie infrarouge comme méthodologie de mesure du flot artériel et quantification de la réaction hyperémique (Harel et. al., Physiol Meas., 2008). Cette étude utilisa un protocole de triples mesures simultanées à l’aide de la pléthysmographie par jauge de contrainte, radio-isotopique et par spectroscopie infrarouge. La technique par spectroscopie fut démontrée précise et reproductible quant à la mesure des flots artériels au niveau de l’avant-bras. Cette nouvelle procédure a présenté des avantages indéniables quant à la diminution d’artéfact et à sa facilité d’utilisation. Le second volet de ma thèse porte sur l’analyse du synchronisme de contraction cardiaque. En effet, plus de 30% des patients recevant une thérapie de resynchronisation ne démontre pas d’amélioration clinique. De plus, ce taux de non-réponse est encore plus élevé lors de l’utilisation de critères morphologiques de réponse à la resynchronisation (réduction du volume télésystolique). Il existe donc un besoin urgent de développer une méthodologie de mesure fiable et précise de la dynamique cardiaque. Le troisième manuscrit expose les bases d’une nouvelle technique radio-isotopique permettant la quantification de la fraction d’éjection du ventricule gauche (Harel et. al. J Nucl Cardiol., 2007). L’étude portant sur 202 patients a démontré une excellente corrélation (r=0.84) avec la méthode de référence (ventriculographie planaire). La comparaison avec le logiciel QBS (Cedar-Sinai) démontrait un écart type du biais inférieur (7.44% vs 9.36%). De plus, le biais dans la mesure ne démontrait pas de corrélation avec la magnitude du paramètre pour notre méthodologie, contrairement au logiciel alterne. Le quatrième manuscrit portait sur la quantification de l’asynchronisme intra-ventriculaire gauche (Harel et. al. J Nucl Cardiol, 2008). Un nouveau paramètre tridimensionnel (CHI: contraction homogeneity index) (médiane 73.8% ; IQ 58.7% - 84.9%) permis d’intégrer les composantes d’amplitude et du synchronisme de la contraction ventriculaire. La validation de ce paramètre fut effectuée par comparaison avec la déviation standard de l’histogramme de phase (SDΦ) (médiane 28.2º ; IQ 17.5º - 46.8º) obtenu par la ventriculographie planaire lors d’une étude portant sur 235 patients. Ces quatre manuscrits, déjà publiés dans la littérature scientifique spécialisée, résument une fraction des travaux de recherche que nous avons effectués durant les trois dernières années. Ces travaux s’inscrivent dans deux axes majeurs de développement de la cardiologie du 21ième siècle. / Cardiovascular diseases remain a major cause of mortality and morbidity in developed countries. The search for predictive determinants of vascular events represents a relevant and timely goal, considering the increasing costs of medical care and the progress in developing countries such as India, Brazil and China. Nuclear cardiology has, for 30 years, played an essential role in the diagnosis and prognosis of various cardiac and vascular diseases. Moreover, new developments will allow earlier and more specific detection of cardiac and peripheral atherosclerosis disease in affected individuals and in primary prevention. In this thesis, we will focus on advances in two major themes of nuclear cardiology. Endothelial dysfunction is regarded as the earliest pathological markers of atherosclerosis. Traditional cardiovascular risks factors impair endothelial function and can initiate the atherosclerosis process, even in the absence of overt endothelial disruption. Quantification of coronary endothelial function is, therefore, of considerable interest as an early biomarker for coronary disease. The radionuclide plethysmography methodology developed during the course of my doctoral studies allows the quantification of peripheral endothelial function, which has been correlated with coronary endothelial function. This methodology is detailed in the first manuscript (Harel et. al., Physiol Meas., 2007). The use of red blood cell radio-labeling permits arterial flow to be measured in the upper limb during local reactive hyperemia. This new procedure was validated against strain gauge plethysmography in a cohort of 26 patients with excellent reproducibility (intraclass coefficient of correlation = 0.89). Moreover, the arterial measurements of flow during the hyperemic reaction correlated well with the reference method (r=0.87). The second manuscript exposes the basis of infrared spectroscopy as a method for measuring arterial flow and quantifying the hyperemic reaction (Harel et. al., Physiol Meas., 2008). The study protocol consisted of simultaneous measurements by strain gauge, radionuclide and infrared spectroscopy plethysmography. The spectroscopy technique was shown to be precise and reproducible for forearm measurement of arterial blood flow. This novel procedure came major advantages in reducing artifacts and in its ease of use. The second axis of my thesis relates to the analysis of cardiac contraction synchrony. Indeed, more than 30% of patients receiving resynchronization therapy do not show clinical improvement. Moreover, this non-response rate is even higher if we consider morphological criteria of resynchronization (end-systolic volume reduction). There is therefore, an urgent need to improve a methodology to reliably and precisely measure cardiac dynamics so as to identify and monitor potential responders. The third manuscript exposes the basis of a new radionuclide technique to quantify left ventricle ejection fraction (Harel et. al. J Nucl Cardiol., 2007). The study of 202 patients showed an excellent correlation (r=0.84) with the reference method (planar ventriculography). The comparison with QBS software (Cedar-Sinai), showed a lower standard deviation of bias (7.44% vs 9.36%). Moreover, unlike the alternative software, the bias did not correlate with the magnitude of the ejection fraction. The fourth manuscript relates to the quantification of the left intra-ventricular synchronism (Harel et. al. J Nucl Cardiol, 2008). A new three-dimensional parameter (CHI: contraction homogeneity index) (median 73.8%; IQ 58.7% - 84.9%) was defined to allow the integration of amplitude and synchrony components of ventricular contraction. Validation of this parameter was undertaken out by comparing the standard deviation of the histogram of phase (SDΦ) (median 28.2º; IQ 17.5º- 46.8º) obtained by planar ventriculography in a study of 235 patients. These four manuscripts, already published in the specialized scientific literature, summarize a fraction of the research tasks that we have carried out during the three last years, representing two major axes of nuclear cardiology advancement in the 21st century.

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Cognitive Impairment in Mild Traumatic Brain Injury| A Diffusional Kurtosis and Perfusion Imaging Study

<p>In magnetic resonance microscopy, insufficient signal-to-noise ratio currently limits imaging performance. Superconducting probes can potentially increase the sensitivity of the magnetic resonance experiment. However, many superconducting probes failed to entirely deliver the expected increase in signal-to-noise ratio. </p><p>We present a method based on finite-element radiofrequency simulations. The radiofrequency model computes several figures of merit of a probe, namely: i) the resonant frequency, ii) the impedance, iii) the magnetic field homogeneity, iv) the filling factor, and v) the sensitivity. The probe is constituted by several components. The method calculates the electromagnetic losses induced by every component within the probe, and identifies the component limiting the sensitivity of the probe. Subsequently, the probe design can be improved iteratively.</p><p>We show that the sensitivity of an existing superconducting Helmholtz pair can be improved by increasing the filling factor of the probe and cooling the radiofrequency shield, which was implemented in the design of a new superconducting probe. The second probe exhibits a sensitivity three times as high, leading to improved imaging performance.</p> / Dissertation

<p>Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the United States. Early detection of PCa is essential for improving treatment outcomes and survival rates. However, diagnosis of PCa at an early stage is challenged by the lack of an imaging method that can accurately visualize PCas. Because pathological processes change the mechanical properties of the tissue, elasticity imaging methods have the potential to differentiate PCas from other prostatic tissues. Acoustic radiation force impulse (ARFI) imaging is a relatively new elasticity imaging method that visualizes the local stiffness variations inside soft tissue.</p><p>The work presented in this dissertation investigates the feasibility of prostate ARFI imaging. Volumetric ARFI data acquisition and display methods were developed to visualize anatomic structures and pathologies in <italic>ex vivo </italic>human prostates. The characteristic appearances of various prostatic tissues in ARFI images were identified by correlating ARFI images with McNeal's zonal anatomy and the correlated histological slides, in which prostatic pathologies were delineated by a pathologist blinded to the ARFI images. The results suggest ARFI imaging is able to differentiate anatomic structures and identify suspicious PCa regions in the prostate.</p><p>To investigate the correlation between ARFI displacement amplitudes and the underlying tissue stiffness in the prostate ARFI images, the mechanical properties of prostatic tissues were characterized using a quantitative method, based upon shear wave elasticity imaging (SWEI). Co-registered ARFI and SWEI datasets were acquired in excised prostate specimens to reconstruct the shear moduli of prostatic tissues. The results demonstrated that variations in ARFI displacement amplitudes were inversely related to the underlying tissue stiffness; and the reconstructed shear moduli of prostatic tissues had good agreements with those reported in literature. The study suggests the matched ARFI and SWEI datasets provide complementary</p><p> information about tissue's elasticity. </p><p>To increase the efficiency of the data acquisition, a novel imaging sequence was developed to acquired matched ARFI-SWEI datasets without increasing the number of excitations compared to a conventional ARFI imaging sequence. Imaging parameters were analyzed both theoretically and experimentally. An analytical model was derived to quantify the fundamental accuracy limit in the reconstructed shear modulus, and demonstrated good agreement with the experimental data. The novel sequence was demonstrated in tissue-mimicking phantoms.</p><p>Finally, ARFI imaging sequences were developed in a transrectal probe, and ARFI images were presented from <italic>in vivo</italic> data acquired in patients under radical prostatectomy. The <italic>in vivo</italic> ARFI images demonstrated decreased contrast and resolution as compared to the matched <italic>ex vivo</italic> ARFI data. However, prostate anatomy and some PCa were successfully visualized in the <italic>in vivo</italic> ARFI images. Thus, we conclude that ARFI imaging has the potential to provide image guidance for locating cancerous regions during PCa diagnosis and treatment.</p> / Dissertation

<p>This thesis research builds upon prior work that developed separate SPECT and CT (computed mammotomography, or breast CT) devices that were independently capable of imaging an uncompressed breast in 3D space. To further develop the system as a clinically viable device, it was necessary to integrate the separate imaging systems onto a single gantry, and to simultaneously design a patient-friendly bed that could routinely and effectively position the patient during dual-modality imaging of her uncompressed breast in the system's common field of view. This thesis describes this process and also investigates practical challenges associated with dedicated breast imaging of a prone patient using the integrated SPECT-CT device.</p> <p>We initially characterized the practicability of implementing the novel x-ray beam ultra-thick K-edge filtration scheme designed for routine use with the breast CT system. Extensive computer simulations and physical measurements were performed to characterize the x-ray beam produced using K-edge filtration with cerium and to compare it to beams produced using other filtration methods and materials. The advantages of using this heavily filtered x-ray beam for uncompressed breast CT imaging were then further evaluated by measuring the dose absorbed by an uncompressed cadaver breast during the course of a routine tomographic scan. It was found that the breast CT device is indeed capable of imaging uncompressed breasts at dose levels below that of the maximum utilized for dual-view screening mammography.</p> <p>To prepare the separate SPECT and CT systems for integration onto a single platform, the cross contamination of the image of one modality by primary and scattered photons of the complementary modality was quantified. It was found that contamination levels of the emission (SPECT) image by the x-ray transmission source were generally far less than 2% when using photopeak energy windows up to ±8%. In addition, while there was some quantifiable evidence of a variation in the transmission image in response to the presence of <super>99m</super>Tc photons in the patient, the effect of primary and scattered <super>99m</super>Tc photons on the visibility of 5 mm acrylic photons in a low contrast x-ray transmission environment was negligible. </p> <p>A novel, tiered, stainless steel patient bed was then designed to allow dual-modality imaging using the integrated SPECT-CT system. The performance of the hybrid SPECT-CT system was evaluated during early stage dual-modality patient imaging trials with particular emphasis placed on the performance of the patient bed. The bed was successful in its primary task of enabling dual-modality imaging of a patient's breast in the common field of view, but practical challenges to more effective patient imaging were identified as well as some novel solutions to these challenges.</p> <p>In the final section of the thesis research, the feasibility of using two of these solutions was investigated with a view to imaging more of the patient's posterior breast volume. Limited angle tomographic trajectories and trajectories that involve raising or lowering the patient bed in mid tomographic acquisition were initially investigated using various geometric phantoms. A very low contrast imaging task was then tested using an observer study to quantify the effect of these trajectories on the ability of observers to maintain visibility of small geometric objects. </p> <p>This initial integrated SPECT-CT imaging system has demonstrated its ability to successfully perform low dose, dual-modality imaging of the uncompressed breast. Challenges and solutions have been identified here that will make future SPECT-CT designs even more powerful and a clinically relevant technique for molecular imaging of the breast.</p> / Dissertation

<p>Cone beam computed tomography (CBCT) is a 3D x-ray imaging technique in which the x-ray beam is transmitted to an object with wide beam geometry producing a 2D image per projection. Due to its faster image acquisition time, wide coverage length per scan, and fewer motion artifacts, the CBCT system is rapidly replacing the conventional CT system and becoming popular in diagnostic and therapeutic radiology. However, there are few studies performed in CBCT dosimetry because of the absence of a standard dosimetric protocol for CBCT. Computed tomography dose index (CTDI), a standardized metric in conventional CT dosimetry, or direct organ dose measurements have been limitedly used in the CBCT dosimetry.</p> <p>This dissertation investigated the CBCT dosimetry from the CTDI method to the organ, effective dose, risk estimations with physical measurements and Monte Carlo (MC) simulations.</p> <p>An On-Board Imager (OBI, Varian Medical Systems, Palo Alto, CA) was used to perform old and new CBCT scan protocols. The new CBCT protocols introduced both partial and full angle scan modes while the old CBCT protocols only used the full angle mode. A metal-oxide-semiconductor-field-effect transistor (MOSFET) and an ion chamber were employed to measure the cone beam CTDI (CTDI_CB) in CT phantoms and organ dose in a 5-year-old pediatric anthropomorphic phantom. Radiochromic film was also employed to measure the axial dose profiles. A point dose method was used in the CTDI estimation.</p> <p>The BEAMnrc/EGSnrc MC system was used to simulate the CBCT scans; the MC model of the OBI x-ray tube was built into the system and validated by measurements characterizing the cone beam quality in the aspects of the x-ray spectrum, half value layer (HVL) and dose profiles for both full-fan and half-fan modes. Using the validated MC model, CTDI_CB, dose profile integral (DPI), cone beam dose length product (DLP_CB), and organ doses were calculated with voxelized MC CT phantoms or anthropomorphic phantoms. Effective dose and radiation risks were estimated from the organ dose results.</p> <p>The CTDI_CB of the old protocols were found to be 84 and 45 mGy for standard dose, head and body protocols. The CTDI_CB of the new protocols were found to be 6.0, 3.2, 29.0, 25.4, 23.8, and 7.7 mGy for the standard dose head, low dose head, high quality head, pelvis, pelvis spotlight, and low dose thorax protocols respectively. The new scan protocols were found to be advantageous in reducing the patient dose while offering acceptable image quality.</p> <p>The mean effective dose (ED) was found to be 37.8 ±0.7 mSv for the standard head and 8.1±0.2 mSv for the low dose head protocols (old) in the 5-year-old phantom. The lifetime attributable risk (LAR) of cancer incidence ranged from 23 to 144 cases per 100,000 exposed persons for the standard-dose mode and from five to 31 cases per 100,000 exposed persons for the low-dose mode. The relative risk (RR) of cancer incidence ranged from 1.003 to 1.054 for the standard-dose mode and from 1.001 to 1.012 for the low-dose mode.</p> <p>The MC method successfully estimated the CTDI_CB, organ and effective dose despite the heavy calculation time. The point dose method was found to be capable of estimating the CBCT dose with reasonable accuracy in the clinical environment.</p> / Dissertation