Background: Parameters of carotid atherosclerosis dynamic contrast-enhanced MRI (DCE-MRI) are associated with stroke risk indices, but studies have only evaluated symptomatic arteries. I hypothesized that DCE-MRI parameters are different between carotid atherosclerotic plaques at high and low risk for precipitating ischemic stroke. Methods: High and low risk carotid plaques undergoing nonmodel-based DCE-MRI (n=18) were compared using two independent schema: 1) clinical standard (high risk defined as ipsilateral stroke/TIA <1 week old or stenosis >70%); 2) MRI standard (high risk defined as presence of intraplaque hemorrhage [IPH]). Results: IPH-positive plaques (n=9) exhibited greater area under the curve, early and late enhancement rate, and peak enhancement than IPH-negative plaques (n=9) (p<0.05 for all). High (n=8) and low (n=7) risk plaques defined by clinical criteria were not differentiated by any DCE-MRI parameters. Conclusions: Nonmodel-based DCE-MRI discriminates high versus low risk carotid plaque based on the presence of IPH, but not by clinical criteria.

Purpose: To compare hemodynamic of malignant and benign SRMs on CT and CEUS. Method: Seventy biopsy proven SRM underwent CEUS. Sixty-three had CT. After injection of 0.2 ml of Definity, 3min and after 0.9 ml infusion, 30 sec of data were acquires. Lesion hemodynamics relative to the cortex was evaluated both qualitatively and quantitatively. Results: Considering 15 and 20 HU as enhancement threshold, 10% to 13% of patients did not enhance on CT, while all lesions enhanced on CEUS. Papillary RCCs showed hypovascularity with 100% specificity. In other RCCs, PI, WI slope 5 to45%, 50 to100%, 10 to 90%, WO slope 100 to 50%, 100 to 10%, WO intensity at peak+30 seconds were statistically higher than benign SRMs. Conclusion: All solid SRMs enhance on CEUS, while CT does not show vascularity in 10-13% of solid SRMs. CEUS can differentiate malignant from benign SRMs by evaluating their hemodynamics.

Cerebral autoregulation is an intrinsic physiological response that maintains a constant cerebral blood flow (CBF) despite dynamic changes in the systemic blood pressure. Autoregulation is achieved through changes in the resistance of the small blood vessels in the brain through reflexive vasodilatation and vasoconstriction. Cerebrovascular reactivity (CVR) is a measure of this response. CVR is defined as a change in CBF in response to a given vasodilatory stimulus. CVR therefore potentially reflects the vasodilatory reserve capacity of the cerebral vasculature to maintain a constant cerebral blood flow. A decrease in CVR (which is interpreted as a reduction in the vasodilatory reserve capacity) in the vascular territory downstream of a larger stenosed supply artery correlates strongly with the risk of a hemodynamic stroke. As a result, the use of CVR studies to evaluate the state of the cerebral autoregulatory capacity has clinical utility. Application of CVR studies in the clinical scenario depends on a thorough understanding of the normal response. The goal of this thesis therefore was to map CVR throughout the brain in normal healthy individuals using Blood Oxygen Level Dependant functional Magnetic Resonance Imaging (BOLD MRI) as an index to CBF and precisely controlled changes in end-tidal partial pressure of carbon dioxide (PETCO2) as the global flow stimulus.

Cerebral autoregulation is an intrinsic physiological response that maintains a constant cerebral blood flow (CBF) despite dynamic changes in the systemic blood pressure. Autoregulation is achieved through changes in the resistance of the small blood vessels in the brain through reflexive vasodilatation and vasoconstriction. Cerebrovascular reactivity (CVR) is a measure of this response. CVR is defined as a change in CBF in response to a given vasodilatory stimulus. CVR therefore potentially reflects the vasodilatory reserve capacity of the cerebral vasculature to maintain a constant cerebral blood flow. A decrease in CVR (which is interpreted as a reduction in the vasodilatory reserve capacity) in the vascular territory downstream of a larger stenosed supply artery correlates strongly with the risk of a hemodynamic stroke. As a result, the use of CVR studies to evaluate the state of the cerebral autoregulatory capacity has clinical utility. Application of CVR studies in the clinical scenario depends on a thorough understanding of the normal response. The goal of this thesis therefore was to map CVR throughout the brain in normal healthy individuals using Blood Oxygen Level Dependant functional Magnetic Resonance Imaging (BOLD MRI) as an index to CBF and precisely controlled changes in end-tidal partial pressure of carbon dioxide (PETCO2) as the global flow stimulus.

Therapeutic response assessment is a key component in adaptive image-guided radiotherapy. Conventional anatomic measures of response offer little information about the spatial distribution of tumor change. Recently developed voxel-wise response assessment methods operating on functional and biological imaging are better capable of evaluating the heterogeneity of response within the tumor, and thus may yield greater sensitivity than conventional approaches. However, voxel-wise analyses are limited by local registration uncertainties inherent to longitudinal imaging of tumors with changing morphology. A multi-resolution local histogram (LH) moment-based measure of voxel similarity was developed for the purpose of assessing the strength of correspondence between voxels of serial tumor images. This measure was first benchmarked through a series of experiments designed to establish robustness to image intensity variation and sensitivity to alterations in tissue structure through application of simulated deformations. The LH similarity method was subsequently developed as a means of mapping the spatial extent of structural change in tumors through the incorporation of an estimate of image complexity. The change maps were applied to a voxel-wise analysis of diffusion-weighted magnetic resonance imaging of patients with glioblastoma, acquired pre- and post-chemoradiotherapy. The sensitivity of the voxel-wise analysis in differentiating responding/stable patients from non-responding/progressing patients was improved by stratifying the analysis voxels according to regions of interest (ROI) based on the LH similarity-based estimate of tumor change. Meaningful correspondence relationships between evaluated voxels are essential for accurate image-based quantification of tumor structure and function with voxel-wise analysis techniques. The LH similarity methods developed here can robustly evaluate the quality of spatial and temporal voxel correspondence relationships and provide an automated tool for ROI selection and voxel change stratification. It is readily extendable to the analysis of the wide array of anatomic, functional and biological imaging currently used to characterize tumors, guide therapy and assess response.

Therapeutic response assessment is a key component in adaptive image-guided radiotherapy. Conventional anatomic measures of response offer little information about the spatial distribution of tumor change. Recently developed voxel-wise response assessment methods operating on functional and biological imaging are better capable of evaluating the heterogeneity of response within the tumor, and thus may yield greater sensitivity than conventional approaches. However, voxel-wise analyses are limited by local registration uncertainties inherent to longitudinal imaging of tumors with changing morphology. A multi-resolution local histogram (LH) moment-based measure of voxel similarity was developed for the purpose of assessing the strength of correspondence between voxels of serial tumor images. This measure was first benchmarked through a series of experiments designed to establish robustness to image intensity variation and sensitivity to alterations in tissue structure through application of simulated deformations. The LH similarity method was subsequently developed as a means of mapping the spatial extent of structural change in tumors through the incorporation of an estimate of image complexity. The change maps were applied to a voxel-wise analysis of diffusion-weighted magnetic resonance imaging of patients with glioblastoma, acquired pre- and post-chemoradiotherapy. The sensitivity of the voxel-wise analysis in differentiating responding/stable patients from non-responding/progressing patients was improved by stratifying the analysis voxels according to regions of interest (ROI) based on the LH similarity-based estimate of tumor change. Meaningful correspondence relationships between evaluated voxels are essential for accurate image-based quantification of tumor structure and function with voxel-wise analysis techniques. The LH similarity methods developed here can robustly evaluate the quality of spatial and temporal voxel correspondence relationships and provide an automated tool for ROI selection and voxel change stratification. It is readily extendable to the analysis of the wide array of anatomic, functional and biological imaging currently used to characterize tumors, guide therapy and assess response.

Historique et Objectif : La littérature est conflictuelle sur le rôle des calcifications aortiques dans la rupture d’anévrisme de l’aorte abdominale (AAA). La prédiction de rupture d’AAA basée sur le sexe et le diamètre est peu précise. Le but de ce projet était donc de déterminer si les calcifications permettent de mieux prédire la rupture d’AAA que le sexe et le diamètre à eux seuls. Méthodologie : Lors de cette étude rétrospective, 80 patients traités pour rupture d’AAA entre Janvier 2001 et Août 2018 ont été appariés à 80 patients non-rompus sur la base du diamètre maximal d’AAA, de l’âge, du sexe et de la présence de contraste lors du scan. La charge et la répartition des calcifications de la paroi aortique ainsi que certaines variables morphologiques d’anévrisme ont été comparées entre les deux groupes par analyse univariée et apprentissage machine. Résultats : L’âge moyen des patients était de 74.0 ± 8.4 ans et 89% étaient des hommes. Les diamètres d’AAA étaient équivalents entre groupes (80.9 ± 17.5 vs 79.0 ± 17.3 mm, p= 0.505). Selon l’analyse univariée, les anévrismes rompus comportaient significativement moins d’agrégats de calcifications (18.0 ± 17.9 vs 25.6 ± 18.9, p=0.010) et étaient moins enclins à avoir un collet (45.0% vs 76.3%, p<0.0001). Les 5 variables les plus importantes délivrées par l’apprentissage machine étaient: collet, antiplaquettaires, nombre de calcifications, distance d’Euler entre calcifications et finalement l’écart-type de la distance d’Euler entre calcifications. Le modèle à 5 variables a produit une aire sous la courbe (AUC) de 0.81 ± 0.02 (sensibilité 83% et spécificité 71%), supérieure à une AUC de 0.67(IC 95%, 0.58-0.77%) (sensibilité 60% et spécificité 77%) obtenues dans une étude antérieure avec une population similaire à celle-ci et ne tenant compte que du sexe et du diamètre. Conclusion : La charge en calcifications des anévrismes rompus était moins bien répartie que celle des non-rompus. Le modèle d’apprentissage machine a mieux prédit la rupture que le modèle basé uniquement sur le diamètre et le sexe. / Background and Purpose: Literature is conflictual regarding the role of aortic calcification in AAA rupture. AAA rupture prediction based on sex and diameter could be improved. The goal of this project was to assess whether aortic calcification could better predict AAA rupture. Methods: In this retrospective study, 80 patients treated for a ruptured AAA between January 2001 and August 2018 were matched with 80 non-ruptured patients based on maximal AAA diameter, age, sex and contrast enhancement status of the CT scan. Calcification load and dispersion, morphologic and clinical variables were compared between both groups using a univariable analysis and machine learning. Results: Mean age of patients was 74.0 ± 8.4 years and 89% were men. AAA diameters were equivalent in both groups (80.9 ± 17.5 vs 79.0 ± 17.3 mm, p= 0.505). Ruptured aneurysms contained a smaller number of calcification chunks than the non-ruptured (18.0 ± 17.9 vs 25.6 ± 18.9, p=0.010) and were less likely to have a proximal neck than the non-ruptured (45.0% vs 76.3%, p<0.0001). In the machine learning analysis, 5 variables were associated to AAA rupture: proximal neck, antiplatelets, calcification number, Euler distance between calcifications and standard deviation of the Euler distance between calcifications. The model including these 5 variables yielded an area under the curve (AUC) of 0.81 ± 0.02 (83% sensitivity and 71% specificity) which was better than a previous study with a similar population reporting a 0.67 AUC (95% CI, 0.58-0.77%) (60% sensitivity and 77% specificity) for sex and diameter only. Conclusion: Ruptured aneurysms were more likely to have their calcification load concentrated in a small number of clusters closer to each other. Our 5-variable model predicted rupture better than the model based on age and sex.

Aim: This study aims to assess the association of biomechanical characteristics of carotid walls and carotid intima-media thickness (IMT), as assessed by ultrasound, when incorporated into prediction models for coronary CT plaque burden in both people living with HIV (PLWH) and HIV-negative control individuals. Methods: In this cross-sectional study, 164 participants (mean age 57 years ± 8 years; 134 males) with low to intermediate cardiovascular risk were recruited from the ongoing prospective Canadian HIV and Aging Cohort Study (CHACS). Among the 164 recruited participants, a total of 154 individuals (mean age, 56.5 years ± 7.55 years; 83 PLWH, 54%; 137 males; 88%) were evaluated. Ten participants were excluded due to unavailable coronary plaque data. The mean time interval between coronary CT and carotid ultrasound per participant was 7.69 ± 20.1 months. Using ultrasound, cumulated axial strain, cumulated shear strain, cumulated axial translation, cumulated lateral translation, and IMT of the common and internal carotid arteries were measured. Participants also underwent cardiac CT for coronary plaque assessment. Univariate and multivariate Poisson regression analyses with robust variance were performed to identify independent associations of cardiovascular risk factors, IMT, and elastography parameters with coronary plaque presence. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to compare different prediction models for coronary plaque presence. Results: The study included 83 PLWH and 71 controls (N=154). The median 10-year Framingham risk score was 12% [IQR, 8 - 16] in PLWH and 9% [IQR, 7 - 15] in controls (p = 0.045). In the PLWH group, coronary plaques were observed in 55 participants (61.1%) compared to 42 (56.8%) in the non-HIV control group (p = .46). Carotid IMT and all elastography features for both the internal and common carotid arteries were similar between PLWH and healthy volunteers. 4 After adjusting for cardiovascular risk using multivariate Poisson regression, smoking exposure was significantly associated with coronary plaque presence on CT (prevalence ratio 1.10, 95% CI 1.04 – 1.13, p < 0.001). No significant associations were found with other coronary artery disease risk factors or HIV status in multivariate analysis. Carotid elastography parameters and carotid intima-media thickness were not associated with coronary atherosclerosis after adjustment. AUC analyses did not reveal any significant differences in predictive accuracy between models when adding either elastography parameters, IMT, or both elastography parameters and IMT results to the cardiovascular risk factor model, with AUC ranging from 0.647 to 0.681 in all models. Conclusion: In our study, models incorporating carotid elastography and IMT did not enhance the prediction of coronary plaque presence in PLWH or controls, compared to models including only traditional cardiovascular risk factors. Key words: HIV, computed tomography, angiography, us elastography, atherosclerosis / Objectif: Évaluer l’association des caractéristiques biomécaniques des parois carotidiennes et de l'épaisseur intima-média (EIM) « Intima-media Thickness » (IMT) carotidienne, telles qu'évaluées par échographie, lorsque celles-ci sont incluses dans les modèles de prédiction de la charge de plaque coronarienne évaluée par tomodensitométrie (CT) chez les personnes vivant avec le VIH (PVVIH) et les personnes contrôles séronégatives. Méthodes : Dans notre étude transversale, 164 participants (âge moyen 57 ans ± 8 ans ; 134 hommes) présentant un risque cardiovasculaire faible/intermédiaire ont été recrutés, provenant tous de l’étude prospective Cohorte canadienne VIH et vieillissement (CHACS, Canadian HIV an Aging Cohort Study). Parmi les 164 participants recrutés, un total de 154 participants (âge moyen, 56.5 ans ±7.55 ans; 83 PPLWH, 54 %; 137 hommes; 88%) ont été évalués. Dix participants ont été exclus en raison de données de plaques non disponibles. L’intervalle de temps moyen entre le CT et l’élastographie carotidienne était de 7.7 ± 20.1 mois Avec l’imagerie par ultrasons, nous avons mesuré la déformation axiale cumulée, la déformation de cisaillement cumulée, la translation axiale cumulée, la translation latérale cumulée et l'IMT des artères carotides commune et interne. Les participants ont également subi une tomodensitométrie cardiaque pour l'évaluation de la plaque coronarienne. Des analyses de régression de Poisson univariées et multivariées avec une variance robuste ont été réalisées pour identifier comment les facteurs de risque cardiovasculaire, les paramètres IMT et élastographie sont indépendamment associés à la présence de plaque coronarienne. La fonction d’efficacité du récepteur (« caractéristique de fonctionnement du récepteur ») (ROC, receiver operating characteristic) et l'analyse de l'aire sous la courbe (AUC, area under the curve) ont également été utilisées pour comparer différents modèles de prédiction de la présence de plaque coronarienne. Résultats: Il y avait 83 PVVIH et 71 contrôles (N=154). Le score médian de risque de Framingham sur 10 ans était de 12% [IQR, 8 - 16] chez les PLWH and de 9% [IQR,7 -15] chez les témoins (p = 0.045). Dans le groupe PVVIH, des plaques coronaires étaient présentes chez 55 participants (61,1 %) contre 42 (56,8 %) dans le groupe contrôle non VIH (p = 0,46). 2 Après ajustement pour les facteurs de risque cardiovasculaire, on note que le tabagisme est associé à la présence de plaque coronarienne (ratio de prévalence 1.10, 95% CI 1.04 – 1.13, p < 0.001). Aucune autre association significative n’a été démontré avec d’autres facteurs de risque cardiovasculaire, ou avec le statut VIH, dans les analyses multivariées. L’analyse multivariée démontre que l'ajout des données d’IMT ou d’élastographie n'augmente pas la précision des modèles, au-delà du modèle n’incluant que les facteurs de risque traditionnels. Les analyses des courbes ROC et AUC n'ont montré aucune différence significative dans la précision prédictive entre les modèles qui incluent les paramètres d'élastographie, d'IMT et les facteurs de risque cardiovasculaire, versus les modèles qui n’incluent que les facteurs de risque cardiovasculaire, avec des AUC allant de 0,65 à 0,68. Conclusion: Dans notre étude, les modèles incluant l'élastographie carotidienne et l'IMT n'ont pas montré d’augmentation de la prédiction de la présence de plaque coronarienne chez les PVVIH ou les contrôles, en comparaison aux modèles incluant uniquement les facteurs de risque traditionnels.

Patients with MDD demonstrate impairments in various components of affective processing, which are believed to persist in the remitted phase of the illness and are believed to underlie the vulnerability for future relapse. Despite advances in neuropsychiatry, the neuroanatomical site of action of various treatment modalities remains unclear, leaving clinicians without an algorithm to guide optimal treatment selection for individual patients. This thesis sought to characterize differences in brain activation during affective processing between MDD treatment responders (RS) and non-responders (NR) by combining clinical and neuroimaging variables in a repeat-measure functional magnetic resonance imaging (fMRI) investigation. We induced increases in positive and negative affect using visual stimuli under fMRI conditions in 21 MDD subjects and 18 healthy controls (HC). Based on previous neuroimaging investigations and preclinical animal data, we hypothesized that increased activation of the amygdala and the pregenual cingulate during negative affect induction (NAI), and decreased activity of the ventral striatum during positive affect induction (PAI), would differentiate ultimate NR from RS. Following the first scan, treatment with fluoxetine and olanzapine was initiated in the MDD group, with follow-up scans at one- and six-weeks thereafter. We hypothesized that decreases in depressive symptoms would be associated with decreased activation of the ventromedial prefrontal cortex (PFC) and amygdala during NAI and increased activation of the hippocampus during PAI. Eleven MDD subjects met criteria for clinical remission at study endpoint. Based on trait differences between MDD and HC, we hypothesized that differences observed during NAI would be limited to brain regions involved in regulation of the affective state, including the dorsolateral PFC and the anterior midcingulate cortex. The results of the analyses confirmed the a-prior hypotheses and additionally demonstrated differential activation of the insular, medial temporal, and premotor cortex during repeat PAI and NAI between HC, RS, and NR. These findings provide: i) a neuroanatomical target of successful antidepressant therapy during PAI/NAI; ii) a differential effect of depressive symptoms and dispositional affect on brain activation during PAI/NAI; and iii) an a-prior method to differentiate RS from NR, and iv) demonstrate the need for additional treatment to prevent relapse in the remitted state.

L'un des principaux défis de l'interprétation radiographique réside dans la compréhension de l’anatomie radiographique, laquelle est intrinsèquement liée à la disposition tridimensionnelle des structures anatomiques et à l’impact du positionnement du tube radiogène vis-à-vis de ces structures lors de l'acquisition de l'image. Traditionnellement, des radiographies obtenues selon des projections standard sont employées pour enseigner l'anatomie radiographique en médecine vétérinaire. La tomodensitométrie − ou communément appelée CT (Computed Tomography) − partage plusieurs des caractéristiques de la radiographie en ce qui a trait à la génération des images. À l’aide d'un plug-in spécialement développé (ORS Visual ©), la matrice contenant les images CT est déformée pour reproduire les effets géométriques propres au positionnement du tube et du détecteur vis-à-vis du patient radiographié, tout particulièrement les effets de magnification et de distorsion. Afin d'évaluer le rendu des images simulées, différentes régions corporelles ont été imagées au CT chez deux chiens, un chat et un cheval, avant d'être radiographiées suivant des protocoles d'examens standards. Pour valider le potentiel éducatif des simulations, dix radiologistes certifiés ont comparé à l'aveugle neuf séries d'images radiographiques simulées aux séries radiographiques standard. Plusieurs critères ont été évalués, soient le grade de visualisation des marqueurs anatomiques, le réalisme et la qualité radiographique des images, le positionnement du patient et le potentiel éducatif de celles-ci pour différents niveaux de formation vétérinaire. Les résultats généraux indiquent que les images radiographiques simulées à partir de ce modèle sont suffisamment représentatives de la réalité pour être employées dans l’enseignement de l’anatomie radiographique en médecine vétérinaire. / Understanding radiographic anatomy, which is intimately linked to the comprehension of tridimensional anatomy and the impact of patient, radiographic tube and x-ray detector positioning, represents a challenge for students. Traditionally, radiographs obtained under specific angles of projection have been used for teaching radiographic anatomy. Computed tomography (CT) shares several features with radiography with regard to image production. A plug-in was developed for a DICOM viewer (ORS visual ©) simulating radiographs using CT datasets. This plug-in distorts the CT image matrix to reproduce the magnification and distortion effects that take place in radiographs due to the variations in radiographic tube, patient and detector positioning and angulation. In order to test this model, specific body parts of two dogs, one cat and one horse were radiographed and CT-scanned. The CT datasets were used to generate a total of nine series of radiographic simulations that could be compared to corresponding standard radiographic projections. Ten board-certified veterinary radiologists blindly scored several parameters in these image series, including the visualization of specific anatomical landmarks, image realism and quality, patient positioning, and the educational potential for students and veterinarians of variable degree of veterinary training Overall results indicate that simulated radiographs are representative enough to be used to teach several concepts of image formation and radiographic anatomy in veterinary radiology.