Résumé : En imagerie médicale, il est courant d’associer plusieurs modalités afin de tirer profit des renseignements complémentaires qu’elles fournissent. Par exemple, la tomographie d’émission par positrons (TEP) peut être combinée à l’imagerie par résonance magnétique (IRM) pour obtenir à la fois des renseignements sur les processus biologiques et sur l’anatomie du sujet. Le but de ce projet est d’explorer les synergies entre l’IRM et la TEP dans le cadre d’analyses pharmacocinétiques. Plus spécifiquement, d’exploiter la haute résolution spatiale et les renseignements sur la perfusion et la perméabilité vasculaire fournis par l’IRM dynamique avec agent de contraste afin de mieux évaluer ces mêmes paramètres pour un radiotraceur TEP injecté peu de temps après. L’évaluation précise des paramètres de perfusion du radiotraceur devrait permettre de mieux quantifier le métabolisme et de distinguer l’accumulation spécifique et non spécifique. Les travaux ont porté sur deux radiotraceurs de TEP (18F-fluorodésoxyglucose [FDG] et 18F-fluoroéthyle-tyrosine [FET]) ainsi que sur un agent de contraste d’IRM (acide gadopentétique [Gd DTPA]) dans un modèle de glioblastome chez le rat. Les images ont été acquises séquentiellement, en IRM, puis en TEP, et des prélèvements sanguins ont été effectués afin d’obtenir une fonction d’entrée artérielle (AIF) pour chaque molécule. Par la suite, les images obtenues avec chaque modalité ont été recalées et l’analyse pharmacocinétique a été effectuée par régions d’intérêt (ROI) et par voxel. Pour le FDG, un modèle irréversible à 3 compartiments (2 tissus) a été utilisé conformément à la littérature. Pour la FET, il a été déterminé qu’un modèle irréversible à 2 tissus pouvait être appliqué au cerveau et à la tumeur, alors qu’un modèle réversible à 2 tissus convenait aux muscles. La possibilité d’effectuer une conversion d’AIF (sanguine ou dérivée de l’image) entre le Gd DTPA et la FET, ou vice versa, a aussi été étudiée et s’est avérée faisable dans le cas des AIF sanguines obtenues à partir de l’artère caudale, comme c’est le cas pour le FDG. Finalement, l’analyse pharmacocinétique combinée IRM et TEP a relevé un lien entre la perfusion du Gd-DTPA et du FDG, ou de la FET, pour les muscles, mais elle a démontré des disparités importantes dans la tumeur. Ces résultats soulignent la complexité du microenvironnement tumoral (p. ex. coexistence de divers modes de transport pour une même molécule) et les nombreux défis rencontrées lors de sa caractérisation chez le petit animal. / Abstract : In medical imaging, different modalities are frequently combined in order to obtain complementary information. For example, positron emission tomography (PET) can be associated with magnetic resonance imaging (MRI) to derive both anatomical and biological information. This project explores the synergies between MRI and PET for pharmacokinetic modeling. Specifically, it exploits the high spatial resolution of MRI as well as the information about perfusion and vascular permeability derived from dynamic contrast-enhanced studies to better assess these parameters in a PET radiotracer injected shortly after the MRI examination. This more precise assessment of perfusion is thought to improve metabolism quantification for the radiotracer and to discriminate between its specific and non-specific accumulation. The present work focussed on 2 PET radiotracers, (18F-fluorodeoxyglucose [FDG] and 18F-fluoroethyltyrosine [FET]) as well as a MRI contrast agent (gadopentetic acid [Gd-DTPA]) applied to a rat glioblastoma model. Images were acquired using a sequential MRI-PET protocol and blood was drawn to derive the arterial input function (AIF) for each molecule. PET and MR images were subsequently registered and pharmacokinetic modeling was performed on regions of interest (ROI) or voxel-wise. For FDG, an irreversible 3 compartments (2-tissue) model was used in accordance to the literature. For FET, it was determined that an irreversible 2-tissue model is applicable for the brain and the tumor and a reversible 2-tissue model is preferred for the muscles. AIF (blood or image-derived) conversion between Gd-DTPA and FET, or vice versa, was also considered and proved feasible for the blood AIF derived from the caudal artery, similar to FDG. Finally, combined kinetic modeling for MRI and PET showed a relationship between the perfusion of FDG, or FET, and that of Gd-DTPA in muscle. Important disparities were noted for the tumor. These results illustrate the complexity of the tumor microenvironment (e.g. presence of various transport mechanisms for the same molecule) and the numerous challenges encountered during its characterization in small animals.

Abstract The purpose of the current study was to evaluate the intercorrelations of magnetic resonance imaging (MRI) findings and clinical symptoms and signs in sciatic patients. Furthermore, determinants of spontaneous HNP resorption and the effect of anti-inflammatory treatments (periradicular methylprednisolone injection and intravenous infliximab) on spontaneous HNP resorption were evaluated. MRI follow-up was performed at baseline, after two months, after six months and after one-year for patients with unilateral sciatica to evaluate determinants of spontaneous HNP resorption and the effect of periradicular methylprednisolone injection on spontaneous HNP resorption. At baseline the study population consisted of 160 patients (group A). MRI follow-up for 21 patients with unilateral sciatica was performed at baseline and after two weeks, after three months and after six months to evaluate the effect of infliximab, a monoclonal TNFα antagonist, infusion on spontaneous HNP resorption (group B). Patients in group A were randomized to receive either periradicular saline or methylprednisolone. Volume of HNP, extent and thickness of enhancement (in Gd-DTPA MRI) and degree of disc displacement were measured and the symptoms and signs were followed repeatedly. The extent of rim enhancement correlated significantly with the degree of disc displacement. The duration of sciatic symptoms correlated negatively with enhancement parameters. The clinical symptoms did not correlate significantly with the different enhancement parameters or disc herniation volume. Achilles reflex abnormality correlated significantly with all enhancement parameters for lesions at L5-S1. Significant decrease in HNP volume occurred from baseline to two moths, and even more so during the whole one year follow-up period. Higher baseline scores of rim enhancement thickness, higher degree of HNP displacement in the Komori classification and age category of 41–50 years were associated with a higher resorption rate. Clinical symptoms alleviation occurred concordantly with a faster resorption rate. No significant difference was noted in the decrease of HNP volume in the saline and methylprednisolone injection groups in follow-up imaging during one year. The enhancement parameters (thickness and extent of rim enhancement) did not differ significantly in the different treatment groups. In group B, 11 patients received intravenous infliximab and 10 saline. Baseline demographic data, pain scores, and clinical status, did not differ between the treatment groups. HNP volume decreased significantly in both groups (P < 0.01). There was no significant difference in HNP volume changes between the treatment groups. By two weeks, enhancement thickness increased significantly in the infliximab compared placebo group (p=0.003). Two patients in each group required back surgery prior to the 6-month assessment.

Abstract Magnetic resonance imaging (MRI) provides methods to study the microstructure and functional properties of tissues that can be utilized to acquire information about the degenerative processes in the spine. The purpose of the current study was to evaluate the value of diffusion-weighted MRI and quantification of delayed gadolinium enhancement in assessing intervertebral disc degeneration. An experimental degeneration model was used to evaluate the sensitivity of diffusion-weighted MRI and T2 relaxation time measurements in detecting early degenerative changes in the disc. In six pigs, an annular disc lesion was induced surgically, after which the discs were repeatedly MR imaged for up to eight weeks. T2 relaxation time of the lesioned discs decreased postoperatively, whereas apparent diffusion coefficient (ADC) initially increased, but at eight weeks decreased when compared to the control discs. The value of ADC in degeneration of human discs was evaluated by imaging 228 voluntary middle-aged men. ADC values of the three lowest lumbar intervertebral discs were measured and disc degeneration was visually graded. The reduction in ADC between visually normal and moderately degenerated discs was 4%, whereas severely degenerated discs showed 5% higher ADC values than normal discs. T2 signal intensity of the discs was significantly correlated with the ADC values. Because of a considerable overlap between ADC values of normal and degenerated discs the clinical relevance of the ADC measurements of lumbar intervertebral discs remains questionable. A method to quantify delayed enhancement of the nucleus pulposus after intravenous gadolinium contrast agent injection was developed to evaluate the diffusion of small solutes into the disc. Twenty male volunteers were imaged in order to correlate the measured change in the T1 relaxation rate with visually evaluated degenerative changes. The percentual change of T1 relaxation rate for individual discs was up to 126%, and a positive trend was observed between the delayed enhancement and the disc degeneration grades. In order to study the factors that determine the intensity of delayed enhancement, T1 relaxation rate measurements were further correlated with lumbar artery stenosis, bone marrow changes adjacent to endplates, endplate defects, and ADC of the disc. Lumbar artery stenosis and ADC values of the discs were not correlated with enhancement, while disc space narrowing and the presence of degenerative endplate changes had a strong correlation, suggesting an important role for the endplate in maintaining the integrity of the disc.