Summary
Introduction: Placental insufficiency is a serious pathology, with a late diagnosis most often, preventing the implementation of an early efficient treatment. Some fetal pathologies with severe repercussions on the function of a vital organ can still not be efficiently assessed or monitored with a non-invasive technique. The purpose of this work is to develop in an animal model and then transpose to humans, functional MRI (fMRI) by BOLD effect for the evaluation of placental and renal function. Materials and methods: Three studies in fMRI constitute this thesis. The first was performed on a rat model of intrauterine growth retardation (IUGR). We measured the T2* in the maternal liver, placenta, liver and brain of normal and IUGR fetuses. The T2* under ambient air (T2*-AA) is compared to that under maternal hyperoxygenation (T2*-O2). The BOLD effect defined as Delta-T2* = 100x (T2-AA-T2-O2) / T2-AA) will be calculated. The T2 * and the BOLD effect will be compared between normal fetuses and those in IUGR. The second study is performed on an animal model of unilateral obstructive uropathy. A multi-echo sequence will be done to measure the T2* of the liver and the normal and the dilated kidney to compare the T2*-AA to the T2*-O2. The T2* and the BOLD effect will be compared between the normal kidneys and the ligated kidneys. The last study is a translational research. It consisted of developing the BOLD effect in fMRI in pregnant women and measuring T2* in the maternal liver and in their placenta. RESULTS: In the IUGR model, we demonstrated a significant BOLD effect in all evaluated organs in all of the feto-placental units (FPU). The BOLD effect in the fetuses was less important than in the placentas. By comparing the normal fetuses with those in IUGR, there was a significant reduction in the BOLD effect in the FPU in IUGR (p = 0.005), with the exception of the fetal liver, in which no difference in the BOLD effect could be demonstrated. The placenta presented two layers and the BOLD effect in the inner and outer layers of the placenta demonstrated a significantly different pattern in all FPUs. For the fetal brain, there was a significant difference in the BOLD effect between the 2 horns (¿T2 * = 3.70 ms vs ¿T2 * = 7.17 ms, p = 0.02). In the obstructive uropathy rat model, there was a significant BOLD effect in the kidneys and liver. There is a notable increase in oxygen consumption in the contralateral normal kidney with a significant decrease in the BOLD effect at the level of the obstructed kidney. In the pregnant woman, we were able to develop the BOLD technique with the selection of the mask and the maternal oxygenation rate (15l/min) and duration (5 min). We validated the significant increase (p <0.00001) of T2*-AA (average 86.63 +/- 23.13) to T2*-O2 (mean-112.2 +/- 24.9). We validated a positive BOLD effect in all the evaluated placentas: Delta-T2* mean = 33.12%. Conclusion: This work illustrates the value of fMRI with the BOLD effect in the diagnosis, follow-up and potential management of placental insufficiency (with associated IUGR). The BOLD effect would also make it possible to evaluate the function of various organs involved in fetal pathologies which can¿t be explored with current techniques. The applicability and feasibility of this technique have also been evaluated and validated in pregnant women, opening a wide window for the diagnosis and management of IUGR and fetal pathologies. This technique would also allow the early introduction of medication or surgical treatments for these pathologies, with the possibility of a non-invasive longitudinal evaluation of these treatments.
