Optimized non-invasive MRI protocols for characterizing tissue microstructures: applications in humans to prostate cancer and fetal brain development

This PhD project was aimed to optimize MRI protocols for pelvis imaging, in particular for the diagnosis of prostate cancer (PCa) and for the fetal brain development. Different non-invasive MRI techniques were employed to investigate biological tissues, with the purpose to obtain information on microstructures and potentially metabolism. Prostate cancer is the second most common malignancy and the fifth leading cause of death in men worldwide. Due to the high incidence of PCa and the limitations of current diagnostic methods, the primary goal of this work was to develop an MRI protocol able to improve the sensitivity of the diagnostic. The investigation of prostate cancer started with ex-vivo experiments conducted on specimens of human prostate gland, obtained after radical prostatectomy, with the 9.4T scanner at the NMR and Medical Physics Laboratory of CNR-ISC (Sapienza). Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI) were performed at high-resolution (70x70 micrometers in plane) to evaluate diffusion metrics in the different prostate compartment and directly compare measurements with the histopathology results. This study proceeded with in-vivo experiments with a 3T clinical MR scanner (Philips Achieva at Policlinico Tor Vergata) on subjects with diagnosed PCa. DTI was performed with the purpose to assess its diagnostic ability in individuating and classifying PCa with different ranges of diffusion weightings, i.e. b-values. Our results showing that the diagnostic accuracy of DTI is improved with high diffusion weightings motivated our interest in performing DKI, a technique that captures water diffusion features when high b-values are employed, providing additional information on tissue microstructures, inaccessible to DTI technique. The second part of this PhD project was conducted at the Center for Magnetic Resonance Research (CMRR) in Minneapolis and was funded by the European Union's Horizon 2020 research and innovation program under the Marie Curie grant agreement No 691110 (MICROBRADAM). The study was dedicated to perform prostate cancer imaging with new contrast mechanisms, based on T1rho and T2rho relaxation times. T1rho and T2rho characterize the relaxation of the nuclear magnetization in the rotating frame and they are sensitive to molecular dynamics occurring at frequencies in the range of kHz, characteristic of several in-vivo processes, enabling the access to important information on tissue microenvironment. T1rho and T2rho imaging is limited by the intensive energy deposited by the acquisition sequence, which it is usually overcome by increasing the acquisition time, preventing the possibility of diagnostic applications. Therefore the aim of this work was to develop a new approach to perform imaging in the rotating frame with a three-dimensional acquisition method, recently developed at the CMRR, in order to address the aforementioned shortcomings. Given the incidence of PCa, this research has international interest and potentially contributes to improve not only the sensitivity of PCa diagnostic but also the knowledge of the tissue micro-changing caused by the tumor development. A part of this project was dedicated to Diffusion MRI application in woman pelvis to image fetuses during gestation. The aim of this work was to develop a fast and reliable protocol for fetal imaging to minimize mother-fetal motion artifact and perfusion effects. The protocol designed for acquisition and post-processing was employed to successfully study fetal brain development during the second and third trimester of gestation, in normal cases and in fetuses affected by ventriculomegaly disease. These preliminary data can contribute to delineate a reference standard to assess the normal progress of sulcation and myelination as well as the normative biometry of the fetal brain, improving the knowledge of brain maturation. Globally, the impact of this research lies in having demonstrated that the sensitivity of DMRI for microstructural changes in body tissue caused by cancer, brain disease or normal condition like brain maturation can be fruitfully utilized in combination with artifact correction methods. Moreover, new strategy of image reconstruction, such as 3D gradient echo, can be successfully employed to perform abdominal imaging, enriching the investigation of in-vivo systems with information on tissue microenvironment and metabolism.