Molecular magnetic resonance imaging for tumour targeting

During my postgraduate training in Radiology at the University of Genoa, Italy, I developed research projects on the application of molecular magnetic resonance imaging for tumour targeting. Molecular imaging (MI) aims to provide “pictures of what is happening inside the body at molecular and cellular level”. Magnetic resonance imaging (MRI) has been applied to many aspects of MI. Although it offers better temporal and spatial resolution than other methodologies, it is less sensitive for molecular or cellular activities, and therefore there is a need to develop more efficient contrast agents. The publications included in this PhD thesis demonstrate the successful application of two classes of MRI contrast agents: ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) and manganese (Mn2+). Novel USPIO-antibody-conjugated probes for investigating lymphoma tumours were applied, and the potential of labelling natural killer cells by SPIO was demonstrated, offering a great opportunity for in vivo investigation of these lymphocytes that play an essential role in cell-based immune defence. The development of a birdcage prototype coil for a clinical 3T MR scanner with a commercial scientific collaboration was carried out. Research projects for investigating tumour calcium metabolism and risk of bone metastases were developed preclinically (by using Mn2+ in human preclinical cancer animal models) and clinically (by using in vivo proton magnetic resonance spectroscopy to investigate human breast cancer). An in vivo Manganese-enhanced-MRI (MEMRI) technique to visualise brown adipose tissue, its physiopathology, and its role in breast or prostate cancer progression, has been included as well. The last research projects carried out as the conclusion of this PhD were focused on: 1) the development of a novel USPIO-MR imaging approach to monitor chronic lymphocytic leukaemia (CLL), induced by interfering with both miR-15 and miR-16 expression; and 2) evaluating response to a potential treatment with the use of miRNA mimics or inhibitors

A novel method for measuring bowel motility and velocity with dynamic magnetic resonance imaging in two and three dimensions

Increasingly, dynamic MRI has potential as a non-invasive and accessible tool for diagnosing and monitoring gastrointestinal motility in healthy and diseased bowel. However, current MRI methods of measuring bowel motility have limitations: requiring bowel preparation or long acquisition times; providing mainly surrogate measures of motion; and estimating bowel-wall movement in just two dimensions. In this proof-of-concept study we apply a method that provides a quantitative measure of motion within the bowel, in both 2D and 3D, using existing, vendor-implemented MRI pulse sequences with minimal bowel-preparation. This method uses a minimised cost function to fit linear vectors in the spatial and temporal domains. It is sensitised to the spatial scale of the bowel and aims to address issues relating to the low signal-to-noise in high-temporal resolution dynamic MRI scans, previously compensated for by performing thick-slice (10 mm) 2D coronal scans. We applied both 2D and 3D scanning protocols in two healthy volunteers. For 2D scanning, analysis yielded bi-modal velocity peaks, with a mean antegrade motion of 5.5 mm/s and an additional peak at ~9 mm/s corresponding to longitudinal peristalsis, as supported by intra-operative data from the literature. Furthermore, 3D scans indicated a mean forward motion of 4.7 mm/s, and degrees of ante- and retrograde motion were also established. These measures show promise for the non-invasive assessment of bowel motility, and have the potential to be tuned to particular regions of interest and behaviours within the bowel

A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).

This work was supported by: Associazione Italiana Ricerca sul Cancro (AIRC) [Grant 5 x mille n.9980, (to M.F., F.M. and A. N.)]; AIRC I.G. [n. 14,326 (to M.F.)], [n.10136 and 16,722 (A.N.)], [n.15426 (to F.F.)]. AIRC and Fondazione CaRiCal co-financed Multi Unit Regional Grant 2014 [n.16695 (to F.M.)]. Italian Ministry of Health 5 × 1000 funds (to F.F). A.G R. was supported by Associazione Italiana contro le Leucemie-Linfomi-Mielomi (AIL) Cosenza - Fondazione Amelia Scorza (FAS). S.M. C.M., F.V., L. E., S. B., were supported by AIRC.Peer reviewedPostprin

Governance of preventive health intervention and on time verification of its efficiency: the GIOVE study

OBJECTIVES: The GIOVE Study was aimed to the achievement of allocative efficiency of the budget allocated to the prevention of human papillomavirus (HPV)-induced diseases. An ex-ante determination of the most efficient allocation of resources between screening and multicohort quadrivalent immunisation programmes was followed by the ex-post assessment of the allocative efficiency actually achieved after a 12-month period. DESIGN: A bound optimisation model was developed to determine the ex-ante allocative efficiency of resources. The alternatives compared were the screening programme alone and the quadrivalent immunisation with access to screening. A sensitivity analysis was carried out to assess the uncertainty associated with the main inputs of the model. Subsequently, a cohort of girls with a complete recorded vaccination history were enrolled in an observational retrospective study for 18 months to ensure full compliance with the recommended schedule of vaccination (0, 2, 6 months) within a 12-month time horizon. SETTING: Basilicata region, in the south of Italy. PARTICIPANTS: 12 848 girls aged 12, 15, 18 or 25 years. INTERVENTION: Immunisation with quadrivalent anti-HPV vaccine. OUTCOME MEASURES: The vaccination coverage rate was considered to be the indicator of the best achievable benefit, given the budgetary constraints. RESULTS: Assuming a vaccine price of €100 per dose, a vaccination coverage rate of 59.6% was required for the most effective allocation of resources. The optimal rate of coverage was initially in favour of the multicohort strategy of vaccination against HPV (72.8%±2%). When the price paid for the quadrivalent vaccine dropped to €85 per dose, the most efficient coverage rate (69.5%) shifted closer to the immunisation rate actually achieved during the 12-month observation period. CONCLUSIONS: The bound optimisation model demonstrated to be a useful approach to the ex-ante allocation and the ex-post assessment of the resources allocated to the implementation of a multicohort quadrivalent anti-HPV vaccination programme

Manganese-enhanced MRI (MEMRI) in breast and prostate cancers: Preliminary results exploring the potential role of calcium receptors.

ProceduresTo preliminary assess the relationship between Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and the expression of calcium receptors in human prostate and breast cancer animal models.MethodsNOD/SCID mice were inoculated with MDA-MB-231 breast cancer cells and prostate PC3 cancer cells to develop orthotopic or pseudometastatic cancer animal models. Mice were studied on a clinical 3T scanner by using a prototype birdcage coil before and after intravenous injection of MnCl2. Assessment of receptor's status was carried out after the MR images acquisition by immunohistochemistry on excised tumours.ResultsManganese contrast enhancement in breast or prostate cancer animal models well correlated with CaSR expression (pConclusionOur preliminary results suggest that MEMRI appears an efficient tool to characterize human breast and prostate cancer animal models in the presence of different expression level of calcium receptors