Low-field magnetic resonance: a sustainable opportunity for an important diagnostic imaging

This PhD thesis advances the frontier of molecular imaging by demonstrating the powerful potential of sustainable, low-field magnetic resonance imaging (MRI) techniques for the non-invasive detection of metabolic and enzymatic biomarkers, particularly in cancer. The core objective was to overcome the traditional sensitivity limitations of low magnetic fields while maximizing diagnostic and therapeutic precision through novel imaging strategies and theranostic agents. In Chapter 1, the research establishes intracellular water residence time (τ_in), measured via Fast Field Cycling (FFC)-NMR, as a sensitive biomarker for glioblastoma aggressiveness and treatment response. By leveraging the enhanced sensitivity of relaxometry in the 0.01–1 MHz range, this work shows that low-field MRI can detect metabolic alterations without the need for contrast agents—minimizing potential side effects and enhancing clinical safety. Chapter 2 introduces a multimodal therapeutic strategy integrating Boron Neutron Capture Therapy (BNCT) with carbonic anhydrase inhibition, using newly synthesized carborane-based agents. This approach enabled tumor-selective boron accumulation and achieved complete cytotoxicity under neutron irradiation, pointing toward highly selective and effective cancer therapies. Chapter 3 presents the design of a dual BNCT/GdNCT probe (Gd-B-CA-SF), offering high MRI relaxivity and specific targeting of CA IX-expressing tumor cells. Although biodistribution studies were conducted at 7T, nuclear magnetic relaxation dispersion (NMRD) profiling revealed optimal performance of the agent at low fields (<20 MHz), reinforcing the viability of low-field MRI for contrast-enhanced imaging and even cell-membrane level therapy monitoring. Chapter 4 introduces a novel, enzyme-responsive micellar probe detectable via Overhauser-enhanced MRI (OMRI) at ultra-low magnetic fields (206 μT). This probe selectively identifies tumor-associated esterase activity, validated through EPR and fluorescence, and demonstrates a cost-effective, sustainable imaging modality with high diagnostic specificity. Overall, this thesis offers a paradigm shift toward low-field MRI as a clinically viable, energy-efficient, and safer imaging platform. It paves the way for personalized, real-time therapy through the integration of metabolic biomarkers, enzyme activity mapping, and smart contrast agents.