Imaging at high fields allows visualization of small tumour mass but lacks a precise evaluation of tumour grading, oxygenation, pH and metastasization. This work aims at developing an innovative diagnostic strategy, based on measuring NMRD profiles with Fast Field Cycling FFC-NMR to obtain quantitative information on tumour characteristics, on the basis of changes in water content and mobility, i.e. characteristics that are not easily detectable by standard MRI. Osmosis and metabolism driven movement of free water molecules across membranes (affecting cell volume and shape) may represent an intrinsic and highly sensitive reporter of the pathology. Cell volume regulation is important in determining the rate of cell proliferation, in aiding cell migration and in responding to external stimuli as hypoxia or extracellular acidosis.
In this work, use of FFC-NMR as reporter of hydrodynamic cellular volume changes has been assessed primarily by comparing cells (mammary adenocarcinoma) grown in normo- or hypoxic conditions and in "hypo-and hyper-osmotic" solutions. Then the same cell types have been injected in leg muscle to generate a tumour xenograft suitable for "in vivo" studies. The Stelar SPINMASTER-FFC-NMR relaxometer herein used is equipped, for the first time, with a 40mm 0.5T magnet with a dedicated 11 mm detection coil allowing to acquire FFC-NMR profiles "in vivo". Due to technical limitations the position to implant tumour cells must be, for the moment, in the mouse legs. The obtained results showed the differences in FFC-NMR profiles (both "in vitro" and "in vivo") report on relevant tumour characteristics. Cell swelling, caused by hypoxia or necrosis, increases both the amount of cytoplasmatic water and its mobility causing an overall increase of T1 of tumour tissues. These findings suggest that FFC relaxometry may be a paradigm-shifting technology which will generate new, quantitative disease biomarkers, relevant either for early diagnoses or for monitoring therapeutic treatments.