7T MRI first exploitation in a chemotherapy induced peripheral neurotoxicity in vivo model

INTRODUCTION Chemotherapy induced peripheral neurotoxicity (CIPN) is a common, long lasting (or even permanent) adverse event of anticancer drugs. No disease-modifying or symptomatic treatments are available due to an incomplete pathogenetic knowledge. Moreover, detection/grading of CIPN in clinical setting still represents a major challenge. High resolution diffusion MRI could be a surrogate, translational, marker to characterize early morphological changes as neuropathy ensues, creating a virtuous link between bench and bed side. METHODS We aimed at characterising MRI changes in a consistent model of CIPN. We selected paclitaxel (PTX) as neurotoxic agent, given expected axonal damage is quite relevant. We compared 2 groups (n=12 each) of female Wistar rats: control (CTRL, vehicle treated, iv) and PTX (10mg/kg, 1qwx4, iv). At the end of treatment, neuropathy development was verified via Dynamic test and nerve conduction studies (NCS) of caudal and digital nerves. 7T MRI was performed on rat tails (paraffin fixed after sacrifice) to study caudal nerves and their anatomical relationship with surrounding structures. High resolution anatomical images were acquired by means of a T1w sequence with a voxel size of 50x50x50 µm3. Diffusion weighted images were acquired in five b-shells: b of 500, 2000, 4500, 6000, 8000 sec*mm-2 with 15, 24, 33, 42, 51 isotropically distributed gradient directions and a voxel size of 125x125x125 µm3. Diffusion data were then fitted with Diffusion Tensor Imaging (DTI) standard model and with Neurite Orientation Dispersion and Density Imaging (NODDI) and Spherical Mean Technique (SMT) microstructural models. RESULTS Dynamic test confirmed mechanical allodynia development (p<0.0001) in PTX group, and NCS showed a moderate-severe axonal polyneuropathy. Therefore, we confirmed PTX group had a relevant neuropathy burden to be used as a test bench for 7T MRI acquisitions. CONCLUSIONS Microstructural metrics allowed to decouple the intra/extracellular water component and evaluate their diffusivity to characterize axonal damage and to draw a parallel with NCS changes.