Evaluating potential of multi-parametric MRI using co-registered histology: Application to a mouse model of glioblastoma

• Published in: Magnetic resonance imaging 2022-01, Vol.85, p.121-127
• Main Authors: Al-Mubarak, H., Vallatos, A., Gallagher, L., Birch, J., Chalmers, A.J., Holmes, W.M.
• Format: Article
• Language: English
• Subjects: Animals; Co-registration; Diffusion Tensor Imaging; Disease Models, Animal; Glioblastoma; Glioblastoma - diagnostic imaging; Humans; Infiltration of tumor cells; Linear regression; Magnetic Resonance Imaging - methods; Mice; mpMRI; Multi-parametric MRI; Multiparametric Magnetic Resonance Imaging
• ISSN: 0730-725X; 1873-5894
• DOI: 10.1016/j.mri.2021.10.030

Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast-enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. MRI is capable of generating a range of image contrasts which are commonly assessed individually by qualitative visual inspection. It has long been hypothesized that better diagnoses could be achieved by combining these multiple images, so called multi-parametric or multi-spectral MRI. However, the lack of clinical histology and the difficulties of co-registration, has meant this hypothesis has never been rigorously tested. Here we test this hypothesis, using a previously published multi-dimensional dataset consisting of registered MR images and histology. Animal Model. Mice bearing orthotopic glioblastoma xenografts generated from a patient-derived glioblastoma cell line. 7 Tesla, T1/T2 weighted, T2 mapping, contrast enhance T1, diffusion-weighted, diffusion tensor imaging. Immunohistochemistry sections were stained for Human Leukocyte Antigen (probing human-derived tumor cells). To achieve quantitative MRI-tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as ‘ground truth’. Sensitivity, specificity, accuracy and Dice similarity indices were calculated. ANOVA, t-test, Bonferroni correction and Pearson coefficients were used for statistical analysis. Correlation coefficient analysis with co-registered 'ground truth' histology showed interactive regression maps had higher correlation coefficients and sensitivity values than T2W, ADC, FA, and T2map. Further, the interaction regression maps showed statistical improved detection of tumor volume. Voxel-by-voxel analysis provided quantitative evidence confirming the hypothesis that mpMRI can, potentially, better distinguish between the tumor region and normal tissue. [Display omitted]