Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region

Abstract

Background 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. Purpose To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration. Study Type Animal model. Subjects Mice bearing orthotopic glioblastoma xenografts generated from a patient‐derived glioblastoma cell line. Field Strength/Sequences 7T perfusion images acquired using a high signal‐to‐noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1/T2 weighted, contrast‐enhanced T1, diffusion‐weighted, and apparent diffusion coefficient). Assessment 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 a “ground truth.” Statistical Tests Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two‐tailed, paired t‐test used for statistical analysis. Results High comparison test results (Dice 0.62–0.72, Accuracy 0.86–0.88, Sensitivity 0.51–0.7, and Specificity 0.92–0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51–0.61). MRI/histology voxel‐to‐voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004). Data Conclusion These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy. Level of Evidence: 1 Technical stage: 2 J. Magn. Reson. Imaging 2019;50:529–540.

Quantitative T1 mapping indicates tumor infiltration beyond the enhancing part of glioblastomas

“…The current study has some limitations: (i) a histopathological confirmation of tumor infiltration beyond the enhancing part of the tumor and beyond the areas of prolonged T2 was not performed, as the resection of brain tissue which was not suspicious in conventional MRI would not be justifiable ethically. However, recent preclinical studies show that glioma cell infiltration reaches beyond the area of signal hyperintensity in T2w images; (ii) to reduce the scanning time, T2 mapping was restricted to 25 slices covering a slab of 5 cm. Therefore, in some patients, the edema region was not completely covered, which may have changed quantitative values for the edema region slightly; and (iii) it should also be noted that CA accumulation remains only an indirect sign of potential glioma cell infiltration.…”

“…Values between the VOIs differ significantly at the P < 0.01 level when indicated with * above the arrows. Only the values between edema and 5 mm zone for the relative qT1-difference and the absolute T1w difference were not significant (indicated with "ns" above the arrows) T2w images 35,36 ; (ii) to reduce the scanning time, T2 mapping was restricted to 25 slices covering a slab of 5 cm. Therefore, in some patients, the edema region was not completely covered, which may have changed quantitative values for the edema region slightly; and (iii) it should also be noted that CA accumulation remains only an indirect sign of potential glioma cell infiltration.…”

Are We Heading to the Future of Musculoskeletal Tumor Imaging with Ultra-High Field 7T MRI?

“…Cell-infiltration is often ill-defined in glioblastoma using contrast-enhanced T1W MRI. Perfusion imaging conducted at UHF illustrated that regions of low tumour infiltration could be probed even in and beyond the oedematous T2 hyperintensity region surrounding macroscopic tumour [50]. UHF anatomical and DW MRI have also been reported as efficient for partial nephrectomy in small renal masses indicating a potential use in perioperative assessment with a maximal sparing or renal parenchyma without compromising oncological outcomes, similarly to sarcoma.…”

Comparative Analysis of MRI and Pathological Findings in a Resected Specimen of Rectal Cancer

“…Of course, in most of the cases the CRM status was easily established by in-vivo MRI, and routine use of smr might be unrealistic. However, small-sized MRI scanners have been developed already for small animals [27], and if some kind of MRI image navigation system for making sections were available in routine work, the pathological diagnostic ability would be improved. In this study, we have shown that the pCRM can be estimated by smrCRM more accurrately, which can reduce the risk of misreading the pCRM status.…”