Automatic Analysis of Cellularity in Glioblastoma and Correlation with ADC Using Trajectory Analysis and Automatic Nuclei Counting

Abstract

Objective: Several studies have analyzed a correlation between the apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI and the tumor cellularity of corresponding histopathological specimens in brain tumors with inconclusive findings. Here, we compared a large dataset of ADC and cellularity values of stereotactic biopsies of glioblastoma patients using a new postprocessing approach including trajectory analysis and automatic nuclei counting.

Materials and methods: Thirty-seven patients with newly diagnosed glioblastomas were enrolled in this study. ADC maps were acquired preoperatively at 3T and coregistered to the intraoperative MRI that contained the coordinates of the biopsy trajectory. 561 biopsy specimens were obtained; corresponding cellularity was calculated by semi-automatic nuclei counting and correlated to the respective preoperative ADC values along the stereotactic biopsy trajectory which included areas of T1-contrast-enhancement and necrosis.

Results: There was a weak to moderate inverse correlation between ADC and cellularity in glioblastomas that varied depending on the approach towards statistical analysis: for mean values per patient, Spearman's ρ = -0.48 (p = 0.002), for all trajectory values in one joint analysis Spearman's ρ = -0.32 (p < 0.001). The inverse correlation was additionally verified by a linear mixed model.

Conclusions: Our data confirms a previously reported inverse correlation between ADC and tumor cellularity. However, the correlation in the current article is weaker than the pooled correlation of comparable previous studies. Hence, besides cell density, other factors, such as necrosis and edema might influence ADC values in glioblastomas.

Fig 1. Visualization of a biopsy trajectory.

The trajectory is defined by the coordinates of the entry point E(104/128/114) and target point T(112/141/53) and biopsy specimens are taken along the trajectory, mainly close to the target point.

Fig 2. Comparison of two exemplary patients (patient 1: A-D, patient 2: E-H).

A,E: Intraoperative cT1-scans. The biopsy location on this slice is marked by a white crosshair. B,F: Preoperative ADC-maps, which have been registered to intraoperative scans as described. The biopsy location on this slice is marked by a white crosshair. C,G: Scanned biopsy specimens of the respective location (HE stain, x20 magnification). D,H: semi-automatic cell counting on 8-bit images by the ImageJ plugin ITCN. Detected cells are marked with red dots. For patient 1(A-D), analysis yielded ADC = 658mm²/s and cellularity = 16840 cells/mm². For patient 2 (E-H), it was ADC = 1479mm²/s and cellularity = 2208 cells/mm².

Fig 3. Scatterplot of ADC and cellularity with regression line and 95% confidence interval.

Aggregated mean ADC and cellularity values per patient are displayed (37 patients). Pearson’s r = -0.40, p = 0.007; Spearman’s ρ = -0.48, p = 0.002