Fully Automated Enhanced Tumor Compartmentalization: Man vs. Machine Reloaded

Abstract

Objective: Comparison of a fully-automated segmentation method that uses compartmental volume information to a semi-automatic user-guided and FDA-approved segmentation technique.

Methods: Nineteen patients with a recently diagnosed and histologically confirmed glioblastoma (GBM) were included and MR images were acquired with a 1.5 T MR scanner. Manual segmentation for volumetric analyses was performed using the open source software 3D Slicer version 4.2.2.3 (www.slicer.org). Semi-automatic segmentation was done by four independent neurosurgeons and neuroradiologists using the computer-assisted segmentation tool SmartBrush® (referred to as SB), a semi-automatic user-guided and FDA-approved tumor-outlining program that uses contour expansion. Fully automatic segmentations were performed with the Brain Tumor Image Analysis (BraTumIA, referred to as BT) software. We compared manual (ground truth, referred to as GT), computer-assisted (SB) and fully-automated (BT) segmentations with regard to: (1) products of two maximum diameters for 2D measurements, (2) the Dice coefficient, (3) the positive predictive value, (4) the sensitivity and (5) the volume error.

Results: Segmentations by the four expert raters resulted in a mean Dice coefficient between 0.72 and 0.77 using SB. BT achieved a mean Dice coefficient of 0.68. Significant differences were found for intermodal (BT vs. SB) and for intramodal (four SB expert raters) performances. The BT and SB segmentations of the contrast-enhancing volumes achieved a high correlation with the GT. Pearson correlation was 0.8 for BT; however, there were a few discrepancies between raters (BT and SB 1 only). Additional non-enhancing tumor tissue extending the SB volumes was found with BT in 16/19 cases. The clinically motivated sum of products of diameters measure (SPD) revealed neither significant intermodal nor intramodal variations. The analysis time for the four expert raters was faster (1 minute and 47 seconds to 3 minutes and 39 seconds) than with BT (5 minutes).

Conclusion: BT and SB provide comparable segmentation results in a clinical setting. SB provided similar SPD measures to BT and GT, but differed in the volume analysis in one of the four clinical raters. A major strength of BT may its independence from human interactions, it can thus be employed to handle large datasets and to associate tumor volumes with clinical and/or molecular datasets ("-omics") as well as for clinical analyses of brain tumor compartment volumes as baseline outcome parameters. Due to its multi-compartment segmentation it may provide information about GBM subcompartment compositions that may be subjected to clinical studies to investigate the delineation of the target volumes for adjuvant therapies in the future.

Conflict of interest statement

Competing Interests: CR is working as Clinical Consultant for Brainlab Sales GmbH Germany. The SmartBrush® software evaluated in this study is commercialized by Brainlab AG. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Set of MRI sequences used in this study for manual, automatic, and semi-automatic tumor volumetry.

Original T1-weighted post-contrast MRI slice (A), manual subcompartmental segmentation into non-enhancing tumor (green), enhancing tumor (blue), and necrotic tissue (red) (B). BT subcompartmental segmentation into non-enhancing tumor (green), enhancing tumor (blue) and necrotic tissue (red) (C). BT core tumor segmentation (dark blue, D), SB1 core tumor segmentation (light red, E), SB2 core tumor segmentation (green, F), SB3 core tumor segmentation (purple, G) and SB4 core tumor segmentation (yellow, H).

Fig 2. Stereotactic biopsy with the frameless neuronavigation system (Brainlab® VarioGuide) using BraTumIA segmentation.

The figures indicate the T1w raw image and the BT subcompartment overlays during biopsy. Upper row left column: original T1wGd without tumor delineation, right column: all automatic segmented tumor subcompartments are visible. Bottom row left column: necrosis and contrast-enhancing tumor volume, right column: only necrotic tumor volume. Color code for segmentations: red = enhancing tumor, yellow = edema, blue = necrosis and green = non-enhancing tumor.

Fig 3. Differences between the SPD metric and the GT for the BT and the four SB segmentations.

Additionally to the general boxplot statistics the mean value is shown (red asterisk). Negative values imply an overestimation by the rater/method whereas positive values indicate an underestimation.

Fig 4

The performances of the different raters (SB1 to 4) and methods (SB vs. BT) were compared with a Bonferroni corrected Wilcoxon signed-rank test in terms of Dice coefficient (A), absolute volume difference (B) and absolute SPD difference (C). A connection denotes a significant difference, with the encircled number being the p-value. The arrow points to the superior method with respect to the GT. The line thickness depicts the p-value in a qualitative manner. The color coding shows to which SB rater BT (white) is significantly different (red) or not (green).

Fig 5. Left to right, top to bottom: Dice coefficient, volume difference, sensitivity and PPV.

The results are obtained when BT and the four SB raters are compared to the GT. The figure depicts the general boxplot statistics with the additional mean value (red asterisk). For the volume differences, negative values denote overestimation and positive values underestimation compared to the GT.

Fig 6. Volumes of the BT and the four SB segmentations (y-axis) plotted against the respective GT segmentations (x-axis).

Perfect agreement with respect to tumor volume means that all data points (volumes) would come to lie on the gray dashed 45-degree line starting from the origin (0,0).

Fig 7. Barplot depicting the SB tumor volumes for the individual patients.

Non-enhancing tumor tissue that was, as confirmed by the GT, correctly segmented with the multi-compartment BT software and was not part of the SB segmented volume, is stacked on top of them. The barplot is horizontally split into two groups of patients with and without additional non-enhancing tissue found by BT. Vertically, the figure is quartered to show the results for all four SB raters.