Performance of Standardized Relative CBV for Quantifying Regional Histologic Tumor Burden in Recurrent High-Grade Glioma: Comparison against Normalized Relative CBV Using Image-Localized Stereotactic Biopsies

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This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects. The authors recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for recurrent tumor versus posttreatment radiation effects. They recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. They measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%–100%) for normalized and standardized values. With binary cutoffs, predictive accuracies were similar for both standardized and normalized metrics and across relative CBV metrics. Standardization of relative CBV achieves similar equivalent performance compared with normalized relative CBV and offers an important step toward workflow optimization and consensus methodology.

Abstract

BACKGROUND AND PURPOSE

Figure 1 from Hoxworth et al
FTB maps in 3 separate biopsy cases correlating with low, medium, and high histologic tumor content. The 3 rows correspond to 3 separate patients and 3 separate biopsy locations, as shown by the green square ROIs on the anatomic postcontrast images in the far-left column (1A, 1B, 1C). The middle and far right columns show the biopsy locations (green square ROIs) in relation to the normalized (Norm) FTB (1B, 2B, 3B) and standardized (Std) FTB (1C, 2C, 3C) maps. On the FTB maps, blue corresponds to predicted PTRE regions with low rCBV ≤1.0. The yellow (1.75 ≥ rCBV >1.0) and red (rCBV >1.75) correspond to predicted tumor regions. For this study, FTB was defined as the percentage of both yellow and red voxels relative to all voxels within an ROI.

Perfusion MR imaging measures of relative CBV can distinguish recurrent tumor from posttreatment radiation effects in high-grade gliomas. Currently, relative CBV measurement requires normalization based on user-defined reference tissues. A recently proposed method of relative CBV standardization eliminates the need for user input. This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects.

MATERIALS AND METHODS

We recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for new contrast-enhancing lesions concerning for recurrent tumor versus posttreatment radiation effects. We recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. We measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. We compared relative CBV performance to predict tumor content, including the Pearson correlation (r), against histologic tumor content (0%–100%) and the receiver operating characteristic area under the curve for predicting high-versus-low tumor content using binary histologic cutoffs (≥50%; ≥80% tumor).

RESULTS

Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%–100%) for normalized (r = 0.63, P < .001) and standardized (r = 0.66, P < .001) values. With binary cutoffs (ie, ≥50%; ≥80% tumor), predictive accuracies were similar for both standardized and normalized metrics and across relative CBV metrics. Median relative CBV achieved the highest area under the curve (normalized = 0.87, standardized = 0.86) for predicting ≥50% tumor, while fractional tumor burden achieved the highest area under the curve (normalized = 0.77, standardized = 0.80) for predicting ≥80% tumor.

CONCLUSIONS

Standardization of relative CBV achieves similar performance compared with normalized relative CBV and offers an important step toward workflow optimization and consensus methodology.

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Performance of Standardized Relative CBV for Quantifying Regional Histologic Tumor Burden in Recurrent High-Grade Glioma: Comparison against Normalized Relative CBV Using Image-Localized Stereotactic Biopsies
Jeffrey Ross
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