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

Abstract

BACKGROUND AND PURPOSE: 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

High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 1: Perfusion and Diffusion Techniques

“…The potential of FTB to predict response to treatment ( 61 ) and to distinguish between tumor or treatment effect, as confirmed by histopathologic examination of resected tissue samples ( 62 ), has been demonstrated. More recently, a prospective study ( 63 ) using image-localized biopsy tissue validated the ability of rCBV to predict tumor content (0–100%), demonstrating similar performance of nRCBV and sRCBV for the creation of FTB. Given that sRCBV does not require choosing a reference ROI, this represents an important step toward workflow optimization for the creation of FTB maps.…”

A multi-reader comparison of normal-appearing white matter normalization techniques for perfusion and diffusion MRI in brain tumors

“…Although NAWM normalization techniques are popular for nrCBV, it is worth mentioning other normalization approaches applied in some other studies. For example, there has also been interest in the automatic normalization, or "standardization," of rCBV parametric maps by transforming rCBV values to a standardized scale, precluding the need for manual NAWM ROIs [1,[14][15][16]. Standardization of rCBV has been shown to reduce variability compared to manual NAWM methods [1,14,15], though standardized rCBV metrics had similar performance with NAWM-based nrCBV metrics for assessing post-treatment tumor burden in stereotactic biopsy samples of recurrent high-grade glioma [16].…”

“…Common normalization methods include placing a reference region of interest (ROI) on the contralateral normal-appearing white matter (NAWM), but numerous regions have been reported such as the white matter directly opposite to the tumor [3][4][5], the posterior limb of the internal capsule [6], the temporal lobe [7], and the centrum semiovale [8][9][10][11][12] along with variations in the placement of a single ROI [9] or multiple ROIs anteriorly to posteriorly [10,11,13]. Automated normalization methods, such as Gaussian-normalized nrCBV [1] and "standardized" nrCBV involving training-set data [1,[14][15][16], have also been described, but these methods require advanced software that limits their clinical feasibility.…”

Magnetic Resonance Imaging Mapping of Brain Tumor Burden: Clinical Implications for Neurosurgical Management: Case Report

“…Creation of FTB maps is based on previous studies validating the rCBV threshold used to distinguish high-grade brain tumor from treatment effect for the creation of FTB. More recent studies demonstrated the relevance of FTB to predict outcomes 5–7 and guide clinical decisions. 8 Introduced here is the idea that FTB can likewise be useful for guiding surgery and diagnosis.…”