Abstract

ObjectivesTo explore the efficacy of diffusion weighted imaging (DWI)-derived metrics under different models as surrogate indicators for molecular biomarkers and tumor microenvironment in gliomas.MethodsA retrospective study was performed for 41 patients with gliomas. The standard apparent diffusion coefficient (ADCst) and ADC under ultra-high b values (ADCuh) (b values: 2500 to 5000 s/mm2) were calculated based on monoexponential model. The fraction of fast diffusion (f), pseudo ADC (ADCfast) and true ADC (ADCslow) were calculated by bi-exponential model (b values: 0 to 2000 s/mm2). The apparent diffusional kurtosis (Kapp) was derived from the simplified diffusion kurtosis imaging (DKI) model (b values: 200 to 3000 s/mm2). Potential correlations between DWI parameters and immunohistological indices (i.e. Aquaporin (AQP)1, AQP4, AQP9 and Ki-67) were investigated and DWI parameters were compared between high- and low-grade gliomas, and between tumor center and peritumor. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were calculated to determine the performance of independent or combined DWI parameters in grading gliomas.ResultsThe ADCslow and ADCuh at tumor center showed a stronger correlation with Ki-67 than other DWI metrics. The ADCst, ADCslow and ADCuh at tumor center presented correlations with AQP1 and AQP4 while AQP9 did not correlate with any DWI metric. Kapp showed a correlation with Ki-67 while no significant correlation with AQPs. ADCst (p < 0.001) and ADCslow (p = 0.001) were significantly lower while the ADCuh (p = 0.006) and Kapp (p = 0.005) were significantly higher in the high-grade than in the low-grade gliomas. ADCst, f, ADCfast, ADCslow, ADCuh, Kapp at the tumor center had significant differences with those in peritumor when the gliomas grade became high (p < 0.05). Involving ADCuh and Kapp simultaneously into an independent ADCst model (AUC = 0.833) could further improve the grading performance (ADCst+ADCuh+Kapp: AUC = 0.923).ConclusionDifferent DWI metrics fitted within different b-value ranges (low to ultra-high b values) have different efficacies as a surrogate indicator for molecular expression or microstructural complexity in gliomas. Further studies are needed to better explain the biological meanings of these DWI parameters in gliomas.

Highlights

  • Gliomas are the most common primary brain tumors in adults and according to World Health Organization (WHO) guidelines are classified into four grades, which reflect increasing malignancy and worse prognosis [1]

  • The Intraclass Correlation Coefficient (ICC) between the two independent pathologists for measuring the IODs of AQP1, AQP4, AQP9 and Ki-67 were 0.861, 0.853, 0.841 and 0.877, respectively

  • Analysis of the histological indices showed that the expression of AQP1, TABLE 1 | The statistical difference analysis of diffusion weighted imaging (DWI)-derived metrics and histological indices between low- and high-grade gliomas

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Summary

Introduction

Gliomas are the most common primary brain tumors in adults and according to World Health Organization (WHO) guidelines are classified into four grades, which reflect increasing malignancy and worse prognosis [1]. Accurate assessment of glioma grade, as well as phenotype and genotype, is of potential importance for the optimization of personalized treatment. Inherently high heterogeneity of gliomas means that biopsy or localized resection may not be representative of the tumor as a whole. DWI is one of the potential tools to provide surrogate noninvasive imaging biomarkers for microenvironment in gliomas as the water diffusion coefficients could intermediately reflect the microstructure, perfusion or water exchange effects associated with transmembrane transport, such as facilitated diffusion [2, 3]

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