Differentiation of high grade glioma and solitary brain metastases by measuring relative cerebral blood volume and fractional anisotropy: a systematic review and meta-analysis of MRI diagnostic test accuracy studies
Authors: Fioni Fioni , Chen Song Jia , Lister I Nyoman Ehrich , Ghalwash Abdelrahman Atef , Long Ma Zhan 
Published: October 2022

Objective:
This study aims to research the efficacy of MRI (I) for differentiating high-grade glioma (HGG) (P) with solitary brain metastasis (SBM) (C) by creating a combination of relative cerebral blood volume (rCBV) (O) and fractional anisotropy (FA) (O) in patients with intracerebral tumors.

Methods:
Searches were conducted on September 2021 with no publication date restriction, using an electronic search for related articles published in English, from PubMed (1994 to September 2021), Scopus (1977 to September 2021), Web of Science (1985 to September 2021), and Cochrane (1997 to September 2021). A total of 1056 studies were found, with 23 used for qualitative and quantitative data synthesis. Inclusion criteria were: patients diagnosed with HGG and SBM without age, sex, or race restriction; MRI examination of rCBV and FA; reliable histopathological diagnostic method as the gold-standard for all conditions of interest; observational and clinical studies. Newcastle-Ottawa quality assessment Scale (NOS) and Cochrane risk of bias tool (ROB) for observational and clinical trial studies were managed to appraise the quality of individual studies included. Data extraction results were managed using Mendeley and Excel, pooling data synthesis was completed using the Review Manager 5.4 software with random effect model to discriminate HGG and SBM, and divided into four subgroups.

Results:
There were 23 studies included with a total sample size of 597 HGG patients and 373 control groups/SBM. The analysis was categorized into four subgroups: (1) the subgroup with rCBV values in the central area of the tumor/intratumoral (399 HGG and 232 SBM) shows that HGG patients are not significantly different from SBM/controls group (SMD [95% CI] = −0.27 [-0.66, 0.13]), 2) the subgroup with rCBV values in the peritumoral area (452 HGG and 274 SBM) shows that HGG patients are significantly higher than SBM (SMD [95% CI] =  −1.23 [-1.45 to -1.01]), (3) the subgroup with FA values in the central area of the tumor (249 HGG and 156 SBM) shows that HGG patients are significantly higher than SBM (SMD [95% CI] = - 0.44 [-0.84,–0.04]), furthermore (4) the subgroup with FA values in the peritumoral area (261 HGG and 168 SBM) shows that the HGG patients are significantly higher than the SBM (SMD [95% CI] = −0.59 [-1.02,–0.16]).

Conclusion:
Combining rCBV and FA measurements in the peritumoral region and FA in the intratumoral region increase the accuracy of MRI examination to differentiate between HGG and SBM patients effectively. Confidence in the accuracy of our results may be influenced by major interstudy heterogeneity. Whereas the I2 for the rCBV in the intratumoral subgroup was 80%, I2 for the rCBV in the peritumoral subgroup was 39%, and I2 for the FA in the intratumoral subgroup was 69%, and I2 for the FA in the peritumoral subgroup was 74%. The predefined accurate search criteria, and precise selection and evaluation of methodological quality for included studies, strengthen this study
Our study has no funder, no conflict of interest, and followed an established PROSPERO protocol (ID: CRD42021279106).

Advances in knowledge:
The combination of rCBV and FA measurements’ results is promising in differentiating HGG and SBM.