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AJNR Am J Neuroradiol. 2019 Jun;40(6):979-986. doi: 10.3174/ajnr.A6063. Epub 2019 May 16.

Association between Tumor Acidity and Hypervascularity in Human Gliomas Using pH-Weighted Amine Chemical Exchange Saturation Transfer Echo-Planar Imaging and Dynamic Susceptibility Contrast Perfusion MRI at 3T.

Author information

1
From the UCLA Brain Tumor Imaging Laboratory (Y.-L.W., J.Y., A.C., C.R., B.M.E.).
2
Department of Radiology (Y.-L.W.), People's Liberation Army General Hospital, Beijing, China.
3
Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences (J.Y., A.C., C.R., N.S., W.B.P., B.M.E.).
4
Department of Bioengineering (J.Y., B.M.E.), Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, California.
5
UCLA Brain Research Institute (L.M.L., A.L., B.M.E.).
6
Department of Neurosurgery (L.M.L.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
7
Department of Neurology (P.L.N., A.L., N.N., M.J., T.F.C.).
8
From the UCLA Brain Tumor Imaging Laboratory (Y.-L.W., J.Y., A.C., C.R., B.M.E.) bellingson@mednet.ucla.edu.
9
Physics and Biology in Medicine (B.M.E.).
10
Department of Psychiatry and Biobehavioral Sciences (B.M.E.).

Abstract

BACKGROUND AND PURPOSE:

Acidification of the tumor microenvironment from abnormal metabolism along with angiogenesis to meet metabolic demands are both hallmarks of malignant brain tumors; however, the interdependency of tumor acidity and vascularity has not been explored. Therefore, our aim was to investigate the association between pH-sensitive amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) and relative cerebral blood volume (CBV) measurements obtained from dynamic susceptibility contrast (DSC) perfusion MRI in patients with gliomas.

MATERIALS AND METHODS:

In this retrospective study, 90 patients with histologically confirmed gliomas were scanned between 2015 and 2018 (median age, 50.3 years; male/female ratio = 59:31). pH-weighting was obtained using chemical exchange saturation transfer echo-planar imaging estimation of the magnetization transfer ratio asymmetry at 3 ppm, and CBV was estimated using DSC-MR imaging. The voxelwise correlation and patient-wise median value correlation between the magnetization transfer ratio asymmetry at 3 ppm and CBV within T2-hyperintense lesions and contrast-enhancing lesions were evaluated using the Pearson correlation analysis.

RESULTS:

General colocalization of elevated perfusion and high acidity was observed in tumors, with local intratumor heterogeneity. For patient-wise analysis, median CBV and magnetization transfer ratio asymmetry at 3 ppm within T2-hyperintense lesions were significantly correlated (R = 0.3180, P = .002), but not in areas of contrast enhancement (P = .52). The positive correlation in T2-hyperintense lesions remained within high-grade gliomas (R = 0.4128, P = .001) and in isocitrate dehydrogenase wild-type gliomas (R = 0.4300, P = .002), but not in World Health Organization II or in isocitrate dehydrogenase mutant tumors. Both magnetization transfer ratio asymmetry at 3 ppm and the voxelwise correlation between magnetization transfer ratio asymmetry and CBV were higher in high-grade gliomas compared with low-grade gliomas in T2-hyperintense tumors (magnetization transfer ratio asymmetry, P = .02; Pearson correlation, P = .01). The same trend held when comparing isocitrate dehydrogenase wild-type gliomas and isocitrate dehydrogenase mutant gliomas (magnetization transfer ratio asymmetry, P = .04; Pearson correlation, P = .01).

CONCLUSIONS:

A positive linear correlation between CBV and acidity in areas of T2-hyperintense, nonenhancing tumor, but not enhancing tumor, was observed across patients. Local heterogeneity was observed within individual tumors.

PMID:
31097430
PMCID:
PMC6527337
[Available on 2019-12-01]
DOI:
10.3174/ajnr.A6063

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