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.
ABBREVIATIONS:
- CEST-EPI
- chemical exchange saturation transfer echo-planar imaging
- IDH
- isocitrate dehydrogenase
- IDHMUT
- IDH mutant
- IDHWT
- IDH wild-type
- LGG
- low-grade glioma
- HGG
- high-grade glioma
- MTRasym
- magnetization transfer ratio asymmetry
- SAGE
- spin and gradient-echo
- WHO
- World Health Organization
- MGMT
- O-6-methylguanine-DNA methyltransferase
Footnotes
Y.L. Wang and J. Yao contributed equally to this work.
Disclosures: Linda M. Liau—UNRELATED: Grants/Grants Pending: Northwest Biotherapeutics*; Stock/Stock Options: Actuate Therapeutics.* Albert Lai—UNRELATED: Consultancy: Merck, Comments: Advisory Board; Payment for Development of Educational Presentations: AbbVie, Comments: Society for NeuroOncology Annual Meeting lecture. Whitney B. Pope—RELATED: Consulting Fee or Honorarium: Bracco, Guerbet. Timothy F. Cloughesy—UNRELATED: Board Membership: Global Coalition for Adaptive Research, 501c3 for sponsoring clinical trials. No payment to author; Consultancy: VBI, VBL, Deciphera Pharmaceuticals, Agios Pharmaceuticals, Tocagen, Merck, Celgene, Puma, AbbVie, Eli Lilly and Company; Stock/Stock Options: Notable Labs. Benjamin M. Ellingson—UNRELATED: Consultancy: MedQIA, Agios Pharmaceuticals, Imaging Endpoints, Hoffman-La Roche/Genentech, Insys Therapeutics, OmniOx, Nativis, Siemens, Janssen Pharmaceutica, Medicenna, Novogen/Kazia; Grants/Grants Pending: Agios Pharmaceuticals, Roche, Janssen Pharmaceutica, Siemens. *Money paid to the institution.
This work was supported by the American Cancer Society Research Scholar Grant (RSG-15-003-01-CCE) (B.M. Ellingson); Art of the Brain (T.F. Cloughesy); UCLA Specialized Program of Research Excellence in Brain Cancer (National Institutes of Health/National Cancer Institute 1P50CA211015-01A1) (B.M. Ellingson, L.M. Liau, P.L. Nghiemphu, A. Lai, W.B. Pope, T.F. Cloughesy); and National Institutes of Health/National Cancer Institute, 1R21CA223757-01 (B.M. Ellingson).
- © 2019 by American Journal of Neuroradiology
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