pH-Weighted amine chemical exchange saturation transfer echo planar imaging visualizes infiltrating glioblastoma cells

• DOI: 10.1093/neuonc/noad150
• Publication Date: 2023-08-17T20:51:59Z
• Authors: Kunal S Patel; Jingwen Yao; Nicholas S Cho; Francesco Sanvito; Kaleab Tessema; Alvaro Alvarado; Lindsey Dudley; Fausto Rodriguez; Richard Everson; Timothy F Cloughesy; Noriko Salamon; Linda M Liau; Harley I Kornblum; Benjamin M Ellingson
• Keywords: Clinical Sciences; Oncology and Carcinogenesis; 610; non-enhancing; Rare Diseases; Clinical Research; Tumor Microenvironment; Humans; Prospective Studies; Oncology & Carcinogenesis; Amines; Cancer; Biomedical and Clinical Sciences; Echo-Planar Imaging; Neurosciences; glioblastoma; Oncology and carcinogenesis; Hydrogen-Ion Concentration; Magnetic Resonance Imaging; Brain Disorders; Brain Cancer; Women's Health; Biomedical Imaging; CEST-EPI; pH MRI; Glioblastoma; 4.2 Evaluation of markers and technologies

Abstract

Background Given the invasive nature of glioblastoma, tumor cells exist beyond the contrast-enhancing (CE) region targeted during treatment. However, areas of non-enhancing (NE) tumors are difficult to visualize and delineate from edematous tissue. Amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) is a pH-sensitive molecular magnetic resonance imaging technique that was evaluated in its ability to identify infiltrating NE tumors and prognosticate survival.

Methods In this prospective study, CEST-EPI was obtained in 30 patients and areas with elevated CEST contrast (“CEST+” based on the asymmetry in magnetization transfer ratio: MTRasym at 3 ppm) within NE regions were quantitated. Median MTRasym at 3 ppm and volume of CEST + NE regions were correlated with progression-free survival (PFS). In 20 samples from 14 patients, image-guided biopsies of these areas were obtained to correlate MTRasym at 3 ppm to tumor and non-tumor cell burden using immunohistochemistry.

Results In 15 newly diagnosed and 15 recurrent glioblastoma, higher median MTRasym at 3ppm within CEST + NE regions (P = .007; P = .0326) and higher volumes of CEST + NE tumor (P = .020; P < .001) were associated with decreased PFS. CE recurrence occurred in areas of preoperative CEST + NE regions in 95.4% of patients. MTRasym at 3 ppm was correlated with presence of tumor, cell density, %Ki-67 positivity, and %CD31 positivity (P = .001; P < .001; P < .001; P = .001).

Conclusions pH-weighted amine CEST-EPI allows for visualization of NE tumor, likely through surrounding acidification of the tumor microenvironment. The magnitude and volume of CEST + NE tumor correlates with tumor cell density, degree of proliferating or “active” tumor, and PFS.