{"doi":"10.1093/neuonc/noad150","title":"pH-Weighted amine chemical exchange saturation transfer echo planar imaging visualizes infiltrating glioblastoma cells","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.","journal":"Neuro-Oncology","year":2023,"id":330092,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9669,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":396762,"name":"Jingwen Yao","orcid":"0000-0002-8828-1841","position":1,"is_corresponding":false},{"id":443406,"name":"Nicholas S. Cho","orcid":"0000-0002-8686-0575","position":2,"is_corresponding":false},{"id":954924,"name":"Francesco Sanvito","orcid":"0000-0003-3379-9958","position":3,"is_corresponding":false},{"id":1053683,"name":"Kaleab Tessema","orcid":"0000-0001-5204-3457","position":4,"is_corresponding":false},{"id":322709,"name":"Alvaro G. Alvarado","orcid":"0000-0002-4049-8400","position":5,"is_corresponding":false},{"id":1054360,"name":"Lindsey Dudley","orcid":null,"position":6,"is_corresponding":false},{"id":288108,"name":"Fausto J. Rodríguez","orcid":"0000-0001-8662-1219","position":7,"is_corresponding":false},{"id":396761,"name":"Richard G. Everson","orcid":"0000-0003-2809-3061","position":8,"is_corresponding":false},{"id":247467,"name":"Timothy F. Cloughesy","orcid":"0000-0002-8656-7483","position":9,"is_corresponding":false},{"id":397177,"name":"Noriko Salamon","orcid":"0000-0002-3520-9467","position":10,"is_corresponding":false},{"id":87673,"name":"Linda M. Liau","orcid":"0000-0002-4053-0052","position":11,"is_corresponding":false},{"id":297479,"name":"Harley I. Kornblum","orcid":"0000-0002-3779-4540","position":12,"is_corresponding":false},{"id":247468,"name":"Benjamin M. Ellingson","orcid":"0000-0002-2764-6640","position":13,"is_corresponding":false},{"id":396760,"name":"Kunal Patel","orcid":"0000-0002-9854-9178","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:09:10.120703Z","pmid":"37591790","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}