Patient cohort

The study was approved by the Institutional Review Boards of Asahikawa Medical University Hospital (approval No. 21041) and the Osaka International Cancer Institute (No. 1612065191). The requirement for written informed consent was waived for data collected retrospectively. Patients in prospectively recruited cohorts were provided with a detailed explanation and written informed consent was obtained from each patient or their family. The investigation was performed in accordance with all relevant local guidelines and regulations, and adhered to the tenets of the Declaration of Helsinki.

We first reanalyzed previously published T1- and T2-relaxometry data of histologically LrGGs¹⁶ and compared these T1- and T2-relaxometry data with rT1/T2 (the reanalyzed cohort, Fig. 1). The T1- and T2-relaxometry had been performed using MP2RAGE and multi-echo T2-weighted images of nine patients with glioma. Thus, we could access the T1- and T2-relaxometry along with the rT1/T2 data of these nine patients, and included the data of eight of these in our analyses, after excluding one patient with a K27M mutant tumor¹⁶.

Overall study cohort. First the correlation of rT1/T2 with T1- and T2-relaxation time was investigated by reanalyzing the raw data from ref.¹⁶. Then, the study was conducted in two stages, as an exploratory cohort study followed by a validation cohort study to investigate the correlation of rT1/T2 and IDH mutation status of histologically confirmed LrGGs. IDHmt, IDH-mutant; IDHwt, IDH-wildtype; AMUH, Asahikawa Medical University Hospital; OICI, Osaka International Cancer Institute; TCIA/TCGA, Cancer Imaging Archive / Cancer Genome Atlas.

We then prepared a new set of three cohorts and conducted a two-stage study (Fig. 1). The first cohort (exploratory cohort) comprised 25 histologically and molecularly confirmed histologically LrGGs (IDHwt: 8, IDHmt: 17) treated at Asahikawa Medical University Hospital (AMUH). The second and third cohorts were used as validation cohorts. Validation cohort 1 comprised 29 patients (IDHwt: 13, IDHmt: 16) from the Osaka International Cancer Institute (OICI) and validation cohort 2 comprised 101 patients (IDHwt: 19, IDHmt: 82) from the Cancer Imaging Archive (TCIA)/Cancer Genome Atlas (TCGA) low-grade glioma collection dataset, accessed on February 1, 2020^20,21. Validation cohort 1 can be considered as a “domestic” and validation cohort 2 as an “international” validation cohort.

The pathological diagnosis was based on the 2016 WHO Classification of Tumors of the Central Nervous System²². IDHwt tumors in the present cohorts could not be fully characterized according to the 2021 WHO classification system, as molecular analyses for such as TERT promoter mutation, EGFR gene amplification, and + 7/− 10 chromosome copy-number alterations had not been performed. The inclusion criterion was availability of T1WI and T2WI. Excluded were patients with failed image co-registration or insufficient or atypical images (e.g., with tumoral hemorrhage). Table ^S1 provides detailed information regarding all three cohorts.