T 1 ρ $$ {}_{1\rho } $$ as a Biomarker for IDH1 Mutation Status in a Glioma Mouse Model

Abstract

Glioma is a common and often aggressive malignant brain cancer for which treatment is in part dependent on the mutation status of the IDH gene. Current diagnostic methods require a biopsy and genetic analysis to obtain IDH status, which can have lengthy wait times. T ${}_{1\rho }$ , the spin-lattice relaxation in the rotating frame, has shown potential to serve as a faster, non-invasive means of IDH1-typing that could be implemented at clinically relevant field strengths; however, there have been few studies to date that have explored its utility. This study consisted of three groups of five mice: naïve controls, IDH1-wild-type glioma bearing and IDH1-mutant glioma bearing, imaged once weekly with a T ${}_{1\rho }$ -prepped EPI sequence. It was found that IDH1-mutant gliomas exhibited significantly higher T ${}_{1\rho }$ values in the tumour compared with the brain, while IDH1-wild-type gliomas presented similar T ${}_{1\rho }$ values in the tumour and brain. T ${}_{1\rho }$ was found to be sensitive to whole-brain changes linked to glioma and IDH status, although further investigations into the confounding effects related to T ${}_1$ and T ${}_2$ differences are needed. A measurement of tumour T ${}_{1\rho }$ normalised to the brain ( $\Delta$ T ${}_{1\rho }$ ) was able to distinguish between IDH1-mutant and -wild-type glioma, with IDH1-mutant mice exhibiting an average $\Delta$ T ${}_{1\rho }$ of $\sim$ 29% and IDH1-wild-type mice having an average $\Delta$ T ${}_{1\rho }$ of only $\sim$ 3%. $\Delta$ T ${}_{1\rho }$ may thus have the capacity to serve as a non-invasive biomarker for IDH1 typing.

Keywords: IDH1; MRI; T 1 ρ $$ {}_{1\rho } $$ ; brain; glioma; preclinical; quantitative imaging.

FIGURE 1

Timeline of the study. All mice from Group 1 (G1), Group 2 (G2) and Group 3 (G3) were imaged once weekly, beginning 1 week after glioma cell injections. Mice were terminated throughout the study if they became significantly ill or the tumour grew too large. Created in BioRender. Brewer, K. (2025) https://BioRender.com/n295w4l.

FIGURE 2

Pulse sequence diagram of the multislice T sequence created for this study, which consists of a composite spin‐lock module to prepare T contrast followed by an EPI readout module and a 2‐s recovery delay to restore magnetisation (not to scale).

FIGURE 3

Same‐slice axial images of a representative mouse from Group 2 (IDH1 wild type; top row, Panels A–C) and Group 3 (IDH1 mutant; bottom row, Panels D–F), taken at Week 3. (A,D) T‐FSE anatomical image, where the tumour can be seen as the lighter contrast within the brain. (B,E) T‐weighted image acquired with TSL = 15 ms and FSL = 2000 Hz. (C,F) T‐FSE with T map from FSL = 2000 Hz overlaid within the ROIs for brain and tumour.

FIGURE 4

Comparisons of T values in brain and tumour ROIs for the three groups at each FSL. Boxes depict sample median along with upper and lower quartiles, with whiskers denoting the maximum and minimum values of the sample. Group means are plotted as filled markers, while open markers denote outliers (points more than 1.5 times the interquartile range away from upper/lower quartiles). Statistically significant differences in ROI values within an FSL are highlighted by *.

FIGURE 5

Comparisons of $\mathrm{\Delta }$T values between Group 2 (IDH1 wild type) and Group 3 (IDH1 mutant) mice at each FSL. Boxes depict sample median along with upper and lower quartiles, with whiskers denoting the maximum and minimum values of the sample. Group means are plotted as filled markers. Statistically significant differences in group values within an FSL are highlighted by *.

FIGURE 6

Comparisons of normalised T dispersion ratios in tumour ROIs between Groups 2 and 3 at each FSL combination. Boxes depict sample median along with upper and lower quartiles, with whiskers denoting the maximum and minimum values of the sample. Group means are plotted as filled markers, while open markers denote outliers (points more than 1.5 times the interquartile range away from upper/lower quartiles).

FIGURE 7

T metrics at FSL = 1000 Hz plotted week‐wise. Boxes depict sample median along with upper and lower quartiles, with whiskers denoting the maximum and minimum values of the sample. Group means are plotted as filled markers. (A) Brain T values for each group. (B) Tumour T values for tumour‐bearing mice. (C) $\mathrm{\Delta }$T values for tumour‐bearing mice.