Prediction of H3K27M-mutant Brainstem Glioma by Amide Proton Transfer Weighted Imaging and Its Derived Radiomics

Abstract

Purpose H3K27M-mutant associated brainstem glioma (BSG) carries a very poor prognosis. We aimed to predict H3K27M mutation status by amide proton transfer weighted (APTw) imaging and radiomic features. Methods Eighty-one BSG patients with APTw imaging at 3T MRI and known H3K27M status were retrospectively studied. APTw values (mean, median and max) and radiomic features within manually delineated 3D tumor masks were extracted. Comparison of APTw measures between H3K27M-mutant and wildtype groups was conducted by two-sample Student’s T/Mann-Whitney U test and receiver operating characteristic curve (ROC) analysis. H3K27M-mutant prediction using APTw-derived radiomics was conducted using a machine-learning algorithm in randomly selected train (n=64) and test (n=17) sets. Sensitivity analysis with additional random splits of train and test sets, 2D tumor masks and other classifiers were conducted. Finally, a prospective cohort including 29 BSG patients was acquired for validation of the radiomics algorithm. Results BSG patients with H3K27M-mutant were younger and had higher max APTw values than those with wildtype. APTw-derived radiomic measures reflecting tumor heterogeneity could predict H3K27M mutation status with an accuracy of 0.88, sensitivity of 0.92 and specificity of 0.80 in the test set. Sensitivity analysis confirmed the predictive ability (accuracy range: 0.71-0.94). In the independent prospective validation cohort, the algorithm reached an accuracy of 0.86, sensitivity of 0.88 and specificity of 0.85 for predicting H3K27M-mutation status. Conclusion BSG patients with H3K27M-mutant had higher max APTw values than those with wildtype. APTw-derived radiomics could accurately predict a H3K27M-mutant status in BSG patients.

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

“…Data from numerous institutions worldwide have demonstrated that APTw imaging adds important value to the standard clinical MRI sequences in brain cancer diagnoses, such as the detection and grading of tumors, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] the assessment of treatment effect versus tumor recurrence, [38][39][40][41][42][43][44][45] prognosis related to tumor progression and survival, [46][47][48] and the identification of genetic markers. [49][50][51][52][53][54][55][56] It is worth mentioning that brain tumor patients require frequent MRI exams, and the exposure to gadolinium (Gd)-based contrast agents has been indicated as a risk for people with moderate to advanced kidney failure and for Gd deposition in the brain. [57][58][59] Although promising, there are several remaining challenging issues for clinical APTw imaging.…”

“…Key abbreviations and nomenclatures used in the field of APTw imaging are listed in Table 1. Data from numerous institutions worldwide have demonstrated that APTw imaging adds important value to the standard clinical MRI sequences in brain cancer diagnoses, such as the detection and grading of tumors, 22–37 the assessment of treatment effect versus tumor recurrence, 38–45 prognosis related to tumor progression and survival, 46–48 and the identification of genetic markers 49–56 . It is worth mentioning that brain tumor patients require frequent MRI exams, and the exposure to gadolinium (Gd)‐based contrast agents has been indicated as a risk for people with moderate to advanced kidney failure and for Gd deposition in the brain 57–59 .…”

Sensitivity and specificity of amide proton transfer-weighted imaging for assessing programmed death-ligand 1 status in non-small cell lung cancer: a comparative study with intravoxel incoherent motion and 18F-FDG PET

“…As a relatively novel MRI molecular imaging method, APTWI presents semiquantitative amide proton maps describing the heterogeneous metabolism of mobile proteins and peptides that can reflect the histopathological and genetic changes in tumors (16,17,39). Previous work has shown that higher APTWI signals indicate a high level of mobile protein and peptide metabolism, which was associated with more active cell proliferation, more microscopic necrosis (40), greater microvascular density (41), and an appropriate pH level (42).…”