An algorithm based on standard MRI sequences and age predicted isocitrate dehydrogenase status in lower grade gliomas with comparable accuracy to advanced MRI sequences and computational methods. Key results • Apparent diffusion coefficient (ADC) measurements (minimum, mean) and their ratios to normal appearing white matter were reproducible (intraclass correlation coefficient 0.83-0.96) and distinguished three lower grade glioma subtypes: isocitrate dehydrogenase (IDH) wild-type, IDH mutant/1p19q intact, and IDH mutant/1p19q co-deleted (p<0.001). • A negative association (β 0.09, Pseudo R 2 0.34) was identified between age and IDH mutations (p<0.001). Glioma location, enhancement characteristics, calcification, and cyst formation were univariable and multivariable predictors of IDH genotype. • Two predictive models incorporating ADC, age and morphology defined IDH genotype with accuracies of 92% and 91% (AUC 0.94-0.96). Commented [BE1]: Thank you for your revision. Most of the reviewers' comments have been addressed. There are a few remaining issues, though. Please see the reviewers' comments and the attached document with changes tracked. If you agree with these changes, please accept them. If you disagree, please annotate your responses. Deleted: clinically relevant Deleted: modalities Commented [BE2]: Or did you really mean other modalities, e.g. PET? Commented [WU3]: Please include numerical data in addition to p values.
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