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.

ObjectivesTo investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis.MethodsVolumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods.ResultsIsocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10−6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9–0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98).ConclusionsADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study.Key Points • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study

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Achalasia is a motility disorder of the esophagus with hallmark features of failed lower esophageal sphincter (LES) relaxation and absence of normal peristalsis in the esophageal body. The former leads to esophageal stasis which is responsible for most of the symptoms in achalasia. All therapies for achalasia aim to disrupt the non-relaxing LES in order to facilitate esophageal emptying. Although achalasia response to therapy is primarily measured subjectively through various symptom scoring systems, objective