Diffusion histogram profiles predict molecular features of grade 4 in histologically lower-grade adult diffuse gliomas following WHO classification 2021.

Objectives: In the latest World Health Organization classification 2021, grade 4 adult diffuse gliomas can be diagnosed with several molecular features even without histological evidence of necrosis or microvascular proliferation. We aimed to explore whole tumor histogram-derived apparent diffusion coefficient (ADC) histogram profiles for differentiating between the presence (Mol-4) and absence (Mol-2/3) of grade 4 molecular features in histologically lower-grade gliomas.

Methods: Between June 2019 and October 2022, 184 adult patients with diffuse gliomas underwent MRI. After excluding 121 patients, 18 (median age, 64.5 [range, 37-84 years]) Mol-4 and 45 (median 40 [range, 18-73] years) Mol-2/3 patients with histologically lower-grade gliomas were enrolled. Whole tumor volume-of-interest-derived ADC histogram profiles were calculated and compared between the two groups. Stepwise logistic regression analysis with Akaike's information criterion using the ADC histogram profiles with p values < 0.01 and age at diagnosis was used to identify independent variables for predicting the Mol-4 group.

Results: The 90th percentile (p < 0.001), median (p < 0.001), mean (p < 0.001), 10th percentile (p = 0.014), and entropy (p < 0.001) of normalized ADC were lower, and kurtosis (p < 0.001) and skewness (p = 0.046) were higher in the Mol-4 group than in the Mol-2/3 group. Multivariate logistic regression analysis revealed that the entropy of normalized ADC and age at diagnosis were independent predictive parameters for the Mol-4 group with an area under the curve of 0.92.

Conclusion: ADC histogram profiles may be promising preoperative imaging biomarkers to predict molecular grade 4 among histologically lower-grade adult diffuse gliomas.

Clinical Relevance Statement: This study highlighted the diagnostic usefulness of ADC histogram profiles to differentiate histologically lower grade adult diffuse gliomas with the presence of molecular grade 4 features and those without.

Key Points: • ADC histogram profiles to predict molecular CNS WHO grade 4 status among histologically lower-grade adult diffuse gliomas were evaluated. • Entropy of ADC and age were independent predictive parameters for molecular grade 4 status. • ADC histogram analysis is useful for predicting molecular grade 4 among histologically lower-grade gliomas.