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To study longitudinal changes in tuber and whole-brain perfusion in children with tuberous sclerosis complex (TSC) using arterial spin labeling (ASL) perfusion MRI and correlate them with pathological EEG slow wave activity and neurodevelopmental outcomes.Retrospective longitudinal cohort study of 13 children with TSC, 3 to 6 serial ASL-MRI scans between 2 months and 7 years of age (53 scans in total), and an EEG examination performed within 2 months of the last MRI. Tuber cerebral blood flow (CBF) values were calculated in tuber segmentation masks, and tuber:cortical CBF ratios were used to study tuber perfusion. Logistic regression analysis was performed to identify which initial tuber characteristics (CBF value, volume, location) in the first MRI predicted tubers subsequently associated with EEG slow waves. Whole-brain and lobar CBF values were extracted for all patient scans and age-matched controls. CBF ratios were compared in patients and controls to study longitudinal changes in whole-brain CBF.Perfusion was reduced in tubers associated with EEG slow waves compared with other tubers. Low tuber CBF values around 6 months of age and large tuber volumes were predictive of tubers subsequently associated with EEG slow waves. Patients with severe developmental delay had more severe whole-brain hypoperfusion than those with no/mild delay, which became apparent after 2 years of age and were not associated with a higher tuber load.Dynamic changes in tuber and brain perfusion occur over time. Perfusion is significantly reduced in tubers associated with EEG slow waves. Whole-brain perfusion is significantly reduced in patients with severe delay.• Tubers associated with EEG slow wave activity were significantly more hypoperfused than other tubers, especially after 1 year of age. • Larger and more hypoperfused tubers at 6 months of age were more likely to subsequently be associated with pathological EEG slow wave activity. • Patients with severe developmental delay had more extensive and severe global hypoperfusion than those without developmental delay.

The diffuse intrinsic pontine gliomas (DIPGs) are now defined by the type of histone H3 mutated at lysine 27. We aimed to correlate the multimodal MRI features of DIPGs, H3K27M mutant, with their histological and molecular characteristics. Twenty-seven treatment-naive children with histopathologically confirmed DIPG H3K27M mutant were prospectively included. MRI performed prior to biopsy included multi-b-value diffusion-weighted imaging, ASL, and dynamic susceptibility contrast (DSC) perfusion imaging. The ADC and cerebral blood flow (CBF) and blood volume (CBV) were measured at the biopsy site. We assessed quantitative histological data, including microvascular density, nuclear density, and H3K27M-positive nuclear density. Gene expression profiling was also assessed in the samples. We compared imaging and histopathological data according to histone subgroup. We correlated MRI quantitative data with histological data and gene expression. H3.1K27M mutated tumors showed higher ADC values (median 3151 μm2/s vs 1741 μm2/s, p = 0.003), and lower perfusion values (DSC-rCBF median 0.71 vs 1.43, p = 0.002, and DSC-rCBV median 1.00 vs 1.71, p = 0.02) than H3.3K27M ones. They had similar microvascular and nuclear density, but lower H3K27M-positive nuclear density (p = 0.007). The DSC-rCBV was positively correlated to the H3K27M-positive nuclear density (rho = 0.74, p = 0.02). ADC values were not correlated with nuclear density nor perfusion values with microvascular density. The expression of gated channel activity–related genes tended to be inversely correlated with ADC values and positively correlated with DSC perfusion. H3.1K27M mutated tumors have higher ADC and lower perfusion values than H3.3K27M ones, without direct correlation with microvascular or nuclear density. This may be due to tissular edema possibly related to gated channel activity–related gene expression. • H3.1K27M mutant DIPG had higher apparent diffusion coefficient (p = 0.003), lower α (p = 0.048), and lower relative cerebral blood volume (p = 0.02) than H3.3K27M mutant DIPG at their biopsy sites. • Biopsy samples obtained within the tumor’s enhancing portion showed higher microvascular density (p = 0.03) than samples obtained outside the tumor’s enhancing portion, but similar H3K27M-positive nuclear density (p = 0.84). • Relative cerebral blood volume measured at the biopsy site was significantly correlated with H3K27M-positive nuclear density (rho = 0.74, p = 0.02).

The diffuse intrinsic pontine gliomas (DIPGs) are now defined by the type of histone H3 mutated at lysine 27. We aimed to correlate the multimodal MRI features of DIPGs, H3K27M mutant, with their histological and molecular characteristics.Twenty-seven treatment-naïve children with histopathologically confirmed DIPG H3K27M mutant were prospectively included. MRI performed prior to biopsy included multi-b-value diffusion-weighted imaging, ASL, and dynamic susceptibility contrast (DSC) perfusion imaging. The ADC and cerebral blood flow (CBF) and blood volume (CBV) were measured at the biopsy site. We assessed quantitative histological data, including microvascular density, nuclear density, and H3K27M-positive nuclear density. Gene expression profiling was also assessed in the samples. We compared imaging and histopathological data according to histone subgroup. We correlated MRI quantitative data with histological data and gene expression.H3.1K27M mutated tumors showed higher ADC values (median 3151 μmH3.1K27M mutated tumors have higher ADC and lower perfusion values than H3.3K27M ones, without direct correlation with microvascular or nuclear density. This may be due to tissular edema possibly related to gated channel activity-related gene expression.• H3.1K27M mutant DIPG had higher apparent diffusion coefficient (p = 0.003), lower α (p = 0.048), and lower relative cerebral blood volume (p = 0.02) than H3.3K27M mutant DIPG at their biopsy sites. • Biopsy samples obtained within the tumor's enhancing portion showed higher microvascular density (p = 0.03) than samples obtained outside the tumor's enhancing portion, but similar H3K27M-positive nuclear density (p = 0.84). • Relative cerebral blood volume measured at the biopsy site was significantly correlated with H3K27M-positive nuclear density (rho = 0.74, p = 0.02).