Automated magnetic resonance imaging quantification of cerebral parenchymal and ventricular volume following subarachnoid hemorrhage: associations with cognition.

This study aims to investigate cerebral parenchymal and ventricular volume changes after subarachnoid hemorrhage (SAH) and their potential association with cognitive impairment. 17 patients with aneurysmal SAH (aSAH) and 21 patients with angiographically negative SAH (anSAH) without visually apparent parenchymal loss on conventional magnetic resonance imaging (MRI) were included, along with 76 healthy controls. Volumetric analyses were performed using an automated clinical segmentation and quantification tool. Measurements were compared to on-board normative reference database (n = 1923) adjusted for age, sex, and intracranial volume. Cognition was assessed with tests for psychomotor speed, attentional control, (working) memory, executive functioning, and social cognition. All measurements took place 5 months after SAH. Lower cerebral parenchymal volumes were most pronounced in the frontal lobe (aSAH: n = 6 [35%], anSAH n = 7 [33%]), while higher volumes were most substantial in the lateral ventricle (aSAH: n = 5 [29%], anSAH n = 9 [43%]). No significant differences in regional brain volumes were observed between both SAH groups. Patients with lower frontal lobe volume exhibited significantly lower scores in psychomotor speed (U = 81, p = 0.02) and attentional control (t = 2.86, p = 0.004). Additionally, higher lateral ventricle volume was associated with poorer memory (t = 3.06, p = 0.002). Regional brain volume changes in patients with SAH without visible parenchymal abnormalities on MRI can still be quantified using a fully automatic clinical-grade tool, exposing changes which may contribute to cognitive impairment. Therefore, it is important to provide neuropsychological assessment for both SAH groups, also including those with clinically mild symptoms.

Spatial distribution of cerebral microbleeds and FLAIR hyperintensities on follow-up MRI after radiotherapy for lower grade glioma.

Background and purpose: Cerebral microbleeds (CMBs) and fluid-attenuated-inversion recovery (FLAIR) hyperintensities on brain MRI scans after radiotherapy (RT) are considered markers for microvascular damage and related cognitive changes. However, the spatial distribution using existing scoring systems as well as colocation of these imaging biomarkers remain unclear, hampering clinical interpretation. This study aims to elucidate the distribution and colocation of these markers in patients with lower grade glioma (LGG). Materials and methods: CMBs were spatially classified on retrospective 1.5 T susceptibility weighted MRI scans according to the existing Microbleed Anatomical Rating Scale (MARS) and were additionally scored for being located in hippocampus, amygdala, cortex, white matter (WM), grey matter (GM), WM/GM junction and for their spatial relation to FLAIR hyperintensities. Scoring was performed for whole, ipsilateral and contralateral cerebrum (with respect to tumour bulk). Results: Fifty-one scans were included of which 28 had at least one CMB. The majority of CMBs were localized in the lobar area and in deep and periventricular white matter (DPWM) - generally in WM. Only few CMBs were found in GM. In scans obtained up to 7 years after RT completion the majority of CMBs were not colocalized with FLAIR hyperintensities. Conclusion: CMBs and FLAIR hyperintensities appear to be separate imaging biomarkers for radiation therapy induced microvascular damage, as they are not colocalized in patients with LGG, especially not early on after completion of RT.

The Correlation of In Vivo MR Spectroscopy and Ex Vivo 2-Hydroxyglutarate Concentration for the Prediction of Isocitrate Dehydrogenase Mutation Status in Diffuse Glioma.

Isocitrate dehydrogenase (IDH) mutation status is an important biomarker in the glioma-defining subtype and corresponding prognosis. This study proposes a straightforward method for 2-hydroxyglutarate (2-HG) quantification by MR spectroscopy for IDH mutation status detection and directly compares in vivo 2-HG MR spectroscopy with ex vivo 2-HG concentration measured in resected tumor tissue. Eleven patients with suspected lower-grade glioma (ten IDH1; one IDHwt) were prospectively included. Preoperatively, 3T point-resolved spectroscopy (PRESS) was acquired; 2-HG was measured as the percentage elevation of Glx3 (the sum of 2-HG and Glx) compared to Glx4. IDH mutation status was assessed by immunochemistry or direct sequencing. The ex vivo 2-HG concentration was determined in surgically obtained tissue specimens using gas chromatography-mass spectrometry. Pearson correlation was used for assessing the correlation between in vivo MR spectroscopy and ex vivo 2-HG concentration. MR spectroscopy was positive for 2-HG in eight patients, all of whom had IDH1 tumors. A strong correlation (r = 0.80, p = 0.003) between 2-HG MR spectroscopy and the ex vivo 2-HG concentration was found. This study shows in vivo 2-HG MR spectroscopy can non-invasively determine IDH status in glioma and demonstrates a strong correlation with ex vivo 2-HG concentration in patients with lower-grade glioma.

Clinical relevance of the radiation dose bath in lower grade glioma, a cross-sectional pilot study on neurocognitive and radiological outcome.

Aim: To investigate the clinical relevance of the radiotherapy (RT) dose bath in patients treated for lower grade glioma (LGG). Methods: Patients (n = 17) treated with RT for LGG were assessed with neurocognitive function (NCF) tests and structural Magnetic Resonance Imaging (MRI) and categorized in subgroups based on tumour lateralisation. RT dose, volumetric results and cerebral microbleed (CMB) number were extracted for contralateral cerebrum, contralateral hippocampus, and cerebellum. The RT clinical target volume (CTV) was included in the analysis as a surrogate for focal tumour and other treatment effects. The relationships between RT dose, CTV, NCF and radiological outcome were analysed per subgroup. Results: The subgroup with left-sided tumours (n = 10) performed significantly lower on verbal tests. The RT dose to the right cerebrum, as well as CTV, were related to poorer performance on tests for processing speed, attention, and visuospatial abilities, and more CMB.In the subgroup with right-sided tumours (n = 7), RT dose in the left cerebrum was related to lower verbal memory performance, (immediate and delayed recall, r = -0.821, p = 0.023 and r = -0.937, p = 0.002, respectively), and RT dose to the left hippocampus was related to hippocampal volume (r = -0.857, p = 0.014), without correlation between CTV and NCF. Conclusion: By using a novel approach, we were able to investigate the clinical relevance of the RT dose bath in patients with LGG more specifically. We used combined MRI-derived and NCF outcome measures to assess radiation-induced brain damage, and observed potential RT effects on the left-sided brain resulting in lower verbal memory performance and hippocampus volume.

Quantifying effects of radiotherapy-induced microvascular injury; review of established and emerging brain MRI techniques.

Microvascular changes are increasingly recognised not only as primary drivers of radiotherapy treatment response in brain tumours, but also as an important contributor to short- and long-term (cognitive) side effects arising from irradiation of otherwise healthy brain tissue. As overall survival of patients with brain tumours is increasing, monitoring long-term sequels of radiotherapy-induced microvascular changes in the context of their potential predictive power for outcome, such as cognitive disability, has become increasingly relevant. Ideally, radiotherapy-induced significant microvascular changes in otherwise healthy brain tissue should be identified as early as possible to facilitate adaptive radiotherapy and to proactively start treatment to minimise the influence on these side-effects on the final outcome. Although MRI is already known to be able to detect significant long-term radiotherapy induced microvascular effects, more recently advanced MR imaging biomarkers reflecting microvascular integrity and function have been reported and might provide a more accurate and earlier detection of microvascular changes. However, the use and validation of both established and new techniques in the context of monitoring early and late radiotherapy-induced microvascular changes in both target-tissue and healthy tissue currently are minimal at best. This review aims to summarise the performance and limitations of existing methods and future opportunities for detection and quantification of radiotherapy-induced microvascular changes, as well as the relation of these findings with key clinical parameters.