Markus Fahlström

Background: Glioblastoma (GBM) shows marked heterogeneity in overall survival (OS), yet robust radiological prognostic markers remain limited. The prognostic value of peritumoral edema and tumor location remains uncertain. Objective: To evaluate whether peritumoral edema, tumor burden, and spatial tumor distribution predict OS using automated MRI analysis and Brain-Grid-based topographical mapping. Methods: In this retrospective study, preoperative T1-contrast-enhanced and T2-FLAIR MRI sequences from 271 patients with IDH-wildtype GBM were analyzed using automated segmentation (Raidionics). Tumor and edema volumes, edema-to-tumor ratio (ETR), and voxel-wise infiltration patterns were extracted. Location was mapped using the Brain-Grid system. Survival was assessed using Kaplan–Meier and multivariable Cox regression adjusted for age and tumor volume, with correction for multiple testing. Results: In multivariable analysis, only age remained a conventional independent predictor of OS (HR 1.03, p < 0.001). Tumor volume, edema volume, and ETR were not associated with survival. In contrast, Brain-Grid analysis identified two centrally located subcortical voxel regions that remained significantly associated with shorter OS after full adjustment and multiple testing correction. Total number of infiltrated voxels showed no prognostic value. Conclusions: Spatially defined subcortical infiltration patterns, rather than global tumor or edema burden, independently stratify survival in GBM. These findings highlight the prognostic relevance of voxel-level tumor topography and support further validation of Brain-Grid-based imaging biomarkers.

Intro: Seizure incidence in diffuse glioma ranges between 60% and 90%. This study aimed to investigate the association between seizures and diffuse glioma in subcortical and cortical brain regions, including white matter tracts.Methods: Adult patients with diffuse glioma at Uppsala University Hospital from 2005 to 2021 were analysed retrospectively. The relationship between tumour location in specific brain voxels and preoperative seizures was examined concerning white matter tract involvement. Tumour volumes were segmented based on T2‐weighted or FLAIR MRI after spatial normalisation to standard space (MNI) and combined to create a location‐specific frequency map.Results: Of the 93 patients meeting the inclusion criteria, 70 (75%) experienced seizures. A significant decreased risk was found in tumours present within the left fronto‐mesial and dorsal voxel (A3C1S1). Increased seizure risk was found in tumours located in the left supramarginal and posterior insular voxel (A4C2S3). The voxels differed in terms of type and extent of white matter networks. Additionally, there was a difference in seizure risk and voxel associations between oligodendrogliomas and astrocytoma, with specific voxels associated with seizures identified in both groups.Conclusion: The study provides new insights into the epileptogenic potential of diffuse gliomas in relation to their spatial distribution, highlighting the need to analyse both cortical and subcortical localisation of tumours. The observed differences in seizure risks across brain regions underscore the need for personalised post‐surgery treatment strategies and further research to understand the pathophysiology of brain tumour‐related epilepsy, BTRE.

Background/Objectives: Olfaction is in many ways the least understood sensory modality. Its organization and connectivity are still under debate. The aim of this study was to investigate the anatomy of the olfactory system by using a cadaver fiber dissection technique and in vivo tractography to attain a deeper understanding of the subcortical connectivity and organization. Methods: Ten cerebral hemispheres were used in this study for white matter dissection according to Klingler’s technique. Measurements of different cortical structures and interhemispheric symmetry were compared. Diffusion tensor imaging sequences from twenty-five healthy individuals from the Human Connectome Project dataset were used to explore the connectivity of the olfactory system using DSI Studio. White matter connectivity between the following were reconstructed in vivo: (1) Olfactory bulb to primary olfactory cortices; (2) Olfactory bulb to secondary olfactory cortices; (3) Primary to secondary olfactory cortices. The DTI metrics of the identified major associative, projection and commissural pathways were subsequently correlated with olfactory function and cognition in seventy-five healthy individuals with Spearman’s rank correlation and the Benjamini–Hochberg method for false discoveries (CI 95%, p < 0.05) using R. Results: 1. The dissection showed that the lateral stria was significantly longer on the left side and projected towards the amygdala, the entorhinal and piriform cortex. 2. The medial stria was not evident as a consistent white matter structure. 3. Both dissection and tractography showed that major associative white matter pathways such as the uncinate fasciculus, the inferior fronto-occipital fasciculus and cingulum supported the connectivity between olfactory areas together with the anterior commissure. 4. No significant correlation was found between DTI metrics and sensory or cognition test results. Conclusions: We present the first combined fiber dissection analysis and tractography of the olfactory system. We propose a novel definition where the primary olfactory network is defined by the olfactory tract/bulb and primary olfactory cortices through the lateral stria only. The uncinate fasciculus, inferior fronto-occipital fasciculus and cingulum are the associative pathways supporting the connectivity between primary and secondary olfactory areas together with the anterior commissure. We suggest considering these structures as a secondary olfactory network. Further work is needed to attain a deeper understanding of the pathological and physiological implications of the olfactory system.

Background: Diffuse astrocytomas preferentially infiltrate eloquent areas affecting the outcome. A preoperative understanding of isocitrate dehydrogenase (IDH) status may offer opportunities for specific targeted therapies impacting treatment management. The aim of this study was to analyze clinical, topographical, radiological in WHO 2 astrocytomas with different IDH status and the long-term patient’s outcome. Methods: A series of confirmed WHO 2 astrocytoma patients (between 2005 and 2015) were retrospectively analyzed. MRI sequences (FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations into the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was used as an overlay for infiltration analysis of each tumor. Long-term follow-up was used to perform a survival analysis. Results: Forty patients with confirmed IDH status (26 IDH-mutant, IDHm/14 IDH-wild type, IDHwt) according to WHO 2021 classification were included with a mean follow-up of 7.8 years. IDHm astrocytomas displayed a lower number of BG-voxels (P < 0.05) and were preferentially located in the anterior insular region. IDHwt group displayed a posterior insular and peritrigonal location. IDHwt group displayed a shorter OS compared with IDHm (P < 0.05), with the infiltration of 7 or more BG-voxels as an independent factor predicting a shorter OS. Conclusions: IDHm and IDHwt astrocytomas differed in preferential location, number of BG-voxels and OS at long follow-up time. The number of BG-voxels affected the OS in IDHwt was possibly reflecting higher tumor invasiveness. We encourage the systematic use of alternative observational tools, such as gradient maps and the Brain-Grid analysis, to better detect differences of tumor invasiveness in diffuse low-grade gliomas subtypes.

Traumatic brain injury (TBI) and sports-related concussion (SRC) may result in chronic functional and neuroanatomical changes. We tested the hypothesis that neuroimaging findings (cerebral blood fl...

Background: Neurological and psychiatric manifestations related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are widely recognised. Standard magnetic resonance imaging (MRI) investigations are normal in 40–80% of symptomatic patients, eventually delaying appropriate treatment when MRI is unrevealing any structural changes. The aim of this study is to investigate white matter abnormalities during an early stage of post-COVID-19 (coronavirus disease 2019) encephalitis while conventional MRI was normal. Methods: A patient with post-COVID-19 autoimmune encephalitis was investigated by serial MRIs and diffusion tensor imaging (DTI). Ten healthy control individuals (HC) were utilised as a control group for the DTI analysis. Major projection, commissural and association white matter pathways were reconstructed, and multiple diffusion parameters were analysed and then compared to the HC average using a z-test for serial examinations. Results: Eleven days after the onset of neurological symptoms, DTI revealed early white matter changes, compared with HC, when standard MRI was normal. On day 68, DTI showed multiple white matter lesions compared with HC, visible at this time also by the MRI images, indicating inflammatory changes in different association and projection white matter pathways. Conclusion: We confirm a limitation in the sensitivity of conventional MRI at the acute setting of post-COVID-19 autoimmune encephalitis. A complementary DTI investigation could be a valuable diagnostic tool in early therapeutic decisions concerning COVID-19-related neurological symptoms.

Traumatic brain injury (TBI) or repeated sport-related concussions (rSRC) may lead to long-term memory impairment. Diffusion tensor imaging (DTI) is helpful to reveal global white matter damage but may underestimate focal abnormalities. We investigated the distribution of post-injury regional white matter changes after TBI and rSRC. Six patients with moderate/severe TBI, and 12 athletes with rSRC were included ≥6 months post-injury, and 10 (age-matched) healthy controls (HC) were analyzed. The Repeatable Battery for the Assessment of Neuropsychological Status was performed at the time of DTI. Major white matter pathways were tracked using q-space diffeomorphic reconstruction and analyzed for global and regional changes with a controlled false discovery rate. TBI patients displayed multiple classic white matter injuries compared with HC (p < 0.01). At the regional white matter analysis, the left frontal aslant tract, anterior thalamic radiation, and the genu of the corpus callosum displayed focal changes in both groups compared with HC but with different trends. Both TBI and rSRC displayed worse memory performance compared with HC (p < 0.05). While global analysis of DTI-based parameters did not reveal common abnormalities in TBI and rSRC, abnormalities to the fronto-thalamic network were observed in both groups using regional analysis of the white matter pathways. These results may be valuable to tailor individualized rehabilitative approaches for post-injury cognitive impairment in both TBI and rSRC patients.

Cerebrovascular reserve capacity (CVR), an important predictor of ischaemic events and a prognostic factor for patients with moyamoya disease (MMD), can be assessed by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Often, a single CBF measurement is performed between 5 and 20 min after ACZ injection. Assessment of the temporal response of the vasodilation secondary to ACZ administration using several repeated CBF measurements has not been studied extensively. Furthermore, the high standard deviations of the group-averaged CVRs reported in the current literature indicate a patient-specific dispersion of CVR values over a wide range. This study aimed to assess the temporal response of the CBF and derived CVR during ACZ challenge using arterial spin labeling in patients with MMD. Eleven patients with MMD were included before or after revascularisation surgery. CBF maps were acquired using pseudo-continuous arterial spin labeling before and 5, 15, and 25 min after an intravenous ACZ injection. A vascular territory template was spatially normalized to patient-specific space, including the bilateral anterior, middle, and posterior cerebral arteries. CBF increased significantly post-ACZ injection in all vascular territories and at all time points. Group-averaged CBF and CVR values remained constant throughout the ACZ challenge in most patients. The maximum increase in CBF occurred most frequently at 5 min post-ACZ injection. However, peaks at 15 or 25 min were also present in some patients. In 68% of the affected vascular territories, the maximum increase in CBF did not occur at 15 min. In individual cases, the difference in CVR between different time points was between 1 and 30% points (mean difference 8% points). In conclusion, there is a substantial variation in CVR between different time points after the ACZ challenge in patients with MMD. Thus, there is a risk that the use of a single post-ACZ measurement time point overestimates disease progression, which could have wide implications for decision-making regarding revascularisation surgery and the interpretation of the outcome thereof. Further studies with larger sample sizes using multiple CBF measurements post-ACZ injection in patients with MMD are encouraged.