Surgery of Motor Eloquent Glioblastoma Guided by TMS-Informed Tractography: Driving Resection Completeness Towards Prolonged Survival.

Background: Surgical treatment of patients with glioblastoma affecting motor eloquent brain regions remains critically discussed given the risk-benefit dilemma of prolonging survival at the cost of motor-functional damage. Tractography informed by navigated transcranial magnetic stimulation (nTMS-informed tractography, TIT) provides a rather robust estimate of the individual location of the corticospinal tract (CST), a highly vulnerable structure with poor functional reorganisation potential. We hypothesised that by a more comprehensive, individualised surgical decision-making using TIT, tumours in close relationship to the CST can be resected with at least equal probability of gross total resection (GTR) than less eloquently located tumours without causing significantly more gross motor function harm. Moreover, we explored whether the completeness of TIT-aided resection translates to longer survival. Methods: A total of 61 patients (median age 63 years, m = 34) with primary glioblastoma neighbouring or involving the CST were operated on between 2010 and 2015. TIT was performed to inform surgical planning in 35 of the patients (group T; vs. 26 control patients). To achieve largely unconfounded group comparisons for each co-primary outcome (i.e., gross-motor functional worsening, GTR, survival), (i) uni- and multivariate regression analyses were performed to identify features of optimal outcome prediction; (ii), optimal propensity score matching (PSM) was applied to balance those features pairwise across groups, followed by (iii) pairwise group comparison. Results: Patients in group T featured a significantly higher lesion-CST overlap compared to controls (8.7 ± 10.7% vs. 3.8 ± 5.7%; p = 0.022). The frequency of gross motor worsening was higher in group T, albeit non-significant (n = 5/35 vs. n = 0/26; p = 0.108). PSM-based paired-sample comparison, controlling for the confounders of preoperative tumour volume and vicinity to the delicate vasculature of the insula, showed higher GTR rates in group T (77% vs. 69%; p = 0.025), particularly in patients with a priori intended GTR (87% vs. 78%; p = 0.003). This translates into a prolonged PFS in the same PSM subgroup (8.9 vs. 5.8 months; p = 0.03), with GTR representing the strongest predictor of PFS (p = 0.001) and OS (p = 0.0003) overall. Conclusion: The benefit of TIT-aided GTR appears to overcome the drawbacks of potentially elevated motor functional risk in motor eloquent tumour localisation, leading to prolonged survival of patients with primary glioblastoma close to the CST.

Invasive versus non-invasive mapping of the motor cortex.

Precise and comprehensive mapping of somatotopic representations in the motor cortex is clinically essential to achieve maximum resection of brain tumours whilst preserving motor function, especially since the current gold standard, that is, intraoperative direct cortical stimulation (DCS), holds limitations linked to the intraoperative setting such as time constraints or anatomical restrictions. Non-invasive techniques are increasingly relevant with regard to pre-operative risk-assessment. Here, we assessed the congruency of neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) with DCS. The motor representations of the hand, the foot and the tongue regions of 36 patients with intracranial tumours were mapped pre-operatively using nTMS and fMRI and by intraoperative DCS. Euclidean distances (ED) between hotspots/centres of gravity and (relative) overlaps of the maps were compared. We found significantly smaller EDs (11.4 ± 8.3 vs. 16.8 ± 7.0 mm) and better spatial overlaps (64 ± 38% vs. 37 ± 37%) between DCS and nTMS compared with DCS and fMRI. In contrast to DCS, fMRI and nTMS mappings were feasible for all regions and patients without complications. In summary, nTMS seems to be the more promising non-invasive motor cortex mapping technique to approximate the gold standard DCS results.

Fully automated detection and segmentation of meningiomas using deep learning on routine multiparametric MRI.

OBJECTIVES: Magnetic resonance imaging (MRI) is the method of choice for imaging meningiomas. Volumetric assessment of meningiomas is highly relevant for therapy planning and monitoring. We used a multiparametric deep-learning model (DLM) on routine MRI data including images from diverse referring institutions to investigate DLM performance in automated detection and segmentation of meningiomas in comparison to manual segmentations. METHODS: We included 56 of 136 consecutive preoperative MRI datasets [T1/T2-weighted, T1-weighted contrast-enhanced (T1CE), FLAIR] of meningiomas that were treated surgically at the University Hospital Cologne and graded histologically as tumour grade I (n = 38) or grade II (n = 18). The DLM was trained on an independent dataset of 249 glioma cases and segmented different tumour classes as defined in the brain tumour image segmentation benchmark (BRATS benchmark). The DLM was based on the DeepMedic architecture. Results were compared to manual segmentations by two radiologists in a consensus reading in FLAIR and T1CE. RESULTS: The DLM detected meningiomas in 55 of 56 cases. Further, automated segmentations correlated strongly with manual segmentations: average Dice coefficients were 0.81 ± 0.10 (range, 0.46-0.93) for the total tumour volume (union of tumour volume in FLAIR and T1CE) and 0.78 ± 0.19 (range, 0.27-0.95) for contrast-enhancing tumour volume in T1CE. CONCLUSIONS: The DLM yielded accurate automated detection and segmentation of meningioma tissue despite diverse scanner data and thereby may improve and facilitate therapy planning as well as monitoring of this highly frequent tumour entity. KEY POINTS: • Deep learning allows for accurate meningioma detection and segmentation • Deep learning helps clinicians to assess patients with meningiomas • Meningioma monitoring and treatment planning can be improved.

Transluminal angioplasty and stenting versus conservative treatment in patients with symptomatic basilar artery stenosis : Perspective for future clinical trials.

PURPOSE: Two recent randomized controlled trials (RCT) consistently showed superiority of aggressive medical treatment versus percutaneous transluminal angioplasty and stenting (PTAS) in patients with intracranial artery stenosis. Patients with symptomatic basilar stenosis have a higher long-term risk of recurrent stroke compared to patients with anterior circulation stenosis but no study has specifically focused on the role of PTAS in this subgroup. The aim of our study was to investigate the subgroup of patients with symptomatic basilar artery stenosis to find evidence for the feasibility of a future clinical trial. METHODS: Patients with ischemic stroke caused by a symptomatic basilar stenosis and admitted to five German tertiary care hospitals were included in this multicenter effectiveness study. Primary outcome was a composite endpoint of stroke recurrence, clinically relevant restenosis, progression and death. Shared frailty Cox regression models were used to compare outcome rates between groups. RESULTS: Of the 139 patients included in the study 79 (57 %) underwent PTAS and 60 (43 %) conservative treatment alone. The median follow-up period was 300 (IQR 18-738) days. Risks of the primary composite outcome (hazard ratio HR 0.49, 95 % confidence interval CI 0.25-0.97, p = 0.039) and of the key secondary outcomes recurrent stroke (HR 0.42, 95 % CI 0.19-0.95, p = 0.037) and clinically relevant restenosis/progression (HR 0.12, 95 % CI 0.03-0.59, p = 0.009) were lower in patients with PTAS compared to conservative treatment. There was no difference in all-cause mortality between groups (HR 0.98, 95 % CI 0.19-5.09, p = 0.979). CONCLUSION: In this retrospective study we could not reproduce the findings from large RCTs on intracranial stenting. Our data could be considered as a basis for a prospective study on patient selection for PTAS in the basilar artery.

Functional MRI vs. navigated TMS to optimize M1 seed volume delineation for DTI tractography. A prospective study in patients with brain tumours adjacent to the corticospinal tract.

BACKGROUND: DTI-based tractography is an increasingly important tool for planning brain surgery in patients suffering from brain tumours. However, there is an ongoing debate which tracking approaches yield the most valid results. Especially the use of functional localizer data such as navigated transcranial magnetic stimulation (nTMS) or functional magnetic resonance imaging (fMRI) seem to improve fibre tracking data in conditions where anatomical landmarks are less informative due to tumour-induced distortions of the gyral anatomy. We here compared which of the two localizer techniques yields more plausible results with respect to mapping different functional portions of the corticospinal tract (CST) in brain tumour patients. METHODS: The CSTs of 18 patients with intracranial tumours in the vicinity of the primary motor area (M1) were investigated by means of deterministic DTI. The core zone of the tumour-adjacent hand, foot and/or tongue M1 representation served as cortical regions of interest (ROIs). M1 core zones were defined by both the nTMS hot-spots and the fMRI local activation maxima. In addition, for all patients, a subcortical ROI at the level of the inferior anterior pons was implemented into the tracking algorithm in order to improve the anatomical specificity of CST reconstructions. As intra-individual control, we additionally tracked the CST of the hand motor region of the unaffected, i.e., non-lesional hemisphere, again comparing fMRI and nTMS M1 seeds. The plausibility of the fMRI-ROI- vs. nTMS-ROI-based fibre trajectories was assessed by a-priori defined anatomical criteria. Moreover, the anatomical relationship of different fibre courses was compared regarding their distribution in the anterior-posterior direction as well as their location within the posterior limb of the internal capsule (PLIC). RESULTS: Overall, higher plausibility rates were observed for the use of nTMS- as compared to fMRI-defined cortical ROIs (p < 0.05) in tumour vicinity. On the non-lesional hemisphere, however, equally good plausibility rates (100%) were observed for both localizer techniques. fMRI-originated fibres generally followed a more posterior course relative to the nTMS-based tracts (p < 0.01) in both the lesional and non-lesional hemisphere. CONCLUSION: NTMS achieved better tracking results than fMRI in conditions when the cortical tract origin (M1) was located in close vicinity to a brain tumour, probably influencing neurovascular coupling. Hence, especially in situations with altered BOLD signal physiology, nTMS seems to be the method of choice in order to identify seed regions for CST mapping in patients.

Quantitative T2* mapping reveals early temporo-spatial dynamics in an ischemic stroke model.

BACKGROUND: Oxyhemoglobin-sensitive sequences, namely T2*, can indirectly depict changes in oxygen extraction. Purpose of this study was to investigate the dynamics of T2* changes in ischemic tissue. NEW METHOD: We investigated earliest temporo-spatial dynamics within ischemic tissue, measured with quantitative T2* imaging in the histologically defined infarct core and surrounding surviving tissue. Middle cerebral artery occlusion (MCAO) was induced by a filament model in mice. Serial multiple gradient-echo T2* sequences and diffusion-weighted images were acquired for 60min after MCAO and repeated for 60min after recanalization. T2* maps were co-registered with histology and T2* changes were compared to the contralateral hemisphere. RESULTS: Within the histologically defined infarct core, relative T2* values decreased significantly by -10.8±2.8% (P=0.003) compared to the contralateral hemisphere within 3.5±0.7min after MCAO. Relative T2* values in volume exceeding the histologically determined infarct core were significantly less decreased (-6.7±2.1%; P=0.02) and increased after recanalization (+3.9±1.9%; P=0.045). Volume with T2* decrease showed continuous growth over 60min after MCAO (P=0.002) and decreased during 60min after recanalization (P=0.026), showing most significant correlations between infarct core volume and T2* abnormality volume (r=0.66; P=0.037) of the last image acquired after recanalization. COMPARISON WITH EXISTING METHOD(S): To our best knowledge, this is the first application of non-invasive quantitative T2* measurements to assess changes in levels of deoxyhemoglobin as an indirect biomarker for metabolic impairment in ischemic tissue. CONCLUSIONS: Quantitative T2* imaging might be a feasible tool to indicate change of oxygenation in acute stroke imaging, without administration of contrast agent.

Improved nTMS- and DTI-derived CST tractography through anatomical ROI seeding on anterior pontine level compared to internal capsule.

Imaging of the course of the corticospinal tract (CST) by diffusion tensor imaging (DTI) is useful for function-preserving tumour surgery. The integration of functional localizer data into tracking algorithms offers to establish a direct structure-function relationship in DTI data. However, alterations of MRI signals in and adjacent to brain tumours often lead to spurious tracking results. We here compared the impact of subcortical seed regions placed at different positions and the influences of the somatotopic location of the cortical seed and clinical co-factors on fibre tracking plausibility in brain tumour patients. The CST of 32 patients with intracranial tumours was investigated by means of deterministic DTI and neuronavigated transcranial magnetic stimulation (nTMS). The cortical seeds were defined by the nTMS hot spots of the primary motor area (M1) of the hand, the foot and the tongue representation. The CST originating from the contralesional M1 hand area was mapped as intra-individual reference. As subcortical region of interests (ROI), we used the posterior limb of the internal capsule (PLIC) and/or the anterior inferior pontine region (aiP). The plausibility of the fibre trajectories was assessed by a-priori defined anatomical criteria. The following potential co-factors were analysed: Karnofsky Performance Scale (KPS), resting motor threshold (RMT), T1-CE tumour volume, T2 oedema volume, presence of oedema within the PLIC, the fractional anisotropy threshold (FAT) to elicit a minimum amount of fibres and the minimal fibre length. The results showed a higher proportion of plausible fibre tracts for the aiP-ROI compared to the PLIC-ROI. Low FAT values and the presence of peritumoural oedema within the PLIC led to less plausible fibre tracking results. Most plausible results were obtained when the FAT ranged above a cut-off of 0.105. In addition, there was a strong effect of somatotopic location of the seed ROI; best plausibility was obtained for the contralateral hand CST (100%), followed by the ipsilesional hand CST (>95%), the ipsilesional foot (>85%) and tongue (>75%) CST. In summary, we found that the aiP-ROI yielded better tracking results compared to the IC-ROI when using deterministic CST tractography in brain tumour patients, especially when the M1 hand area was tracked. In case of FAT values lower than 0.10, the result of the respective CST tractography should be interpreted with caution with respect to spurious tracking results. Moreover, the presence of oedema within the internal capsule should be considered a negative predictor for plausible CST tracking.