The parietal architecture binding cognition to sensorimotor integration: a multimodal causal study.

Despite human's praxis abilities are unique among primates, comparative observations suggest that these cognitive motor skills could have emerged from exploitation and adaptation of phylogenetically older building blocks, namely the parieto-frontal networks subserving prehension and manipulation. Within this framework, investigating to which extent praxis and prehension-manipulation overlap and diverge within parieto-frontal circuits could help in understanding how human cognition shapes hand actions. This issue has never been investigated by combining lesion mapping and direct electrophysiological approaches in neurosurgical patients. To this purpose, 79 right-handed left-brain tumour patient candidates for awake neurosurgery were selected based on inclusion criteria. First, a lesion mapping was performed in the early postoperative phase to localize the regions associated with an impairment in praxis (imitation of meaningless and meaningful intransitive gestures) and visuo-guided prehension (reaching-to-grasping) abilities. Then, lesion results were anatomically matched with intraoperatively identified cortical and white matter regions, whose direct electrical stimulation impaired the Hand Manipulation Task. The lesion mapping analysis showed that prehension and praxis impairments occurring in the early postoperative phase were associated with specific parietal sectors. Dorso-mesial parietal resections, including the superior parietal lobe and precuneus, affected prehension performance, while resections involving rostral intraparietal and inferior parietal areas affected praxis abilities (covariate clusters, 5000 permutations, cluster-level family-wise error correction P < 0.05). The dorsal bank of the rostral intraparietal sulcus was associated with both prehension and praxis (overlap of non-covariate clusters). Within praxis results, while resection involving inferior parietal areas affected mainly the imitation of meaningful gestures, resection involving intraparietal areas affected both meaningless and meaningful gesture imitation. In parallel, the intraoperative electrical stimulation of the rostral intraparietal and the adjacent inferior parietal lobe with their surrounding white matter during the hand manipulation task evoked different motor impairments, i.e. the arrest and clumsy patterns, respectively. When integrating lesion mapping and intraoperative stimulation results, it emerges that imitation of praxis gestures first depends on the integrity of parietal areas within the dorso-ventral stream. Among these areas, the rostral intraparietal and the inferior parietal area play distinct roles in praxis and sensorimotor process controlling manipulation. Due to its visuo-motor 'attitude', the rostral intraparietal sulcus, putative human homologue of monkey anterior intraparietal, might enable the visuo-motor conversion of the observed gesture (direct pathway). Moreover, its functional interaction with the adjacent, phylogenetic more recent, inferior parietal areas might contribute to integrate the semantic-conceptual knowledge (indirect pathway) within the sensorimotor workflow, contributing to the cognitive upgrade of hand actions.

Stimulation of frontal pathways disrupts hand muscle control during object manipulation.

The activity of frontal motor areas during hand-object interaction is coordinated by dense communication along specific white matter pathways. This architecture allows the continuous shaping of voluntary motor output but, despite extensive investigation in non-human primate studies, remains poorly understood in humans. Disclosure of this system is crucial for predicting and treatment of motor deficits after brain lesions. For this purpose, we investigated the effect of direct electrical stimulation on white matter pathways within the frontal lobe on hand-object manipulation. This was tested in 34 patients (15 left hemisphere, mean age 42 years, 17 male, 15 with tractography) undergoing awake neurosurgery for frontal lobe tumour removal with the aid of the brain mapping technique. The stimulation outcome was quantified based on hand-muscle activity required by task execution. The white matter pathways responsive to stimulation with an interference on muscles were identified by means of probabilistic density estimation of stimulated sites, tract-based lesion-symptom (disconnectome) analysis and diffusion tractography on the single patient level. Finally, we assessed the effect of permanent tract disconnection on motor outcome in the immediate postoperative period using a multivariate lesion-symptom mapping approach. The analysis showed that stimulation disrupted hand-muscle activity during task execution at 66 sites within the white matter below dorsal and ventral premotor regions. Two different EMG interference patterns associated with different structural architectures emerged: (i) an 'arrest' pattern, characterized by complete impairment of muscle activity associated with an abrupt task interruption, occurred when stimulating a white matter area below the dorsal premotor region. Local middle U-shaped fibres, superior fronto-striatal, corticospinal and dorsal fronto-parietal fibres intersected with this region. (ii) a 'clumsy' pattern, characterized by partial disruption of muscle activity associated with movement slowdown and/or uncoordinated finger movements, occurred when stimulating a white matter area below the ventral premotor region. Ventral fronto-parietal and inferior fronto-striatal tracts intersected with this region. Finally, only resections partially including the dorsal white matter region surrounding the supplementary motor area were associated with transient upper-limb deficit (P = 0.05; 5000 permutations). Overall, the results identify two distinct frontal white matter regions possibly mediating different aspects of hand-object interaction via distinct sets of structural connectivity. We suggest the dorsal region, associated with arrest pattern and postoperative immediate motor deficits, to be functionally proximal to motor output implementation, while the ventral region may be involved in sensorimotor integration required for task execution.

Distinct Functional and Structural Connectivity of the Human Hand-Knob Supported by Intraoperative Findings.

Fine motor skills rely on the control of hand muscles exerted by a region of primary motor cortex (M1) that has been extensively investigated in monkeys. Although neuroimaging enables the exploration of this system also in humans, indirect measurements of brain activity prevent causal definitions of hand motor representations, which can be achieved using data obtained during brain mapping in tumor patients. High-frequency direct electrical stimulation delivered at rest (HF-DES-Rest) on the hand-knob region of the precentral gyrus has identified two sectors showing differences in cortical excitability. Using quantitative analysis of motor output elicited with HF DES-Rest, we characterized two sectors based on their excitability, higher in the posterior and lower in the anterior sector. We studied whether the different cortical excitability of these two regions reflected differences in functional connectivity (FC) and structural connectivity (SC). Using healthy adults from the Human Connectome Project (HCP), we computed FC and SC of the anterior and the posterior hand-knob sectors identified within a large cohort of patients. The comparison of FC of the two seeds showed that the anterior hand-knob, relative to the posterior hand-knob, showed stronger functional connections with a bilateral set of parietofrontal areas responsible for integrating perceptual and cognitive hand-related sensorimotor processes necessary for goal-related actions. This was reflected in different patterns of SC between the two sectors. Our results suggest that the human hand-knob is a functionally and structurally heterogeneous region organized along a motor-cognitive gradient.SIGNIFICANCE STATEMENT The capability to perform complex manipulative tasks is one of the major characteristics of primates and relies on the fine control of hand muscles exerted by a highly specialized region of the precentral gyrus, often termed the "hand-knob" sector. Using intraoperative brain mapping, we identify two hand-knob sectors (posterior and anterior) characterized by differences in cortical excitability. Based on resting-state functional connectivity (FC) and tractography in healthy subjects, we show that posterior and anterior hand-knob sectors differ in their functional connectivity (FC) and structural connectivity (SC) with frontoparietal regions. Thus, anteroposterior differences in cortical excitability are paralleled by differences in FC and SC that likely reflect a motor (posterior) to cognitive (anterior) organization of this cortical region.

Motor impairment evoked by direct electrical stimulation of human parietal cortex during object manipulation.

In primates, the parietal cortex plays a crucial role in hand-object manipulation. However, its involvement in object manipulation and related hand-muscle control has never been investigated in humans with a direct and focal electrophysiological approach. To this aim, during awake surgery for brain tumors, we studied the impact of direct electrical stimulation (DES) of parietal lobe on hand-muscles during a hand-manipulation task (HMt). Results showed that DES applied to fingers-representation of postcentral gyrus (PCG) and anterior intraparietal cortex (aIPC) impaired HMt execution. Different types of EMG-interference patterns were observed ranging from a partial (task-clumsy) or complete (task-arrest) impairment of muscles activity. Within PCG both patterns coexisted along a medio (arrest)-lateral (clumsy) distribution, while aIPC hosted preferentially the task-arrest. The interference patterns were mainly associated to muscles suppression, more pronounced in aIPC with respect to PCG. Moreover, within PCG were observed patterns with different level of muscle recruitment, not reported in the aIPC. Overall, EMG-interference patterns and their probabilistic distribution suggested the presence of different functional parietal sectors, possibly playing different roles in hand-muscle control during manipulation. We hypothesized that task-arrest, compared to clumsy patterns, might suggest the existence of parietal sectors more closely implicated in shaping the motor output.

Morphometric study of the ventricular indexes in healthy ovine BRAIN using MRI.

BACKGROUND: Sheep (Ovis aries) have been largely used as animal models in a multitude of specialties in biomedical research. The similarity to human brain anatomy in terms of brain size, skull features, and gyrification index, gives to ovine as a large animal model a better translational value than small animal models in neuroscience. Despite this evidence and the availability of advanced imaging techniques, morphometric brain studies are lacking. We herein present the morphometric ovine brain indexes and anatomical measures developed by two observers in a double-blinded study and validated via an intra- and inter-observer analysis. RESULTS: For this retrospective study, T1-weighted Magnetic Resonance Imaging (MRI) scans were performed at 1.5 T on 15 sheep, under general anaesthesia. The animals were female Ovis aries, in the age of 18-24 months. Two observers assessed the scans, twice time each. The statistical analysis of intra-observer and inter-observer agreement was obtained via the Bland-Altman plot and Spearman rank correlation test. The results are as follows (mean ± Standard deviation): Indexes: Bifrontal 0,338 ± 0,032 cm; Bicaudate 0,080 ± 0,012 cm; Evans' 0,218 ± 0,035 cm; Ventricular 0,241 ± 0,039 cm; Huckman 1693 ± 0,174 cm; Cella Media 0,096 ± 0,037 cm; Third ventricle ratio 0,040 ± 0,007 cm. Anatomical measures: Fourth ventricle length 0,295 ± 0,073 cm; Fourth ventricle width 0,344 ± 0,074 cm; Left lateral ventricle 4175 ± 0,275 cm; Right lateral ventricle 4182 ± 0,269 cm; Frontal horn length 1795 ± 0,303 cm; Interventricular foramen left 1794 ± 0,301 cm; Interventricular foramen right 1,78 ± 0,317 cm. CONCLUSIONS: The present study provides baseline values of linear indexes of the ventricles in the ovine models. The acquisition of these data contributes to filling the knowledge void on important anatomical and morphological features of the sheep brain.

Intraoperative AIRO mobile computer tomography in frameless stereotactic procedures.

BACKGROUND: Multiple factors can affect the accuracy of neuronavigation, that is a relevant issue, particularly for frameless stereotactic procedures, where precision and optimal image-guidance is crucial for the surgical performance, workflow, and outcome. OBJECTIVE: To investigate the impact of AIRO Mobile Computer Tomography in frameless stereotactic approaches. METHODS: A retrospective study on 12 patients was performed. All the procedures were deployed using a frameless stereotactic technique, both for the collection of biopsy pathological specimens for diagnosis and insertion of drainage in the treatment of intracranial cystic lesions. RESULTS: Twelve patients (eight males, four females) underwent the frameless stereotactic procedure. Mean age at surgery was 55 (±5 SE). The mean volume of the lesion was 23.85 cm3 (±3.13). Six diagnostic biopsies and six cyst drainages were performed. The mean trajectory length was 75.9 ± 11.8 mm. Three posterior fossa lesions (27%) were approached through a retro-sigmoidal burr-hole. A craniotomy for draining a haematoma was performed after detection with AIRO-CT. No permanent neurological dysfunction, in-hospital or 30-day mortality were recorded. CONCLUSION: The AIRO-CT resulted feasible with a potential utility for stereotactic procedures. We showed how it could grant the efficacy of the stereotactic procedures reducing some technical and physical sources of inaccuracy, also enhancing safety and allowing prompt detection and management of intraoperative complications.

Insights into Infusion-Based Targeted Drug Delivery in the Brain: Perspectives, Challenges and Opportunities.

Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as in convection-enhanced delivery (CED), provide an important opportunity; however, poor understanding of the pressure-driven drug transport mechanisms in the brain has hindered its ultimate success in clinical applications. In this review, we focus on the biomechanical and biochemical aspects of infusion-based targeted drug delivery in the brain and look into the underlying molecular level mechanisms. We discuss recent advances and challenges in the complementary field of medical robotics and its use in targeted drug delivery in the brain. A critical overview of current research in these areas and their clinical implications is provided. This review delivers new ideas and perspectives for further studies of targeted drug delivery in the brain.

Along-tract statistics of neurite orientation dispersion and density imaging diffusion metrics to enhance MR tractography quantitative analysis in healthy controls and in patients with brain tumors.

Along-tract statistics analysis enables the extraction of quantitative diffusion metrics along specific white matter fiber tracts. Besides quantitative metrics derived from classical diffusion tensor imaging (DTI), such as fractional anisotropy and diffusivities, new parameters reflecting the relative contribution of different diffusion compartments in the tissue can be estimated through advanced diffusion MRI methods as neurite orientation dispersion and density imaging (NODDI), leading to a more specific microstructural characterization. In this study, we extracted both DTI- and NODDI-derived quantitative microstructural diffusion metrics along the most eloquent fiber tracts in 15 healthy subjects and in 22 patients with brain tumors. We obtained a robust intraprotocol reference database of normative along-tract microstructural metrics, and their corresponding plots, from healthy fiber tracts. Each diffusion metric of individual patient's fiber tract was then plotted and statistically compared to the normative profile of the corresponding metric from the healthy fiber tracts. NODDI-derived metrics appeared to account for the pathological microstructural changes of the peritumoral tissue more accurately than DTI-derived ones. This approach may be useful for future studies that may compare healthy subjects to patients diagnosed with other pathological conditions.

Proposed definition of competencies for surgical neuro-oncology training.

OBJECTIVE: The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. METHODS: We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. RESULT: In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families. CONCLUSIONS AND RELEVANCE: The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.

Direct Electrical Stimulation of Premotor Areas: Different Effects on Hand Muscle Activity during Object Manipulation.

Dorsal and ventral premotor (dPM and vPM) areas are crucial in control of hand muscles during object manipulation, although their respective role in humans is still debated. In patients undergoing awake surgery for brain tumors, we studied the effect of direct electrical stimulation (DES) of the premotor cortex on the execution of a hand manipulation task (HMt). A quantitative analysis of the activity of extrinsic and intrinsic hand muscles recorded during and in absence of DES was performed. Results showed that DES applied to premotor areas significantly impaired HMt execution, affecting task-related muscle activity with specific features related to the stimulated area. Stimulation of dorsal vPM induced both a complete task arrest and clumsy task execution, characterized by general muscle suppression. Stimulation of ventrocaudal dPM evoked a complete task arrest mainly due to a dysfunctional recruitment of hand muscles engaged in task execution. These results suggest that vPM and dPM contribute differently to the control of hand muscles during object manipulation. Stimulation of both areas showed a significant impact on motor output, although the different effects suggest a stronger relationship of dPM with the corticomotoneuronal circuit promoting muscle recruitment and a role for vPM in supporting sensorimotor integration.

Large scale networks for human hand-object interaction: Functionally distinct roles for two premotor regions identified intraoperatively.

The development of awake intraoperative brain-mapping procedures for resection of brain tumors is of growing interest in neuroscience, because it enables direct testing of brain tissue, previously only possible in non-human primates. In a recent study performed in this setting specific effects can be induced by direct electrical stimulation on different sectors of premotor cortex during the execution of a hand manipulation task. Specifically, direct electrical stimulation applied on a dorsal sector of precentral cortex led to an increase in motor unit recruitment in hand muscles during execution of a hand manipulation task (Recruitment sector). The opposite effect was elicited when electrical stimulation was delivered more ventrally on the precentral cortex (Suppression sector). We studied whether the different effects on motor behavior induced by direct electrical stimulation applied on the two sites of the precentral cortex underlie differences in their functional connectivity with other brain areas, measured using resting state fMRI. Using healthy adults scanned as part of the Human Connectome Project, we computed the functional connectivity of each sector used as seeds. The functional connectivity patterns of the two intraoperative seeds was similar but cross-comparison revealed that the left and right Recruitment sectors had stronger functional connections with the hand region of the sensorimotor cortex, while the right Suppression region displayed stronger functional connectivity with a bilateral set of parieto-frontal areas crucial for the integration of perceptual and cognitive hand-related sensorimotor processes required for goal-related hand actions. Our results suggest that analyzing data obtained in the intraoperative setting with resting state functional magnetic resonance imaging in healthy brains can yield useful insight into the roles of different premotor sectors directly involved in hand-object interaction.

Frontal pathways in cognitive control: direct evidence from intraoperative stimulation and diffusion tractography.

A key aspect of cognitive control is the management of conflicting incoming information to achieve a goal, termed 'interference control'. Although the role of the right frontal lobe in interference control is evident, the white matter tracts subserving this cognitive process remain unclear. To investigate this, we studied the effect of transient network disruption (by means of direct electrical stimulation) and permanent disconnection (resulting from neurosurgical resection) on interference control processes, using the Stroop test in the intraoperative and extraoperative neurosurgical setting. We evaluated the sites at which errors could be produced by direct electrical stimulation during an intraoperative Stroop test in 34 patients with frontal right hemisphere glioma. Lesion-symptom mapping was used to evaluate the relationship between the resection cavities and postoperative performance on the Stroop test of this group compared with an additional 29 control patients who did not perform the intraoperative test (63 patients in total aged 17-77 years; 28 female). We then examined tract disruption and disconnection in a subset of eight patients who underwent both the intraoperative Stroop test and high angular resolution diffusion imaging (HARDI) tractography. The results showed that, intraoperatively, the majority of sites associated with errors during Stroop test performance and concurrent subcortical stimulation clustered in a region of white matter medial to the right inferior frontal gyrus, lateral and superior to the striatum. Patients who underwent the intraoperative test maintained cognitive control ability at the 1-month follow-up (P = 0.003). Lesion-symptom analysis showed resection of the right inferior frontal gyrus was associated with slower postoperative Stroop test ability (corrected for multiple comparisons, 5000 permutations). The stimulation sites associated with intraoperative errors most commonly corresponded with the inferior fronto-striatal tracts and anterior thalamic radiation (over 75% of patients), although the latter was commonly resected without postoperative deficits on the Stroop test (in 60% of patients). Our results show converging evidence to support a critical role for the inferior frontal gyrus in interference control processes. The intraoperative data combined with tractography suggests that cortico-subcortical tracts, over cortico-cortical connections, may be vital in maintaining efficiency of cognitive control processes. This suggests the importance of their preservation during resection of right frontal tumours.

Prognostic factors and outcome of HER2+ breast cancer with CNS metastases.

Aim: Trastuzumab prolongs progression-free and overall survival in HER2+ breast cancer (BC), but these are associated with increased distant recurrences and central nervous system metastases (CNSm). We retrospectively evaluated outcome and prognostic factors in CNSm and non-CNSm patients. Methods: Records of HER2+ BC treated in 2000-2017 were reviewed. Results: 283/1171 (24%) HER2+ BC patients developed metastatic disease. 109/283 patients (39%) have CNSm associated with worse prognosis and increased risk of death (hazard ratio: 4.7; 95% CI: 3.5-6.4). Prognostic factors were: number of CNSm (single vs multiple lesions; 3-year overall survival 39 vs 18%; p = 0.003); brain radiation (30 vs 14%; p < 0.001); new HER2-targeting therapies (30.6 vs 22.5%; p = 0.025). Conclusion: Prognosis of BC patients with CNSm has improved using HER2-targeting therapies but remains poor.

Efficacy of initial temozolomide for high-risk low grade gliomas in a phase II AINO (Italian Association for Neuro-Oncology) study: a post-hoc analysis within molecular subgroups of WHO 2016.

INTRODUCTION: The optimal management of high risk WHO grade II gliomas after surgery is debated including the role of initial temozolomide to delay radiotherapy and risk of cognitive defects. METHODS: A post-hoc analysis of a phase II multicenter study on high risk WHO grade II gliomas, receiving initial temozolomide alone, has re-evaluated the long-term results within the molecular subgroups of WHO 2016. The primary endpoint of the study was response according to RANO, being seizure response, PFS and OS secondary endpoints. RESULTS: Response rate among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency > 50% was observed in 87% of patients and a seizure freedom in 72%. The probability of seizure reduction > 50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Sixty-seven percent of patients with oligodendroglioma IDH mutant and 1p/19q codeleted did not recur with a median follow up of 9.3 years, while 59% did not receive radiotherapy at recurrence with a median follow up of 8.2 years. CONCLUSIONS: The beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery alone, or with intractable seizures, should receive temozolomide as initial treatment with salvage radiotherapy and/o reoperation and/or second-line chemotherapy at recurrence.

Correction to: Efficacy of initial temozolomide for high­risk low grade gliomas in a phase II AINO (Italian Association for Neuro­Oncology) study: a post­hoc analysis within molecular subgroups of WHO 2016.

The third and fourth authors' affiliation was incorrectly specified in the original publication. It is correctly shown here.

Frameless stereotactic biopsy for precision neurosurgery: diagnostic value, safety, and accuracy.

BACKGROUND: Stereotactic biopsy is consistently employed to characterize cerebral lesions in patients who are not suitable for microsurgical resection. In the past years, technical improvement and neuroimaging advancements contributed to increase the diagnostic yield, the safety, and the application of this procedure. Currently, in addition to histological diagnosis, the molecular analysis is considered essential in the diagnostic process to properly select therapeutic and prognostic algorithms in a personalized approach. The present study reports our experience with frameless stereotactic brain biopsy in this molecular era. METHODS: One hundred forty consecutive patients treated from January 2013 to September 2018 were analyzed. Biopsies were performed using the Brainlab Varioguide® frameless stereotactic system. Patients' clinical and demographic data, the time of occupation of the operating room, the surgical time, the morbidity, and the diagnostic yield in providing a histological and molecular diagnosis were recorded and evaluated. RESULTS: The overall diagnostic yield was 93.6% with nine procedures resulting non-diagnostic. Among 110 patients with glioma, the IDH-1 mutational status was characterized in 108 cases (98.2%), resulting wild-type in all subjects but 3; MGMT methylation was characterized in 96 cases (87.3%), resulting present in 60 patients, and 1p/19q codeletion was founded in 6 of the 20 cases of grade II-III gliomas analyzed. All the specimens were apt for molecular analysis when performed. Bleeding requiring surgical drainage occurred in 2.1% of the cases; 8 (5.7%) asymptomatic hemorrhages requiring no treatment were observed. No biopsy-related mortality was recorded. Median length of hospital stay was 5 days (IQR 4-8) with mean surgical time of 60.77 min (± 23.12) and 137.44 ± 24.1 min of total occupation time of the operative room. CONCLUSIONS: Stereotactic frameless biopsy is a safe, feasible, and fast procedure to obtain a histological and molecular diagnosis.

Prediction of Isocitrate Dehydrogenase Genotype in Brain Gliomas with MRI: Single-Shell versus Multishell Diffusion Models.

Purpose The primary aim of this prospective observational study was to assess whether diffusion MRI metrics correlate with isocitrate dehydrogenase (IDH) status in grade II and III gliomas. A secondary aim was to investigate whether multishell acquisitions with advanced models such as neurite orientation dispersion and density imaging (NODDI) and diffusion kurtosis imaging offer greater diagnostic accuracy than diffusion-tensor imaging (DTI). Materials and Methods Diffusion MRI (b = 700 and 2000 sec/mm2) was performed preoperatively in 192 consecutive participants (113 male and 79 female participants; mean age, 46.18 years; age range, 14-77 years) with grade II (n = 62), grade III (n = 58), or grade IV (n = 72) gliomas. DTI, diffusion kurtosis imaging, and NODDI metrics were measured in regions with or without hyperintensity on diffusion MR images and compared among groups defined according to IDH genotype, 1p/19q codeletion status, and tumor grade by using Mann-Whitney tests. Results In grade II and III IDH wild-type gliomas, the maximum fractional anisotropy, kurtosis anisotropy, and restriction fraction were significantly higher and the minimum mean diffusivity was significantly lower than in IDH-mutant gliomas (P = .011, P = .002, P = .044, and P = .027, respectively); areas under the receiver operating characteristic curve ranged from 0.72 to 0.76. In IDH wild-type gliomas, no difference among grades II, III, and IV was found. In IDH-mutant gliomas, no difference between those with and those without 1p/19q loss was found. Conclusion Diffusion MRI metrics showed correlation with isocitrate dehydrogenase status in grade II and III gliomas. Advanced diffusion MRI models did not add diagnostic accuracy, supporting the inclusion of a single-shell diffusion-tensor imaging acquisition in brain tumor imaging protocols. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.

OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Is surgical resection useful in elderly newly diagnosed glioblastoma patients? Outcome evaluation and prognostic factors assessment.

ASTRACT: BACKGROUND: The incidence of glioblastoma among elderly patients is constantly increasing. The value of radiation therapy and concurrent/adjuvant chemotherapy has been widely assessed. So far, the role of surgery has not been thoroughly investigated. The study aimed to evaluate safety and impact of several entities of surgical resection on outcome of elderly patients with newly diagnosed glioblastoma treated by a multimodal approach. METHODS: Patients ≥ 65 years, underwent surgery were included. The extent of surgical resection (EOR) was defined as complete resection (CR = 100%), gross total resection (GTR = 90-99%), sub-total resection (STR = 78-90%), partial resection (PR = 30-78%), and biopsy. After surgery, all patients received adjuvant radiotherapy (60/2 Gy fraction) with concomitant/adjuvant temozolomide chemotherapy. RESULTS: From March 2004 to December 2015, 178 elderly with a median age of 71 years (range 65-83 years) were treated. CR was obtained in 8 (4.5%), GTR in 63 (35.4%), STR in 46 (25.8%), PR in 16 (9.0%), and biopsy in 45 (25.3%). RT was started in all patients, concurrent/adjuvant CHT in 149 (83.7%) and 132 (74.2%). The median follow-up time was 12.2 months (range 0.4-50.4 months). The median, 1- and 2-year progression-free survival was 8.9 months (95%CI 7.8-100 months), 32.0 ± 3.5%, and 12.9 ± 2.6%. The median, 1- and 2-year overall survival were 12.2 (95%CI 11.3-13.1 months), 51.1 ± 3.7%, and 16.3 ± 2.9%. Tumor location, extent of resection, and neurological status after surgery statistically affected survival (p ≪ 0.01). CONCLUSION: Maximal surgical resection is safe and feasible in elderly patients with influence on survival. A preoperative evaluation has to be carried out.