A "glympse" into neurodegeneration: Diffusion MRI and cerebrospinal fluid aquaporin-4 for the assessment of glymphatic system in Alzheimer's disease and other dementias.

The glymphatic system (GS) is a whole-brain perivascular network, consisting of three compartments: the periarterial and perivenous spaces and the interposed brain parenchyma. GS dysfunction has been implicated in neurodegenerative diseases, particularly Alzheimer's disease (AD). So far, comprehensive research on GS in humans has been limited by the absence of easily accessible biomarkers. Recently, promising non-invasive methods based on magnetic resonance imaging (MRI) along with aquaporin-4 (AQP4) quantification in the cerebrospinal fluid (CSF) were introduced for an indirect assessment of each of the three GS compartments. We recruited 111 consecutive subjects presenting with symptoms suggestive of degenerative cognitive decline, who underwent 3 T MRI scanning including multi-shell diffusion-weighted images. Forty nine out of 111 also underwent CSF examination with quantification of CSF-AQP4. CSF-AQP4 levels and MRI measures-including perivascular spaces (PVS) counts and volume fraction (PVSVF), white matter free water fraction (FW-WM) and mean kurtosis (MK-WM), diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) (mean, left and right)-were compared among patients with AD (n = 47) and other neurodegenerative diseases (nAD = 24), patients with stable mild cognitive impairment (MCI = 17) and cognitively unimpaired (CU = 23) elderly people. Two runs of analysis were conducted, the first including all patients; the second after dividing both nAD and AD patients into two subgroups based on gray matter atrophy as a proxy of disease stage. Age, sex, years of education, and scanning time were included as confounding factors in the analyses. Considering the whole cohort, patients with AD showed significantly higher levels of CSF-AQP4 (exp(b) = 2.05, p = .005) and FW-WM FW-WM (exp(b) = 1.06, p = .043) than CU. AQP4 levels were also significantly higher in nAD in respect to CU (exp(b) = 2.98, p < .001). CSF-AQP4 and FW-WM were significantly higher in both less atrophic AD (exp(b) = 2.20, p = .006; exp(b) = 1.08, p = .019, respectively) and nAD patients (exp(b) = 2.66, p = .002; exp(b) = 1.10, p = .019, respectively) compared to CU subjects. Higher total (exp(b) = 1.59, p = .013) and centrum semiovale PVS counts (exp(b) = 1.89, p = .016), total (exp(b) = 1.50, p = .036) and WM PVSVF (exp(b) = 1.89, p = .005) together with lower MK-WM (exp(b) = 0.94, p = .006), mean and left ALPS (exp(b) = 0.91, p = .043; exp(b) = 0.88, p = .010 respectively) were observed in more atrophic AD patients in respect to CU. In addition, more atrophic nAD patients exhibited higher levels of AQP4 (exp(b) = 3.39, p = .002) than CU. Our results indicate significant changes in putative MRI biomarkers of GS and CSF-AQP4 levels in AD and in other neurodegenerative dementias, suggesting a close interaction between glymphatic dysfunction and neurodegeneration, particularly in the case of AD. However, the usefulness of some of these biomarkers as indirect and standalone indices of glymphatic activity may be hindered by their dependence on disease stage and structural brain damage.

Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications.

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-ß protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.

Synthetic MRI with Magnetic Resonance Spin TomogrAphy in Time-Domain (MR-STAT): Results from a Prospective Cross-Sectional Clinical Trial.

BACKGROUND: Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) can reconstruct whole-brain multi-parametric quantitative maps (eg, T1 , T2 ) from a 5-minute MR acquisition. These quantitative maps can be leveraged for synthetization of clinical image contrasts. PURPOSE: The objective was to assess image quality and overall diagnostic accuracy of synthetic MR-STAT contrasts compared to conventional contrast-weighted images. STUDY TYPE: Prospective cross-sectional clinical trial. POPULATION: Fifty participants with a median age of 45 years (range: 21-79 years) consisting of 10 healthy participants and 40 patients with neurological diseases (brain tumor, epilepsy, multiple sclerosis or stroke). FIELD STRENGTH/SEQUENCE: 3T/Conventional contrast-weighted imaging (T1 /T2 weighted, proton density [PD] weighted, and fluid-attenuated inversion recovery [FLAIR]) and a MR-STAT acquisition (2D Cartesian spoiled gradient echo with varying flip angle preceded by a non-selective inversion pulse). ASSESSMENT: Quantitative T1 , T2 , and PD maps were computed from the MR-STAT acquisition, from which synthetic contrasts were generated. Three neuroradiologists blinded for image type and disease randomly and independently evaluated synthetic and conventional datasets for image quality and diagnostic accuracy, which was assessed by comparison with the clinically confirmed diagnosis. STATISTICAL TESTS: Image quality and consequent acceptability for diagnostic use was assessed with a McNemar's test (one-sided α = 0.025). Wilcoxon signed rank test with a one-sided α = 0.025 and a margin of Δ = 0.5 on the 5-level Likert scale was used to assess non-inferiority. RESULTS: All data sets were similar in acceptability for diagnostic use (≥3 Likert-scale) between techniques (T1 w:P = 0.105, PDw:P = 1.000, FLAIR:P = 0.564). However, only the synthetic MR-STAT T2 weighted images were significantly non-inferior to their conventional counterpart; all other synthetic datasets were inferior (T1 w:P = 0.260, PDw:P = 1.000, FLAIR:P = 1.000). Moreover, true positive/negative rates were similar between techniques (conventional: 88%, MR-STAT: 84%). DATA CONCLUSION: MR-STAT is a quantitative technique that may provide radiologists with clinically useful synthetic contrast images within substantially reduced scan time. EVIDENCE LEVEL: 1 Technical Efficacy: Stage 2.

Embolic Stroke of Undetermined Source: Role of Implantable Loop Recorder in Secondary Prevention.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most important cause of embolic stroke of undetermined source (ESUS). Implantable loop recorder (ILR) demonstrated the highest sensitivity for detecting it. This register was created to confirm the high prevalence of AF in patients after ESUS and to verify possible benefits on clinical outcomes such as TIA (Transient Ischaemic Attack)/stroke recurrence and death using ILR. METHODS: A total of 278 patients admitted to "Molinette" Hospital in Stroke Unit department between 2011 and 2016, diagnosed with ESUS, underwent ILR implantation if they had at least one risk factor for AF. A total of 165 patients admitted to other departments in the same center for the same pathology, without ILR, represent the control group. We used propensity score to select 132 patients from each group (matching age, sex, CHADS-VASC, and HAS-BLEED baseline characteristics). RESULTS: The detection rate of AF episodes was significantly higher in the ILR group (p < 0.001). No significant protective role of ILR for clinical endpoints was found on univariate analysis, although a trend towards significance has been pointed for the composite outcome of death and ischemic events recurrence (OR 0.52, CI 0.26-1.04, p = 0.06). A protective role of ILR was found for deaths (OR 0.4, CI 0.17-0.94, p 0.03) and for the composite outcome (OR 0.41, CI 0.19-0.87, p 0.02) on multivariate analysis in the best subsets. CONCLUSION: With our statistical models, we identified a significant clinical benefit from ILR monitoring, evidenced by a trend of less death and TIA/stroke recurrence and relevant ILR protection for prediction of TIA/stroke recurrence.

Cerebellum and Emotion Recognition.

In this chapter, after having clarified which definition of emotion we followed, starting from Darwin and evolutionary psychology, we tried to examine the main mechanisms of emotional recognition from a behavioral and cerebral point of view: emotional contagion and cognitive empathy. The link between these skills and social cognition has been discussed. We tried to understand through the description of comparative studies on animals, studies on populations with cerebellar lesions in animals and humans, neurostimulation studies, and studies on neuropsychiatric pathologies with alterations to the cerebellar networks the possible involvement of the cerebellum in these mechanisms, also investigating its possible causal role. The evidence, even if mainly of a correlational type, is numerous and robust enough to be able to affirm the existence of significant involvement of the cerebellum in social cognition and in the recognition of negative emotions, especially fear.

Hippocampal volumes in anorexia nervosa at different stages of the disorder.

INTRODUCTION: Hippocampus is involved in a range of cognitive and behavioural processes, and its volume has been found to be reduced in different psychiatric disorders. The present study aims at exploring hippocampal volumes in anorexia nervosa (AN) at different stages of the disorder (a few months after onset, more than 1 year after onset and after recovery). METHODS: Two samples were included in the present study. The first was composed of 58 patients (38 with present AN, 20 full recovered from AN) and 38 age-matched healthy women (HW); the second, recruited at a different site, included 20 patients with AN and 16 HW. Hippocampal volume has been estimated using an automated segmentation algorithm. Age, site of scanning and total intracranial volumes were used as covariates in the statistical analyses. RESULTS: AN patients showed a reduced hippocampal volume in comparison to HW, with no substantial differences between patients with recent onset and those with a longer duration of illness. Among patients, hippocampal volumes correlated with body mass index, anxiety and drive for thinness. DISCUSSION: Our findings suggest an early role of malnutrition in the morphologic alterations of the hippocampus in AN and a possible role of this brain structure in mediating specific psychopathological traits.

Step-by-Step Design of New Theranostic Nanoformulations: Multifunctional Nanovectors for Radio-Chemo-Hyperthermic Therapy under Physical Targeting.

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = -29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = -18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.

Pushing functional MRI spatial and temporal resolution further: High-density receive arrays combined with shot-selective 2D CAIPIRINHA for 3D echo-planar imaging at 7 T.

To be able to examine dynamic and detailed brain functions, the spatial and temporal resolution of 7 T MRI needs to improve. In this study, it was investigated whether submillimeter multishot 3D EPI fMRI scans, acquired with high-density receive arrays, can benefit from a 2D CAIPIRINHA sampling pattern, in terms of noise amplification (g-factor), temporal SNR and fMRI sensitivity. High-density receive arrays were combined with a shot-selective 2D CAIPIRINHA implementation for multishot 3D EPI sequences at 7 T. In this implementation, in contrast to conventional inclusion of extra kz gradient blips, specific EPI shots are left out to create a CAIPIRINHA shift and reduction of scan time. First, the implementation of the CAIPIRINHA sequence was evaluated with a standard receive setup by acquiring submillimeter whole brain T2 *-weighted anatomy images. Second, the CAIPIRINHA sequence was combined with high-density receive arrays to push the temporal resolution of submillimeter 3D EPI fMRI scans of the visual cortex. Results show that the shot-selective 2D CAIPIRINHA sequence enables a reduction in scan time for 0.5 mm isotropic 3D EPI T2 *-weighted anatomy scans by a factor of 4 compared with earlier reports. The use of the 2D CAIPIRINHA implementation in combination with high-density receive arrays, enhances the image quality of submillimeter 3D EPI scans of the visual cortex at high acceleration as compared to conventional SENSE. Both the g-factor and temporal SNR improved, resulting in a method that is more sensitive to the fMRI signal. Using this method, it is possible to acquire submillimeter single volume 3D EPI scans of the visual cortex in a subsecond timeframe. Overall, high-density receive arrays in combination with shot-selective 2D CAIPIRINHA for 3D EPI scans prove to be valuable for reducing the scan time of submillimeter MRI acquisitions.

Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System.

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

Brain tumors in eloquent areas: A European multicenter survey of intraoperative mapping techniques, intraoperative seizures occurrence, and antiepileptic drug prophylaxis.

Intraoperative mapping and monitoring techniques for eloquent area tumors are routinely used world wide. Very few data are available regarding mapping and monitoring methods and preferences, intraoperative seizures occurrence and perioperative antiepileptic drug management. A questionnaire was sent to 20 European centers with experience in intraoperative mapping or neurophysiological monitoring for the treatment of eloquent area tumors. Fifteen centers returned the completed questionnaires. Data was available on 2098 patients. 863 patients (41.1%) were operated on through awake surgery and intraoperative mapping, while 1235 patients (58.8%) received asleep surgery and intraoperative electrophysiological monitoring or mapping. There was great heterogeneity between centers with some totally AW oriented (up to 100%) and other almost totally ASL oriented (up to 92%) (31% SD). For awake surgery, 79.9% centers preferred an asleep-awake-asleep anesthesia protocol. Only 53.3% of the centers used ECoG or transcutaneous EEG. The incidence of intraoperative seizures varied significantly between centers, ranging from 2.5% to 54% (p < 0.001). It there appears to be a statistically significant link between the mastery of mapping technique and the risk of intraoperative seizures. Moreover, history of preoperative seizures can significantly increase the risk of intraoperative seizures (p < 0.001). Intraoperative seizures occurrence was similar in patients with or without perioperative drugs (12% vs. 12%, p = 0.2). This is the first European survey to assess intraoperative functional mapping and monitoring protocols and the management of peri- and intraoperative seizures. This data can help identify specific aspects that need to be investigated in prospective and controlled studies.

The rehabilitative effects on written language of a combined language and parietal dual-tDCS treatment in a stroke case.

In this paper we report the effect of a combined transcranial direct current stimulation (tDCS) and speech language therapy on linguistic deficits following left brain damage in a stroke case. We show that simultaneous electrical excitatory stimulation to the left and inhibitory stimulation to the right parietal regions (dual-tDCS) affected writing and reading rehabilitation, enhancing speech therapy outcomes. The results of a comparison with healthy controls showed that application of dual-tDCS could improve, in particular, sub-lexical transcoding and, specifically, the reading of non-words with increasing length and complexity. Positive repercussions on patient's quality of functional communication were also ascertained. Significant changes were also found in other language and cognitive tasks not directly treated (comprehension and constructive apraxia).

Magnetic Nanoparticles in the Central Nervous System: Targeting Principles, Applications and Safety Issues.

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in-or are close to-clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity.

Selective Vulnerability of Cortical Border Zone to Microembolic Infarct.

BACKGROUND AND PURPOSE: Endovascular procedures, including atrial fibrillation transcatheter ablation, may cause microembolization of brain arteries. Microemboli often cause small sized and clinically silent cerebral ischemias (SCI). These lesions are clearly visible on early postoperative magnetic resonance diffusion-weighted images. We analyzed SCI distribution in a population of patients submitted to atrial fibrillation transcatheter ablation. METHODS: Seventy-eight of 927 consecutive patients submitted to atrial fibrillation transcatheter ablation were found positive for acute SCI on a postoperative magnetic resonance. SCI were identified and marked, and their coordinates were transformed from native space into the International Consortium for Brain Mapping/Montreal Neurological Institute space. We then computed the voxel-wise probability distribution map of the SCI using the activation likelihood estimation approach. RESULTS: SCI were more commonly found in the cortex. In supratentorial regions, SCI selectively involved cortical border zone between anterior, middle, and posterior cerebral arteries; in infratentorial regions, distal territory of posteroinferior cerebellar artery. Possible explanations include selective embolization, linked to the vascular anatomy of pial arteries supplying those territories, reduced clearance of emboli in a relatively hypoperfused zone, or a combination of both. This particular distribution of lesions has been reported in both animal models and in patients with microemboli of different sources. CONCLUSIONS: A selective vulnerability of cortical border zone to microemboli occurring during atrial fibrillation transcatheter ablation was observed. We hypothesize that such selectivity may apply to microemboli of different sources.

Brain correlates of alexithymia in eating disorders: A voxel-based morphometry study.

AIMS: Alexithymia is a personality trait that consists of difficulty in identifying and acknowledging one's own and others' feelings. Recent studies reported that alexithymia is present in both anorexia (AN) and bulimia nervosa (BN). Brain morphological studies on healthy subjects showed that alexithymia correlates with several brain regions involved in emotions processing. The aim of this study was to investigate the anatomical correlates of alexithymia in AN and BN. METHODS: We performed a voxel-based morphometry study on 21 patients with AN and 18 with BN. Seventeen healthy subjects were used as a control group. Alexithymia, depression and anxiety were assessed with self-administered questionnaires and correlated to gray matter (GM) density in each group. RESULTS: In BN, alexithymia was correlated with the GM of the parietal lobe, in particular of the right angular gyrus. The correlation was predominantly linked with Difficulty Describing Feelings. In AN, we did not find correlations between GM and alexithymia. CONCLUSIONS: In BN, our results support the hypothesis that this trait may represent a relevant pathogenic or maintenance factor that contributes to relational difficulties, present in this pathology. In AN, the lack of correlation between GM volume and alexithymia may be influenced by atrophy in several brain regions that in turn can be, as previously reported, a consequence of caloric restriction. Also, the nature of alexithymia may be different from that of BN and controls and this trait could be secondary to a psychopathologic process specific to AN.

Drawing lines while imagining circles: Neural basis of the bimanual coupling effect during motor execution and motor imagery.

When people simultaneously draw lines with one hand and circles with the other hand, both trajectories tend to assume an oval shape, showing that hand motor programs interact (the so-called "bimanual coupling effect"). The aim of the present study was to investigate how motor parameters (drawing trajectories) and the related brain activity vary during bimanual movements both in real execution and in motor imagery tasks. In the 'Real' modality, subjects performed right hand movements (lines) and, simultaneously, Congruent (lines) or Non-congruent (circles) left hand movements. In the 'Imagery' modality, subjects performed only right hand movements (lines) and, simultaneously, imagined Congruent (lines) or Non-congruent (circles) left hand movements. Behavioral results showed a similar interference of both the real and the imagined circles on the actually executed lines, suggesting that the coupling effect also pertains to motor imagery. Neuroimaging results showed that a prefrontal-parietal network, mostly involving the pre-Supplementary Motor Area (pre-SMA) and the posterior parietal cortex (PPC), was significantly more active in Non-congruent than in Congruent conditions, irrespective of task (Real or Imagery). The data also confirmed specific roles of the right superior parietal lobe (SPL) in mediating spatial interference, and of the left PPC in motor imagery. Collectively, these findings suggest that real and imagined Non-congruent movements activate common circuits related to the intentional and predictive operation generating bimanual coupling, in which the pre-SMA and the PPC play a crucial role.

Concordance of white matter and gray matter abnormalities in autism spectrum disorders: a voxel-based meta-analysis study.

There are at least two fundamental unanswered questions in the literature on autism spectrum disorders (ASD): Are abnormalities in white (WM) and gray matter (GM) consistent with one another? Are WM morphometric alterations consistent with alterations in the GM of regions connected by these abnormal WM bundles and vice versa? The aim of this work is to bridge this gap. After selecting voxel-based morphometry and diffusion tensor imaging studies comparing autistic and normally developing groups of subjects, we conducted an activation likelihood estimation (ALE) meta-analysis to estimate consistent brain alterations in ASD. Multidimensional scaling was used to test the similarity of the results. The ALE results were then analyzed to identify the regions of concordance between GM and WM areas. We found statistically significant topological relationships between GM and WM abnormalities in ASD. The most numerous were negative concordances, found bilaterally but with a higher prevalence in the right hemisphere. Positive concordances were found in the left hemisphere. Discordances reflected the spatial distribution of negative concordances. Thus, a different hemispheric contribution emerged, possibly related to pathogenetic factors affecting the right hemisphere during early developmental stages. Besides, WM fiber tracts linking the brain structures involved in social cognition showed abnormalities, and most of them had a negative concordance with the connected GM regions. We interpreted the results in terms of altered brain networks and their role in the pervasive symptoms dramatically impairing communication and social skills in ASD patients.

Behavioral and neuroplastic effects of low-frequency rTMS of the unaffected hemisphere in a chronic stroke patient: a concomitant TMS and fMRI study.

Repetitive Transcranial Magnetic Stimulation (rTMS) ameliorates motor and neuropsychological deficits following stroke, but little is known about the underlying neuroplasticity. We investigated neuroplastic changes following 5 days of low-frequency rTMS on the intact motor cortex to promote motor recovery in a chronic patient with subcortical stroke. The feasibility of administering multiple treatments was also assessed 6 months later by applying the same protocol over the patient's parietal cortex to improve visuospatial disorders. Behavioral improvements and no adverse events were observed. Neuroimaging findings indicated that motor symptoms amelioration was associated with downregulation and cortical reorganization of hyperactive contralesional hemisphere.

Speech and lexico-semantic errors during direct cortical stimulation mapping of the language-dominant hemisphere: effects of object and action naming.

OBJECTIVE: In this retrospective study, the authors aimed to establish the stereotactically defined probability distribution for speech (i.e., anarthria, speech arrest) and lexico-semantic errors (i.e., anomia) through direct cortical stimulation (DCS) by using two tasks: action naming and object naming. They also analyzed the patterns of interindividual variability in the localization of the language sites involved, and investigated whether any patient or lesion location factors were associated with greater variability. METHODS: Eighty-one Italian-speaking patients who underwent awake surgery between 2010 and 2021 for low- and high-grade gliomas in eloquent areas of the language-dominant hemisphere were entered in the analyses. The intraoperative DCS protocol included automatic speech tasks, object naming, and action naming. The position of the tags, as depicted on the intraoperative video or photograph, was transposed into Montreal Neurological Institute space. Subsequently, a 2D scatterplot and cluster analysis were performed. Associations between various clinical and radiological characteristics and the quantity of positive stimulated sites were determined by univariate analyses using binary logistic regression. Associated variables (p < 0.2) were included in stepwise multivariate logistic regression with backward elimination (p < 0.05). RESULTS: A total of 1380 cortical sites were stimulated, with a positive response in 511 cases (37%). Most anarthric errors were triggered when stimulating the left precentral gyrus, and most speech arrest errors were elicited when stimulating the left posterior inferior frontal gyrus. Anomias were found in the left inferior frontal gyrus and in the posterior part of the left temporal lobe for object naming. DCS to the left dorsal premotor cortex elicited anomic errors for action naming. Anomias were also elicited during DCS to the left posterior temporal lobe, with both object and action naming. CONCLUSIONS: The distribution of speech and lexico-semantic errors is in line with the current literature. The action-naming results are new and mostly involve the dorsal premotor cortex. These findings stress the importance of maximizing the use of different language tasks during surgery, because even when looking for the same type of errors, different tasks may be better suited to map specific brain regions. DCS with action and object naming identifies more positive sites than object naming alone.

Neural network-derived perfusion maps: A model-free approach to computed tomography perfusion in patients with acute ischemic stroke.

Objective: In this study, we investigate whether a Convolutional Neural Network (CNN) can generate informative parametric maps from the pre-processed CT perfusion data in patients with acute ischemic stroke in a clinical setting. Methods: The CNN training was performed on a subset of 100 pre-processed perfusion CT dataset, while 15 samples were kept for testing. All the data used for the training/testing of the network and for generating ground truth (GT) maps, using a state-of-the-art deconvolution algorithm, were previously pre-processed using a pipeline for motion correction and filtering. Threefold cross validation had been used to estimate the performance of the model on unseen data, reporting Mean Squared Error (MSE). Maps accuracy had been checked through manual segmentation of infarct core and total hypo-perfused regions on both CNN-derived and GT maps. Concordance among segmented lesions was assessed using the Dice Similarity Coefficient (DSC). Correlation and agreement among different perfusion analysis methods were evaluated using mean absolute volume differences, Pearson correlation coefficients, Bland-Altman analysis, and coefficient of repeatability across lesion volumes. Results: The MSE was very low for two out of three maps, and low in the remaining map, showing good generalizability. Mean Dice scores from two different raters and the GT maps ranged from 0.80 to 0.87. Inter-rater concordance was high, and a strong correlation was found between lesion volumes of CNN maps and GT maps (0.99, 0.98, respectively). Conclusion: The agreement between our CNN-based perfusion maps and the state-of-the-art deconvolution-algorithm perfusion analysis maps, highlights the potential of machine learning methods applied to perfusion analysis. CNN approaches can reduce the volume of data required by deconvolution algorithms to estimate the ischemic core, and thus might allow the development of novel perfusion protocols with lower radiation dose deployed to the patient.