Evaluation of a nnU-Net type automated clinical volumetric tumor segmentation tool for diffuse low-grade glioma follow-up.

BACKGROUND AND PURPOSE: Diffuse low-grade gliomas (DLGG) are characterized by a slow and continuous growth and always evolve towards an aggressive grade. Accurate prediction of the malignant transformation is essential as it requires immediate therapeutic intervention. One of its most precise predictors is the velocity of diameter expansion (VDE). Currently, the VDE is estimated either by linear measurements or by manual delineation of the DLGG on T2 FLAIR acquisitions. However, because of the DLGG's infiltrative nature and its blurred contours, manual measures are challenging and variable, even for experts. Therefore we propose an automated segmentation algorithm using a 2D nnU-Net, to 1) gain time and 2) standardize VDE assessment. MATERIALS AND METHODS: The 2D nnU-Net was trained on 318 acquisitions (T2 FLAIR & 3DT1 longitudinal follow-up of 30 patients, including pre- & post-surgery acquisitions, different scanners, vendors, imaging parameters…). Automated vs. manual segmentation performance was evaluated on 167 acquisitions, and its clinical interest was validated by quantifying the amount of manual correction required after automated segmentation of 98 novel acquisitions. RESULTS: Automated segmentation showed a good performance with a mean Dice Similarity Coefficient (DSC) of 0.82±0.13 with manual segmentation and a substantial concordance between VDE calculations. Major manual corrections (i.e., DSC<0.7) were necessary only in 3/98 cases and 81% of the cases had a DSC>0.9. CONCLUSION: The proposed automated segmentation algorithm can successfully segment DLGG on highly variable MRI data. Although manual corrections are sometimes necessary, it provides a reliable, standardized and time-winning support for VDE extraction to asses DLGG growth.

Low levels of peripheral blood activated and senescent T cells characterize people with HIV-1-associated neurocognitive disorders.

Background: HIV infection induces a 75% increase in the risk of developing neurocognitive impairment (NCI), which has been linked to immune activation. We therefore looked for immune activation markers correlating with NCI. Method: Sixty-five people aged 55-70 years living with controlled HIV-1 infection were enrolled in the study and their neurocognitive ability was assessed according to the Frascati criteria. Fifty-nine markers of T4 cell, T8 cell, NK cell, and monocyte activation, inflammation and endothelial activation were measured in their peripheral blood. White matter hyperintensities (WMH) were identified by magnetic resonance imaging. Double hierarchical clustering was performed for the activation markers and 240 patients including the 65 whose neurocognitive performance had been evaluated. Results: Thirty-eight percent of volunteers presented NCI. Twenty-four percent of them were asymptomatic and fourteen percent had a mild disorder. Strikingly, activated (HLA-DR+) as well as senescent (CD57+CD28-CD27±) T4 cells and T8 cells were less prevalent in the peripheral blood of participants with NCI than in participants without the disorder. Accordingly, the percentage of HLA-DR+ T4 cells was lower in volunteers with periventricular and deep WMH. The double hierarchical clustering unveiled six different immune activation profiles. The neurocognitive performances of participants with two of these six profiles were poor. Here again, these two profiles were characterized by a low level of T4 and T8 cell activation and senescence. Conclusion: Our observation of low circulating levels of activated and senescent T cells in HIV-1 patients with NCI raises the interesting hypothesis that these lymphocytes may be recruited into the central nervous system.

Functional PET Neuroimaging in Consciousness Evaluation: Study Protocol.

Ensuring a robust and reliable evaluation of coma deepness and prognostication of neurological outcome is challenging. We propose to develop PET neuroimaging as a new diagnostic and prognosis tool for comatose patients using a recently published methodology to perform functional PET (fPET). This exam permits the quantification of task-specific changes in neuronal metabolism in a single session. The aim of this protocol is to determine whether task-specific changes in glucose metabolism during the acute phase of coma are able to predict recovery at 18 months. Participation will be proposed for all patients coming for a standard PET-CT in our center in order to evaluate global cerebral metabolism during the comatose state. Legally appointed representative consent will be obtained to slightly modify the exam protocol: (1) 18F-fluorodeoxyglucose (18F-FDG) bolus plus continuous infusion instead of a simple bolus and (2) more time under camera to perform dynamic acquisition. Participants will undergo a 55-min fPET session with a 20% bolus + 80% infusion protocol. Two occurrences of three block (5-min rest, 10-min auditory stimulation and 10-min emotional auditory stimulation) will be performed after reaching equilibrium of FDG arterial concentration. We will compare the regional brain metabolism at rest and during the sessions of auditory and emotional auditory stimulation to search for a determinant of coma recovery (18 months of follow-up after the exam). Emotional auditory stimulation should induce an activation of: the auditory cortex, the consciousness areas and the neural circuitry for emotion (function to coma deepness). An activation analysis will be carried out to highlight regional brain activation using dedicated custom-made software based on Python statistical and image processing toolboxes. The association between activation levels and the Coma Recovery Scale-Revisited (CRS-R) will be assessed using multivariate analysis. If successful, the results from this study will help improve coma prognosis evaluation based on the pattern of neuronal metabolism at the onset of the pathology. The study protocol, rationale and methods are described in this paper.

The central role of the left inferior longitudinal fasciculus in the face-name retrieval network.

Unsuccessful retrieval of proper names (PNs) is commonly observed in patients suffering from neurological conditions such as stroke or epilepsy. While a large body of works has suggested that PN retrieval relies on a cortical network centered on the left anterior temporal lobe (ATL), much less is known about the white matter connections underpinning this process. Sparse studies provided evidence for a possible role of the uncinate fasciculus, but the inferior longitudinal fasciculus (ILF) might also contribute, since it mainly projects into the ATL, interconnects it with the posterior lexical interface and is engaged in common name (CN) retrieval. To ascertain this hypothesis, we assessed 58 patients having undergone a neurosurgery for a left low-grade glioma by means of a famous face naming (FFN) task. The behavioural data were processed following a multilevel lesion approach, including location-based analyses, voxel-based lesion-symptom mapping (VLSM) and disconnection-symptom mapping. Different statistical models were generated to control for sociodemographic data, familiarity, biographical knowledge and control cognitive performances (i.e., semantic and episodic memory and CN retrieval). Overall, VLSM analyses indicated that damage to the mid-to-anterior part of the ventro-basal temporal cortex was especially associated with PN retrieval deficits. As expected, tract-oriented analyses showed that the left ILF was the most strongly associated pathway. Our results provide evidence for the pivotal role of the ILF in the PN retrieval network. This novel finding paves the way for a better understanding of the pathophysiological bases underlying PN retrieval difficulties in the various neurological conditions marked by white matter abnormalities.

Concurrent validity and reliability of suicide risk assessment instruments: A meta-analysis of 20 instruments across 27 international cohorts.

OBJECTIVE: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. METHOD: Here, we examine this issue through two approaches: (a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N ∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA-Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior. RESULTS: We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15-0.97; r range: 0.21-0.94) reported in the literature. Two common multi-item instruments, the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicidal Ideation were highly correlated with each other (r = 0.83). Sensitivity analyses identified sources of heterogeneity such as the time frame of the instrument and whether it relies on self-report or a clinical interview. Finally, construct-specific analyses suggest that suicide ideation items from common psychiatric questionnaires are most concordant with the suicide ideation construct of multi-item instruments. CONCLUSIONS: Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behavior but share a modest core factor with single suicidal ideation items. Retrospective, multisite collaborations including distinct instruments should be feasible provided they harmonize across instruments or focus on specific constructs of suicidality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The effect of early trauma on suicidal vulnerability depends on fronto-insular sulcation.

Improving our understanding of pathophysiology of suicidal behavior (SB) is an important step for prevention. Assessment of suicide risk is based on socio-demographic and clinical risk factors with a poor predictivity. Current understanding of SB is based on a stress-vulnerability model, whereby early-life adversities are predominant. SB may thus result from a cascade of developmental processes stemming from early-life abuse and/or neglect. Some cerebral abnormalities, particularly in fronto-limbic regions, might also provide vulnerability to develop maladaptive responses to stress, leading to SB. We hypothesized that SB is associated with interactions between early trauma and neurodevelopmental deviations of the frontal and insular cortices. We recruited 86 euthymic women, including 44 suicide attempters (history of depression and SB) and 42 affective controls (history of depression without SB). The early development of prefrontal cortex (PFC) and insula was inferred using 3D magnetic resonance imaging-derived regional sulcation indices, which are indirect markers of early neurodevelopment. The insula sulcation index was higher in emotional abused subjects; among those patients, PFC sulcation index was reduced in suicide attempters, but not in affective controls. Such findings provide evidence that SB likely traced back to early stages of brain development in interaction with later environmental factors experienced early in life.

Precuneal gliomas promote behaviorally relevant remodeling of the functional connectome.

OBJECTIVE: The precuneus hosts one of the most complex patterns of functional connectivity in the human brain. However, due to the extreme rarity of neurological lesions specifically targeting this structure, it remains unknown how focal damage to the precuneus may impact resting-state functional connectivity (rsFC) at the brainwide level. The aim of this study was to investigate glioma-induced rsFC modulations and to identify patterns of rsFC remodeling that accounted for the maintenance of cognitive performance after awake-guided surgical excision. METHODS: In a unique series of patients with IDH1-mutated low-grade gliomas (LGGs) infiltrating the precuneus who were treated at a single neurosurgical center (Montpellier University Medical Center, 2014-2021), the authors gauged the dynamic modulations induced by tumors on rsFC in comparison with healthy participants. All patients received a preoperative resting-state functional MRI and underwent operation guided by awake cognitive mapping. Connectome multivariate pattern analysis (MVPA), seed-network analysis, and graph theoretical analysis were conducted and correlated to executive neurocognitive scores (i.e., phonological and semantic fluencies, Trail-Making Test [TMT] parts A and B) obtained 3 months after surgery. RESULTS: Seventeen patients with focal precuneal infiltration were selected (mean age 38.1 ± 11.2 years) and matched to 17 healthy participants (mean age 40.5 ± 10.4 years) for rsFC analyses. All patients underwent awake cognitive mapping, allowing total resection (n = 3) or subtotal resection (n = 14), with a mean extent of resection of 90.6% ± 7.3%. Using MVPA (cluster threshold: p-false discovery rate corrected < 0.05, voxel threshold: p-uncorrected < 0.001), remote hotspots with significant rsFC changes were identified, including both insulas, the anterior cingulate cortex, superior sensorimotor cortices, and both frontal eye fields. Further seed-network analyses captured 2 patterns of between-network redistribution especially involving hyperconnectivity between the salience, visual, and dorsal attentional networks. Finally, the global efficiency of the salience-visual-dorsal attentional networks was strongly and positively correlated to 3-month postsurgical scores (n = 15) for phonological fluency (r15 = 0.74, p = 0.0027); TMT-A (r15 = 0.65, p = 0.012); TMT-B (r15 = 0.70, p = 0.005); and TMT-B-A (r15 = 0.62, p = 0.018). CONCLUSIONS: In patients with LGGs infiltrating the precuneus, remote and distributed functional connectivity modulations in the preoperative setting are associated with better maintenance of cognitive performance after surgery. These findings provide a new vision of the mechanistic principles underlying neural plasticity and cognitive compensation in patients with LGGs.

Glucometabolic Changes Are Associated with Structural Gray Matter Alterations in Prodromal Dementia.

BACKGROUND: Glucometabolic changes, such as high glycemic load (GL) diet and insulin resistance (IR), are potential risk factor of Alzheimer's disease (AD). Yet, the effect of these factors on brain alterations that contribute to AD pathology has not been clearly demonstrated. OBJECTIVE: We aimed to assess the relationship of GL and IR with gray matter volumes involved in prodromal dementia. METHODS: GL and Triglyceride-Glucose (TyG) index, an IR surrogate marker, were calculated in 497 participants who underwent magnetic resonance imaging (MRI). The gray matter volumes most related to prodromal dementia/mild cognitive impairment (diagnosed in 18/158 participants during the 7-year follow-up) were identified using a data-driven machine learning algorithm. RESULTS: Higher GL diet was associated with reduced amygdala volume. The TyG index was negatively associated with the hippocampus, amygdala, and putamen volumes. CONCLUSION: These results suggest that GL and IR are associated with lower gray matter volumes in brain regions involved in AD pathology.

Impact of multidomain preventive strategies on functional brain connectivity in older adults with cognitive complaint: Subset from the Montpellier center of the ancillary MAPT-MRI study.

Introduction: The impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC). Methods: To determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints. Results: No global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden. Discussion: These results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

Combining Electrostimulation With Fiber Tracking to Stratify the Inferior Fronto-Occipital Fasciculus.

The inferior fronto-occipital fasciculus (IFOF) is one of the longest association fiber tracts of the brain. According to the most recent anatomical studies, it may be formed by several layers, suggesting a role in multiple cognitive functions. However, to date, no attempt has been made to dissociate the functional contribution of the IFOF subpathways. In this study, real-time, cortico-subcortical mapping with direct electrostimulation was performed in 111 patients operated on in wide-awake surgery for a right low-grade glioma. Patients performed two behavioral tasks during stimulation, tapping, respectively, mentalizing and visual semantic cognition-two functions supposed to be partly mediated by the IFOF. Responsive white matter sites were first subjected to a clustering analysis to assess potential topological differences in network organization. Then they were used as seeds to generate streamline tractograms based on the HC1021 diffusion dataset (template-based approach). The tractograms obtained for each function were overlapped and contrasted to determine whether some fiber pathways were more frequently involved in one or the other function. The obtained results not only provided strong evidence for a role of the right IFOF in both functions, but also revealed that the tract is dissociable into two functional strata according to a ventral (semantic) and dorsal (mentalizing) compartmentalization. Besides, they showed a high degree of anatomo-functionnal variability across patients in the functional implication of the IFOF, possibly related to symmetrical/hemispheric differences in network organization. Collectively, these findings support the view that the right IFOF is a functionally multi-layered structure, with nevertheless interindividual variations.

Prefrontal activity during experimental ostracism and daily psychache in suicide attempters.

BACKGROUND: Suicidal behaviors can result from a complex interaction between social stressors and individual vulnerability. Evidence suggests a specific neural processing of social cues in suicide attempters without knowledge of how it relates to real-world experiences. OBJECTIVE: To investigate the association between brain activity during experimental social exclusion (measured by functional MRI) and psychological pain in daily life (assessed by Ecological Momentary Assessment) in patients with a lifetime history of suicide attempt. METHODS: Thirty-three euthymic females with a history of a major depressive episode were recruited: 13 suicide attempters and 20 affective controls (no history of suicide attempt). Functional MRI scans were acquired while participants played the Cyberball game, a validated social exclusion paradigm. After fMRI, participants completed EMA for a one-week period. Five times per day, they were asked to rate their psychological pain, hopelessness and the negativity of daily events. EMA indices (psychological pain, hopelessness and their interaction with negative events) were correlated with cerebral activations using a ROI approach (orbitofrontal, dorsal and ventrolateral prefrontal cortices, anterior cingulate cortex and insula) in each group. RESULTS: We found a negative correlation between daily ratings of psychological pain and orbitofrontal activation for exclusion versus inclusion during the Cyberball game in suicide attempters but not in affective controls. We did not find correlations between cerebral activation and daily hopelessness ratings. LIMITATIONS: Small sample size CONCLUSION: Scanner-based orbitofrontal activity during social exclusion relates to psychological pain in daily life which participates in suicide risk among vulnerable individuals.

Homotopic redistribution of functional connectivity in insula-centered diffuse low-grade glioma.

OBJECTIVE: In the event of neural injury, the homologous contralateral brain areas may play a compensatory role to avoid or limit the functional loss. However, this dynamic strategy of functional redistribution is not clearly established, especially in the pathophysiological context of diffuse low-grade glioma. Our aim here was to assess the extent to which unilateral tumor infiltration of the insula dynamically modulates the functional connectivity of the contralesional one. METHODS: Using resting-state functional connectivity MRI, a seed-to-ROI approach was employed in 52 insula-centered glioma patients (n = 30 left and 22 right) compared with 19 age-matched healthy controls. RESULTS: Unsurprisingly, a significant decrease of the inter-insular connectivity was observed in both patient groups. More importantly, the analyses revealed a significant increase of the contralesional insular connectivity towards both cerebral hemispheres, especially in cortical areas forming the visual and the sensorimotor networks. This functional redistribution was not identified when the analyses were performed on three control regions for which the homologous area was not impaired by the tumor. This overall pattern of results indicates that massive infiltration of the insular cortex causes a significant redeployment of the contralesional functional connectivity. CONCLUSION: This general finding suggests that the undamaged insula plays a role in the functional compensation usually observed in this patient population, and thus provides compelling support for the concept of homotopic functional plasticity in brain-damaged patients.

Cerebral Vasoreactivity as an Indirect MRI Marker of White Matter Tracts Alterations in Multiple Sclerosis.

Patients with multiple sclerosis (MS) show a diffuse cerebral perfusion decrease, presumably related to multiple metabolism and vascular alterations. It is assumed that white matter fiber alterations cause a localized cerebral vasoreactivity (CVR) disruption through astrocytes metabolism alteration, leading to hypoperfusion. We proposed to (1) evaluate the CVR disruptions in MS, (2) in relation to white matter lesions and (3) compare CVR disruptions maps with standard imaging biomarkers. Thirty-five MS patients (10 progressive, 25 relapsing-remitting) and 22 controls underwent MRI with hypercapnic challenge, DTI imaging and neuropsychological assessment. Areas with disrupted CVR were assessed using a general linear model. Resulting maps were associated with clinical scores, compared between groups, and related to DTI metrics and white matter lesions. MS patients showed stronger disrupted CVR within supratentorial white matter, linking the left anterior insula to both the precentral gyrus and the right middle and superior frontal gyrus through the corpus callosum (P < 0.05, FWE corrected). Patient's verbal intellectual quotient was negatively associated with a pathway linking both hippocampi to the ispilateral prefrontal cortex (P < 0.05, FWE corrected). Disrupted CVR maps unrelated to DTI metrics and white matter lesions. We have demonstrated for the first time that white matter alterations can be indirectly identified through surrounding vessel alterations, and are related to clinical signs of MS. This offers a new, likely independent marker to monitor MS and supports a mediator role of the astrocytes in the fibers/vessels relationship.

Task- and Rest-based Functional Brain Connectivity in Food-related Reward Processes among Healthy Adolescents.

It is known that the nucleus accumbens, orbitofrontal cortex and insula play a role in food-related reward processes. Although their interconnectedness would be an ideal topic for understanding food intake mechanisms, it nevertheless remains unclear especially in adolescent. Therefore, this study aims to investigate the effect of hunger on functional connectivity in healthy adolescents using task- and rest-based imaging. Fifteen participants underwent two MRI sessions, pre-lunch (hunger) and post-lunch (satiety), including food cue task and resting-state. During task- and rest-based imaging, functional connectivity was greater when hungry as opposed to satiated between the right posterior insula/nucleus accumbens, suggesting involvement of salient interoceptive stimuli signals. During task-based imaging, an increase was observed in functional connectivity when hungry as opposed to satiated between the medial and lateral orbitofrontal cortex which contributes to the perception of food deprivation as a frustration. A decrease was identified when hungry as opposed to satiated in functional connectivity in the right anterior orbitofrontal/accumbens and posterior insula/medial orbitofrontal cortices reflecting suppression of the affective and sensorial information. Conversely, functional connectivity was increased during aversive stimuli between the right medial orbitofrontal cortex and right posterior insula when hungry as opposed to satiated. This suggests that the value of valence could occur in the shift in connectivity between these two regions. In addition, during rest-based imaging, a left-sided lateralization was reported (accumbens/lateral orbitofrontal and accumbens/posterior insula) when hungry as opposed to satiated which may represent changes in internal state due to focus on the benefit of an upcoming meal.

Machine Learning Analysis of the Cerebrovascular Thrombi Proteome in Human Ischemic Stroke: An Exploratory Study.

Objective: Mechanical retrieval of thrombotic material from acute ischemic stroke patients provides a unique entry point for translational research investigations. Here, we resolved the proteomes of cardioembolic and atherothrombotic cerebrovascular human thrombi and applied an artificial intelligence routine to examine protein signatures between the two selected groups. Methods: We specifically used n = 32 cardioembolic and n = 28 atherothrombotic diagnosed thrombi from patients suffering from acute stroke and treated by mechanical thrombectomy. Thrombi proteins were successfully separated by gel-electrophoresis. For each thrombi, peptide samples were analyzed by nano-flow liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) to obtain specific proteomes. Relative protein quantification was performed using a label-free LFQ algorithm and all dataset were analyzed using a support-vector-machine (SVM) learning method. Data are available via ProteomeXchange with identifier PXD020398. Clinical data were also analyzed using SVM, alone or in combination with the proteomes. Results: A total of 2,455 proteins were identified by nano-LC-MS/MS in the samples analyzed, with 438 proteins constantly detected in all samples. SVM analysis of LFQ proteomic data delivered combinations of three proteins achieving a maximum of 88.3% for correct classification of the cardioembolic and atherothrombotic samples in our cohort. The coagulation factor XIII appeared in all of the SVM protein trios, associating with cardioembolic thrombi. A combined SVM analysis of the LFQ proteome and clinical data did not deliver a better discriminatory score as compared to the proteome only. Conclusion: Our results advance the portrayal of the human cerebrovascular thrombi proteome. The exploratory SVM analysis outlined sets of proteins for a proof-of-principle characterization of our cohort cardioembolic and atherothrombotic samples. The integrated analysis proposed herein could be further developed and retested on a larger patients population to better understand stroke origin and the associated cerebrovascular pathophysiology.

Prefrontal activation in suicide attempters during decision making with emotional feedback.

Emotional feedback, such as faces showing emotions, can influence decision making. Decision making and emotional face processing, mainly mediated by the prefrontal and cingulate cortices, are impaired in suicide attempters. Here, we used functional MRI (fMRI) to study prefrontal activation in suicide attempters during a modified version of the Iowa Gambling Task (IGT) that included emotional face feedback. We randomly distributed the 116 euthymic women (n = 45 suicide attempters, n = 41 affective controls with history of depression without suicide attempt, and n = 30 healthy controls) included in the study in three emotional IGT groups: concordant (safe and risky choices followed by happy and angry faces, respectively), discordant (safe and risky choices followed by angry and happy faces, respectively), and neutral condition (safe and risky choices followed by neutral faces). Considering the two IGT phases (ambiguous and risky), we then analyzed five regions of interest during the risky vs. safe choices: orbitofrontal (OFC), anterior cingulate (ACC), ventrolateral (VLPFC), medial (MPFC) and dorsal prefrontal (DPFC) cortices. We found: (1) impaired decision making and increased DPFC and OFC activation in suicide attempters vs. controls in the discordant condition during the risky phase; (2) reduced VLPFC activation in suicide attempters in the concordant condition during the ambiguous phase; and (3) decreased OFC, ACC and DPFC activation in both control groups in the concordant condition during the ambiguous phase. Suicide attempters showed prefrontal alterations during reward-learning decision making with emotional feedback. Suicide attempters may guide their decisions to avoid social negative feedback despite the expected outcome.

Serum GFAP in multiple sclerosis: correlation with disease type and MRI markers of disease severity.

Neurofilament light chain (NfL) has been demonstrated to correlate with multiple sclerosis disease severity as well as treatment response. Nevertheless, additional serum biomarkers are still needed to better differentiate disease activity from disease progression. The aim of our study was to assess serum glial fibrillary acid protein (s-GFAP) and neurofilament light chain (s-NfL) in a cohort of 129 multiple sclerosis (MS) patients. Eighteen primary progressive multiple sclerosis (PPMS) and 111 relapsing remitting MS (RRMS) were included. We showed that these 2 biomarkers were significantly correlated with each other (R = 0.72, p < 0.001). Moreover, both biomarkers were higher in PPMS than in RRMS even if multivariate analysis only confirmed this difference for s-GFAP (130.3 ± 72.8 pg/ml vs 83.4 ± 41.1 pg/ml, p = 0.008). Finally, s-GFAP was correlated with white matter lesion load and inversely correlated with WM and GM volume. Our results seem to confirm the added value of s-GFAP in the context of multiple sclerosis.

Quantitative assessment of near-infrared spectroscopy time course under hypercapnia using an a priori model-based fitting.

BACKGROUND: Partial arterial pressure of carbon dioxide (CO2) modulates cerebral blood flow through a vasoreactivity mechanism. Near infrared spectroscopy (NIRS) can be used to record these changes in cerebral hemodynamics. However, no laterality comparison of the NIRS signal has been performed despite being a prerequisite for the use of such a method in a vasoreactivity monitoring context. We propose to investigate the NIRS signal laterality in response to a CO2-inhalation-based hypercapnia paradigm in healthy volunteers. METHODS: Eleven healthy volunteers (6 women, 5 men, mean age: 31 ± 11) underwent a 3-block-design inhalation paradigm: normoxia (5min, "baseline") - hypercapnia (2min, "stimulation") - normoxia (5min, "post-stimulation"). NIRS signal was measured using a two-channel oximeter (INVOS 5100C, Medtronic, USA) with sensors placed symmetrically on both left and right sides on each subject's forehead. Additional heart rate (HR) monitoring was performed simultaneously. Based on the NIRS mean signal pattern, an a priori model of parametric identification was applied for each channel to quantify parameters of interest (amplitude, time delay, excitation and post-stimulation time) for each inhalation block. RESULTS: HR increased significantly during the stimulation block. The quality of the model was satisfactory: mean absolute errors between modeled and experimental signals were lower than the resolution of the device. No significant lateralization was found between left and right values of most of the parameters. CONCLUSION: Due to the lack of lateralization, this parametric identification of NIRS responses to hypercapnia could bring light to a potential asymmetry and be used as a biomarker in patients with cerebrovascular diseases.

Differential effects of hunger on cerebral blood flow in healthy adolescents.

Adolescence represents a key developmental period in terms of both mood and overweight and is linked to disturbed eating behavior. Therefore, it is essential to investigate the basis of food intake in healthy adolescents by considering mood impacts which remain largely unexplored. Hence this study aims to investigate the impact of hunger and mood on cerebral blood flow (CBF) changes in healthy adolescents. Fifteen participants underwent two MRI sessions including a 3D pseudo-continuous arterial spin labeling sequence: pre-lunch (hunger) and post-lunch (satiety). Mood was assessed using the Multiscore Depression Inventory for Children. We found higher CBF values in the posterior insula in response to hunger compared to satiety, an area of the brain which contributes to the anticipation and motivation of feeding. In response to satiation, we observed higher CBF values in the precuneus, lingual gyrus and cuneus which are involved in the aspects of response inhibition related to food intake. Furthermore, we show that correlation between mood assessment and CBF is modulated by appetite in the precuneus, anterior cingulate gyrus, anterior orbitofrontal gyrus, occipital gyrus and cuneus, suggesting that participants affected by depressed mood could use ruminative processing in order to evaluate the reward of an upcoming meal.

Retinal vascular fractal dimension and cerebral blood flow, a pilot study.

PURPOSE: Ocular and brain microcirculation share embryological and histological similarities. The retinal vascular fractal dimension (FD) is a marker of retinal vascular complexity of the vascular tree. The purpose of this study was to explore the relationship between cerebral blood flow (CBF), retinal vascular FD and other retinal vascular markers. METHODS: Cross-sectional analysis comprising 26 individuals ≥65 years old from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) cohort of relative healthy older adults. Retinal vascular FD was measured from fundus photographs by using the semi-automated Singapore Eye Vessel Assessment (SIVA) software. CBF was estimated using a 2D pulsed ASL MRI sequence. Associations between blood flow and retinal parameters were analysed using linear regression models adjusted for age and sex. RESULTS: Cerebral blood flow was positively associated with venular FD (R2  = 0.32, p = 0.03). This association was stronger in the anterior versus posterior brain territories (R2  = 0.35 [p = 0.001] versus R2  = 0.16 [p = 0.07], respectively). Global CBF was correlated with arteriolar branching angle (R2  = 0.23, p = 0.01) and tortuosity (R2  = 0.20, p = 0.02). Global CBF was not correlated with other SIVA parameters. CONCLUSIONS: Retinal venular complexity summarized by the FD was associated with cerebral blood flow as well as retinal arteriolar tortuosity and branching angle. Larger prospective clinical studies are needed to confirm these results.