Functional connectivity-hemodynamic (un)coupling changes in chronic mild brain injury are associated with mental health and neurocognitive indices: a resting state fMRI study.

peer reviewedPURPOSE: To examine hemodynamic and functional connectivity alterations and their association with neurocognitive and mental health indices in patients with chronic mild traumatic brain injury (mTBI). METHODS: Resting-state functional MRI (rs-fMRI) and neuropsychological assessment of 37 patients with chronic mTBI were performed. Intrinsic connectivity contrast (ICC) and time-shift analysis (TSA) of the rs-fMRI data allowed the assessment of regional hemodynamic and functional connectivity disturbances and their coupling (or uncoupling). Thirty-nine healthy age- and gender-matched participants were also examined. RESULTS: Patients with chronic mTBI displayed hypoconnectivity in bilateral hippocampi and parahippocampal gyri and increased connectivity in parietal areas (right angular gyrus and left superior parietal lobule (SPL)). Slower perfusion (hemodynamic lag) in the left anterior hippocampus was associated with higher self-reported symptoms of depression (r =  - 0.53, p = .0006) and anxiety (r =  - 0.484, p = .002), while faster perfusion (hemodynamic lead) in the left SPL was associated with lower semantic fluency (r =  - 0.474, p = .002). Finally, functional coupling (high connectivity and hemodynamic lead) in the right anterior cingulate cortex (ACC)) was associated with lower performance on attention and visuomotor coordination (r =  - 0.50, p = .001), while dysfunctional coupling (low connectivity and hemodynamic lag) in the left ventral posterior cingulate cortex (PCC) and right SPL was associated with lower scores on immediate passage memory (r =  - 0.52, p = .001; r =  - 0.53, p = .0006, respectively). Uncoupling in the right extrastriate visual cortex and posterior middle temporal gyrus was negatively associated with cognitive flexibility (r =  - 0.50, p = .001). CONCLUSION: Hemodynamic and functional connectivity differences, indicating neurovascular (un)coupling, may be linked to mental health and neurocognitive indices in patients with chronic mTBI

Anxiety and depression severity in neuropsychiatric SLE are associated with perfusion and functional connectivity changes of the frontolimbic neural circuit: a resting-state f(unctional) MRI study.

peer reviewed[en] OBJECTIVE: To examine the hypothesis that perfusion and functional connectivity disturbances in brain areas implicated in emotional processing are linked to emotion-related symptoms in neuropsychiatric SLE (NPSLE). METHODS: Resting-state fMRI (rs-fMRI) was performed and anxiety and/or depression symptoms were assessed in 32 patients with NPSLE and 18 healthy controls (HC). Whole-brain time-shift analysis (TSA) maps, voxel-wise global connectivity (assessed through intrinsic connectivity contrast (ICC)) and within-network connectivity were estimated and submitted to one-sample t-tests. Subgroup differences (high vs low anxiety and high vs low depression symptoms) were assessed using independent-samples t-tests. In the total group, associations between anxiety (controlling for depression) or depression symptoms (controlling for anxiety) and regional TSA or ICC metrics were also assessed. RESULTS: Elevated anxiety symptoms in patients with NPSLE were distinctly associated with relatively faster haemodynamic response (haemodynamic lead) in the right amygdala, relatively lower intrinsic connectivity of orbital dlPFC, and relatively lower bidirectional connectivity between dlPFC and vmPFC combined with relatively higher bidirectional connectivity between ACC and amygdala. Elevated depression symptoms in patients with NPSLE were distinctly associated with haemodynamic lead in vmPFC regions in both hemispheres (lateral and medial orbitofrontal cortex) combined with relatively lower intrinsic connectivity in the right medial orbitofrontal cortex. These measures failed to account for self-rated, milder depression symptoms in the HC group. CONCLUSION: By using rs-fMRI, altered perfusion dynamics and functional connectivity was found in limbic and prefrontal brain regions in patients with NPSLE with severe anxiety and depression symptoms. Although these changes could not be directly attributed to NPSLE pathology, results offer new insights on the pathophysiological substrate of psychoemotional symptomatology in patients with lupus, which may assist its clinical diagnosis and treatment

Converging evidence of impaired brain function in systemic lupus erythematosus: changes in perfusion dynamics and intrinsic functional connectivity.

peer reviewed[en] PURPOSE: Τhe study examined changes in hemodynamics and functional connectivity in patients with systemic lupus erythematosus (SLE) with or without neuropsychiatric manifestations. METHODS: Participants were 44 patients with neuropsychiatric SLE (NPSLE), 20 SLE patients without such manifestations (non-NPSLE), and 35 healthy controls. Resting-state functional MRI (rs-fMRI) was used to obtain whole-brain maps of (a) perfusion dynamics derived through time shift analysis (TSA), (b) regional functional connectivity (intrinsic connectivity contrast (ICC) coefficients), and (c) hemodynamic-connectivity coupling. Group differences were assessed through independent samples t-tests, and correlations of rs-fMRI indices with clinical variables and neuropsychological test scores were, also, computed. RESULTS: Compared to HC, NPSLE patients demonstrated intrinsic hypoconnectivity of anterior Default Mode Network (DMN) and hyperconnectivity of posterior DMN components. These changes were paralleled by elevated hemodynamic lag. In NPSLE, cognitive performance was positively related to higher intrinsic connectivity in these regions, and to higher connectivity-hemodynamic coupling in posterior DMN components. Uncoupling between hemodynamics and connectivity in the posterior DMN was associated with worse task performance. Non-NPSLE patients displayed hyperconnectivity in posterior DMN and sensorimotor regions paralleled by relatively increased hemodynamic lag. CONCLUSION: Adaptation of regional brain function to hemodynamic changes in NPSLE may involve locally decreased or locally increased intrinsic connectivity (which can be beneficial for cognitive function). This process may also involve elevated coupling of hemodynamics with functional connectivity (beneficial for cognitive performance) or uncoupling, which may be detrimental for the cognitive skills of NPSLE patients

Chronic Mild Traumatic Brain Injury: Aberrant Static and Dynamic Connectomic Features Identified Through Machine Learning Model Fusion.

peer reviewedTraumatic Brain Injury (TBI) is a frequently occurring condition and approximately 90% of TBI cases are classified as mild (mTBI). However, conventional MRI has limited diagnostic and prognostic value, thus warranting the utilization of additional imaging modalities and analysis procedures. The functional connectomic approach using resting-state functional MRI (rs-fMRI) has shown great potential and promising diagnostic capabilities across multiple clinical scenarios, including mTBI. Additionally, there is increasing recognition of a fundamental role of brain dynamics in healthy and pathological cognition. Here, we undertake an in-depth investigation of mTBI-related connectomic disturbances and their emotional and cognitive correlates. We leveraged machine learning and graph theory to combine static and dynamic functional connectivity (FC) with regional entropy values, achieving classification accuracy up to 75% (77, 74 and 76% precision, sensitivity and specificity, respectively). As compared to healthy controls, the mTBI group displayed hypoconnectivity in the temporal poles, which correlated positively with semantic (r = 0.43, p < 0.008) and phonemic verbal fluency (r = 0.46, p < 0.004), while hypoconnectivity in the right dorsal posterior cingulate correlated positively with depression symptom severity (r = 0.54, p < 0.0006). These results highlight the importance of residual FC in these regions for preserved cognitive and emotional function in mTBI. Conversely, hyperconnectivity was observed in the right precentral and supramarginal gyri, which correlated negatively with semantic verbal fluency (r=-0.47, p < 0.003), indicating a potential ineffective compensatory mechanism. These novel results are promising toward understanding the pathophysiology of mTBI and explaining some of its most lingering emotional and cognitive symptoms

Μελέτη της σκλήρυνσης κατα πλάκας με νεότερες τεχνικές μαγνητικής τομογραφίας

The aim of the current study is to perform non conventional Magnetic Resonance Imaging techniques , like magnetization transfer, T2 relaxation time analysis, perfusion weighted imaging and diffusion weighted imaging for quantitative evaluation of multiple sclerosis (MS) and correlation with clinical disability. For that purpose 60 patients with clinically definite MS and EDSS ranged from1-7.5, were examined. On 31 of them (26 with RRMS, 4 with SPMS, and 1 with PPMS) a magnetization transfer technique, T2 relaxation time analysis, and perfusion weighted imaging were performed, while on the other 29 patients (27 with RRMS and 2 with SPMS) perfusion weighted imaging and diffusion weighted imaging were applied. 6 of the patients were examined monthly and for 6 months with a magnetization transfer technique, T2 relaxation time analysis, and perfusion weighted imaging for the evaluation of the short term clinical evolution of the disease. 20 age-matched healthy volunteers were also investigated. 555 measurements , evenly divided between subjects, of Magnetization Transfer Ratio (MTR) , magnetization transfer rate (Kfor),native T1 relaxation time (T1free) and T2 relaxation time were performed on the 31 patients . 207 of them corcerned MS lesions, which were identified on T2 sequences and classified according their signal intensity on T1 sequences and their behavior after Gd administration, divided to mild hypointense (HYPO), isointense (ISO) , severe hypointense(BH) and enhancing (EL) lesions. 72 of the measurements concerned Dirty White Matter areas(DWM) and 248 of them areas of Normal Appearing White Matter (NAWM). 80 areas of normal white matter (NWM) were, also, measured. Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) were measured on 213 focal lesions , 96 areas of DWM and 288 areas of NAWM of the other 29 patients, while rCBV (% of each subjects caudate nucleus) was estimated on the total of both the 60 patients and the measurements. MTR, Kfor, T1free, T2 relaxation time, ADC, FA and rCBV% of the different white matter lesions and the NWM areas were compared using a student t-test. Possibly linearity between the different parameters and, also, between them and the EDSS score was evaluated using linear regression analysis. There were statistically significant differences between MTR, Kfor, T1free, T2 relaxation time, ADC, FA and rCBV% values of NAWM, DWM and focal white matter lesions. Statistically significant different values were, also,proved between MTR, Kfor, T2 relaxation time and FA of NAWM compared to NWM. Linear regression analysis demonstrated correlation between the different measured MR parameters for the DWM areas and BH, which represent lesions where inflammation and demyelination predominates, respectively. Correlation was, also, demonstrated between all the measured MR parameters and the EDSS score when all the measurements were added. Correlation with clinical disability was also found when MTR of DWM, rCBV% and ADC of BH, and FA of NAWM were calculated. During the short-term clinical evolution of the disease in patients with RRMS, a gradual decline of the whole measurements' mean MTR values and the DWM rCBV% values were demonstrated. In conclusion non conventional MRI techniques improve MS lesions detection and characterization and therefore may be used as part of the basic MR protocol in the evaluation of MS patients. Correlation between different MR parameters was demonstrated for certain focal lesions, while correlation between them and the clinical disability was also proved,when all the measurements were added together with the exception of T1free and FA. DWM areas, although underestimated in the literature,probably have a significant role in the pathogenesis and clinical evolution of multiple sclerosis.Σκοπός της παρούσας μελέτης είναι η εφαρμογή μη συμβατικών τεχνικών Μαγνητικής Τομογραφίας, όπως η μεταφορά μαγνήτισης, η ανάλυση των χρόνων χαλάρωσης T2, η τεχνική αιματικής διήθησης και η τεχνική κυτταρικής διάχυσης σε ασθενείς με σκλήρυνση κατά πλάκας (ΣΚΠ) , για την ποσοτική εκτίμηση των αλλοιώσεων της λευκής ουσίας και το συσχετισμό τους με την κλινική λειτουργική κατάσταση των ασθενών. Για τον σκοπό αυτό μελετήθησαν 60 οι ασθενείς με κλινικά βέβαιη ΣΚΠ και τιμές EDSS που κυμαίνονταν από 1-7.5. Στους 31 από αυτούς (26 με RRMS, 4 με SPMS, και 1 με PPMS) εφαρμόσθηκαν η τεχνική μεταφοράς μαγνήτισης, η ανάλυση των χρόνων χαλάρωσης T2, και η τεχνική αιματικής διήθησης, ενώ στους υπόλοιπους 29 ασθενείς (27 με RRMS και 2 με SPMS) η τεχνική αιματικής διήθησης και η τεχνική κυτταρικής διάχυσης. 6 από τους ασθενείς εξετάστηκαν /μήνα και για 6 μήνες με τεχνική μεταφοράς μαγνήτισης, ανάλυση των χρόνων χαλάρωσης Τ2 και τεχνική αιματικής διήθησης με στόχο την αξιολόγηση των βραχυπρόθεσμων μεταβολών της νόσου.Μελετήθησαν επίσης 20 ανάλογης ηλικίας υγιείς εθελοντές. Στους 31 ασθενείς εκτελέσθηκαν 555 μετρήσεις που αφορούσαν τις παραμέτρους : δείκτης μεταφοράς μαγνήτισης (MTR), ρυθμός μεταφοράς μαγνήτισης (Kfor), ενδογενής χρόνος χαλάρωσης T1 (T1free) και χρόνος χαλάρωσης T2. 207 από αυτές αφορούσαν εστιακές αλλοιώσεις της λευκής ουσίας που αναγνωρίσθηκαν στις ακολουθίες T2 προσανατολισμού και ταξινομήθηκαν ανάλογα με την ένταση σήματός τους στις ακολουθίες T1 προσανατολισμού και τη συμπεριφορά τους μετά από τη χορήγηση Γαδολίνιου,διαιρούμενες σε μέτριας ελαττωμένης έντασης σήματος (HYPO), ίσης έντασης σήματος (ISO), και έντονα ελαττωμένης έντασης σήματος (BH) αλλοιώσεις, σε σύγκριση με την παρακείμενη λευκή ουσία , καθώς και προσλαμβάνουσες (EL).72 μετρήσεις αφορούσαν περιοχές "βρώμικης λευκής ουσίας» (DWM)and 248 περιοχές φυσιολογικά απεικονιζόμενης λευκής ουσίας (NAWM). Μετρήθησαν επίσης 80 περιοχές φυσιολογικής λευκής ουσίας (NWM). Ο σχετικός συντελεστής διάχυσης (ADC) και η κλασματική ανισοτροπία (FA) εκτιμήθηκαν σε 213 εστιακές αλλοιώσεις, 96 περιοχές DWM και 288 περιοχές NAWM των υπόλοιπων 29 αθενών, ενώ ο rCBV ( υπολογιζόμενος σαν εκατοστιαίο ποσοστό της τιμής του κερκοφόρου πυρήνα κάθε ατόμου) υπολογίστηκε στο σύνολο και των 60 ασθενών και μετρήσεων. Οι τιμές των MTR, Kfor, T1free, χρόνου χαλάρωσης T2, ADC, FA και rCBV% των διαφορετικών αλλοιώσεων της λευκής ουσίας και της NWM συγκρίθηκαν με την χρήση student t-test.Η ενδεχόμενη γραμμική συσχέτιση μεταξύ των διαφορετικών παραμέτρων και, επίσης, μεταξύ αυτών και της κλινικήςλειτουργικής κατάστασης, βαθμονομούμενης με την κλιμακα EDSS αξιολογήθηκε με την χρήση linear regression analysis. Διαπιστώθηκαν στατιστικά σημαντικές διαφορές μεταξύ των τιμών MTR, Kfor, T1free, μέσου χρόνου χαλάρωσης T2, ADC, FA και rCBV% των περιοχών NAWM, DWM και των εστιακών αλλοιώσεων της λευκής ουσίας. Στατιστικώς σημαντικά διαφορετικές τιμές αναδείχθηκαν, επίσης, μεταξύ των τιμών MTR, Kfor, μέσου χρόνου χαλάρωσης T2 και του FA της NAWM σε σύγκριση με τη NWM. Ανεδείχθη παρουσία γραμμικής συσχέτισης μεταξύ των διαφορετικών μελετούμενων παραμέτρων των νεότερων τεχνικών Μαγνητικής Τομογραφίας για τις περιοχές DWM καθώς και τις BH, αλλοιώσεις, δηλαδή, όπου κυριαρχούν η φλεγμονή και η απομυελίνωση, αντίστοιχα. Βαθμός συσχέτισης αναγνωρίσθηκε και μεταξύ των τιμών των διαφορετικών παραμέτρων ,όταν υπολογίσθηκαν μαζί όλες οι αντίστοιχες μετρήσεις, και των τιμών του EDSS. Τέλος, αναγνωρίσθηκε συσχετιση με την κλινική λειτουργική κατάσταση των τιμών MTR των περιοχών DWM, καθώς και των τιμών rCBV% και ADC των BH, και των τιμών FA των περιοχών NAWM. Κατά τη μελέτη των βραχυπρόθεσμων μεταβολών της νόσου στους ασθενείς με RRMS,παρατηρήθηκε βαθμιαία ελάττωση των μέσων τιμών MTR του συνόλου των μετρήσεων, καθώς και των τιμών rCBV% των περιοχών DWM. Συμπερασματικά, οι μη συμβατικές τεχνικές ΜΤ βελτιώνουν την ανίχνευση και το χαρακτηρισμό των αλλοιώσεων της λευκής ουσίας και επομένως θα μπορούσαν να χρησιμοποιηθούν ως μέρος του βασικού πρωτοκόλλου ΜΤ στα πλαίσια της απεικονιστικής διερεύνησης των ασθενών με ΣΚΠ. Αποδείχθηκε παρουσία συσχέτισης μεταξύ διαφορετικών παραμέτρων των νεότερων τεχνικών μαγνητικής Τομογραφίας για συγκεκριμένες εστιακές αλλοιώσεις, ενώ αναγνωρίσθηκε,επίσης, συσχέτιση μεταξύ αυτών και της κλινικής λειτουργικής κατάστασης, όταν συνυπολογίζονται όλες οι μετρήσεις, με την εξαίρεση των παραμέτρων T1free and FA. Σημειώνεται, τέλος, ότι οι περιοχές DWM, αν και έχουν υποεκτιμηθεί στη διεθνή βιβλιογραφία, πιθανότατα κατέχουν έναν σημαντικό ρόλο στην παθογένεση και την κλινική εξέλιξη των ασθενών που πασχουν από σκλήρυνση κατά πλάκας

Multinodular and vacuolating neuronal tumor incidentally discovered in a young man: Conventional and advanced MRI features

Multinodular and Vacuolating Neuronal Tumor (MVNT) has been included in the most recent (2016) World Health Organization Classification of Tumors of the Central Nervous System as unique cytoarchitectural pattern of gangliocytoma. We present a case of a MVNT incidentally discovered in a 22-year old male, who presented with seizures after a head injury. Conventional MRI revealed a left parietal lesion with characteristic tiny, coalescent, well-defined, non-enhancing nodules, located in the juxtacortical white matter with partial involvement of an otherwise normal adjacent cortex and characterized by slight relative increase of the cerebral blood volume (CBV), compared to the contralateral white matter (lesional CBV/contralateral CBV = 1.112) and mild increase of choline and reduction of NAA (lesional choline/creatine ratio =1.36 and choline/NAA ratio=0.77, compared to 0.87 and 0.51, respectively). The patient fully responded to treatment with phenytoin and a follow-up MRI, six months later, showed the lesion without any substantial difference. Keywords: Multinodular and vacuolating neuronal tumor, Magnetic resonance imaging, Diffusion-weighted imaging, Perfusion imaging, Magnetic resonance spectroscop

Posterior Reversible Encephalopathy Syndrome, Multiple Sclerosis and interferon therapy: Association, co-incidence or convoluted interplay?

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) has only rarely been reported in patients with multiple sclerosis (MS). METHODS: Case report of a patient with relapsing remitting (RR) MS patient on interferon (INF) treatment, who developed posterior fossa PRES. RESULTS: A 46-year-old male diagnosed with RR MS in 2010 was placed on INF beta-1a therapy. He remained in clinical remission for seven years. He then presented with headache of one month duration and worsening upper extremity ataxia. Cranial MRI revealed two new enhancing cerebellar lesions (one with tumefactive features). Within the next 10 days the patient developed severe holocephalic headache, vomiting, altered consciousness and gait instability. Urgent brain MRI revealed diffuse hyperintense lesions in T2WI and FLAIR sequences in bilateral cerebellar hemispheres and the right thalamus, with marked swelling, increased diffusivity indicative of vasogenic edema and patchy-nodular enhancement, while smaller lesions were also found in posterior temporal, parietal and occipital lobes. Severely elevated blood pressure was noted. Treatment with hypertonic agents, esmolol drip and IV steroids was instituted, resulting in remarkable improvement within the next several days. Repeat MRI showed almost complete resolution of the cerebellar lesions. Interferon beta was discontinued and blood pressure remained well controlled. CONCLUSIONS: Patients with RR MS on IFN beta therapy can develop PRES via the combination of hypertension and endothelial dysfunction by IFN, even when stable on this treatment. Neurologists should be keen to differentiate the appearance of PRES lesions from those of fulminant MS relapse, opportunistic infections or malignancy

Anxiety and depression severity in neuropsychiatric SLE are associated with perfusion and functional connectivity changes of the frontolimbic neural circuit: a resting-state f(unctional) MRI study

Objective To examine the hypothesis that perfusion and functional connectivity disturbances in brain areas implicated in emotional processing are linked to emotion-related symptoms in neuropsychiatric SLE (NPSLE).Methods Resting-state fMRI (rs-fMRI) was performed and anxiety and/or depression symptoms were assessed in 32 patients with NPSLE and 18 healthy controls (HC). Whole-brain time-shift analysis (TSA) maps, voxel-wise global connectivity (assessed through intrinsic connectivity contrast (ICC)) and within-network connectivity were estimated and submitted to one-sample t-tests. Subgroup differences (high vs low anxiety and high vs low depression symptoms) were assessed using independent-samples t-tests. In the total group, associations between anxiety (controlling for depression) or depression symptoms (controlling for anxiety) and regional TSA or ICC metrics were also assessed.Results Elevated anxiety symptoms in patients with NPSLE were distinctly associated with relatively faster haemodynamic response (haemodynamic lead) in the right amygdala, relatively lower intrinsic connectivity of orbital dlPFC, and relatively lower bidirectional connectivity between dlPFC and vmPFC combined with relatively higher bidirectional connectivity between ACC and amygdala. Elevated depression symptoms in patients with NPSLE were distinctly associated with haemodynamic lead in vmPFC regions in both hemispheres (lateral and medial orbitofrontal cortex) combined with relatively lower intrinsic connectivity in the right medial orbitofrontal cortex. These measures failed to account for self-rated, milder depression symptoms in the HC group.Conclusion By using rs-fMRI, altered perfusion dynamics and functional connectivity was found in limbic and prefrontal brain regions in patients with NPSLE with severe anxiety and depression symptoms. Although these changes could not be directly attributed to NPSLE pathology, results offer new insights on the pathophysiological substrate of psychoemotional symptomatology in patients with lupus, which may assist its clinical diagnosis and treatment

Evidence of Age-Related Hemodynamic and Functional Connectivity Impairment: A Resting State fMRI Study.

peer reviewedPurpose: To assess age-related changes in intrinsic functional brain connectivity and hemodynamics during adulthood in the context of the retrogenesis hypothesis, which states that the rate of age-related changes is higher in late-myelinating (prefrontal, lateral-posterior temporal) cerebrocortical areas as compared to early myelinating (parietal, occipital) regions. In addition, to examine the dependence of age-related changes upon concurrent subclinical depression symptoms which are common even in healthy aging. Methods: Sixty-four healthy adults (28 men) aged 23-79 years (mean 45.0, SD = 18.8 years) were examined. Resting-state functional MRI (rs-fMRI) time series were used to compute voxel-wise intrinsic connectivity contrast (ICC) maps reflecting the strength of functional connectivity between each voxel and the rest of the brain. We further used Time Shift Analysis (TSA) to estimate voxel-wise hemodynamic lead or lag for each of 22 ROIs from the automated anatomical atlas (AAL). Results: Adjusted for depression symptoms, gender and education level, reduced ICC with age was found primarily in frontal, temporal regions, and putamen, whereas the opposite trend was noted in inferior occipital cortices (p < 0.002). With the same covariates, increased hemodynamic lead with advancing age was found in superior frontal cortex and thalamus, with the opposite trend in inferior occipital cortex (p < 0.002). There was also evidence of reduced coupling between voxel-wise intrinsic connectivity and hemodynamics in the inferior parietal cortex. Conclusion: Age-related intrinsic connectivity reductions and hemodynamic changes were demonstrated in several regions-most of them part of DMN and salience networks-while impaired neurovascular coupling was, also, found in parietal regions. Age-related reductions in intrinsic connectivity were greater in anterior as compared to posterior cortices, in line with implications derived from the retrogenesis hypothesis. These effects were affected by self-reported depression symptoms, which also increased with age