Статті в журналах з теми "MRI, Diffusion, MEG"

Brain imaging techniques, especially those based on magnetic resonance imaging (MRI) and magnetoencephalography (MEG), have been increasingly applied to study multiple large-scale distributed brain networks in healthy people and neurological patients. With regard to neurodegenerative disorders, amyotrophic lateral sclerosis (ALS), clinically characterized by the predominant loss of motor neurons and progressive weakness of voluntary muscles, and frontotemporal lobar degeneration (FTLD), the second most common early-onset dementia, have been proven to share several clinical, neuropathological, genetic, and neuroimaging features. Specifically, overlapping or mildly diverging brain structural and functional connectivity patterns, mostly evaluated by advanced MRI techniques—such as diffusion tensor and resting-state functional MRI (DT–MRI, RS–fMRI)—have been described comparing several ALS and FTLD populations. Moreover, though only pioneering, promising clues on connectivity patterns in the ALS–FTLD continuum may derive from MEG investigations. We will herein overview the current state of knowledge concerning the most advanced neuroimaging findings associated with clinical and genetic patterns of neurodegeneration across the ALS–FTLD continuum, underlying the possibility that network-based approaches may be useful to develop novel biomarkers of disease for adequately designing and monitoring more appropriate treatment strategies.

Accurate localization of the seizure onset zone is important for better seizure outcomes and preventing deficits following epilepsy surgery. Recent advances in neuroimaging techniques have increased our understanding of the underlying etiology and improved our ability to noninvasively identify the seizure onset zone. Using epilepsy-specific magnetic resonance imaging (MRI) protocols, structural MRI allows better detection of the seizure onset zone, particularly when it is interpreted by experienced neuroradiologists. Ultra-high-field imaging and postprocessing analysis with automated machine learning algorithms can detect subtle structural abnormalities in MRI-negative patients. Tractography derived from diffusion tensor imaging can delineate white matter connections associated with epilepsy or eloquent function, thus, preventing deficits after epilepsy surgery. Arterial spin-labeling perfusion MRI, simultaneous electroencephalography (EEG)-functional MRI (fMRI), and magnetoencephalography (MEG) are noinvasive imaging modalities that can be used to localize the epileptogenic foci and assist in planning epilepsy surgery with positron emission tomography, ictal single-photon emission computed tomography, and intracranial EEG monitoring. MEG and fMRI can localize and lateralize the area of the cortex that is essential for language, motor, and memory function and identify its relationship with planned surgical resection sites to reduce the risk of neurological impairments. These advanced structural and functional imaging modalities can be combined with postprocessing methods to better understand the epileptic network and obtain valuable clinical information for predicting long-term outcomes in pediatric epilepsy.

IntroductionThis MRC Confidence in Concept funded study (Clinical Trials reference:NCT03867513) combined magnetoencephalography (MEG) with ultrahigh field 7T MRI, to look for functional and struc- tural abnormalities in mild traumatic brain injury (mTBI).ObjectivesCan those with mTBI be differentiated from non-head injured orthopaedic trauma controls by measuring brain wave activity.MethodsWe scanned 40 participants within two weeks of an emergency department visit and they underwent resting state and task specific MEG followed by 7T MRI including structural, susceptibility, and diffusion sequences. Questionnaire assessment was completed at baseline, three, and six months.ResultsWhilst most individuals with mTBI recover a significant proportion have persistent difficulties. Using a Hidden Markov Model in the mTBI cohort, we were able to demonstrate reduced beta band connec- tivity results from a loss in the temporal coincidence of bursts of activity in spatially distinct regions. This replicates our findings in a distinct sub-acute mTBI cohort. Susceptibility weight imaging revealed only two mTBI participants with microhaemorrhages, their clinical care, markers of injury severity, and recovery did not differentiate them from others in the mTBI cohort.ConclusionsOur results suggests that mTBI may impair the dynamic coordination of neural network activity and this requires further exploration.

This tutorial/review covers functional brain-imaging methods and results used to study language and reading disabilities. Although the main focus is on functional MRI and functional MR spectroscopy, other imaging techniques are discussed briefly such as positron emission tomography (PET), electroencephalography (EEG), magnetoencepholography (MEG), and MR diffusion imaging. These functional brain-imaging studies have demonstrated that dyslexia is a brain-based disorder and that serial imaging studies can be used to study the effect of treatment on functional brain activity.

Background. Dystonia is a syndrome with varied phenomenology but our understanding of its mechanisms is deficient. With neuroimaging techniques, such as fiber tractography (FT) and magnetoencephalography (MEG), pathway connectivity can be studied to that end. We present a hemidystonia patient treated with deep brain stimulation (DBS). Methods. After 10 years of left axial hemidystonia, a 45-year-old male underwent unilateral right globus pallidus internus (GPi) DBS. Whole brain MEG before and after anticholinergic medication was performed prior to surgery. 26-direction diffusion tensor imaging (DTI) was obtained in a 3 T MRI machine along with FT. The patient was assessed before and one year after surgery by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Results. In the eyes-closed MEG study there was an increase in brain coherence in the gamma band after medication in the middle and inferior frontal region. FT demonstrated over 50% more intense ipsilateral connectivity in the right hemisphere compared to the left. After DBS, BFMDRS motor and disability scores both dropped by 71%. Conclusion. Multimodal neuroimaging techniques can offer insights into the pathophysiology of dystonia and can direct choices for developing therapeutics. Unilateral pallidal DBS can provide significant symptom control in axial hemidystonia poorly responsive to medication.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no effective treatment or cure. ALS is characterized by the death of lower motor neurons (LMNs) in the spinal cord and upper motor neurons (UMNs) in the brain and their networks. Since the lower motor neurons are under the control of UMN and the networks, cortical degeneration may play a vital role in the pathophysiology of ALS. These changes that are not apparent on routine imaging with CT scans or MRI brain can be identified using modalities such as diffusion tensor imaging, functional MRI, arterial spin labelling (ASL), electroencephalogram (EEG), magnetoencephalogram (MEG), functional near-infrared spectroscopy (fNIRS), and positron emission tomography (PET) scan. They can help us generate a representation of brain networks and connectivity that can be visualized and parsed out to characterize and quantify the underlying pathophysiology in ALS. In addition, network analysis using graph measures provides a novel way of understanding the complex network changes occurring in the brain. These have the potential to become biomarker for the diagnosis and treatment of ALS. This article is a systematic review and overview of the various connectivity and network-based studies in ALS.

Tools from the field of graph signal processing, in particular the graph Laplacian operator, have recently been successfully applied to the investigation of structure-function relationships in the human brain. The eigenvectors of the human connectome graph Laplacian, dubbed “connectome harmonics”, have been shown to relate to the functionally relevant resting-state networks. Whole-brain modelling of brain activity combines structural connectivity with local dynamical models to provide insight into the large-scale functional organization of the human brain. In this study, we employ the graph Laplacian and its properties to define and implement a large class of neural activity models directly on the human connectome. These models, consisting of systems of stochastic integrodifferential equations on graphs, are dubbed graph neural fields, in analogy with the well-established continuous neural fields. We obtain analytic predictions for harmonic and temporal power spectra, as well as functional connectivity and coherence matrices, of graph neural fields, with a technique dubbed CHAOSS (shorthand for Connectome-Harmonic Analysis Of Spatiotemporal Spectra). Combining graph neural fields with appropriate observation models allows for estimating model parameters from experimental data as obtained from electroencephalography (EEG), magnetoencephalography (MEG), or functional magnetic resonance imaging (fMRI). As an example application, we study a stochastic Wilson-Cowan graph neural field model on a high-resolution connectome graph constructed from diffusion tensor imaging (DTI) and structural MRI data. We show that the model equilibrium fluctuations can reproduce the empirically observed harmonic power spectrum of resting-state fMRI data, and predict its functional connectivity, with a high level of detail. Graph neural fields natively allow the inclusion of important features of cortical anatomy and fast computations of observable quantities for comparison with multimodal empirical data. They thus appear particularly suitable for modelling whole-brain activity at mesoscopic scales, and opening new potential avenues for connectome-graph-based investigations of structure-function relationships.

Magnetic resonance imaging is widely used to create detailed images of the organs and tissues. In daily clinical practice of diagnosing liver cirrhosis, it is still a challenge to find the best clinical diagnosis for detection hepatic lesions like hemangioma or hepatoma. In this study, we tried to compare the accuracy of method non-contrast enhancement multiparametric MRI (mpMRI) with conventional liver MRI. A total of 120 patients with liver cirrhosis were enrolled and were divided into two groups, 60 patients with hepatic hemangioma (HH, group A) and 60 patients with hepatocellular carcinoma (HCC, group B). MRI was first used for different diagnosis hepatic lesions without any invasive procedure or surgical treatment. All acquired MRI images were divided into 2 parts: the first part was the non-contrast enhancement multiparametric MRI (mpMRI), and the second part named the conventional liver MRI, was covered all images including non-contrast enhancement and dynamic contrast material-enhanced. The MRI images were interpreted by two experience gastrointestinal radiologists (I and II). Before analysis, the clinical manifestations, laboratory data, tissue biopsy results were not known. Paired samples t-test was used to analyze the significant difference of two-tailed probability (P < 0.05), and its Hemangioma and Hepatoma of receiver operating characteristic curve and area under the ROC curves values were evaluated. In the results, two-tailed probability of non-contrast enhancement mpMRI sequences and the conventional liver MRI in group A was found to be P = 0.109, while that in group B was found to be P = 0.115. After Wilcoxon sign-ranked test, the two-tailed probability reached 0.557 in group A, while that of group B reached 0.624; both showed not difference between the two groups. In conclusion, the non-contrast enhancement mpMRI that included the half-Fourier single-shot turbo spin-echo (HASTE) with fat suppression T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and susceptibility-weighted imagining (SWI) sequence can provide reliable information for effectively differentiate HH and HCC without using contrast materials. This study is expected to provide a reference for the application of MRI in clinical diagnose for a better enhanced method.

Abstract Bilateral medial medullary infarction (BMMI) is an extremely rare type of cerebrovascular accident often resulting in poor functional consequences. “Heart appearance” on diffusion-weighted imaging (DWI) of magnetic resonance imaging (MRI) is the unique presentation of BMMI. In this article, we present an acute ischemic stroke patient whose brain MRI showed the atypical “heart appearance” sign, manifested unusual bilateral central facial paralysis concurrently. For an early diagnosis of BMMI, it is essential to recognize the characteristic clinical and MRI findings of this rare type of stroke. Abnormal small dot or linear DWI signal at the midline of the brainstem should not be ignored at the early stage of stroke.

Objective: To assess the accuracy of application of diffusion weighted imaging in the diagnosis and evaluation of acute onset ischemic strokes. Study Design: Cross sectional validation study. Place and Duration: Department of Diagnostic Radiology, Mardan Medical Complex, Hospital, Mardan from 15th October 2020 to 15th April 2021. Methodology: Patients whose presentation was highly suggestive of acute stroke, were undergone a non-contrast Computed tomography scan of the brain immediately by Asteion VP single slice. Those found negative for acute hemorrhage on Computed tomography images were subjected to Magnetic resonance imaging on Achieva 1.5 Tesla. Diffusion-weighted imaging technique of MRI scan was done in addition to the conventional T1W, T2W, and FLAIR scans of MRI which were also done. DWI was performed as early as possible not later than 24 hours after symptoms onset. Both DWI imaging technique and conventional routine T1W, T2W and FLAIR scans of MRI were repeated after 7 days. Results: The mean age of the sample was 57.6 + 5.9 years. On Diffusion-weighted imaging, stroke was observed in 60.2% of patients. Later on follow-up conventional magnetic resonance imaging scans were done after 7 days, stroke was recorded in 69.9% of patients confirming the diagnostic accuracy of DWI imaging in sub-acute stroke in early diagnosis. Conclusion: Conventional MRI scans like T1W, T2W and FLAIR have diagnostic accuracy only after some days. It has poor diagnostic accuracy in early onset sub-acute ischemic strokes. On the other hand, DWI imaging scans of MRI can be a useful tool for early detection of ischemic strokes as it diagnosed stroke in 60.2% of patients which were later confirmed by conventional MRI scans done after 7 days. Conventional MRI scans have high accuracy of detection of strokes but only after some days. So DW1 imaging may be applied for early diagnosis of strokes in sub-acute onset strokes. Keywords: Ischemic stroke, Magnetic Resonance Imaging, Diffusion Weighted Imaging, Hemorrhage, Computed Tomography How to Cite This: Afridi SQ, Baig H, Janan Z, Begum T, Shuaib M. Accuracy of diffusion-weighted imaging in the diagnosis and Evaluation of acute ischemic strokes. Isra Med J. 2022; 14(3): 99-103. DOI: https://doi.org/10.55282/imj.oa1314

Abstract Non-small cell lung cancer (NSCLC), a commonly diagnosed lung cancer, is characterized by a high incidence of metastatic spread to the brain, which adversely impacts prognosis. The present study aimed to assess the value of combined dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the treatment outcomes of whole-brain radiotherapy (WBRT) and gefitinib in brain metastases from non-small cell lung cancer (NSCLC) from the perspectives of response rate and short- and long-term efficacy. These results suggested that the indicators measured by DCE-MRI combined with DWI can be used as key imaging-derived markers that predicted the efficacy of WBRT combined with gefitinib in NSCLC patients with brain metastases. Specifically, patients with higher ΔADCmid and ΔADCpost values showed better treatment outcomes. ROC curve analysis indicated ADCpost, ΔADCpost, ΔADCpost (%), and tumor regression rate as the best predictors of efficacy of WBRT combined with gefitinib in these patients. The short-term and long-term effects noted were also significant. Taken together, the findings of this study reveal that tumor regression rate, ADCpost, ΔADCpost, and ΔADCpost (%) can be used as important imaging indicators that predict the therapeutic effect of WBRT combined with gefitinib in NSCLC patients with brain metastases.

2006 Background: After promising early results in the pilot phase (N= 30) reported by Shah 2007, we report on final results of a multicenter phase II study (N=52) in newly diagnosed PCNSL combining R-MPV-A and rdWBRT, expanded to address long-term disease control and cognitive outcomes in pts who actually received rdWBRT. Methods: Pts received 5 cycles of R-MPV (MTX dose: 3.5g/m2). Those with partial response (PR) received additional 2 cycles. Pts with a complete response (CR) after 5-7 cycles received rdWBRT (23.4 Gy), otherwise standard WBRT was offered (45 Gy). Consolidation cytarabine was given to all pts. Primary end-point was 2-y progression-free survival (PFS) in pts receiving rdWBRT (n=30 pts in CR required). Exploratory end-points included comprehensive neuropsychological testing, white matter changes (WMC) analysis (Fazekas scale) and apparent diffusion coefficient (ADC) on MRI. Results: Accrual was completed (N=52; 22 women); median (med) age= 60 (30-79); med KPS= 70 (50-100). In total, 31 (59%) pts were assessable for the primary endpoint (achieved a CR after induction and received rdWBRT). The 2-y PFS for this group was 78% (95% ci: 64%- 92%); med PFS= 7.7 y; the med OS was not reached (med follow-up= 6y); 3y-OS= 88% (ci 70-95); 5y-OS= 81% (ci 62-91). Cognitive testing showed improvement in executive function (P < 0.01) and verbal memory (P < 0.05) following induction chemotherapy; follow-up scores remained stable across the various domains. Minimal WMC developed in long term survivors: 36% of pts showed no change in Fazekas’ scores, 64% of pts developed scores 1 or 2 and no pt showed scores 3-6. The intent-to-treat (n=52) med PFS was 3.3y; med OS= 6.6 y. Differences in ADC values did not predict response (p=0.15), PFS (p=0.41) or OS (p=0.48). Conclusions: Consolidation rdWBRT is a highly effective and safe treatment for newly diagnosed PCNSL. Long term follow-up showed robust PFS and OS, comparable or superior to full dose WBRT, with excellent cognitive outcomes and no significant WMC over time. An RTOG randomized trial has been initiated comparing R-MPV-A with vs without rdWBRT.

Background:Brain models of drug addiction are being tackled in humans, using PET and MRI.Results:1.Whereas tobacco and cannabis do not interact directly with dopamine sites, positron emission tomography detected lower availability in sites regulating the catecholamines homeostasis, notably in dopamine transporter sites in striatal and in extrastriatal regions. This further supports repeated and long term substance use progress towards an adaptative diminished basal dopamine level that would contribute to the switch to an addicted brain.2.Alcohol: abnormalities in brain macro- and micro- structure were searched in detoxified alcohol-dependents with preserved psychosocial functioning:-Brain function (fMRI): fronto-cerebellar overactivation detected during an auditory language task in alcohol-dependents may reflect the compensatory effort required for patients to maintain the same level of performance as controls.-Brain macrostructure (MRI). Widespread lower white matter volumes, and lower grey matter volumes in the frontal lobe, insula, hippocampus, thalami and cerebellum, were detected. Poorer neuropsychological performance correlated with smaller grey matter volumes in these regions and with lower white matter volume in the brainstem.-Brain microstructure (DTI): tractography of white matter fiber bundles revealed that brainstem bundles alteration may contribute to cognitive flexibility impairment. Regression analyses showed memory scores were related to brain microstructure in parahippocampal areas, frontal cortex, and left temporal cortex. This suggest diffusion imaging (DTI) is a useful probe to early alcohol-induced brain alterations.Conclusion:While indices of dopamine down-regulation are consistency detected in several drug addictions, even “socially-adapted” alcohol dependence may induce change in brain structure.Psychol Med. 1998 28:1039-48.Neuropsychopharmacology. 2007 32:429-38.IEEE Trans Med Imaging. 2007 26:553-65J Nucl Med. 2007 48:538-46.Neuropsychopharmacology (Chanraud S et al., 2008 Jul 9. [Epub ahead of print]).J Clin Psychopharmacol (Leroy C et al, in press).

Abstract BACKGROUND: Diffuse midline gliomas are aggressive pediatric brain tumors frequently associated with somatic mutations in histone genes H3F3A (H3.3) and HIST1H3B (H3.1), which promote gliomagenesis through reprograming of the epigenetic landscape by inhibiting the tri-methylation of H3K27 (H3K27-me3). H3K27M-mutant gliomas comprise over 80% of diffuse midline gliomas, and are characterized by dismal outcomes as well as near-ubiquitous absence of MGMT promoter methylation. The subset of H3K27-wildtype diffuse midline gliomas remains incompletely understood with regards to underlying pathogenesis, therapeutic targets, and prognosis. We present the clinical, imaging, histopathologic, and molecular characteristics of a pediatric patient with a bithalamic H3K27-wildtype diffuse midline glioma, EGFR-altered with methylated MGMT. CASE: A 10-year-old female presented with an infiltrative bithalamic T2-hyperintense mass lacking diffusion restriction or contrast enhancement on MRI. Initial pathological inspection from biopsy was consistent with high-grade neuroepithelial tumor favoring high-grade glioma, however, immunohistochemistry was negative for H3K27M and demonstrated reduced H3K27-me3. DNA sequencing uncovered mutations in EGFR (exon 20 insertion) and TP53 (R175H), with overexpression of EGFR and CDK6 (but not EZHIP) identified by RNA-sequencing. Methylation profiling was consistent with high-grade glioma, matching closest with glioblastoma, IDH-wildtype, with positive MGMT promoter methylation. Treatment was initiated with focal chemoradiotherapy with concurrent temozolomide, with plans for adjuvant temozolomide/ lomustine.DISCUSSION: Our case adds to growing evidence suggesting bithalamic tumors represent a distinct genetic and epigenetic subset of diffuse midline gliomas often defined by H3K27-wildtype status, loss of H3K27-me3, and EGFR receptor alterations. Our patient’s H3K27-wildtype, EGFR-altered tumor had reduced H3K27-me3 as well as positive MGMT promoter methylation, a molecular characteristic that has not been well-studied in H3K27-wildtype bithalamic gliomas, but is suspected to confer sensitivity to alkylating chemotherapy. The prevalence, prognostic impact, and therapeutic implications of MGMT promoter methylation in bithalamic H3K27-wildtype diffuse midline gliomas, including potential association with EGFR aberrations, requires further exploration.

Thyroid hormones play a critical role in the adult brain impacting mood and cognition. Some psychiatric symptoms are produced by thyroid illnesses and there is a frequent association of thyroid dysfunction with mood disorders. It is now clear that without optimal thyroid function, mood disturbance, cognitive impairment and other phychiatric symptoms can emerge. The usefulness of adding thyroid hormones to antidepressive treatment in euthyroid patients to obtain a potentiation effect has been proved repeatedly. The most common strategy is potentiation with T3 , but high doses of T4 have been also used in patients with resistant depression. Brain imaging techniques evaluating cerebral metabolism, perfusion, and anatomy enabled encouraging insights into the thyroid-brain relationship. The most consistent finding in patients with hypothyroidism is global diffuse hypoperfusion more pronounced in posterior brain region or in parietal lobe. Functional MRI in patients with thyroid diseases of different length and severity could help to identify functional aberrations such as memory impairments or altered emotional processing, which has long been suggested from animal studies. Structural changes related to myelin, which have been observed in various animal models, can now be studied with quantitative T2 or quantitative magnetization transfer (MT) imaging. Diffusion tensor imaging (DTI) can reveal information on white matter integrity.Bangladesh J. Nuclear Med. 17(2): 146-152, July 2014

High-temperature proton exchange membrane fuel cell (HT-PEMFC) is promising with its low demand for hydrogen purity, simple water management, and high waste heat utilization [1][2]. Although polybenzimidazole (PBI), as a typical high-temperature fuel cell membrane, has been developed for a long period, it still has defects such as phosphoric acid leaching and insufficient mechanical properties under high acid doping level [3][4]. With its unique 2D hexagonal grid structure and its electron cloud arrangement, single-layer graphene (SLG) can block the passage of any atoms [5]. However, hydrogen protons can easily penetrate SLG through a unique intermediate state mechanism to make it have excellent proton conductivity [6]. SLG's high proton conductivity combined with its excellent mechanical properties and thermal conductivity make it an ideal material for blocking phosphoric acid leaching. The SLG prepared by the chemical vapor deposition (CVD) method was transferred to the surface of catalyst layer of electrodes by the wet chemical transfer method. Due to the rupture and incompleteness of the SLG during the transfer process, the coverage rate of the SLG on the electrode surface is about 55%. This incomplete coverage facilitates small quantities of phosphoric acid leaching from PBI membrane to electrodes, which increases the three-phase boundary area and improves the performance of the HT-PEMFC. After 70 hours of accelerated stress testing (AST), the peak power density of membrane-electrode-assembly (MEA) with SLG on both sides of the cathode and anode can reach 480 mW cm-2, while the peak power density of MEA based on pure PBI membrane is only 249 mW cm-2. The quantification of phosphoric acid in the electrode by Lab based X-ray micro-computed tomography and the Raman spectroscopic mapping of the MEA cross-section shows that SLG can mitigate the leaching of phosphoric acid in the PBI film and improve the durability of HT-PEMFC. Graphene oxide (GO) is a low-cost application of graphene. Its doping in the PBI membrane can also reduce the leaching of phosphoric acid through enhancing the interaction between phosphoric acid and the PBI membrane [7]. A reactor based on 3D printing was designed so that natural graphite flakes can be used for electrochemical exfoliation to achieve rapid, safe, environmentally friendly, and mass production of GO. The electrochemically exfoliated (E)GO is doped in the PBI membrane. The 0.5%, 1% and 2% EGO loadings in the PBI membrane increased the peak power density by 13.8%, 24.4% and 29.2%, respectively. [1] Y.-L. Ma, J.S. Wainright, M.H. Litt, R.F. Savinell, Conductivity of PBI Membranes for High-Temperature Polymer Electrolyte Fuel Cells, Journal of The Electrochemical Society. 151 (2004) A8. https://doi.org/10.1149/1.1630037/XML. [2] H. Su, S. Pasupathi, B. Bladergroen, V. Linkov, B.G. Pollet, Optimization of gas diffusion electrode for polybenzimidazole-based high temperature proton exchange membrane fuel cell: Evaluation of polymer binders in catalyst layer, International Journal of Hydrogen Energy. 38 (2013) 11370–11378. https://doi.org/10.1016/J.IJHYDENE.2013.06.107. [3] S. Galbiati, A. Baricci, A. Casalegno, R. Marchesi, Degradation in phosphoric acid doped polymer fuel cells : A 6000 h parametric investigation, International Journal of Hydrogen Energy. 38 (2013) 6469–6480. https://doi.org/10.1016/j.ijhydene.2013.03.012. [4] S.H. Eberhardt, F. Marone, M. Stampanoni, F.N. Büchi, T.J. Schmidt, Quantifying phosphoric acid in high-temperature polymer electrolyte fuel cell components by X-ray tomographic microscopy, Journal of Synchrotron Radiation. 21 (2014) 1319–1326. https://doi.org/10.1107/S1600577514016348. [5] S. Hu, M. Lozada-Hidalgo, F.C. Wang, A. Mishchenko, F. Schedin, R.R. Nair, E.W. Hill, D.W. Boukhvalov, M.I. Katsnelson, R.A.W. Dryfe, I. V. Grigorieva, H.A. Wu, A.K. Geim, Proton transport through one-atom-thick crystals, Nature. 516 (2014) 227–230. https://doi.org/10.1038/nature14015. [6] S.M. Holmes, P. Balakrishnan, V.S. Kalangi, X. Zhang, M. Lozada-Hidalgo, P.M. Ajayan, R.R. Nair, 2D Crystals Significantly Enhance the Performance of a Working Fuel Cell, Advanced Energy Materials. 7 (2017) 1–7. https://doi.org/10.1002/aenm.201601216. [7] J. Li, X. Zeng, T. Ren, E. van der Heide, The Preparation of Graphene Oxide and Its Derivatives and Their Application in Bio-Tribological Systems, Lubricants 2014, Vol. 2, Pages 137-161. 2 (2014) 137–161. https://doi.org/10.3390/LUBRICANTS2030137.

Background:High-resolution computed tomography (HRCT) is the gold standard diagnostic test for Interstitial lung disease (ILD), a significant cause of morbidity and mortality in systemic sclerosis (SSc). Different algorithms have been proposed for the screening of SSc-ILD, including the use of pulmonary function tests (Forced Vital Capacity - FVC, Lung Diffusion of Carbone Monoxyde - DLCO). A prior survey reported that 50-66% of general rheumatologists and SSc experts ordered HRCT for ILD screening in newly diagnosed SSc patients (1).Objectives:Given the recent availability of on-label treatment for SSc-ILD (2), the publication of consensus recommendations for the identification of SSc-ILD (3) and recent awareness programs for the use of HRCT to detect SSc-ILD, we aimed to re-evaluate the use of HRCT for screening, re-screening and follow-up of SSc-ILD.Methods:An invitation was sent to the European Scleroderma Trials and Research (EUSTAR) and Scleroderma Clinical Trials Consortium (SCTC) members, also advertised through social media. Answers were recorded between Nov 25th and Dec 31st 2020. Questions were asked on the use of chest HRCT at baseline, the re-screening of patients with a negative baseline HRCT and the follow-up of HRCT positive SSc-ILD patients. When HRCT was not routinely requested, additional details were collected about the parameters guiding its use. The results of the survey were tested for association with geographical origin, medical specialty, working environment, SSc referral institute and scientific group membership of the responders, using Chi-squared test.Results:205/630 (32.5%) physicians replied to the survey. Participants were widely distributed in terms of geographical origin (130 Europe, 23 Asia, 23 North America, 31 other continents), medical specialty (156 rheumatology, 21 internal medicine, 14 clinical immunology, 14 other), working environment (176 University Hospital, 12 community hospital, 17 other), SSc dedicated clinic (179 referral and 26 non-referral) and scientific group membership (98 EUSTAR, 42 SCTC, 42 EUSTAR and SCTC, 23 not declared).At SSc diagnosis, 95.7% of responders would perform HRCT: 66.7% as routine screening for ILD (67,4% of SSc referral and 62% for non-referral physicians) and 29% for diagnostic purposes (among the latter, if crackles on auscultation – 92.5%, FVC<80% predicted - 86.6%, FVC±DLCO relative decline reaching the current definition of ILD progression, 86.6% or dyspnea at rest/exercise - 85.1/83.3%).During follow-up, 78.8% of responders would repeat an HRCT in baseline negative cases: 20.3% as a yearly routine screening and 64.5% for diagnostic aims (decision on the latter group was more frequently driven by FVC±DLCO relative decline indicative of ILD progression– 90.6%, new onset or worsening of dyspnoea at rest/exercise – 80.5/86.6%, new onset or worsening of lung crackles on auscultation – 82.6%).Finally, 94.5% of responders would repeat a chest HRCT after SSc-ILD diagnosis: 36.8% as a yearly routine and 56.7% according to clinical evaluation (driven by new FVC±DLCO relative decline based ILD progression – 90.8%, new onset or worsening of dyspnoea at rest/exercise – 83.2/81.7%; 5.2% to evaluate treatment effects). We found no difference in the distribution of answers among groups.Conclusion:The use of baseline HRCT for the screening of SSc-ILD has slightly increased in non-referral and remained stable in referral centers compared to previous surveys, indicating that the implementation of guidelines might be successful and awareness programs should be continued. In addition, we provide new data on use of HRCT in re-screening and follow-up. The development of validated algorithms to further support the appropriate application of HRCT at follow-up is highly needed.References:[1]Bernstein EJ et al. Arthritis Rheumatol. 2018 Jun;70(6):971-972.[2]Distler O et al. N Engl J Med. 2019 Jun 27;380(26):2518-2528.[3]Hoffmann-Vold AM et al. The Lancet Rheumatology, Volume 2, Issue 2, e71 - e83.Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Foundation for Research in Rheumatology (FOREUM), Gruppo Italiano Lotta alla Sclerodermia (GILS), Fondazione Italiana per la Ricerca sull’Artrite (FIRA), New Horizon Fellowship, European Sclerodermia Trial and Reserach (EUSTAR) Group., Lorinda Chung Consultant of: Boehringer Ingelheim, Eicos, Mitsubishi Tanabe, Reata., Anna-Maria Hoffmann-Vold Consultant of: Actelion, ARXX therapeutics, Bayer, Boehringer-Ingelheim, Medscape, MSD, Lilly, Roche, Shervin Assassi Speakers bureau: Integrity Continuing Education, Consultant of: Boehringer Ingelheim, Novartis, and Corbus, Armando Gabrielli: None declared, Dinesh Khanna Consultant of: Acceleron, Actelion, Abbvie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead, Galapagos, Genentech/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis, and United Therapeutics Leadership, Grant/research support from: NIH, Immune Tolerance Network, Bayer, BMS, Horizon, Pfizer, Employee of: Equity position – Chief Medical Officer, Eicos Sciences, Inc., Elana Bernstein Consultant of: Boehringer Ingelheim, Oliver Distler Consultant of: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB., Grant/research support from: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143).

Introdução: Lesões endoperiodontais são lesões originadas de produtos inflamatórios encontrados tanto em periodonto quanto em polpa. Tais lesões podem se originar devido a uma infecção pulpar ou periodontal. Visando o prognóstico favorável, é imprescindível o conhecimento da etiologia, realização do correto diagnóstico e elaboração do plano de tratamento que envolve o tratamento endodôntico precedido do tratamento periodontal. Objetivo: O propósito do presente trabalho foi de relatar um caso clínico de lesão endoperiodontal e o tratamento realizado. Relato de caso clínico: Paciente gênero feminino, 51 anos, compareceu à clínica com uma fístula na região do dente 46, procedeu-se com exame radiográfico, rastreamento de fístula, testes endodônticos e avaliação periodontal. Foi diagnosticada lesão endoperiodontal. Executou-se, então, o tratamento endodôntico em sessões múltiplas, utilizando hidróxido de cálcio como medicação intracanal e o tratamento periodontal concomitante; finalizou-se endodontia obturando-se os canais radiculares. Conclusão: Observou-se, no controle, que a associação de tratamentos foi eficaz e houve melhora significativa do quadro, constatando-se silêncio clínico e sucesso do tratamento. Realizar o tratamento conservador a despeito da exodontia foi a melhor escolha para a paciente. Descritores: Endodontia; Periodontia; Polpa Dentária; Periodonto. Referências Sunitha VR, Emmadi P, Namasivayam A, Thyegarajan R, Rajaraman V. The periodontal - endodontic continuum A review. J Conserv Dent. 2008;11(2):54-62. Betancourt P, Elgueta R, Fuentes R. Treatment of endo-periodontal lesion using leukocyte-platelet-rich fibrin - a case report. Colomb Med. 2017;48(4):204-7. Lopes HP, Siqueira JF. Endodontia: Biologia e Técnica. Rio de Janeiro: Medsi-Guanabara Koogan; 2015. Lindhe J, Karring T, Lang NP. Tratado de periodontia clínica e implantologia oral. Rio de Janeiro: Guanabara Koogan; 2010. Anand V, Govila V, Gulati M. Endo-perio lesion part II (the treatment) - a review. 2012;3(1):10-6. Rotstein I, Simon JH. Diagnosis, prognosis and decision-making in the treatment of combined periodontal-endodontic lesions. J Periodontol. 2004;34:165-203. Parolia A, Gait TC, Porto ICCM, Mala K. Endo-perio lesion: a dilemma from 19th until 21st century. J Interdisp Dent. 2013;3(1):2-11. Kim E, Song JS, Jung IY, Lee SJ, Kim S. Prospective clinical study evaluating endodontic microsurgery outcomes for cases with lesions of endodontic origin compared with cases with lesions of combined periodontal-endodontic origin. J Endod. 2008;34(5):546-51. Heasman PA. An endodontic conundrum: the association between pulpal infection and periodontal disease. Br Dent J. 2014;216(6):275-9. Schmidt JC, Walter C, Amato M, Weiger R. Treatment of periodontal-endodontic lesions--a systematic review. J Clin Periodontol. 2014; 41(8):779-90. Jivoinovici R, Suciu I, Dimitriu B, Perlea P, Bartok R, Malita M, Ionescu C. Endo-periodontal lesion--endodontic approach. J Med Life. 2014;7(4):542-44. Estrela C. Endodontia laboratorial e clínica, Série Abeno: Odontologia Essencial - Parte Clínica. São Paulo: Artes Médicas; 2013. Vera J, Siqueira JF Jr, Ricucci D, Loghin S, Fernández N, Flores B et al. One-versus two-visit endodontic treatment of teeth with apical periodontitis: a histobacteriologic study. J Endod. 2012;38(8):1040-52. Mohammadi Z, Dummer PMH. Properties and applications of calcium hydroxide in endodontics and dental traumatology. Inter Endod J. 2011;44(8):697-730. Batista VES, Olian DA, Mori GG. Diffusion of hydroxyl ions from calcium hydroxide and aloe vera pastes. Braz Dent J. 2014;25(3):212-16. Pereira TC, da Silva Munhoz Vasconcelos LR, Graeff MSZ, Ribeiro MCM, Duarte MAH, de Andrade FB. Intratubular decontamination ability and physicochemical properties of calcium hydroxidepastes. Clin Oral Investig. 2019;23(3):1253-62. Andolfatto C, da Silva GF, Cornélio AL, Guerreiro-Tanomaru JM, Tanomaru-Filho M, Faria G, Bonetti-Filho I, Cerri PS. Biocompatibility of intracanal medications based on calcium hydroxide. ISRN Dent. 2012;2012:904963. Duque TM, Prado M, Herrera DR, Gomes BPFA. Periodontal and endodontic infectious/inflammatory profile in primary periodontal lesions with secondary endodontic involvement after a calcium hydroxide-based intracanal medication. Clin Oral Investig. 2019;23(1):53-63. Kim D, Kim E. Antimicrobial effect of calcium hydroxide as an intracanal medicament in root canal treatment: a literature review - Part I. In vitro studies. Restor Dent Endod. 2014; 39(4):241-52. Adl A, Motamedifar M, Shams MS, Mirzaie A. Clinical investigation of the effect of calcium hydroxide intracanal dressing on bacterial lipopolysaccharide reduction from infected root canals. Aust Endod J. 2015;41(1):12-6. Hilton TJ, Ferracane JL, Mancl L; Northwest Practice-based Research Collaborative in Evidence-based Dentistry (NWP). Comparison of CaOH with MTA for direct pulp capping: a PBRN randomized clinical trial. J Dent Res. 2013;92(7 Suppl):16S-22S. Labban N, Yassen GH, Windsor LJ, Platt JA. The direct cytotoxic effects of medicaments used in endodontic regeneration on human dental pulp cells. Dent Traumatol. 2014;30(6):429-34. McIntyre PW, Wu JL, Kolte R, Zhang R, Gregory RL, Bruzzaniti A, Yassen GH. The antimicrobial properties, cytotoxicity, and differentiation potential of double antibiotic intracanal medicaments loaded into hydrogel system. Clin Oral Investig. 2019;23(3):1051-59. Bergenholtz, G., Hasselgren, G. Endodontics and periodontics. In: Lindhe, K., Karring, T., Lang, N. Clinical periodontology and implant dentistry. Copenhagen:Munksgaard; 2015. Harrington GW, Steiner DR, Ammons WF. The periodontal-endodontic controversy. Periodontol 2000. 2002;30:123-30. Fernandes LA, Martins TM, Almeida JM, Nagata MJ, Theodoro LH, Garcia VG, Bosco AF. Experimental periodontal disease treatment by subgingival irrigation with tetracycline hydrochloride in rats. J Appl Oral Sci. 2010;18(6):635-40. Storrer CM, Bordin GM, Pereira TT. How to diagnose and treat periodontal endodontic lesions? 2012;9(4):427-33. Verma PK, Srivastava R, Gupta KK, Srivastava A. Combined endodontic periodontal lesions: A clinical dilema. J Interdiscip Dent. 2011;1(2):119-24. Oh SL, Fouad AF, Park SH. Treatment strategy for guided tissue regeneration in combined endodontic-periodontal lesions: case report and review. J Endod. 2009;35(10):1331-36. Malli R, Lele P, Vishakha. Guided tissue regeneration in communicating periodontal and endodontic lesions - a hope for the hopeless. J Indian Soc Periodontol. 2011;15(4):410-13. Ghezzi C, Virzì M, Schupbach P, Broccaioli A, Simion M. Treatment of combined endodontic-periodontic lesions using guided tissue regeneration: clinical case and histology. Int J Periodontics Restorative Dent. 2012;32(4):433-9. Sun J, Liu Q. [Bio-Oss collagen bone grafting in the treatment of endodontic-periodontic lesion]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29(9):1905-6. Sharma R, Hegde V, Siddharth M, Hegde R, Manchanda G, Agarwal P. Endodontic-periodontal microsurgery for combined endodontic-periodontal lesions: An overview. J Conserv Dent. 2014;17(6):510-16. Li Y, Wang X, Xu J, Zhou X, Xie K. [The clinical study on the use of diode laser irradiation in the treatment of periodontal-endodontic combined lesions]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2012;30(2):161-64, 168. Narang S, Narang A, Gupta R. A sequential approach in treatment of perio-endo lesion. J Indian Soc Periodontol. 2011;15(2):177-80. Pereira AL, Orzechowski PR, Filho SB, Cortelli JR. Subepithelial connective tissue graft: an alternative application for treating endoperiodontal lesions. Gen Dent. 2013;61(2):50-3. Yoneda M, Motooka N, Naito T, Maeda K, Hirofuji T. Resolution of furcation bone loss after non-surgical root canal treatment: application of a peptidase-detection kit for treatment of type I endoperiodontal lesion. J Oral Sci. 2005; 47(3):143-47. Shenoy N, Shenoy A. Endo-perio lesions: diagnosis and clinical considerations. Indian J Dent Res. 2010;21(4):579-85. Gerritsen AE, Allen PF, Witter DJ, Bronkhorst EM, Creugers NH. Tooth loss and oral health-related quality of life: a systematic review and meta-analysis. Health Qual Life Outcomes. 2010;8:126.

AbstractHumans differ from each other in a wide range of biometrics, but to what extent brain connectivity varies between individuals remains largely unknown. By combining diffusion-weighted imaging (DWI) and magnetoencephalography (MEG), this study characterizes the inter-subject variability (ISV) of multimodal brain connectivity. Structural connectivity is characterized by higher ISV in association cortices including the core multiple-demand network and lower ISV in the sensorimotor cortex. MEG ISV exhibits frequency-dependent signatures, and the extent of MEG ISV is consistent with that of structural connectivity ISV in selective macroscopic cortical clusters. Across the cortex, the ISVs of structural connectivity and beta-band MEG functional connectivity are negatively associated with cortical myelin content indexed by the quantitative T1 relaxation rate measured by high-resolution 7 T MRI. Furthermore, MEG ISV from alpha to gamma bands relates to the hindrance and restriction of the white-matter tissue estimated by DWI microstructural models. Our findings depict the inter-relationship between the ISV of brain connectivity from multiple modalities, and highlight the role of tissue microstructure underpinning the ISV.

AbstractThe NIMH Healthy Research Volunteer Dataset is a collection of phenotypic data characterizing healthy research volunteers using clinical assessments such as assays of blood and urine, mental health assessments, diagnostic and dimensional measures of mental health, cognitive and neuropsychological functioning, structural and functional magnetic resonance imaging (MRI), along with diffusion tensor imaging (DTI), and a comprehensive magnetoencephalography battery (MEG). In addition, blood samples of healthy volunteers are banked for future analyses. All data collected in this protocol are broadly shared in the OpenNeuro repository, in the Brain Imaging Data Structure (BIDS) format. In addition, task paradigms and basic pre-processing scripts are shared on GitHub. There are currently few open access MEG datasets, and multimodal neuroimaging datasets are even more rare. Due to its depth of characterization of a healthy population in terms of brain health, this dataset may contribute to a wide array of secondary investigations of non-clinical and clinical research questions.

AbstractThis paper reviews a candidate biomarker for ASD, the M50 auditory evoked response component, detected by magnetoencephalography (MEG) and presents a position on the roles and opportunities for such a biomarker, as well as converging evidence from allied imaging techniques (magnetic resonance imaging, MRI and spectroscopy, MRS). Data is presented on prolonged M50 latencies in ASD as well as extension to include children with ASD with significant language and cognitive impairments in whom M50 latency delays are exacerbated. Modeling of the M50 latency by consideration of the properties of auditory pathway white matter is shown to be successful in typical development but challenged by heterogeneity in ASD; this, however, is capitalized upon to identify a distinct subpopulation of children with ASD whose M50 latencies lie well outside the range of values predictable from the typically developing model. Interestingly, this subpopulation is characterized by low levels of the inhibitory neurotransmitter GABA. Following from this, we discuss a potential use of the M50 latency in indicating “target engagement” acutely with administration of a GABA-B agonist, potentially distinguishing “responders” from “non-responders” with the implication of optimizing inclusion for clinical trials of such agents. Implications for future application, including potential evaluation of infants with genetic risk factors, are discussed. As such, the broad scope of potential of a representative candidate biological marker, the M50 latency, is introduced along with potential future applications.This paper outlines a strategy for understanding brain dysfunction in individuals with intellectual and developmental disabilities (IDD). It is proposed that a multimodal approach (collection of brain structure, chemistry, and neuronal functional data) will identify IDD subpopulations who share a common disease pathway, and thus identify individuals with IDD who might ultimately benefit from specific treatments. After briefly demonstrating the need and potential for scope, examples from studies examining brain function and structure in children with autism spectrum disorder (ASD) illustrate how measures of brain neuronal function (from magnetoencephalography, MEG), brain structure (from magnetic resonance imaging, MRI, especially diffusion MRI), and brain chemistry (MR spectroscopy) can help us better understand the heterogeneity in ASD and form the basis of multivariate biological markers (biomarkers) useable to define clinical subpopulations. Similar approaches can be applied to understand brain dysfunction in neurodevelopmental disorders (NDD) in general. In large part, this paper represents our endeavors as part of the CHOP/Penn NICHD-funded intellectual and developmental disabilities research center (IDDRC) over the past decade.

Brain activity during rest displays complex, rapidly evolving patterns in space and time. Structural connections comprising the human connectome are hypothesized to impose constraints on the dynamics of this activity. Here, we use magnetoencephalography (MEG) to quantify the extent to which fast neural dynamics in the human brain are constrained by structural connections inferred from diffusion MRI tractography. We characterize the spatio-temporal unfolding of whole-brain activity at the millisecond scale from source-reconstructed MEG data, estimating the probability that any two brain regions will significantly deviate from baseline activity in consecutive time epochs. We find that the structural connectome relates to, and likely affects, the rapid spreading of neuronal avalanches, evidenced by a significant association between these transition probabilities and structural connectivity strengths (r = 0.37, p<0.0001). This finding opens new avenues to study the relationship between brain structure and neural dynamics.

AbstractWe present a synchronized multimodal neuroimaging dataset for studying brain language processing (SMN4Lang) that contains functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) data on the same 12 healthy volunteers while the volunteers listened to 6 hours of naturalistic stories, as well as high-resolution structural (T1, T2), diffusion MRI and resting-state fMRI data for each participant. We also provide rich linguistic annotations for the stimuli, including word frequencies, syntactic tree structures, time-aligned characters and words, and various types of word and character embeddings. Quality assessment indicators verify that this is a high-quality neuroimaging dataset. Such synchronized data is separately collected by the same group of participants first listening to story materials in fMRI and then in MEG which are well suited to studying the dynamic processing of language comprehension, such as the time and location of different linguistic features encoded in the brain. In addition, this dataset, comprising a large vocabulary from stories with various topics, can serve as a brain benchmark to evaluate and improve computational language models.

Abstract Executive functioning (EF) is a higher-order cognitive process that is thought to depend on a network organization facilitating integration across subnetworks, in the context of which the central role of the frontoparietal network (FPN) has been described across imaging and neurophysiological modalities. However, the potentially complementary unimodal information on the relevance of the FPN for EF has not yet been integrated. We employ a multilayer framework to allow for integration of different modalities into one ‘network of networks’. We used diffusion MRI, resting-state functional MRI, MEG, and neuropsychological data obtained from 33 healthy adults to construct modality-specific single-layer networks as well as a single multilayer network per participant. We computed single-layer and multilayer eigenvector centrality of the FPN as a measure of integration in this network and examined their associations with EF. We found that higher multilayer FPN centrality, but not single-layer FPN centrality, was related to better EF. We did not find a statistically significant change in explained variance in EF when using the multilayer approach as compared to the single-layer measures. Overall, our results show the importance of FPN integration for EF, and underline the promise of the multilayer framework towards better understanding cognitive functioning.

Conductivity tensor imaging (CTI) has been recently proposed to map the conductivity tensor in 3D using magnetic resonance imaging (MRI) at the frequency range of the brain at rest, i.e., low-frequencies. Conventional CTI mapping methods process the trans-receiver phase of the MRI signal using the MR electric properties tomography (MR-EPT) technique, which in turn involves the application of the Laplace operator. This results in CTI maps with a low signal-to-noise ratio (SNR), artifacts at tissue boundaries and a limited spatial resolution. In order to improve on these aspects, a methodology independent from the MR-EPT method is proposed. This relies on the strong assumption for which electrical conductivity is univocally pre-determined by water concentration. In particular, CTI maps are calculated by combining high-frequency conductivity derived from water maps and multi b-value diffusion tensor imaging (DTI) data. Following the implementation of a pipeline to optimize the pre-processing of diffusion data and the fitting routine of a multi-compartment diffusivity model, reconstructed conductivity images were evaluated in terms of the achieved spatial resolution in five healthy subjects scanned at rest. We found that the pre-processing of diffusion data and the optimization of the fitting procedure improve the quality of conductivity maps. We achieve reproducible measurements across healthy participants and, in particular, we report conductivity values across subjects of 0.55 ± 0.01Sm, 0.3 ± 0.01Sm and 2.15 ± 0.02Sm for gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), respectively. By attaining an actual spatial resolution of the conductivity tensor close to 1 mm in-plane isotropic, partial volume effects are reduced leading to good discrimination of tissues with similar conductivity values, such as GM and WM. The application of the proposed framework may contribute to a better definition of the head tissue compartments in electroencephalograpy/magnetoencephalography (EEG/MEG) source imaging and be used as biomarker for assessing conductivity changes in pathological conditions, such as stroke and brain tumors.

In this review article we have consolidated the imaging literature of patients with schizophrenia across the full spectrum of modalities in radiology including computed tomography (CT), morphologic magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and magnetoencephalography (MEG). We look at the impact of various subtypes of schizophrenia on imaging findings and the changes that occur with medical and transcranial magnetic stimulation (TMS) therapy. Our goal was a comprehensive multimodality summary of the findings of state-of-the-art imaging in untreated and treated patients with schizophrenia. Clinical imaging in schizophrenia is used to exclude structural lesions which may produce symptoms that may mimic those of patients with schizophrenia. Nonetheless one finds global volume loss in the brains of patients with schizophrenia with associated increased cerebrospinal fluid (CSF) volume and decreased gray matter volume. These features may be influenced by the duration of disease and or medication use. For functional studies, be they fluorodeoxyglucose positron emission tomography (FDG PET), rs-fMRI, task-based fMRI, diffusion tensor imaging (DTI) or MEG there generally is hypoactivation and disconnection between brain regions. However, these findings may vary depending upon the negative or positive symptomatology manifested in the patients. MR spectroscopy generally shows low N-acetylaspartate from neuronal loss and low glutamine (a neuroexcitatory marker) but glutathione may be elevated, particularly in non-treatment responders. The literature in schizophrenia is difficult to evaluate because age, gender, symptomatology, comorbidities, therapy use, disease duration, substance abuse, and coexisting other psychiatric disorders have not been adequately controlled for, even in large studies and meta-analyses.

Abstract Multiple sclerosis (MS) features extensive connectivity changes, but how structural and functional connectivity relate, and whether this relation could be a useful biomarker for cognitive impairment in MS is unclear. This study included 79 MS patients and 40 healthy controls (HCs). Patients were classified as cognitively impaired (CI) or cognitively preserved (CP). Structural connectivity was determined using diffusion MRI and functional connectivity using resting-state magnetoencephalography (MEG) data (theta, alpha1, and alpha2 bands). Structure-function coupling was assessed by correlating modalities, and further explored in frequency bands that significantly correlated with whole-brain structural connectivity. Functional correlates of short- and long-range structural connections (based on tract length) were then specifically assessed. Receiving operating curve analyses were performed on coupling values to identify biomarker potential. Only the theta band showed significant correlations between whole-brain structural and functional connectivity (rho = −0.26, p = 0.023, only in MS). Long-range structure-function coupling was stronger in CI patients compared to HCs (p = 0.005). Short-range coupling showed no group differences. Structure-function coupling was not a significant classifier of cognitive impairment for any tract length (short-range area under the curve (AUC) = 0.498, p = 0.976, long-range AUC = 0.611, p = 0.095). Long-range structure-function coupling was stronger in CI MS compared to HCs, but more research is needed to further explore this measure as biomarkers in MS.

Objective: To determine the diagnostic accuracy of DWI in differentiating benign and malignant meningiomas keeping histopathology as gold standard. Methods: This was a descriptive analytical study conducted at Radiology Department, DUHS/Dr. Ruth K. M. Pfau Civil Hospital Karachi, from August 2016 to March 2018. It included152 patients clinically suspected of meningioma on conventional neuroimaging. Imaging features of DWI were compared with histopathology findings. The diagnostic accuracy of DWI was calculated in terms of sensitivity, specificity, accuracy, PPV and NPV using histopathology as gold standard. Results: There were 59 male and 93 female patients with mean age of 55.38±9.8 years. Mean duration of sign and symptoms was 5.67±2.57 months. Out of 152 patients, 117(77%) and 35(23%) were differentiated into benign and malignant meningiomas respectively by DWI while 135(88.82%) and17(11.18%) patients were diagnosed respectively on histopathology. The sensitivity, specificity, PPV, NPV and accuracy of DWI of 84.4%, 82.3%, 97.4%, 40%, and 84.2% respectively keeping histopathology as gold standard. Conclusion: DWI features along with calculation of ADC values is a reliable non-invasive technique for differentiating benign and malignant meningiomas. However the low negative predictive value necessitates the use of histopathology. doi: https://doi.org/10.12669/pjms.35.3.1011 How to cite this:Sohu DM, Sohail S, Shaikh R. Diagnostic accuracy of diffusion weighted mri in differentiating benign and malignant meningiomas. Pak J Med Sci. 2019;35(3):---------. doi: https://doi.org/10.12669/pjms.35.3.1011 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in detection of intra-axial gliomas in suspected cases keeping histopathology as gold standard. Methods: This cross-sectional study was conducted at Dow Institute of Radiology, DUHS from October 2017 - April 2018. Patients of either gender aged 30-70 years presenting with headache were included. Patients already diagnosed and referred for follow up were excluded. MRI was performed on 1.5T scanner by a trained MRI technician. T1, T2, FLAIR, diffusion weighted and T1 post contrast images were acquired and reviewed by two radiologists having more than five years post fellowship experience. Sensitivity, specificity, PPV, NPV and diagnostic accuracy of MRI for intraaxial gliomas was calculated taking histopathology findings as gold standard. Results: Mean age of the patient`s was 51.71 ±10.85 years. Positive intraaxial gliomas on MRI were observed in 123 (79.90%) patients while on histopathology, positive intraaxial gliomas were observed in 131 (85.10%) patients. Diagnostic accuracy of MRI in detection of intra-axial gliomas taking histopathology findings as gold standard showed sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV) and overall diagnostic accuracy as 89.31%, 73.91%, 95.12%, 54.84% and 87.01%. Conclusions: MRI has high sensitivity, moderate specificity and high diagnostic accuracy in detection of intraaxial gliomas. doi: https://doi.org/10.12669/pjms.37.1.2489 How to cite this:Munir S, Khan SA, Hanif H, Khan M. Diagnostic accuracy of magnetic resonance imaging in detection of intra-axial gliomas. Pak J Med Sci. 2021;37(1):125-130. doi: https://doi.org/10.12669/pjms.37.1.2489 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

BACKGROUND: Preclinical studies have shown that the MED system developed by Pulse Therapeutics, Inc. appears efficient in delivering co-administered agents by affecting the fluid dynamics in targeted occluded arteries. The system is an adjunct to IV rt-PA, and is composed of biologically-safe magnetic particles and a portable magnet system for use in the ED. Preclinical studies support strong efficacy and safety of the MED technology. The primary objective of this feasibility study is to establish the safety (sICH at 24 hours post onset) of the technology when used as an adjunct to IV rt-PA for moderate-to-large (10≤NIHSSS≤24, occlusion confirmed by CTA) ischemic strokes within three hours of acute onset. METHODS: 10 subjects with moderate-to-large ischemic strokes between ages 18-80 will be enrolled at 2 centers in Australia (Box Hill and John Hunter hospitals). All candidates must possess an intracranial arterial occlusion of the middle cerebral, anterior cerebral, internal carotid, posterior cerebral or distal basilar artery confirmed by CTA or MRA, and must be administered rt-PA within 3 hours of acute onset. Artery selection is input into the MED system and the magnet energized for the entirety of the rt-PA infusion, plus 30min. The primary endpoint is safety as assessed by incidence and evaluation of any adverse effects associated with the investigational procedure compared with historical controls treated with rt-PA alone. The secondary endpoint is the degree of recanalization (partial and complete) and reperfusion as measured by CTA at 2-4hrs and MRI at 24±6hrs post MED therapy. TIMI Grade Flow of 2 or 3 will be considered responsive to treatment. CONCLUSIONS: This feasibility trial will attempt to establish the safety (sICH) and recanalization efficacy of the MED technology as an adjunctive therapy to standard-dose IV rt-PA. As of August 2012, Box Hill and John Hunter hospitals have enrolled 2 patients.

Objective: This paper summarizes the MRI imaging findings of primary central nervous system lymphoma (PCNSL) in the posterior cranial fossa to improve the accuracy of PCNSL diagnosis in the posterior cranial fossa. Methods: This study retrospectively analyzed the MRI imaging manifestations of 15 PCNSL posterior cranial fossa cases confirmed by puncture or surgical pathology from June 2017 to May 2018, including their occurrence sites, the number of lesions, MRI plain and enhanced manifestations, and diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy. Imaging (MRS) performance. Results: A total of 15 cases were enrolled, including 10 cases of single lesion and five cases of multiple lesions. The total number of lesions was 25, which were in the cerebellar hemisphere and cerebellar vermis, midbrain, fourth ventricle, and pontine cerebellum. The lesions were round, irregular, nodular, patchy, with low or medium signals on T1WI, equal or slightly higher signals on T2WI, and enhanced with 25 meningiomas-like gray matter signals. All of them were significantly strengthened. “Acupoint sign” and “umbilical depression sign” were seen in eight lesions. There were 17 massive and nodular enhancements, four striped enhancements, three patchy enhancements, and one circular enhancement. five cases of DWI showed homogeneous high signal, two cases showed uneven high signal, and 3 cases showed medium signal. The ADC value of tumor parenchyma in 10 patients was (0.62±0.095)×10-3mm2/s. MRS examination showed obvious Lip peak in two cases. Conclusion: PCNSL in posterior cranial fossa has certain characteristics. DWI, ADC value and MRS are helpful to improve the correct diagnosis rate of PCNSL. doi: https://doi.org/10.12669/pjms.37.6-WIT.4843 How to cite this:Lu G, Li Y, Liang X, Zhao Z. Diagnosis and analysis of primary central nervous system lymphoma based on MRI segmentation algorithm. Pak J Med Sci. 2021;37(6):1585-1589. doi: https://doi.org/10.12669/pjms.37.6-WIT.4843 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objectives: To evaluate the clinical value of susceptibility weighted imaging (SWI) combined with diffusion weighted imaging (DWI) in patients with liver cirrhosis complicated with small hepatocellular carcinoma (SHCC). Methods: A total of 40 patients with liver cirrhosis and 44 nodules were treated with conventional nuclear magnetic scanning (T1WI, T2WI) and SWI combined with DWI; the results were judged by two senior physicians; the t test, χ2 test, rank sum test, and other methods were used for contrastive analysis of the pathological results of different scanning methods after operation or puncture. Results: Contrast analysis of the different MRI scanning methods and pathological results showed that among the 32 nodules of small hepatocellular carcinoma, 24 cases were diagnosed by conventional MRI, with the coincidence rate being 75%, 30 cases were diagnosed by SWI DWI, with the coincidence rate being 96%; significant difference was found between the two groups (p=0. 04). Significant differences were found in the specificity, sensitivity and accuracy of different scanning methods in the diagnosis of small hepatocellular carcinoma (specificity, accuracy, p=0.04; sensitivity p=0.01). The SWI of small hepatocellular carcinoma nodules showed hyperintensity, and the degree of iron deposition was low. Significant difference was found between small hepatocellular carcinoma nodules and other nodules (comparison of SWI signal degree, p=0.01; comparison of iron deposition degree, p=0.00). Conclusion: The SWI of small hepatocellular carcinoma nodules showed hyperintensity, and the degree of iron deposition was low. The coincidence rate of SWI+DWI scanning is higher than that of conventional scanning methods in the diagnosis of small hepatocellular carcinoma, and the difference in specificity, sensitivity and accuracy has obvious advantages. SWI+DWI scanning can improve the detection rate of liver cirrhosis complicated with small hepatocellular carcinoma. doi: https://doi.org/10.12669/pjms.37.3.3822 How to cite this:Hou ZB, Zhao F, Zhang B, Zhang CZ. Study on clinical application of susceptibility weighted imaging combined with diffusion weighted imaging in patients with Liver Cirrhosis complicated with small Hepatocellular Carcinoma. Pak J Med Sci. 2021;37(3):---------. doi: https://doi.org/10.12669/pjms.37.3.3822 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction: Advances in diagnostic imaging of stroke include the use of multimodal techniques, including noninvasive angiography to evaluate the intracranial and cervical vasculature as well as perfusion imaging. Despite increased adoption of these imaging techniques in academic medical centers, the current practice of multimodal imaging utilization among stroke patients in the community has remained largely uncharacterized. Methods: We quantified neuroimaging utilization in the ED among 1700 hyperacute stroke patients participating in the NIH Field Administration of Stroke Therapy Magnesium (FAST-MAG) study throughout Los Angeles and Orange Counties. Subjects were enrolled in the field <2 hours from symptom onset and transported to their usual care hospital, one of 58 centers throughout a single urban region. There was no recommendation as to what type of imaging should be utilized. Results: Of 1700 cases 1699 were imaged a median (IQR) of 92 (74-120) minutes after last known well time and 28 (19-40.75) minutes after ED arrival. The mean age was 71 (SD13) years old and the final diagnosis was cerebral ischemia in 73%, intracerebral hemorrhage in 23%, and mimic in 4%. Initial imaging scanner used in the ED was CT in a preponderance of cases (N=1612, 95%), with MRI in 88 cases (5%). Parenchymal CT scan was almost always performed without contrast and most commonly as the only study. However, CT angiography was obtained in 192 (11%) and perfusion CT in 91 (5.4%) cases in the first 24 hours. MRI imaging was universally obtained using diffusion-weighted images, 60% with MR angiography and 33% included perfusion imaging. Rates of multimodal (CTA and/or CTP) CT imaging utilization increased in the later years of the study from 4% in 2005-2006, 2% in 2007-2008, 8% in 2009-2010 and 26% in 2011-2012 (p for trend <0.001). There was no change in rates of multimodal MRI imaging as one academic medical center accounted for >80% of all studies. Conclusions: Among acute stroke patients presenting in the time window for TPA use, noncontrast CT was the most common initial imaging strategy in clinical practice in the 2005-2012 time period, though use of concomitant CTA grew to one-quarter of cases.

Objectives: This article is based on deep learning algorithms and uses MRI to study the development of congenital heart septal defects in neonatal brain tissue. Methods: From January 2018 to December 2019, 150 cases of congenital cardiac paper septal defect were retrospectively analyzed on 50 cases of normal newborns and neonates. The four index parametersbrain MR imaging, lateral ventricle pre-angle measurement index (F/F’), body index (D/ D’), caudal nucleus index (C/C’) were analyzed. The independent sample t test is performed to compare the difference parameters between groups. Results: F congenital heart disease group and control group/F ‘values were 0.301 ± 0.035 and 0.296 ± 0.031; Evans index was 0.239 ± 0.052 and 0.233 ± 0.025; 2 sets of D/D’ values were 0.261 ± 0.039 and 0.234 ± 0.032; C/C ‘value was 0.138 ± 0.018 and 0.124 ± 0.015 respectively. The congenital heart disease group D/D ‘, and the value of C/C’ obtained under the ROC curve area value, respectively 0.698 and 0.750, Youden index corresponding to the maximum D/D ‘, and the value of C/C’ values were 0.28 and 0.12. Conclusion: Lateral ventricle D/D ‘and C/C’ is more sensitive indicator which can be evaluated with the difference between the volume of congenital heart septal defects in newborn normal neonatal brain; when the D/D ‘value> 0.28, C/C’ value> 0.12. For the diagnosis and evaluation of congenital heart septal defect neonatal brain volume abnormalities have a certain reference value. List of acronyms: MRI: Magnetic Resonance Imaging. POX: Pulse oximetry. CHD: Congenital Heart Disease.DWI: Diffusion-weighted Imaging. T1WI: T1-weighted imaging T2WITSE: T2-weighted imaging, Turbo Spin Echo. FOV: Field of View. FLAIR: Fluid Attenuated Inversion Recovery. TE: Echo Time. TR: Repetition Time. ICC: Intra-group Correlation Coefficient. doi: https://doi.org/10.12669/pjms.37.6-WIT.4863 How to cite this:Zhu J, Chen J, Zhang Y, Ji J. Brain tissue development of neonates with Congenital Septal Defect: Study on MRI Image Evaluation of Deep Learning Algorithm. Pak J Med Sci. 2021;37(6):1652-1656. doi: https://doi.org/10.12669/pjms.37.6-WIT.4863 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Partendo dalla considerazione del fatto che in alcune parti del mondo, malattie come la rosolia sono ancora epidemiche, che l’infezione di queste malattie contratta da donne gravide causa gravi danni e può portare addirittura alla morte del feto, e che la vaccinazione su larga scala rappresenta un mezzo irrinunciabile nella lotta contro queste malattie infettive, l’articolo affronta la questione della liceità della produzione, della diffusione e dell’uso di vaccini la cui produzione è connessa con atti di aborto procurato. Alcuni vaccini di ampia diffusione contro malattie come la rosolia e la varicella, infatti, sono stati sviluppati utilizzando ceppi di virus ottenuti da feti umani volontariamente abortiti. L’Autore, in particolare, riflette sul problema etico sollevato sia da medici impegnati nelle campagne di vaccinazione sia da coloro che necessitano dei vaccini (soprattutto dai genitori che devono vaccinare i propri figli), che si chiedono se l’uso di tali vaccini non sia in contraddizione con il rifiuto etico di ogni forma di aborto volontario. Per rispondere a questo interrogativo, l’Autore analizza il problema riflettendo sulle diverse modalità e i vari gradi della cooperazione al male, concludendo che esiste il dovere grave di usare i vaccini alternativi, laddove esistano, e di invocare l’obiezione di coscienza riguardo a quelli il cui uso presenta dei problemi morali. Per quanto riguarda i vaccini senza alternative, si dovrebbe ribadire sia il dovere di lottare perché ne vengano approntati altri che non sollevino problemi morali, sia la liceità del loro uso nella misura in cui ciò è necessario per evitare un pericolo grave per le condizioni sanitarie della popolazione. La liceità di tale uso, in ogni caso, va interpretata come una cooperazione materiale passiva, moralmente giustificata come extrema ratio dal dovere di provvedere al bene dei propri figli (nel caso dei genitori) e della popolazione in generale, e mai come una dichiarazione di liceità della loro produzione. ---------- This paper deals with the issue of the lawfulness of producing, spreading and using of vaccines whose production is linked to act of induced abortion, starting from the consideration of the fact that in some part of the world diseases like German measles are still epidemic, that infection of pregnant women causes serious injures and may result even in the death of the foetus, and that vaccination on a large scale represents an essential means to fight against this infective diseases. Same common vaccines against German measles and chickenpox, indeed, have been produced using stocks of virus obtained from voluntarily aborted human foetuses. The Author particularly reflects on the ethical problem raised both from physicians engaged in the vaccination campaigns and from those who need vaccines (specially parents that have to vaccinate their children), who wonder if using these vaccines is in contradiction with the ethical refusing of every form of voluntary abortion. To answer to this question, the Author analyzes the problem reflecting on the different forms and degrees of the cooperation in evil, concluding that there is the grave duty to use alternative vaccines, when they exist, and to invoke conscience objection for those whose use shows moral problems. When it comes to vaccines without alternatives, one should confirm both the necessity to fight to obtain others without moral problems, and the lawfulness of using them when it necessary to avoid a grave danger for the health condition of the people. The lawfulness of using them, in every case, must be intended as a passive material cooperation, morally justified as extrema ratio from the duty of providing for the children’s good (in the case of parents) and the population in general, and never as a declaration of lawfulness of their production.

Introduction: We present a case report of posterior reversible leukoencephalopathy syndrome (PRES) following transarterial chemoembolization (TACE) of liver metastasis of an intestinal neuroendocrine tumour.Case presentation: A 62-year-old female was evaluated for progressive bilateral vision loss following transarterial chemoembolization (TACE) of hepatic metastasis of a midgut carcinoid tumour with cisplatin. Vital signs were remarkable for significant hypertension (170-210/85-110) since having undergone TACE (baseline BP 136/74), despite pre-procedure administration of octreotide. Blood pressure failed to correct with administration of amlodipine, hydralazine, captopril and labetalol infusion but responded promptly to octreotide infusion. Magnetic resonance imaging showed findings compatible with PRES. The patient’s vision gradually corrected to her baseline over 2 days. Conclusion: TACE for neuroendocrine tumours can be complicated by carcinoid crisis despite pre-administration of octreotide. Rarely, this may present as a hypertensive emergency of which PRES is a manifestation. Prompt recognition and treatment with high dose octreotide are important and can avoid permanent neurological injury in patients.RésuméIntroduction : Il s’agit d’une étude de cas de syndrome de leuco encéphalopathie réversible postérieure (SERP) consécutive à la chimioembolisation transartérielle (CETA) d’une métastase hépatique d’une tumeur neuro-endocrinine intestinale.Présentation du dossier: Une femme de 62 ans est évaluée pour une perte de vision bilatérale progressive à la suite de la chimioembolisation transartérielle (CETA) de métastases hépatiques d’une tumeur du tube digestif effectuée au moyen du cisplatine. Les signes vitaux sont remarquables malgré une hypertension importante (170-210/85-110) depuis la CETA (p.a. de base 136/74) et l’administration d’octréotide préalable à l’intervention. La pression artérielle ne s’est pas corrigée avec l’administration d’amlodipine, d’hydralazine, de captopril et de labétalol en perfusion, mais a répondu promptement à l’octréotide en perfusion. Une imagerie par résonnance magnétique a fourni des résultats compatibles avec un diagnostic de SERP. La vision de la patiente s’est graduellement corrigée pour revenir à son état habituel en deux jours.Conclusion : Dans le cas de tumeurs neuro-endocriniennes, la CETA peut être compliquée d’une crise carcinoïde malgré l’administration d’octréotide au préalable. Cette condition peut, quoique rarement, représenter une urgence hypertensive dont le SERP est une manifestation. L’identification rapide de la condition et un traitement à l’aide d’octréotide à dose élevée sont de la plus haute importance et peuvent éviter des dommages neurologiques permanents.Carcinoid syndrome is a syndrome classically consisting of diarrhea, paroxysms of cutaneous flushing with or without hypotension and bronchospasm arising most frequently in the setting of hepatic metastases originating from midgut carcinoid tumours. However, these neuroendocrine tumours can synthesize a wide variety of polypeptides, prostaglandins, and biogenic amines and hence present atypical clinical manifestations such as pellagra, abdominal pain, right-sided heart failure from valvular lesions and paroxysmal hypertension. Tumour manipulation may result in a massive influx of hormones into the systemic vasculature, potentially resulting in life threatening swings in blood pressure, cardiac arrhythmias and bronchoconstriction, even in patients without liver metastases or preoperative carcinoid syndrome.1 We present a case report of hypertensive emergency presenting as posterior reversible leukoencephalopathy syndrome (PRES) after transarterial chemoembolization (TACE) of a hepatic metastasis of carcinoid tumour.Case PresentationA 62-year-old caucasian female was evaluated on the surgical ward for progressive bilateral vision loss about 10 hours following transarterial chemoembolization (TACE) of a hepatic metastasis of a midgut carcinoid tumour (Figure 1, Figure 2) with Lipiodol and cisplatin. Premedication with octreotide 100 mcg subcutaneously and dexamethasone 8 mg IV pre-procedure was given, and post-procedure orders were given for dexamethasone 4 mg bid, ondansetron as needed and D5% NaCl 0.45% at a rate of 150 mL/h. The rest of her past medical history was unremarkable, specifically without history of hypertension, cerebrovascular disease, or clinical manifestations of carcinoid syndrome prior to admission. She had undergone two intra-abdominal surgeries without complication. Her usual medication was limited to inhaled glycopyrronium and indacaterol. Figure 1. Axial computed tomography scan of hepatic metastasis. A mass is visible in hepatic parenchyma corresponding to a metastasis of the midgut carcinoid tumour. Figure 2. Fluroscopic image of transarterial chemoembolization of hepatic metastasis. Upon evaluation, the patient was somnolent but otherwise well oriented. Eye exam confirmed bilateral 0/20 vision though pupils were 4 mm and reactive. On motor exam, the patient had diffuse hyperreflexia with upgoing plantar reflexes but without focal weakness. Chart review was remarkable for blood pressures ranging from 170-210/85-110 since TACE (pre-procedure blood pressure 136/74). A presumptive diagnosis of PRES due to cisplatin was made.Initial cerebral computed tomography scan was suspicious for a right occipital sub-cortical hypodensity of 3 cm, possibly of ischemic nature. IV fluids were discontinued (NaCl 0.9% at a rate of 250 mL/h) and anti-hypertensive agents were begun. After failure of improvement of blood pressure or symptoms despite amlodipine, hydralazine, labetalol, and captopril, a diagnosis of carcinoid crisis was suspected and octreotide 300mcg IV bolus followed by an infusion of 50 mcg/h was started. The suspected diagnosis of carcinoid crisis was later confirmed by 24h urinary 5-HIAA dosing at 141.4 umol/day (normal 0–42, previously within normal limits pre-operatively). Serum chromogranin A was also elevated at 138.2 ug/L (normal 0–82), compatible with a neuroendocrine tumour.Characteristic changes of PRES were seen on cerebral magnetic resonance imaging (MRI) (Figure 3) including predominantly sub-cortical hyperintensities in the bilateral parietal and occipital lobes on T2 and FLAIR sequences which were also hyperintense on diffusion-weighted imaging (DWI), likely from T2 shine through, and apparent diffusion coefficient (ADC) maps without restricted diffusion, hence confirming the finding of vasogenic edema compatible with PRES. Figure 3. FLAIR sequence, axial slice, cerebral magnetic resonance imaging. Subcortical hyperintensies in the bilateral occipital lobes reflecting vasogenic edema of the visual white matter tracts are seen. The patient’s blood pressure and her visual symptoms progressively normalized over 48 hours. On last follow-up 1 month after procedure, vital signs were normal (blood pressure 115/54) and vision was normal.DiscussionCarcinoid tumours are classically described as slow growing, mainly affecting the gastrointestinal (GI) tract. They are known to internists mainly for their capability to produce the carcinoid syndrome. However, only about 25% of carcinoids actually produce the mediators which produce the carcinoid syndrome and less than 10% of patients actually develop the carcinoid syndrome.2 The syndrome usually presents when midgut carcinoids metastasize to the liver, hence bypassing hepatic metabolism. Typical symptoms include secretory diarrhea (80%) and flushing of the head, neck, and upper torso (90%) which may be associated with hypotension and tachycardia. Less frequent manifestations are right heart failure due to carcinoid valve disease (30%), bronchospasm (15%) and pellagra (5%). 3 The classic triad of flushing, diarrhea and wheezing is infrequently found. Foregut (e.g., bronchial) and extra-digestive midgut (e.g., ovarian) bypass the liver and may result carcinoid syndrome without hepatic metastasis, although symptoms are usually atypical in these cases.Perioperative carcinoid crisis occurs in 10–30% of patients undergoing operative resection. Absence of preoperative carcinoid syndrome decreases the risk of carcinoid crisis, however it may still occur.1 This has led to the recommendation by some that patients be premedicated with somatostatin analogues to block bioactive peptide release and action, with or without other hormone antagonists (e.g., anti-histamines).3 However, the benefit of octreotide prophylaxis has been questioned by other studies.1 Once a carcinoid crisis has occurred, bolus doses of 25–500 mcg and intravenous infusions at rates of 50–150 mcg/h have been effective in case reports and case series, with higher doses being potentially required in patients on maintenance octreotide therapy or with carcinoid heart disease.4Despite a lack of data comparing it to surgical management, transarterial chemoembolization (TACE).5 is a frequent management strategy for patients with liver metastases, especially when patients present with hormonal symptoms and multiple metastases preclude resection. Rates of complication from TACE are difficult to estimate ranging from 0 to 100%, likely due to variable definitions and reporting. Only one study reported on the incidence of post embolization carcinoid crisis,6 with 2 of 12 patients developing the complication. Both had a history of carcinoid syndrome and had been premedicated with octreotide 200 mcg SC before procedure and q8h afterward. One group7 did report a patient who developed transient cortical blindness following TACE which possibly could have been due to PRES.PRES is a syndrome of failure of cerebral blood pressure autoregulation with acute onset elevations of blood pressure from baseline and a combination of altered level of consciousness, visual symptoms, headache and seizures.8 Blood pressure is often only moderately elevated, though significantly above the patient’s baseline. Etiologies are varied but include cytotoxic chemotherapy, eclampsia and other causes of hypertensive emergency. It was originally felt that the patient’s PRES was due to the cisplatin received during TACE with contribution from dexamethasone and iatrogenic fluid overload (NaCl 0.9% at 150 mL/h had been running for several hours) as she had no history of carcinoid syndrome, had been premedicated and had no other findings associated with the disease. However, her lack of response to standard anti-hypertensives and prompt response to octreotide suggest carcinoid crisis as the cause.Neuroimaging with MRI confirms the diagnosis. Findings are compatible with symmetrical white matter edema in the posterior cerebral hemispheres, particularly the parieto-occipital regions. The cortex, basal ganglia, brainstem, and cerebellar may also be involved though less so than the subcortical white matter, while anterior cortical involvement is seen only with the most severe cases. Importantly, the distribution is not confined to a single vascular territory. Classically lesions appear as punctate or confluent areas of hyperintensity on T2 and FLAIR sequences.9 DWI usually shows hypo or iso-intense signal (though sometimes mildly hyperintense from T2 shine through) while ADC maps show increased signal, thus distinguishing PRES from ischemic stroke. With prompt recognition and management, full recovery over a period of days to weeks can be expected. ConclusionsCarcinoid crisis is a well-known and dreaded complication of surgical manipulation of carcinoid tumours. Transarterial chemoembolization of these tumours may also result in carcinoid crisis and our report suggests that pre-procedure carcinoid syndrome is not a prerequisite for this. Presentation may be atypical, as it was in our patient, and so clinical suspicion should be high. When suspected, prompt management with octreotide and other supportive therapies should be instituted.Key Points1. Patients undergoing transarterial chemoembolization for carcinoid tumour metastases are at risk for carcinoid crisis, even if they have been premedicated with octreotide and have no history of carcinoid syndrome.2. Carcinoid crisis may present as hypertensive crisis rather than hypotension, and may give rise to PRES.References1. Condron ME, Pommier SJ, Pommier RF. Continuous infusion of octreotide combined with perioperative octreotide bolus does not prevent intraoperative carcinoid crisis. Surgery 2016;159:358–67.2. Van Der Lely AJ, Herder WWd. Carcinoid syndrome: diagnosis and medical management. Arquivos Brasileiros de Endocrinologia & Metabologia 2005;49:850–60.3. Mancuso K, Kaye AD, Boudreaux JP, et al. Carcinoid syndrome and perioperative anesthetic considerations. J Clin Anesth 2011;23:329–41.4. Seymour N, Sawh SC. Mega-dose intravenous octreotide for the treatment of carcinoid crisis: a systematic review. Can J Anesth/J can d'anesthés2013;60:492–9.5. Kennedy A, Bester L, Salem R, Sharma RA, Parks RW, Ruszniewski P. Role of hepatic intra‐arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET‐Liver‐Metastases Consensus Conference. HPB 2015;17:29–37.6. Maire F, Lombard-Bohas C, O’Toole D, et al. Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases from well-differentiated midgut endocrine tumours: a prospective randomized study. Neuroendocrinology 2012;96:294–300.7. Gupta S, Johnson MM, Murthy R, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumours. Cancer 2005;104:1590–602.8. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494–500.9. Pedraza R, Marik PE, Varon J. Posterior reversible encephalopathy syndrome: a review. Crit Care Shock 2009;12:135–43.