Diffusion-weighted MRI and PET/CT reproducibility in epithelial ovarian cancers during neoadjuvant chemotherapy

PurposeTo investigate the reproducibility of diffusion-weighted (DW) MRI and ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG)-Positron emission tomography/CT (PET/CT) in monitoring response to neoadjuvant chemotherapy in epithelial ovarian cancer.Materials and methodsTen women (median age, 67 years; range: 41.8–77.3 years) with stage IIIC-IV epithelial ovarian cancers were included in this prospective trial (NCT02792959) between 2014 and 2016. All underwent initial laparoscopic staging, four cycles of carboplatine-paclitaxel-based chemotherapy and interval debulking surgery. PET/CT and DW-MRI were performed at baseline (C0), after one cycle (C1) and before surgery (C4). Two nuclear physicians and two radiologists assessed five anatomic sites for the presence of ≥ 1 lesion. Target lesions in each site were defined and their apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV-max), SUV-mean, SUL-peak, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were monitored (i.e., 10 patients × 5 sites × 3 time-points). Their relative early and late changes were calculated. Intra/inter-observer reproducibilities of qualitative and quantitative analysis were estimated with Kappa and intra-class correlation coefficients (ICCs).ResultsFor both modalities, inter- and intra-observer agreement percentages were excellent for initial staging but declined later for DW-MRI, leading to lower Kappa values for inter- and intra-observer variability (0.949 and 1 at C0, vs. 0.633 and 0.643 at C4, respectively) while Kappa values remained > 0.8 for PET/CT. Inter- and intra-observer ICCs were > 0.75 for SUV-max, SUL-peak, SUV-mean and their change regardless the time-point. ADC showed lower ICCs (range: 0.013–0.811). ANOVA found significant influences of the evaluation time, the measurement used (ADC, SUV-max, SUV-mean, SUV-max, SUL-peak, MTV or TLG) and their interaction on ICC values (P = 0.0023, P< 0.0001 and P =0.0028, respectively).ConclusionWhile both modalities demonstrated high reproducibility at baseline, only SUV-max, SUL-peak, SUV-mean and their changes maintained high reproducibility during chemotherapy.     

Cancer Cell-Specific Major Histocompatibility Complex II Expression as a Determinant of the Immune Infiltrate Organization and Function in the NSCLC Tumor Microenvironment

IntroductionIn patients with NSCLC, the prognostic significance of the tumor microenvironment (TME) immune composition has been revealed using single- or dual-marker staining on sequential tissue sections. Although these studies reveal that relative abundance and localization of immune cells are important parameters, deeper analyses of the NSCLC TME are necessary to refine the potential application of these findings to clinical care. Currently, the complex spatial relationships between cells of the NSCLC TME and potential drivers contributing to its immunologic composition remain unknown.MethodsWe used multispectral quantitative imaging on the lung adenocarcinoma TME in 153 patients with resected tumors. On a single slide per patient, we evaluated the TME with markers for CD3, CD8, CD14, CD19, major histocompatibility complex II (MHCII), cytokeratin, and 4′,6-diamidino-2-phenylindole (DAPI). Image analysis, including tissue segmentation, phenotyping, and spatial localization, was performed.ResultsSpecimens wherein greater than or equal to 5% of lung cancer cells expressed MHCII (MHCII^hi TME) had increased levels of CD4⁺ and CD8⁺ T cells and CD14⁺ cell infiltration. In the MHCII^hi TME, the immune infiltrate was closer to cancer cells and expressed an activated phenotype. Morphologic image analysis revealed cancer cells in the MHCII^hi TME more frequently interfaced with CD4⁺ and CD8⁺ T cells. Patients with an MHCII^hi TME experienced improved overall survival (p = 0.046).ConclusionsLung cancer cell-specific expression of MHCII associates with levels of immune cell infiltration, spatial localization, and activation status within the TME. This suggests that cancer cell-specific expression of MHCII may represent a biomarker for the immune system’s recognition and activation against the tumor.     

Automated assessment of the substantia nigra on susceptibility map-weighted imaging using deep convolutional neural networks for diagnosis of Idiopathic Parkinson's disease

ObjectivesDespite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD).MethodsIn this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the “pROC” package of R (version 1.16.2).ResultsThe area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912–1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment.ConclusionsOur deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.     

The Open Brain Consent: Informing research participants and obtaining consent to share brain imaging data

Having the means to share research data openly is essential to modern science. For human research, a key aspect in this endeavor is obtaining consent from participants, not just to take part in a study, which is a basic ethical principle, but also to share their data with the scientific community. To ensure that the participants'' privacy is respected, national and/or supranational regulations and laws are in place. It is, however, not always clear to researchers what the implications of those are, nor how to comply with them. The Open Brain Consent (https://open-brain-consent.readthedocs.io) is an international initiative that aims to provide researchers in the brain imaging community with information about data sharing options and tools. We present here a short history of this project and its latest developments, and share pointers to consent forms, including a template consent form that is compliant with the EU general data protection regulation. We also share pointers to an associated data user agreement that is not only useful in the EU context, but also for any researchers dealing with personal (clinical) data elsewhere.     

Cost-Effectiveness Study of Initial Imaging Selection in Acute Ischemic Stroke Care

PurposeNational guidelines recommend prompt identification of candidates for acute ischemic stroke (AIS) treatment, requiring timely neuroimaging with CT and/or MRI. CT is often preferred because of its widespread availability and rapid acquisition. Despite higher diagnostic accuracy of MRI, it commonly involves complex workflows that could potentially cause treatment time delays. The purpose of this study was to analyze the impact on outcomes of imaging utilization before treatment decisions at comprehensive stroke centers for patients presenting with suspected AIS in the anterior circulation with last-known-well-to-arrival time 0 to 24 hours.MethodsA decision simulation model based on the American Heart Association’s recommendations for AIS care pathways was developed from a health care perspective to compare initial imaging strategies: (1) stepwise-CT: noncontrast CT (NCCT) at the time of presentation, with CT angiography (CTA) ± CT perfusion (CTP) only in select patients (initial imaging to exclude hemorrhage and extensive ischemia) for mechanical thrombectomy (MT) evaluation; (2) stepwise-hybrid: NCCT at the time of presentation, with MR angiography (MRA) ± MR perfusion (MRP) only for MT evaluation; (3) stepwise-advanced: NCCT + CTA at presentation, with MR diffusion-weighted imaging (MR DWI) + MRP only for MT evaluation; (4) comprehensive-CT: NCCT + CTA + CTP at the time of presentation; and (5) comprehensive-MR: MR DWI + MRA + MRP at the time of presentation. Model parameters were defined using evidence-based data. Cost-effectiveness and sensitivity analyses were performed.ResultsThe cost-effectiveness analyses revealed that comprehensive-CT and comprehensive-MR yield the highest lifetime quality-adjusted life-years (QALYs) (4.81 and 4.82, respectively). However, the incremental cost-effectiveness ratio of comprehensive-MR is $233,000/QALY compared with comprehensive-CT. Stepwise-CT, stepwise-hybrid, and stepwise-advanced strategies are dominated, yielding lower QALYs and higher costs compared with comprehensive-CT.ConclusionsPerforming comprehensive-CT at presentation is the most cost-effective initial imaging strategy at comprehensive stroke centers.     

Thalamic volume mediates associations between cardiorespiratory fitness (VO2max) and cognition in Parkinson's disease

IntroductionCognitive deficits occur in Parkinson's disease (PD). Cardiorespiratory fitness (CRF) is associated with better cognitive performance in aging especially in executive function (EF) and memory. The association between CRF and cognitive performance is understudied in people with PD. Brain structures underlying associations also remains unknown. This cross-sectional study examined the associations between CRF and cognitive performance in PD. We also examined associations between CRF and brain structures impacted in PD. Mediation analysis were conducted to examine whether brain structures impacted in PD mediate putative associations between CRF and cognitive performance.MethodsIndividuals with PD (N = 33) underwent magnetic resonance imaging (MRI), CRF evaluation (estimated VO₂max), and neuropsychological assessment. Composite cognitive scores of episodic memory, EF, attention, language, and visuospatial functioning were generated. Structural equation models were constructed to examine whether MRI volume estimates (thalamus and pallidum) mediated associations between CRF and cognitive performance (adjusting for age, education, PD disease duration, sex, MDS-UPDRS motor score, and total intracranial volume).ResultsHigher CRF was associated with better episodic memory (Standardized β = 0.391; p = 0.008), EF (Standardized β = 0.324; p = 0.025), and visuospatial performance (Standardized β = 0.570; p = 0.005). Higher CRF was associated with larger thalamic (Standardized β = 0.722; p = 0.004) and pallidum (Standardized β = 0.635; p = 0.004) volumes. Thalamic volume mediated the association between higher CRF and better EF (Indirect effect = 0.309) and episodic memory (Indirect effect = 0.209) performance (p < 0.05). The pallidum did not significantly mediate associations between CRF and cognitive outcomes.ConclusionThe thalamus plays an important role in the association between CRF and both EF and episodic memory in PD.     

Dynamic functional connectivity of the EEG in relation to outcome of postanoxic coma

ObjectiveEarly EEG contains reliable information for outcome prediction of comatose patients after cardiac arrest. We introduce dynamic functional connectivity measures and estimate additional predictive values.MethodsWe performed a prospective multicenter cohort study on continuous EEG for outcome prediction of comatose patients after cardiac arrest. We calculated Link Rates (LR) and Link Durations (LD) in the α, δ, and θ band, based on similarity of instantaneous frequencies in five-minute EEG epochs, hourly, during 3 days after cardiac arrest. We studied associations of LR and LD with good (Cerebral Performance Category (CPC) 1–2) or poor outcome (CPC 3–5) with univariate analyses. With random forest classification, we established EEG-based predictive models. We used receiver operating characteristics to estimate additional values of dynamic connectivity measures for outcome prediction.ResultsOf 683 patients, 369 (54%) had poor outcome. Patients with poor outcome had significantly lower LR and longer LD, with largest differences 12 h after cardiac arrest (LR_θ 1.87 vs. 1.95 Hz and LD_α 91 vs. 82 ms). Adding these measures to a model with classical EEG features increased sensitivity for reliable prediction of poor outcome from 34% to 38% at 12 h after cardiac arrest.ConclusionPoor outcome is associated with lower dynamics of connectivity after cardiac arrest.SignificanceDynamic functional connectivity analysis may improve EEG based outcome prediction.     

Therapeutic effectiveness of a single exercise session combined with Walk Aide functional electrical stimulation in post-stroke patients:a crossover design study

A growing body of evidence has suggested that the imbalance of epigenetic markers and oxidative stress appears to be involved in the pathophysiology and progression of stroke. Thus, strategies that modulate these biomarkers might be considered targets for neuroprotection and novel therapeutic opportunities for these patients. Physical exercise has been reported to induce changes in these epigenetic markers and improve clinical outcomes in different populations. However, little is reported on this in post-stroke patients. The purpose of this study was to investigate the effect of a single exercise session with Walk Aide functional electrical stimulation(FES) on cognitive performance, clinical functional parameters, oxidative stress and epigenetic modulation in post-stroke individuals. In this crossover design study, 12 post-stroke individuals aged 54–72 years of either sexes were included and subjected to a single session of exercise(45 minutes) without Walk Aide functional electrical stimulation(EXE alone group), followed by another single session of exercise(45 minutes) with Walk Aide functional electrical stimulation(EXE + FES group). The clinical functional outcome measures, cognitive performance and blood collections for biomarker measurements were assessed pre-and post-intervention. After intervention, higher Berg Balance Scale scores were obtained in the EXE + FES group than in the EXE alone group. There was no significant difference in the Timed Up and Go test results post-intervention between EXE alone and EXE + FES groups. After intervention, a better cognitive performance was found in both groups compared with before the intervention. After intervention, the Timed Up and Go test scores were higher in the EXE + FES group than in the EXE alone group. In addition, the intervention induced lower levels of lipid peroxidation. After intervention, carbonyl level was lower, superoxide dismutase activity and superoxide dismutase/catalase activity ratio were higher in the EXE + FES group, compared with the EXE group alone. In each group, both histone deacetylase(HDAC2) and histone acetyltransferase activities were increased after intervention compared with before the intervention. These findings suggest that a single exercise session with Walk Aide FES is more effective on balance ability and cognitive performance compared with conventional exercise alone in post-stroke patients. This is likely to be related to the regulation of oxidative stress markers. The present study was approved by the Research Ethics Committee of the Methodist University Center-IPA(approval No. 2.423.376) on December 7, 2017 and registered in the Brazilian Registry of Clinical Trials—Re BEC(RBR-9 phj2 q) on February 11, 2019.     

磁共振弥散张量成像在脑小血管病中的应用进展

随着人口老龄化进程的加速,脑小血管病(CSVD)的发病率也在不断上升,其导致的多种症状严重影响了患者的生活质量。MRI弥散张量成像(DTI)作为新近发展的影像技术,有无创显示白质纤维超微结构等优点,已被广泛用于疾病早期诊断、病情预测、治疗评估等多方面的研究。本文即就DTI技术在CSVD中的研究现状和未来发展前景进行综述。