T1w/FLAIR ratio standardization as a myelin marker in MS patients

Image calibration; Integrity; Multiple sclerosisCalibración de imagen; Integridad; Esclerosis múltipleCalibració d'imatge; Integritat; Esclerosi múltipleIntroduction Calculation of a T1w/T2w ratio was introduced as a proxy for myelin integrity in the brain of multiple sclerosis (MS) patients. Since nowadays 3D FLAIR is commonly used for lesion detection instead of T2w images, we introduce a T1w/FLAIR ratio as an alternative for the T1w/T2w ratio. Objectives Bias and intensity variation are widely present between different scanners, between subjects and within subjects over time in T1w, T2w and FLAIR images. We present a standardized method for calculating a histogram calibrated T1w/FLAIR ratio to reduce bias and intensity variation in MR sequences from different scanners and at different time-points. Material and methods 207 Relapsing Remitting MS patients were scanned on 4 different 3 T scanners with a protocol including 3D T1w, 2D T2w and 3D FLAIR images. After bias correction, T1w/FLAIR ratio maps and T1w/T2w ratio maps were calculated in 4 different ways: without calibration, with linear histogram calibration as described by Ganzetti et al. (2014), and by using 2 methods of non-linear histogram calibration. The first nonlinear calibration uses a template of extra-cerebral tissue and cerebrospinal fluid (CSF) brought from Montreal Neurological Institute (MNI) space to subject space; for the second nonlinear method we used an extra-cerebral tissue and CSF template of our own subjects. Additionally, we segmented several brain structures such as Normal Appearing White Matter (NAWM), Normal Appearing Grey Matter (NAGM), corpus callosum, thalami and MS lesions using Freesurfer and Samseg. Results The coefficient of variation of T1w/FLAIR ratio in NAWM for the no calibrated, linear, and 2 nonlinear calibration methods were respectively 24, 19.1, 9.5, 13.8. The nonlinear methods of calibration showed the best results for calculating the T1w/FLAIR ratio with a smaller dispersion of the data and a smaller overlap of T1w/FLAIR ratio in the different segmented brain structures. T1w/T2w and T1w/FLAIR ratios showed a wider range of values compared to MTR values. Conclusions Calibration of T1w/T2w and T1w/FLAIR ratio maps is imperative to account for the sources of variation described above. The nonlinear calibration methods showed the best reduction of between-subject and within-subject variability. The T1w/T2w and T1w/FLAIR ratio seem to be more sensitive to smaller changes in tissue integrity than MTR. Future work is needed to determine the exact substrate of T1w/FLAIR ratio and to obtain correlations with clinical outcome

Town of Jay Annual Report Year Ending June 30, 2014

status: publishe

Blood and neuroimaging biomarkers of cognitive sequelae in breast cancer patients throughout chemotherapy:A systematic review

Breast cancer treatment can induce alterations in blood-and neuroimaging-based markers. However, an overview of the predictive value of these markers for cognition is lacking for breast cancer survivors. This systematic review summarized studies of the last decade, using the PubMed database, evaluating blood markers, and the association between blood-or structural neuroimaging markers and cognition across the chemotherapy trajectory for primary breast cancer, following PRISMA guidelines. Forty-four studies were included. Differences were observed in all blood marker categories, from on-therapy until years post-chemotherapy. Associations were found between cognitive functioning and (1) blood markers (mainly inflammation-related) during, shortly-, or years post-chemotherapy and (2) white and gray matter metrics in frontal, temporal and parietal brain regions months up until years post-chemotherapy. Preliminary evidence exists for epigenetic and metabolic changes being associated with cognition, only after chemotherapy. This review demonstrated time-dependent associations between specific blood-based and structural neuroimaging markers with cognitive impairment in patients with breast cancer. Future studies are encouraged to include both neuroimaging-and blood markers (e.g. of neuronal integrity, epigenetics and metabolism) to predict long-term cognitive effects of chemotherapy

The impact of mindfulness on functional brain connectivity and peripheral inflammation in breast cancer survivors with cognitive complaints

Simple Summary Cognitive impairment is a common side effect of cancer treatment and impacts the quality of life of cancer survivors. As there is currently no golden standard for the treatment of cancer-related cognitive impairment (CRCI), we investigated the potential of a mindfulness-based intervention to impact the underlying mechanisms of CRCI. Breast cancer survivors with cognitive complaints (n = 117) were randomly assigned to a mindfulness, physical training, or waitlist control group. Resting state functional MRI data and serum blood samples were collected and compared before and after the intervention. We could not identify differences between the groups in resting state functional connectivity. However, the functional organization of attention-, salience- and executive functioning-related neural networks differed between both intervention groups and the waitlist control group. Additionally, physical training could alter therapy-induced immune deregulation. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI. Background: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI. Methods: Female breast cancer survivors reporting cognitive complaints (n = 117) were randomly assigned to a mindfulness-based intervention (n = 43), physical training (n = 36), or waitlist control condition (n = 38). Region-of-interest (ROI) and graph theory analyses of resting state functional MRI data were performed to study longitudinal group differences in functional connectivity and organization in the default mode, dorsal attention, salience, and frontoparietal network. Additionally, bead-based immunoassays were used to investigate the differences in inflammatory profiles on serum samples. Measures were collected before, immediately after and three months post-intervention. Results: No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-& gamma;, IL-1 & beta;, and IL-8). Conclusion: Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI

Neuroinflammation as potential precursor of leukoencephalopathy in early-stage breast cancer patients:A cross-sectional PET-MRI study

BACKGROUND: Although chemotherapy-induced leukoencephalopathy has been described in case and cohort studies, literature remains inconclusive about its prevalence and mechanisms. Therefore, we investigated the presence of leukoencephalopathy after multiagent chemotherapy in women treated for breast cancer and potential underlying neuroinflammatory processes. METHODS: In this exploratory study, 15 chemotherapy-treated and 15 age-matched chemotherapy-naïve patients with early-stage breast cancer, as well as 15 healthy controls underwent simultaneous PET-MR neuroimaging, including T1-weighted MPRAGE, T2-weighted FLAIR and dynamic PET with the 18-kDA translocator protein (TSPO) radioligand [(18)F]DPA-714. Total and regional (juxtacortical, periventricular, deep white matter and infratentorial) lesion burden were compared between the groups with one-way ANOVA. With paired t-tests, [(18)F]DPA-714 volume of distribution [V(T), including partial volume correction (PVC)] in lesioned and normal appearing white matter (NAWM) were compared within subjects, to investigate inflammation. Finally, two general linear models were used to examine the predictive values of neurofilament light-chain (NfL) serum levels on (1) total lesion burden or (2) PVC [(18)F]DPA-714 V(T) of lesions showing elevated inflammation. RESULTS: No significant differences were found in total or localized lesion burden. However, significantly higher (20–45%) TSPO uptake was observed in juxtacortical lesions (p ≤ 0.008, t ≥ 3.90) compared to NAWM in both cancer groups, but only persisted for chemotherapy-treated patients after PVC (p = 0.005, t = 4.30). NfL serum levels were not associated with total lesion volume or tracer uptake in juxtacortical lesions. CONCLUSION: This multimodal neuroimaging study suggests that neuroinflammatory processes could be involved in the development of juxtacortical, but not periventricular or deep white matter, leukoencephalopathy shortly after chemotherapy for early-stage breast cancer

Functional magnetic resonance imaging : cerebral function alterations in subthreshold and suprathreshold spinal cord stimulation

Peer reviewedPublisher PD

The effect of spaceflight and microgravity on the human brain

peer reviewedMicrogravity, confinement, isolation, and immobilization are just some of the features astronauts have to cope with during space missions. Consequently, long-duration space travel can have detrimental effects on human physiology. Although research has focused on the cardiovascular and musculoskeletal system in particular, the exact impact of spaceflight on the human central nervous system remains to be determined. Previous studies have reported psychological problems, cephalic fluid shifts, neurovestibular problems, and cognitive alterations, but there is paucity in the knowledge of the underlying neural substrates. Previous space analogue studies and preliminary spaceflight studies have shown an involvement of the cerebellum, cortical sensorimotor, and somatosensory areas and the vestibular pathways. Extending this knowledge is crucial, especially in view of long-duration interplanetary missions (e.g., Mars missions) and space tourism. In addition, the acquired insight could be relevant for vestibular patients, patients with neurodegenerative disorders, as well as the elderly population, coping with multisensory deficit syndromes, immobilization, and inactivity

Simultaneous Segmentation and Anatomical Labeling of the Cerebral Vasculature

We present a novel algorithm for the simultaneous segmentation and anatomical labeling of the cerebral vasculature. The method first constructs an over-complete graph capturing the vasculature. It then selects and labels the subset of edges that most likely represents the true vasculature. Unlike existing approaches that first attempt to obtain a good segmentation and then perform labeling, we jointly optimize for both by simultaneously taking into account the image evidence and the prior knowledge about the geometry and connectivity of the vasculature. This results in an Integer Program (IP), which we solve optimally using a branch-and-cut algorithm. We evaluate our approach on a public dataset of 50 cerebral MRA images, and demonstrate that it compares favorably against state-of-the-art methods

Isabelle Modelchecking for insider threats

The Isabelle Insider framework formalises the technique of social explanation for modeling and analysing Insider threats in infrastructures including physical and logical aspects. However, the abstract Isabelle models need some refinement to provide sufficient detail to explore attacks constructively and understand how the attacker proceeds. The introduction of mutable states into the model leads us to use the concepts of Modelchecking within Isabelle. Isabelle can simply accommodate classical CTL type Modelchecking. We integrate CTL Modelchecking into the Isabelle Insider framework. A running example of an IoT attack on privacy motivates the method throughout and illustrates how the enhanced framework fully supports realistic modeling and analysis of IoT Insiders