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Ce chapitre traite de l’imagerie IRM des tissus à temps de relaxation transverse ultra-courts (T2

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

Background. Dementia with Lewy bodies (DLB) is a neurodegenerative disorder with a wide heterogeneity of symptoms, which suggests the existence of different subtypes. Objectives. We used data-driven analysis of MRI data to investigate DLB subtypes. Methods. We included 165 probable DLB from the Mayo Clinic and 3 centers from the European DLB consortium and performed a hierarchical cluster analysis to identify subtypes based on gray matter (GM) volumes. To characterize the subtypes, we used demographic and clinical data, as well as β-amyloid and cerebrovascular biomarkers at baseline, and cognitive decline over three years. Results. We identified 3 subtypes: an older subtype with reduced cortical GM volumes, worse cognition, and faster cognitive decline (n=49, 30%); a subtype with low GM volumes in fronto-occipital regions (n=76, 46%); and a subtype of younger patients with the highest cortical GM volumes, proportionally lower GM volumes in basal ganglia and the highest frequency of cognitive fluctuations (n=40, 24%). Conclusions. This study shows the existence of MRI subtypes in DLB, which may have implications for clinical workout, research, and therapeutic decisions.

Background Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair. It is demonstrated that testosterone can act through neural androgen receptors and several clinical observations stimulated an interest in the potential protective effects of testosterone treatment for MS. Here, we sought to demonstrate the effects of a testosterone supplementation in testosterone-deficient men with relapsing-remitting MS. Methods/design This report presents the rationale and methodology of TOTEM RRMS, a French, phase 2, multicenter, randomized, placebo-controlled, and double-blind trial, which aims to prevent the progression of MS in men with low testosterone levels by administration of testosterone undecanoate, who were kept under natalizumab (Tysabri®) to overcome the anti-inflammatory effect of testosterone. Forty patients will be randomized into two groups receiving either a testosterone treatment (Nebido®) or a matching placebo. The intervention period for each group will last 66 weeks (treatment will be injected at baseline, week 6, and then every 12 weeks). The main objective is to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyses. As secondary objectives, impacts of the testosterone supplementation will be studied using other conventional and unconventional MRI parameters and with clinical outcomes. Discussion The action of testosterone is observed in different experimental autoimmune encephalomyelitis models and epidemiological studies in humans. However, despite several preclinical data and some small clinical trials in MS, clear evidence for a therapeutic effect of hormone therapy is still missing. Therefore, our goal is to demonstrate the effects of testosterone therapies in MS. As there is no effective treatment currently available on fatigue in MS, careful attention should also be paid to secondary endpoints: fatigue, cognitive functions, and other symptoms that may improve life quality. Assuming a positive outcome of the trial, this treatment could be considered as a new neuroprotective and remyelinating therapy in relapsing-remitting MS and could be applicable to other demyelinating diseases. Trial registration ClinicalTrials.gov NCT03910738. Registered on 10 April 2019.

8544 Background: In 2010 the British Thoracic Society (BTS) guidelines introduced clinical decision based on patient perception of risk to make surgery more permissive and revised recommendations for broader oncologic criteria such as surgery for N2 disease to improve surgical resection rates. In 2011 the National Institute for Health and Care Excellence (NICE) guidelines were updated with similar recommendations, but notable disagreement on surgery for N2 disease. We sought to conduct one of the largest cross-sectional studies to ascertain the impact of national clinical guidelines (with conflicting recommendations) on clinician behaviour. Methods: We analysed data from the UK national registry (National Lung Cancer Audit) comprising all patients diagnosed with lung cancer between 2008 to 2013 within England and Wales. Categorical data was summarised as frequency (%) and continuous data was summarised as mean (SD). Linear and logistic regression analyses were used with each year as an independent categorical outcome to determine global and year specific changes in FEV1 and proportions with N2 undergoing surgery respectively. Results: From January 2008 to December 2013, data from 167,192 patients with primary lung cancers were submitted to the NLCA. In 2008, 23,293 new lung cancers were diagnosed in England and Wales increasing annually by 2013 to 29,224. The most common presentation was advanced disease stage IV (49.7%), IIIB (13.2%) and IIIA (12.0%) and early-stage disease was less frequent with presentations IA (7.0%), IB (6.7%), IIA (2.9%) and IIB (4.27%). Lung function tests were undertaken in a subset of 53,905 of all diagnosed patients from 2008 to 2013. The mean FEV1 (SD) increased annually from 67 (22)% in 2008 to 71 (24)% in 2013 (p < 0.001). Overall, 28% (n = 46,742) of the patients were preoperatively staged as N2 disease at diagnosis. The proportion of patients with N2 disease increased from 24 to 29% in this timeframe (P = 0.003). The proportion of patients undergoing surgery for lung cancer increased from 9.5% in 2008 to 20.5% in 2013 (p < 0.001). Mean FEV1 of surgical patients were higher at 79 (22)% than the population average of 69 (23)%, an accepted reflection of surgical selection. Over time, mean FEV1 of surgical patients increased from 76 (22)% in 2008 to 81 (22)% in 2013 (p < 0.001). Of the patients undergoing surgery, the proportion of patients across the 6-year interval were broadly consistent between 8 to 11% without any evidence of trend (P = 0.125). Conclusions: Within 3 years of new clinical guidelines, we did not observe any overall change in selection based on lower levels of lung function and when presented with conflicting recommendation no observable change in attitudes of clinicians on surgery for N2 disease. The observed increase in surgical resection rates is more likely due to (greater access to surgery by) increasing number of surgeons rather than any impact of guideline recommendations.

Dementia with Lewy bodies (DLB) patients show few significant macroscopic structural changes, especially at the early stages of the disease, making quantitative MRI especially interesting to explore more subtle changes that are not detectable by conventional volumetric techniques. Microstructural alterations have been reported in DLB at the dementia stage, but no study to date was conducted in prodromal patients. Here, quantitative MRI data were collected from 46 DLB prodromal patients and 20 healthy elderly subjects, who also underwent a detailed clinical examination including the Mayo Clinic Fluctuation Scale. We conducted voxel-wise between-group comparisons in diffusion tensor imaging (DTI) metrics and in R2* mapping, along with a multivariate analysis combining the two modalities. We highlighted multiple grey matter and white matter microstructural changes in DLB patients at the prodromal stage, compared to control subjects. Our multivariate analysis identified three distinct regional patterns of DTI and R2* changes (anterior, anteromedial, posterior) in DLB patients, that could reflect different neuropathological processes across brain regions. We also observed an association between R2* alterations in the thalamus, and the severity of fluctuations, in the DLB group. These preliminary findings are promising and require future investigations to better understand the biological underpinnings of microstructural alterations.

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/. The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord., Measurement(s)spinal cordTechnology Type(s)magnetic resonance imagingFactor Type(s)manufacturer • siteSample Characteristic - OrganismHomo sapiensSample Characteristic - LocationCanada • Switzerland • Australia • United States of America • United Kingdom • Germany • French Republic • Czech Republic • Italy • Japan • Kingdom of Spain • China Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.14052269

Background Cortical and subcortical cognitive impairments are usually found in dementia with Lewy bodies (DLB). Roughly, they comprise visuo-constructive/executive function and attention/processing speed impairments, whereas memory would remain relatively spared. In this study, we focused on the neuro-anatomical substrates of attention and processing speed, which is still poorly understood. For the purpose of the study, we examined the correlations between behavioral scores measuring the speed of processing and the degree of cerebral atrophy in patients with prodromal to moderate DLB. Methods Ninety-three prodromal to moderate DLB patients (mean MMSE = 25.5) were selected to participate in the study as well as 28 healthy elderly subjects (mean MMSE = 28.9), matched in terms of age and educational level. The Trail Making Test A (TMTA) and the Digit Symbol Substitution Test (DSST) were used to assess attention and processing speed. Behavioral performances were compared between patients and healthy control subjects. Three-dimensional MRI images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry (VBM). Results The behavioral results on both the TMTA (p = .026) and the DSST (p p p Conclusions The behavioral results are in line with the literature on the DLB cognitive profile and confirm the existence of attention and processing speed impairment. Interestingly, VBM analysis revealed the involvement of the basal ganglia, in particular, the left caudate nucleus, which is part of the attention cerebral network, suggesting an important role of this structure for attentional processing speed. This also suggests the clinical implication of damage in this region relatively early in the course of the disease.

Down syndrome (DS) is the most common genetic form of intellectual disability caused by the presence of an additional copy of human chromosome 21 (Hsa21). To provide novel insights into genotype–phenotype correlations, we used standardized behavioural tests, magnetic resonance imaging and hippocampal gene expression to screen several DS mouse models for the mouse chromosome 16 region homologous to Hsa21. First, we unravelled several genetic interactions between different regions of chromosome 16 and how they contribute significantly to altering the outcome of the phenotypes in brain cognition, function and structure. Then, in-depth analysis of misregulated expressed genes involved in synaptic dysfunction highlighted six biological cascades centred around DYRK1A, GSK3β, NPY, SNARE, RHOA and NPAS4. Finally, we provide a novel vision of the existing altered gene–gene crosstalk and molecular mechanisms targeting specific hubs in DS models that should become central to better understanding of DS and improving the development of therapies.

According to the Construction-Integration model (Kintsch 1988; Kintsch 1998), two forms of representation are activated during the reading and the comprehension of a text: 1) the text base, which includes semantic propositions and 2) the situation model, corresponding to the integration of the information contained in the text to the memories and knowledge of the reader. Functional neuroimaging studies in healthy subjects have shown that the text base is underpinned by frontal regions and lateral temporal regions whereas the situation model would rather depend on the posterior cingulate cortex, the precuneus and other regions depending on the dimension studied. However, the brain regions highlighted so far were only involved in comprehension and not necessary for this cognitive ability. For the first time, we explored the brain structures necessary to understand texts using a combined VBM/DTI approach in neuropsychological patients with whom we obtained comprehension scores (text base and situation model) after the reading of narrative texts. To our great surprise and contrary to our hypotheses, which were based on the results of functional neuroimaging studies, our own results show that it is the hippocampal region that is necessary to activate and memorize/remember the text base and the situation model. The highlighting of a link between the integrity of a portion of the uncinate fasciculus which is well known to play a role in semantic processing and the performance scores of the text base suggests that the hippocampal region is necessary not only for the retrieval of the text base and of the situation model thanks to episodic memory, but also for the activation of the text base during the reading and the comprehension of a text.

International audience; PurposeTo determine optimal constrained tissue parameters and off-resonance sequence parameters for single-point macromolecular proton fraction (SP-MPF) mapping based on a comprehensive quantitative magnetization transfer (qMT) protocol in healthy and demyelinated living mice at 7T.MethodsUsing 3D spoiled gradient echo-based sequences, a comprehensive qMT protocol is performed by sampling the Z-spectrum of mice brains, in vivo. Provided additional T1, urn:x-wiley:07403194:media:mrm28397:mrm28397-math-0001 and B0 maps allow for the estimation of qMT tissue parameters, among which three will be constrained, namely the longitudinal and transverse relaxation characteristics of the free pool (R1,fT2,f), the cross-relaxation rate (R) and the bound pool transverse relaxation time (T2,r). Different sets of constrained parameters are investigated to reduce the bias between the SP-MPF and its reference based on the comprehensive protocol.ResultsBased on a whole-brain histogram analysis about the constrained parameters, the optimal experimental parameters that minimize the global bias between reference and SP-MPF maps consist of a 600° and 6 kHz off-resonance irradiation pulse. Following a Bland-Altman analysis over regions of interest, optimal constrained parameters were R1,fT2,f = 0.0129, R = 26.5 s−1, and T2,r = 9.1 µs, yielding an overall MPF bias of 10−4 (limits of agreement [−0.0068;0.0070]) and a relative variation of 0.64% ± 5.95% between the reference and the optimal single-point method across all mice.ConclusionThe necessity of estimating animal model- and field-dependent constrained parameters was demonstrated. The single-point MPF method can be reliably applied at 7T, as part of routine preclinical in vivo imaging protocol in mice.

Fibrosis is a key pathological feature in muscle disorders, but its quantification mainly relies on histological and biochemical assays. Muscle fibrosis most frequently is entangled with other pathological processes, as cell membrane lesions, inflammation, necrosis, regeneration, or fatty infiltration, making in vivo assessment difficult. Here, we (1) describe a novel mouse model with variable levels of induced skeletal muscle fibrosis displaying minimal inflammation and no fat infiltration, and (2) report how fibrosis affects non-invasive metrics derived from nuclear magnetic resonance (NMR) and ultrasound shear-wave elastography (SWE) associated with a passive biomechanical assay. Our findings show that collagen fraction correlates with multiple non-invasive metrics. Among them, muscle stiffness as measured by SWE, T2, and extracellular volume (ECV) as measured by NMR have the strongest correlations with histology. We also report that combining metrics in a multi-modality index allowed better discrimination between fibrotic and normal skeletal muscles. This study demonstrates that skeletal muscle fibrosis leads to alterations that can be assessed in vivo with multiple imaging parameters. Furthermore, combining NMR and SWE passive biomechanical assay improves the non-invasive evaluation of skeletal muscle fibrosis and may allow disentangling it from co-occurring pathological alterations in more complex scenarios, such as muscular dystrophies.

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/ . The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.

Objectives To determine the prevalence, localization and associations of cerebral microbleeds (CMB) in dementia with Lewy bodies (DLB) with its core clinical symptoms and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). We hypothesize DLB patients with CMB have increased amyloid burden compared to those without CMB, which could also translate into clinical differences. Methods Retrospective cross-sectional analysis from the AlphaLewyMA study (https://clinicaltrials.gov/ct2/show/NCT01876459). Patients underwent a standardized protocol of brain MRI including 3D T1, 3D FLAIR and T2* sequences, and CSF analysis of AD biomarkers. CMB and white matter hyperintensities (WMHs) were visually assessed in prodromal and mild demented (DLB, N = 91) and AD (AD, N = 67) patients. Results CMB prevalence did not differ among DLB and AD (24.2% vs. 37.3%; p = 0.081). CMB were mainly distributed in lobar topographies in both DLB (74%) and AD (89%). CMB in DLB was not associated with global cognitive performance, executive functioning, speed of information processing, or AD CSF biomarkers. Similarly, there was no difference regarding specific clinical symptoms: fluctuations, psychotic phenomena, sleep behavior disorder and Parkinsonism between DLB patients with and without CMB. AD patients with CMB had increased burden of WMH compared to those without (2.1 ± 0.86 vs. 1.4 ± 0.89; p = 0.005), according to Fazekas scale, whereas no significant difference was observed in DLB patients (1.68 ± 0.95 vs. 1.42 ± 0.91; p = 0.25). Conclusion CMB were equally prevalent with similar topographic distribution in both DLB and AD patients. CMB was not associated with CSF AD biomarkers or core clinical symptoms in DLB.

Background Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage. Methods All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d), and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42, and Aβ40) were also measured. Results The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. Conclusions The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer’s biomarker does not improve the differential diagnosis between AD and DLB. Trial registration ClinicalTrials.gov, NCT01876459 (AlphaLewyMa)

Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d) and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42 and Aβ40) were also measured.Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. Furthermore, alpha-synuclein levels were elevated not only in AD patients with a typical “Alzheimer” profile (i.e. 2 or 3 pathological biomarkers) but also in AD patients with an atypical “Alzheimer” profile (i.e. one or no pathological biomarkers).Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. Moreover, alpha-synuclein assay appears to be of particular interest in the differential diagnosis of AD in cases where the Alzheimer biomarkers do not have a typical profile of the disease, i.e. when there is only one or no pathological biomarkers.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)

Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and Dementia with Lewy Bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage. Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD) and 32 AD patients at the demented stage (AD-d). CSF levels of total alpha-synuclein were assessed using commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer's biomarkers (t-Tau, P-Tau, Aβ42 and Aβ40) were also measured.Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels are significantly higher in AD patients than in DLB patients. Interestingly is that the levels seem to be altered from the prodromal stage in both AD and DLB. Furthermore, by dividing the patients according to the profiles of Alzheimer's biomarkers typically found or not for each of the two pathologies and then classifying the patients according to the level of alpha-synuclein, we find that alpha-synuclein levels are elevated not only for AD patients with typical “Alzheimer” profile (i.e. 2 or 3 pathological biomarkers) but also for AD patients with a non-typical “Alzheimer” profile (i.e. none or one pathological biomarker).Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early from the prodromal stage. Moreover, alpha-synuclein assay appears to be of particular interest in the differential diagnosis of AD in cases where the Alzheimer biomarkers do not have a typical profile of the disease, i.e. when there is only one or no pathological biomarker.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)

Purpose To introduce a novel method for long-T2 signal physical suppression in steady-state based on configuration states combination and modulation using diffusion weighting. Its efficiency in yielding a high contrast in short-T2 structures using an ultrashort echo time acquisition module (Diff-UTE) is compared to the adiabatically prepared Inversion-Recovery-UTE sequence (IR-UTE). Theory and methods Using a rectangular-pulse prepared 3D-UTE sequence, the possibility of long-T2 component signal cancellation through diffusion effects is addressed, and the condition met for sets of sequence parameters. Simultaneously, the short-T2 component signal is maximized using a Bloch equation-based optimization process. The method is evaluated from simulations, and experiments are conducted on a phantom composed of short and long-T2 components, as well as on an ex vivo mouse head. Results Within equal scan times, the proposed method allowed for an efficient long-T2 signal suppression, and expectedly yielded a higher signal to noise ratio in short-T2 structures compared to the IR-UTE technique, although an intrinsic short-T2 signal loss is expected through the preparation module. Conclusion The Diff-UTE method represents an interesting alternative to the IR-UTE technique. Diffusion weighting allowing for a long-T2 suppression results in a less penalizing method to generate a high and selective contrast in short-T2 components. Magn Reson Med 80:548-559, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Background Never-smokers with lung cancer often present late as there are no established aetiological risk factors. The aim of the study is to define the frequency over time and characterise clinical features of never-smokers presenting sufficiently early to determine if it is possible to identify patients at risk. Methods We retrospectively analysed data from a prospectively collected database of patients who underwent surgery. The frequency was defined as number of never-smokers versus current and ex-smokers by year. Clinical features at presentation were collated as frequency. Results A total of 2170 patients underwent resection for lung cancer from March 2008 to November 2014. The annual frequency of developing lung cancer in never-smokers increased from 13% to 28%, attributable to an absolute increase in numbers and not simply a change in the ratio of never-smokers to current and ex-smokers. A total of 436 (20%) patients were never-smokers. The mean age was 60 (16 SD) years and 67% were female. Presenting features were non-specific consisting of cough in 34%, chest infections in 18% and haemoptysis in 11%. A total of 14% were detected on incidental chest film, 30% on computed tomography, 7% on positron-emission tomography/computed tomography and 1% on MRI. Conclusions We observed more than a double of the annual frequency of never-smokers in the last 7 years. Patients present with non-specific symptoms and majority were detected on incidental imaging, a modality that is likely to play an increasingly important role for early detection in this cohort that does not have any observable clinical risk factors.

Diffuse atrophy including the insula was previously demonstrated in dementia with Lewy bodies (DLB) patients but little is known about the prodromal stage of DLB (pro-DLB). In this prospective study, we used SPM8-DARTEL to measure gray matter (GM) and white matter (WM) atrophy in pro-DLB patients (n = 54), prodromal Alzheimer’s disease (pro-AD) patients (n = 16), DLB patients at the stage of dementia (mild-DLB) (n = 15), and Alzheimer’s disease patients at the stage of dementia (mild-AD) (n = 28), and compared them with healthy elderly controls (HC, n = 22). Diminished GM volumes were found in bilateral insula in pro-DLB patients, a trend to significance in right hippocampus and parahippocampal gyrus in pro-AD patients, in left insula in mild-DLB patients, and in medial temporal lobes and insula in mild-AD patients. The comparison between prodromal groups did not showed any differences. The comparison between groups with dementia revealed atrophy around the left middle temporal gyrus in mild-AD patients. Reduced WM volume was observed in mild-DLB in the pons. The insula seems to be a key region in DLB as early as the prodromal stage. MRI studies looking at perfusion, and functional and anatomical connectivity are now needed to better understand the role of this region in DLB.

Periodic catatonia (PC) is a psychomotor phenotype with a progressive-remitting course. While it can fit any disorder diagnosis of the schizoaffective spectrum, its core features consist of a mix of hypo- and hyperkinesias resulting in distortions of expressive movements such as grimacing and parakinesias. The replication of cerebral blood flow (CBF) increases in the left supplementary motor area (L-SMA) and lateral premotor cortex (L-LPM) in acute and remitting PC patients indicates that these increases could be used as diagnostic biomarkers. In this proof-of-concept study, 2 different MRI sequences were repeated on 3 separate days to get reliable measurement values of CBF in 9 PC and 26 non-PC patients during different cognitive tasks. Each patient was compared to 37 controls. In L-SMA [–9; +10; +60] and L-LPM [–46; –12; +43], a test was positive if the t value was >2.02 (α < 0.05; two tailed). The measurements had good analytical performance. Regarding the tests, their sensitivities and specificities were significantly different from the chance level on both measures, except for L-SMA sensitivities. When combining all the tests, among regions and methods, sensitivity was 98% (95% credible interval [CI] 76–100%) and specificity 88% (72–97%). Bayesian inferences of its negative predictive values for PC were >95% regardless of the context, while its positive predictive values reached 94% but only when used in combination with clinical criteria. The case-by-case analysis suggests that non-PC patients with neurological motor deficits are at risk to be false positive.

8504 Background: Video assisted thoracoscopic surgery (VATS) is a popular access for lung cancer resection. However, there is limited information from RCTs from in-hospital to one-year clinical efficacy, safety and oncologic outcomes of a minimal access approach. Methods: VIOLET is a parallel group multi-center RCT conducted in 9 centers in the United Kingdom that recruited participants with known or suspected (cT1-3, N0-1 and M0) lung cancer (ISRCTN13472721). Trial protocol: https://bmjopen.bmj.com/content/9/10/e029507.info. Results: From July 2015 to February 2019, 503 participants were randomized to VATS (n=247) or open (n=256) lobectomy. Patients allocated to VATS had less pain with a mean difference (MD) in visual analogue score of -0.54 (95%CI -0.99 to -0.10) despite less analgesic consumption (mean ratio 0.90, 95%CI 0.80 to 1.01). After discharge pain was consistent on multiple sub-scales including overall pain (MD -7.19, -10.59 to -3.80), chest pain (MD -4.66, -7.96 to -1.36) and an 18% relative risk (RR) reduction in incision pain (RR 0.82; 0.72 to 0.94) up to one-year. Better functional recovery continued in VATS arm after discharge with better physical function (primary outcome) with MD of 4.65 (1.69 to 7.61; P=0.002) at 5 weeks and overall improvement in global health status with a MD of 4.21 (1.62 to 6.79; P=0.001). In hospital, VATS arm had fewer complications (RR 0.74, 0.66 to 0.84; P

Au cours des dernieres annees, les traitements de nombreuses maladies neuromusculaires, jusqu’ici incurables, ont beneficie d’importants progres. Ce bouleversement contextuel a eu pour consequence de stimuler le developpement de nouveaux outils d’evaluation atraumatiques. Ceux-ci peuvent etre classes en trois grandes categories : les explorations fonctionnelles musculaires, les marqueurs des fluides biologiques et l’imagerie musculaire. Au sein de cette derniere, l’imagerie par resonance magnetique nucleaire (IRMN) offre un tres large eventail de possibilites pour caracteriser la composition, la fonction et le metabolisme du muscle strie squelettique. Aujourd’hui, trois indicateurs RMN sont couramment integres dans les protocoles de recherche clinique : 1) le volume musculaire ou l’aire d’une section musculaire transversale ciblee, 2) le pourcentage de graisse intramusculaire et 3) le T2 de l’eau musculaire. Ils permettent de quantifier respectivement la trophicite du muscle, les degenerescences graisseuses chroniques et l’oedeme tissulaire (ou plus generalement « l’activite de la maladie »). Un quatrieme indicateur, le volume de tissu contractile est facilement derivable des deux premiers. Les cartographies de fraction graisseuse, souvent issues de sequences Dixon, ont fait la preuve de leur utilite pour detecter de subtils changements de composition musculaire et se sont, a plusieurs reprises, revelees plus sensibles que les evaluations fonctionnelles standards. Cet indicateur sera probablement le premier parmi ceux proposes a etre valide comme parametre principal par les organismes de regulation. La diversite des contrastes obtenus par RMN permet d’explorer de nombreuses autres pistes de caracterisation du muscle squelettique et de nouveaux biomarqueurs RMN sont a attendre dans un avenir plus ou moins proche. Des sequences a TE ultra-courts (UTE), le rehaussement tardif post-injection de gadolinium et l’elastographie par RMN sont en cours d’etude pour l’evaluation de la fibrose interstitielle du muscle squelettique. De nombreuses options existent pour mesurer la perfusion et l’oxygenation du muscle par RMN. La RMN de diffusion ainsi que l’utilisation d’algorithmes d’analyse de texture pourraient apporter des informations supplementaires sur l’organisation musculaire aux echelles respectivement microscopiques et mesoscopiques. La spectroscopie RMN du phosphore 31 P est la technique de reference pour l’evaluation atraumatique de l’energetique musculaire pendant et apres exercice. Le spectre 31 P du muscle dystrophique au repos est notablement altere, et plusieurs de ses resonances informent sur l’integrite de la membrane cellulaire. D’importants efforts sont consacres a l’acceleration de l’acquisition des images au travers plusieurs approches, allant de l’extraction du contenu en graisse et des cartographies T2 au depart d’une unique sequence, jusqu’a l’utilisation de scenarios d’acquisition partielle des matrices. Dans un avenir proche, une diminution spectaculaire du temps d’acquisition est attendue. Cela renforcera l’attractivite des indicateurs RMN et facilitera leur integration aux essais de recherche clinique.

Skeletal muscle inflammation/necrosis and fat infiltration are strong indicators of disease activity and progression in many neuromuscular disorders. They can be assessed by muscle T2 relaxometry and water-fat separation techniques, respectively. In the present work, we exploited differences between water and fat T1 and T2 relaxivities by applying a bi-component extended phase graph (EPG) fitting approach to simultaneously quantify the muscle water T2 and fat fraction from standard multi-slice multi-echo (MSME) acquisitions in the presence of stimulated echoes. Experimental decay curves were adjusted to the theoretical model using either an iterative non-negative least-squares (NNLS) procedure or a pattern recognition approach. Twenty-two patients (age, 49 ± 18 years) were selected to cover a large range of muscle fat infiltration. Four cases of chronic or subchronic juvenile dermatomyositis (age, 8 ± 3 years) were investigated before and 3 months following steroid treatment. For control, five healthy volunteers (age, 25 ± 2 years) were recruited. All subjects underwent the MSME sequence and EPG fitting procedure. The EPG fitting algorithm allowed a precise estimation of water T2 and fat fraction in diseased muscle, even in the presence of large B1(+) inhomogeneities. In the whole cohort of patients, there was no overall correlation between water T2 values obtained with the proposed method and the fat fraction estimated inside muscle tissues (R(2) = 0.02). In the patients with dermatomyositis, there was a significant decrease in water T2 (-4.09 ± 3.7 ms) consequent to steroid treatment. The pattern recognition approach resulted in a 20-fold decrease in processing time relative to the iterative NNLS procedure. The fat fraction derived from the EPG fitting approach correlated well with the fat fraction derived from a standard three-point Dixon method (≈1.5% bias). The bi-component EPG fitting analysis is a precise tool to monitor muscle tissue disease activity and is able to handle bias introduced by fat infiltration and B1(+) inhomogeneities.

International audience; Myelin imaging in the central nervous system is essential for monitoring pathologies involving white matter alterations. Various quantitative MRI protocols relying on the modeling of the interactions of water protons with myelinated tissues have shown sensitivities in case of myelin disruption. Some extracted model parameters are more sensitive to demyelination, such as the bound pool fraction (f) in quantitative magnetization transfer imaging (qMTI), the radial diffusivity in diffusion tensor imaging (DTI), and the myelin water fraction (MWF) in myelin water imaging (MWI). A 3D ultrashort echo time (UTE) sequence within an appropriate water suppression condition (Diff-UTE) is also considered for the direct visualization of the myelin semi-solid matrix (Diff-UTE normalized signal; rSPF). In this paper, we aimed at assessing the sensitivities and correlations of the parameters mentioned above to an immuno-histological study of the Myelin Basic Protein (MBP) in a murine model of demyelination at 7 T. We demonstrated a high sensitivity of the MRI metrics to demyelination, and strong Spearman correlations in the corpus callosum between histology, macromolecular proton fraction (ρ > 0.87) and Diff-UTE signal (ρ > 0.76), but moderate ones with radial diffusivity and MWF (|ρ| < 0.70).

A better understanding of how social factors relate to the psychological processes in thought disorder (TD) is necessary for the development of effective psychological interventions. Sixty-eight participants diagnosed with psychosis (18–65; 47.1% female) were recruited and evaluated on social cognition (Hinting Task, HT; and reading the mind in the eyes test, RMET), social isolation (size of social network, frequency and quality of contact), psychotic symptoms (Positive and Negative Syndrome Scale, PANSS) and TD (Thought, Language and Communication Disorders Scale, TLC). A mediation model was tested with isolation as the predictor, TD as the outcome, and performance on HT and RMET as the mediators. The final model, with adjustment for comorbid symptoms (i.e. delusions, suspiciousness, hallucinations, and negative symptoms), supported full mediation and explained a significant amount of the observed variance (60%). Performance on the HT was a significant mediator of the relationship between social isolation and TD. From the covariates, delusions contributed independently and significantly to TD. The implications of the findings for psychological practice, and TD-specific interventions, are discussed as well as the limitations of the study. Further avenues for symptom-specific research are discussed, in particular with reference to more complex psychosocial models. © 2018

BackgroundPoor social cognition is prevalent in schizophrenia spectrum disorders. Some authors argue that these effects are symptom-specific and that socio-cognitive difficulties (e.g. theory of mind) are strongly associated with thought disorder and symptoms of disorganisation.AimsThe current review tests the strength of this association.MethodWe meta-analysed studies published between 1980 and 2016 that tested the association between social cognition and these symptoms in schizophrenia spectrum disorders.ResultsOur search (PsycINFO, MEDLINE and Web of Science) identified 123 studies (N = 9107). Overall effect size as r = −0.313, indicating a moderate association between symptoms and social cognition. Subanalyses yielded a moderate association between symptoms and theory of mind (r = −0.349) and emotion recognition (r = −0.334), but smaller effect sizes for social perception (r = −0.188), emotion regulation (r = −0.169) and attributional biases (r = −0.143).ConclusionsThe association is interpreted within models of communication that highlight the importance of mentalisation and processing of partner-specific cues in conversational alignment and grounding.Declaration of interestsNone.

International audience; Introduction: Magnetic resonance imaging (MRI) shows slight spatial variations in brain white matter (WM). We used quantitative multi-parametric MRI to evaluate in what respect these inhomogeneities could correspond to WM subtypes with specific characteristics and spatial distribution.Materials and methods: Twenty-six controls (12 women, 38 ±9 Y) took part in a 60-min session on a 3T scanner measuring 7 parameters: R1 and R2, diffusion tensor imaging which allowed to measure Axial and Radial Diffusivity (AD, RD), magnetization transfer imaging which enabled to compute the Macromolecular Proton Fraction (MPF), and a susceptibility-weighted sequence which permitted to quantify R2* and magnetic susceptibility (χm). Spatial independent component analysis was used to identify WM subtypes with specific combination of quantitative parameters values.Results: Three subtypes could be identified. t-WM (track) mostly mapped on well-formed projection and commissural tracts and came with high AD values (all p < 10−18). The two other subtypes were located in subcortical WM and overlapped with association fibers: f-WM (frontal) was mostly anterior in the frontal lobe whereas c-WM (central) was underneath the central cortex. f-WM and c-WM had higher MPF values, indicating a higher myelin content (all p < 1.7 10−6). This was compatible with their larger χm and R2, as iron is essentially stored in oligodendrocytes (all p < 0.01). Although R1 essentially showed the same, its higher value in t-WM relative to c-WM might be related to its higher cholesterol concentration.Conclusions: Thus, f- and c-WMs were less structured, but more myelinated and probably more metabolically active regarding to their iron content than WM related to fasciculi (t-WM). As known WM bundles passed though different WM subtypes, myelination might not be uniform along the axons but rather follow a spatially consistent regional variability. Future studies might examine the reproducibility of this decomposition and how development and pathology differently affect each subtype.

Purpose The aim of this study is to validate the current applicability of arteriovenous access banding in high flow access (HFA) and/or haemodialysis access-induced distal ischaemia (HAIDI). Methods This retrospective study was conducted at the GEV (Grupo de Estudos Vasculares) vascular access centre. The clinical records of consecutive patients undergoing banding for HAIDI and HFA symptoms, between June 2011 and January 2015, were reviewed until April 2015. All vascular access patients’ consultation records and surgical notes were reviewed. We analysed and compared patients’ age, gender, comorbidities, symptoms and intraoperative ultrasound control. We defined technical failure as recurrence of symptoms, requiring new banding. Excessive banding, access thrombosis, rupture and false aneurysm development were registered as complications. Primary clinical success was defined as improvement of symptoms or effective flow reduction after banding, with no need for reintervention. If one reintervention was necessary, we have defined it as secondary clinical success. Results Overall, 119 patients underwent banding: 64 (54%) with HAIDI and 55 (46%) with HFA. The HAIDI group was significantly older (65 ± 13 years compared with 56 ± 22 years, p = 0.001) and had significantly greater number of patients with diabetes (56% vs 24%, p = 0.004). Primary success was achieved in 85 patients (71.4%) and the secondary success rate was 84.9%. Older age (p = 0.016) and intraoperative ultrasound control (p = 0.012) were significantly associated with primary success. Conclusions Our results do not corroborate the high incidence of thrombosis previously reported as associated with AV access banding and suggest that ultrasound control is crucial for preventing technical failure. The procedure was effective on both compared groups.