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Preterm birth still represents a concrete emergency to be managed and addressed globally. Since cerebral white matter injury is the major form of brain impairment in survivors of premature birth, the identification of reliable, non-invasive markers of altered white matter development is of utmost importance in diagnostics. Diffusion MRI has recently emerged as a valuable tool to investigate these kinds of alterations. In this work, rather than focusing on a single MRI modality, we worked on a compound of beyond-DTI High Angular Resolution Diffusion Imaging (HARDI) techniques in a group of 46 preterm babies studied on a 3T scanner at term equivalent age and in 23 control neonates born at term. After extracting relevant derived parameters, we examined discriminative patterns of preterm birth through (i) a traditional voxel-wise statistical method such as the Tract-Based Spatial Statistics approach (TBSS); (ii) an advanced Machine Learning approach such as the Support Vector Machine (SVM) classification; (iii) establishing the degree of association between the two methods in voting white matter most discriminating areas. Finally, we applied a multi-set Canonical Correlation Analysis (CCA) in search for sources of linked alterations across modalities. TBSS analysis showed significant differences between preterm and term cohorts in several white matter areas for multiple HARDI features. SVM classification performed on skeletonized HARDI measures produced satisfactory accuracy rates, especially as for highly informative parameters about fibers’ directionality. Assessment of the degree of overlap between the relevant measures identified by the two methods exhibited a good, though parameter-dependent rate of agreement. Finally, CCA analysis identified joint changes precisely for those features exhibiting less correspondence between TBSS and SVM. Our results suggest that a data-driven intramodal imaging approach is crucial to extract deep and complementary information that cannot be extracted from a single modality.

Diffusion Kurtosis Imaging (DKI) has undisputed advantages over more classical diffusion Magnetic Resonance Imaging (dMRI), as witnessed by a fast-increasing number of clinical applications and software packages widely adopted in brain imaging domain. Despite its power in probing tissue microstructure compared to conventional MRI, DKI is still largely underutilized in Spinal Cord (SC) imaging because of its inherently demanding technological requirements. If state-of-the-art hardware advancements have recently allowed to make great strides in applying this emerging method to adult and child SC, the same does not apply to neonatal setting. Indeed, amplified technical issues related to SC district in this age range have made this field still unexplored. However, results arising from recent application of DKI to adult and child SC are promising enough to suggest how informative this technique would be in investigating newborns, too. Due to its extreme sensitivity to non-gaussian diffusion, DKI proves particularly suitable for detecting complex, subtle, fast microstructural changes occurring in this area at this early and critical stage of development, and not identifiable with only DTI. Given the multiplicity of congenital anomalies of the spinal canal, their crucial effect on later developmental outcome, and the close interconnection between SC region and the above brain, managing to apply such a method to neonatal cohort becomes of utmost importance. In this work, we illustrate the first semi-automated pipeline for handling with DKI data of neonatal SC, from acquisition setting to estimation of diffusion (DTI & DKI) measures, through accurate adjustment of processing algorithms customized for adult SC. Each processing step of this pipeline, built on Spinal Cord Toolbox (SCT) software, has undergone Quality Control check by supervision of an expert pediatric neuroradiologist, and the overall procedure has preliminarily been tested in a pilot clinical case study. Results of this application agree with findings achieved in a corresponding adult survey, thus confirming validity of adopted pipeline and diagnostic value of DKI in pediatrics. This novel tool hence paves the wave for extending its application also to other promising advanced dMRI models, such as Neurite Orientation Dispersion and Density Imaging (NODDI), and to a wider range of potential clinical applications concerning neonatal period.

Cognitive decline is a common trait of neurodegenerative diseases of central nervous system and one of the major risk factors associated with faster phenoconversion from prodromal stages. In the transition to full-blown clinical syndromes, increased phase synchronization in the theta, alpha or beta EEG rhythms is thought to reflect the activation of compensatory mechanisms that may counterbalance the cognitive decline of patients affected by Mild Cognitive Impairment (MCI). Patients suffering from idiopathic Rapid eye-movement sleep Behavior Disorder (iRBD) have high risk of developing Parkinson Disease (PD) or Dementia with Lewy Bodies (DLB) and cognitive impairment is among the strongest risk factors together with motor symptoms. Here we wanted to investigate whether altered phase synchronization and amplitude couplings of the brain oscillations could be linked to the balancing of cognitive decline in a longitudinal cohort (N=18) of iRBD patients. We measured high-density Electroencephalographic (HD-EEG) activity at baseline and follow-up and quantified power distribution, orthogonalized amplitude correlation and weighted phase lag index. Despite the overt neurodegenerative progression (three patients converted to PD and one to DLB), cognitive decline was not evident from Mini Mental State Examination (MMSE) or neuropsychological tests. On the other hand, alpha phase synchronization and delta amplitude correlations were significantly different at follow-up compared to baseline. In particular, alpha synchrony was enhanced while delta amplitude coupling was reduced. Those differences were more pronounced among central-posterior channels while frontal channels showed a reduced number of significant edges with respect to surrogates. Both large-scale amplitude and phase coupling significantly correlated with cognitive or neuropsychological scores but not with sleep quality indices. Altogether, these results suggest that increased alpha phase-synchronization and reduced delta amplitude correlation may be considered as electrophysiological signs of an active compensatory mechanism of the cognitive impairment in RDB patients. Large-scale functional modifications could thus be used as significant biomarker in the characterization of prodromal stages of PD.Statement of SignificanceCognitive impairment and RBD emerge much earlier than the better-known motor symptoms distinctive of synucleinopathies. An improved investigation of RBD may constitute an important biomarker for an early diagnosis of the actual neurodegenerative diseases. For the first time, this preliminary study aims to quantify the large-scale network couplings as electrophysiological manifestation of the compensatory mechanism to the cognitive impairment in a longitudinal study of idiopathic RBD patients. Unfortunately, the small number of the subjects limits the generalizability of our observations, but this is only preliminary works in a larger project that aims to investigate advanced electrophysiological markers for an early diagnosis of the synucleinopathies.

Study Objectives Increased phase synchronization in electroencephalography (EEG) bands might reflect the activation of compensatory mechanisms of cognitive decline in people with neurodegenerative diseases. Here, we investigated whether altered large-scale couplings of brain oscillations could be linked to the balancing of cognitive decline in a longitudinal cohort of people with idiopathic rapid eye-movement sleep behavior disorder (iRBD). Methods We analyzed 18 patients (17 males, 69.7 ± 7.5 years) with iRBD undergoing high-density EEG (HD-EEG), presynaptic dopaminergic imaging, and clinical and neuropsychological (NPS) assessments at two time points (time interval 24.2 ± 5.9 months). We thus quantified the HD-EEG power distribution, orthogonalized amplitude correlation, and weighted phase-lag index at both time points and correlated them with clinical, NPS, and imaging data. Results Four patients phenoconverted at follow-up (three cases of parkinsonism and one of dementia). At the group level, NPS scores decreased over time, without reaching statistical significance. However, alpha phase synchronization increased and delta amplitude correlations decreased significantly at follow-up compared to baseline. Both large-scale network connectivity metrics were significantly correlated with NPS scores but not with sleep quality indices or presynaptic dopaminergic imaging data. Conclusions These results suggest that increased alpha phase synchronization and reduced delta amplitude correlation may be considered electrophysiological signs of an active compensatory mechanism of cognitive impairment in people with iRBD. Large-scale functional modifications may be helpful biomarkers in the characterization of prodromal stages of alpha-synucleinopathies.

Background This pilot study was designed to develop a fully automatic and quantitative scoring system of B-lines (QLUSS: quantitative lung ultrasound score) involving the pleural line and to compare it with previously described semi-quantitative scores in the measurement of extravascular lung water as determined by standard thermo-dilution. Methods This was a prospective observational study of 12 patients admitted in the intensive care unit with acute respiratory distress and each provided with 12 lung ultrasound (LUS) frames. Data collected from each patient consisted in five different scores, four semi-quantitative (nLUSS, cLUSS, qLUSS, %LUSS) and quantitative scores (QLUSS). The association between LUS scores and extravascular lung water (EVLW) was determined by simple linear regression (SLR) and robust linear regression (RLR) methods. A correlation analysis between the LUS scores was performed by using the Spearman rank test. Inter-observer variability was tested by computing intraclass correlation coefficient (ICC) in two-way models for agreement, basing on scores obtained by different raters blinded to patients’ conditions and clinical history. Results In the SLR, QLUSS showed a stronger association with EVLW (R2 = 0.57) than cLUSS (R2 = 0.45) and nLUSS (R2 = 0.000), while a lower association than qLUSS (R2 = 0.85) and %LUSS (R2 = 0.72) occurred. By applying RLR, QLUSS showed an association for EVLW (R2 = 0.86) comparable to qLUSS (R2 = 0.85) and stronger than %LUSS (R2 = 0.72). QLUSS was significantly correlated with qLUSS (r = 0.772; p = 0.003) and %LUSS (r = 0.757; p = 0.005), but not with cLUSS (r = 0.561; p = 0.058) and nLUSS (r = 0.105; p = 0.744). Moreover, QLUSS showed the highest ICC (0.998; 95%CI from 0.996 to 0.999) among the LUS scores. Conclusions This study demonstrates that computer-aided scoring of the pleural line percentage affected by B-lines has the potential to assess EVLW. QLUSS may have a significant impact, once validated with a larger dataset composed by multiple real-time frames. This approach has the potentials to be advantageous in terms of faster data analysis and applicability to large sets of data without increased costs. On the contrary, it is not useful in pleural effusion or consolidations. Electronic supplementary material The online version of this article (10.1186/s13054-019-2569-4) contains supplementary material, which is available to authorized users.