Implementation of ISO/IEEE 11073 PHD SpO2 and ECG Device Specializations over Bluetooth HDP following Health Care Profile for Smart Living.

Current m-Health scenarios in the smart living era, as the interpretation of the smart city at each person's level, present several challenges associated with interoperability between different clinical devices and applications. The Continua Health Alliance establishes design guidelines to standardize application communication to guarantee interoperability among medical devices. In this paper, we describe the implementation of two IEEE agents for oxygen saturation level (SpO2) measurements and electrocardiogram (ECG) data acquisition, respectively, and a smartphone IEEE manager for validation. We developed both IEEE agents over the Bluetooth Health Device Profile following the Continua guidelines and they are part of a telemonitoring system. This system was evaluated in a sample composed of 10 volunteers (mean age 29.8 ± 7.1 y/o; 5 females) under supervision of an expert cardiologist. The evaluation consisted of measuring the SpO2 and ECG signal sitting and at rest, before and after exercising for 15 min. Physiological measurements were assessed and compared against commercial devices, and our expert physician did not find any relevant differences in the ECG signal. Additionally, the system was assessed when acquiring and processing different heart rate data to prove that warnings were generated when the heart rate was under/above the thresholds for bradycardia and tachycardia, respectively.

Implementation and validation of ASL perfusion measurements for population imaging.

PURPOSE: Pseudocontinuous arterial spin labeling (pCASL) allows for noninvasive measurement of regional cerebral blood flow (CBF), which has the potential to serve as biomarker for neurodegenerative and cardiovascular diseases. This work aimed to implement and validate pCASL on the dedicated MRI system within the population-based Rotterdam Study, which was installed in 2005 and for which software and hardware configurations have remained fixed. METHODS: Imaging was performed on two 1.5T MRI systems (General Electric); (I) the Rotterdam Study system, and (II) a hospital-based system with a product pCASL sequence. An in-house implementation of pCASL was created on scanner I. A flow phantom and three healthy volunteers (<27 years) were scanned on both systems for validation purposes. The data of the first 30 participants (86 ± 4 years) of the Rotterdam Study undergoing pCASL scans on scanner I only were analyzed with and without partial volume correction for gray matter. RESULTS: The validation study showed a difference in blood flow velocity, sensitivity, and spatial coefficient of variation of the perfusion-weighted signal between the two scanners, which was accounted for during post-processing. Gray matter CBF for the Rotterdam Study participants was 52.4 ± 8.2 ml/100 g/min, uncorrected for partial volume effects of gray matter. In this elderly cohort, partial volume correction for gray matter had a variable effect on measured CBF in a range of cortical and sub-cortical regions of interest. CONCLUSION: Regional CBF measurements are now included to investigate novel biomarkers in the Rotterdam Study. This work highlights that when it is not feasible to purchase a novel ASL sequence, an in-house implementation is valuable.

Disparate connectivity for structural and functional networks is revealed when physical location of the connected nodes is considered.

Macroscopic brain networks have been widely described with the manifold of metrics available using graph theory. However, most analyses do not incorporate information about the physical position of network nodes. Here, we provide a multimodal macroscopic network characterization while considering the physical positions of nodes. To do so, we examined anatomical and functional macroscopic brain networks in a sample of twenty healthy subjects. Anatomical networks are obtained with a graph based tractography algorithm from diffusion-weighted magnetic resonance images (DW-MRI). Anatomical connections identified via DW-MRI provided probabilistic constraints for determining the connectedness of 90 different brain areas. Functional networks are derived from temporal linear correlations between blood-oxygenation level-dependent signals derived from the same brain areas. Rentian Scaling analysis, a technique adapted from very-large-scale integration circuits analyses, shows that functional networks are more random and less optimized than the anatomical networks. We also provide a new metric that allows quantifying the global connectivity arrangements for both structural and functional networks. While the functional networks show a higher contribution of inter-hemispheric connections, the anatomical networks highest connections are identified in a dorsal-ventral arrangement. These results indicate that anatomical and functional networks present different connectivity organizations that can only be identified when the physical locations of the nodes are included in the analysis.

Changes in resting-state functionally connected parietofrontal networks after videogame practice.

Neuroimaging studies provide evidence for organized intrinsic activity under task-free conditions. This activity serves functionally relevant brain systems supporting cognition. Here, we analyze changes in resting-state functional connectivity after videogame practice applying a test-retest design. Twenty young females were selected from a group of 100 participants tested on four standardized cognitive ability tests. The practice and control groups were carefully matched on their ability scores. The practice group played during two sessions per week across 4 weeks (16 h total) under strict supervision in the laboratory, showing systematic performance improvements in the game. A group independent component analysis (GICA) applying multisession temporal concatenation on test-retest resting-state fMRI, jointly with a dual-regression approach, was computed. Supporting the main hypothesis, the key finding reveals an increased correlated activity during rest in certain predefined resting state networks (albeit using uncorrected statistics) attributable to practice with the cognitively demanding tasks of the videogame. Observed changes were mainly concentrated on parietofrontal networks involved in heterogeneous cognitive functions.

Grapheme-color synesthetes show peculiarities in their emotional brain: cortical and subcortical evidence from VBM analysis of 3D-T1 and DTI data.

Grapheme-color synesthesia is a neurological phenomenon in which viewing achromatic letters/numbers leads to automatic and involuntary color experiences. In this study, voxel-based morphometry analyses were performed on T1 images and fractional anisotropy measures to examine the whole brain in associator grapheme-color synesthetes. These analyses provide new evidence of variations in emotional areas (both at the cortical and subcortical levels), findings that help understand the emotional component as a relevant aspect of the synesthetic experience. Additionally, this study replicates previous findings in the left intraparietal sulcus and, for the first time, reports the existence of anatomical differences in subcortical gray nuclei of developmental grapheme-color synesthetes, providing a link between acquired and developmental synesthesia. This empirical evidence, which goes beyond modality-specific areas, could lead to a better understanding of grapheme-color synesthesia as well as of other modalities of the phenomenon.

Optimized voxel brain morphometry: association between brain volumes and the response to atypical antipsychotics.

To date, few studies have addressed the relationship between brain structure alterations and responses to atypical antipsychotics in schizophrenia. To this end, in this study, magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) were used to assess the relationship between the brain volumes of gray (GM) and white (WM) matters and the clinical response to risperidone or olanzapine in 30 schizophrenia patients. In comparison with healthy controls, the patients in this study showed a bilateral decrease in the anteromedial cerebellar hemispheres, the rectal gyrus and the insula, together with bilateral increases in GM in the basal ganglia. Both patient groups had a significantly smaller volume of WM in a region encompassing the internal and external capsules as compared to the controls. We found an inverse association between striatal size and the degree of clinical improvement, and a direct association between the degree of insular volume deficit and its improvement. The non-responder patient group showed a significant decrease in their left rectal gyrus as compared with the responder group. This study reveals a pattern of structural alterations in schizophrenia associated with the response to risperidone or olanzapine.

Predicting conversion to multiple sclerosis by assessing cognitive impairment in radiologically isolated syndrome.

Up to a third of patients with radiologically isolated syndrome (RIS) exhibit lower-than-expected cognitive performances in neuropsychological evaluations, but the relationship between cognitive impairment (CI) and quantitative magnetic resonance (MRI) measures has not been stablished. Furthermore, the prognostic role of CI in RIS for conversion to MS is currently unknown. We assessed 17 patients with RIS and 17 matched healthy controls (HC) with a neurophychological battery and a 3T MRI. Six patients (35,3%) fulfilled our criterion for CI (scores 2 SDs below the mean of HC in at least two cognitive tests) (ci-RIS). The ci-RIS subgroup showed lower values of normalized brain and gray matter volumes when compared to HC. After a median follow-up time of 4.5 years, the ci-RIS subgroup presented a higher conversion rate to MS, suggesting that CI might be an independent risk factor for conversion to MS.

Refining memory assessment of elderly people with cognitive impairment: Insights from the short-term memory binding test.

Alzheimer's disease (AD) affects temporary memory for bound features more remarkably than for individual features. Such selective impairments manifest from presymptomatic through dementia stages via titration procedures. A recent study suggested that without titration and with high memory load the binding selectivity may disappear in people at risk of AD such as those with Mild Cognitive Impairment (MCI). We compared data from two studies on temporary binding which assessed people with MCI and controls using different memory loads (2 or 3 items). Selective binding impairments were found in MCI, but relative to controls, such selectivity was contingent upon memory load (i.e., present with 2 items). Further analysis with MCI people who tested positive to neuroimaging biomarkers (i.e., hippocampal atrophy) confirmed that this specific binding impairments are a feature of prodromal AD. The temporary binding task has been recently suggested by consensus papers as a potential screening tool for AD. The results presented here inform on task properties that can maximize the reliability of this new assessment tool for the detection of memory impairments in prodromal cases of AD.

Relationship between episodic memory and volume of the brain regions of two functional cortical memory systems in multiple sclerosis.

BACKGROUND/OBJECTIVE: Two functional networks are proposed as neuronal support for the complex processes of memory: the anterior temporal and the medial posterior systems. We examined the atrophy of hippocampus (HC) and of those areas constituting the two functional memory systems in multiple sclerosis (MS) patients with low disability. METHODS: Episodic memory (EM) was assessed in 88 relapsing MS patients and in 40 healthy controls using Wechsler Memory Scale III (Spanish adaptation). FreeSurfer software was used to calculate normalized volume of total cortex, grey matter, white matter, subcortical grey matter (thalamus and striatum), HC and both the anterior temporal (entorhinal, ventral temporopolar, lateral orbitofrontal, amygdala) and posterior medial systems (thalamus, parahippocampal, posterior cingulate, precuneus, lateral parietal and medial prefrontal). Linear regression analysis was used to identify predictors of memory performance. RESULTS: Total grey matter and cortex volumes correlated with all subtypes of EM, and the precuneus volume correlated with overall, immediate and delayed memories. Univariant regression analysis identified an association between the volumes of the posterior medial memory network regions and EM scores. The volume of the left precuneus area was the unique and independent predictor for all EM subtypes except for visual memory, for which left HC volume was also an independent predictor. CONCLUSION: Left precuneus volume was the best predictor of memory in relapsing MS patients with low disability and mild deficits in EM.

Author Correction: White matter microstructural changes are related to cognitive dysfunction in essential tremor.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

White matter microstructural changes are related to cognitive dysfunction in essential tremor.

Diffusion tensor imaging (DTI) studies have detected white matter microstructural changes in essential tremor (ET). However, it is still unclear whether these changes are related to cognitive deficits, which have been described in ET patients. DTI-derived fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity measures were compared between 23 ET patients and 23 age-, gender-, and education-matched healthy individuals, using whole-brain tract-based spatial statistics. Correlations of white matter changes with scores obtained from a detailed neuropsychological assessment were subsequently examined. ET patients demonstrated increases in MD in the bilateral posterior corona radiata, bilateral superior longitudinal fasciculus, bilateral fornix (cres)/stria terminalis, genu and splenium of the corpus callosum, bilateral anterior and posterior limbs of internal capsule, bilateral retrolenticular region part of internal capsule, and left posterior thalamic radiation. Except for the genu of the corpus callosum, an increase in AD values was also found in these same tracts. Furthermore, increased MD and AD values in different white matter areas was negatively correlated with performance on language and verbal memory and positively with visuospatial ability. These correlations suggest that white matter changes might be involved in the pathogenesis of cognitive deficits in ET.

ASAP (Automatic Software for ASL Processing): A toolbox for processing Arterial Spin Labeling images.

The method of Arterial Spin Labeling (ASL) has experienced a significant rise in its application to functional imaging, since it is the only technique capable of measuring blood perfusion in a truly non-invasive manner. Currently, there are no commercial packages for processing ASL data and there is no recognized standard for normalizing ASL data to a common frame of reference. This work describes a new Automated Software for ASL Processing (ASAP) that can automatically process several ASL datasets. ASAP includes functions for all stages of image pre-processing: quantification, skull-stripping, co-registration, partial volume correction and normalization. To assess the applicability and validity of the toolbox, this work shows its application in the study of hypoperfusion in a sample of healthy subjects at risk of progressing to Alzheimer's disease. ASAP requires limited user intervention, minimizing the possibility of random and systematic errors, and produces cerebral blood flow maps that are ready for statistical group analysis. The software is easy to operate and results in excellent quality of spatial normalization. The results found in this evaluation study are consistent with previous studies that find decreased perfusion in Alzheimer's patients in similar regions and demonstrate the applicability of ASAP.

The influence of the COMT genotype in the underlying functional brain activity of context processing in schizophrenia and in relatives.

UNLABELLED: Context processing deficits have been shown to be present in chronic and first episode schizophrenia patients and in their relatives. This cognitive process is linked to frontal functioning and is highly dependent on dopamine levels in the prefrontal cortex (PFC). The catechol-O-methyltransferase (COMT) enzyme plays a prominent role in regulating dopamine levels in PFC. Genotypic variations in the functional polymorphism Val(158)Met COMT appear to have an impact in dopamine signaling in the PFC of healthy subjects and schizophrenia patients. We aimed to explore the effect of the Val(158)Met COMT polymorphism on brain activation during the performance of a context processing task in healthy subjects, schizophrenia spectrum patients and their healthy relatives. METHODS: 56 participants performed the Dot Probe Expectancy task (DPX) during the fMRI session. Subjects were genotyped and only the Val and Met homozygotes participated in the study. RESULTS: Schizophrenia spectrum patients and their relatives showed worse performance on context processing measures than healthy control subjects. The Val allele was associated with more context processing errors in healthy controls and in relatives compared to patients. There was a greater recruitment of frontal areas (supplementary motor area/cingulate gyrus) during context processing in patients relative to healthy controls. Met homozygotes subjects activated more frontal areas than Val homozygotes subjects. CONCLUSIONS: The Val(158)Met COMT polymorphism influences context processing and on its underlying brain activation, showing less recruitment of frontal areas in the subjects with the genotype associated to lower dopamine availability in PFC.

Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI.

To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (-3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity.

Gray Matter Involvement in Radiologically Isolated Syndrome.

The unanticipated magnetic resonance imaging (MRI) detection in the brain of asymptomatic subjects of white matter lesions suggestive of multiple sclerosis has recently been named as radiologically isolated syndrome (RIS). The pathophysiological processes of RIS remain largely unknown and questions as to whether gray matter alterations actually occur in this entity are yet to be investigated in more detail. By means of a 3 T multimodal MRI approach, we searched for cortical and deep gray matter changes in a cohort of RIS patients. Seventeen RIS patients, 17 clinically isolated syndrome (CIS) patients (median disease duration from symptom onset = 12 months), and 17 healthy controls underwent MRI and neuropsychological testing. Normalized deep gray matter volumes and regional cortical thickness were assessed using FreeSurfer. SIENAX was used to obtain normalized global and cortical brain volumes. Voxelwise morphometry analysis was performed by using SPM8 software to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Although no differences were observed between CIS and healthy controls groups, RIS patients showed significantly lower normalized cortical volume (673 ±â€Š27.07 vs 641 ±â€Š35.88 [cm³â€Š× 10³, Tukey P test = 0.009) and mean thalamic volume (0.0051 ±â€Š0.4 vs 0.0046 ±â€Š0.4 mm, P = 0.014) compared with healthy controls. RIS patients also showed significant thinning in a number of cortical areas, that were primarily distributed in frontal and temporal lobes (P < 0.05, uncorrected). Strong correlations were observed between T2-white matter lesion volume and regional cortical thickness (rho spearman ranging from 0.60 to 0.80). Our data suggest that white matter lesions on T2-weighted images are not the only hallmark of RIS. Future longitudinal studies with larger samples are warranted to better clarify the effect of RIS-related white matter lesions on gray matter tissue.

Effect of Water T2 Shortening in the Quantification of in-vitro Proton MR Spectroscopy.

PURPOSE: This work studies the relationship between in-vitro Proton Magnetic Resonance Spectroscopy metabolite quantification and water T2 decay. MATERIALS AND METHODS: An in-vitro correspondence is established between the iron accumulation and the shortening of water T2 relaxation times using seven spherical phantoms, 6 of them were doped with an increasing concentration of iron metal nanoparticles solution. This is later proposed as a source of error during the LCModel metabolite quantification of either absolute concentrations or ratios. RESULTS: The Pearson's correlation coefficient between water T2 values against absolute metabolite concentrations was on average [r] = 0.97 and on average [r] = 0.85 for metabolite ratios. CONCLUSION: These results suggest that the shortening of T2 values should be taken into account when performing metabolite quantification. Also, the need of demonstrated similar results in in-vivo studies, since the presence of iron deposits or other factors affecting the water T2 decay measurements could explain part of the inter-subject variability in the metabolite concentration and ratio quantification.

Altered brain rhythms and functional network disruptions involved in patients with generalized fixation-off epilepsy.

Generalized Fixation-off Sensitivity (CGE-FoS) patients present abnormal EEG patterns when losing fixation. In the present work, we studied two CGE-FoS epileptic patients with simultaneous EEG-fMRI. We aim to identify brain areas that are specifically related to the pathology by identifying the brain networks that are related to the EEG brain altered rhythms. Three main analyses were performed: EEG standalone, where the voltage fluctuations in delta, alpha, and beta EEG bands were obtained; fMRI standalone, where resting-state fMRI ICA analyses for opened and closed eyes conditions were computed per subject; and, EEG-informed fMRI, where EEG delta, alpha and beta oscillations were used to analyze fMRI. Patient 1 showed EEG abnormalities for lower beta band EEG brain rhythm. Fluctuations of this rhythm were correlated with a brain network mainly composed by temporo-frontal areas only found in the closed eyes condition. Patient 2 presented alterations in all the EEG brain rhythms (delta, alpha, beta) under study when closing eyes. Several biologically relevant brain networks highly correlated (r > 0.7) to each other in the closed eyes condition were found. EEG-informed fMRI results in patient 2 showed hypersynchronized patterns in the fMRI correlation spatial maps. The obtained findings allow a differential diagnosis for each patient and different profiles with respect to healthy volunteers. The results suggest a different disruption in the functional brain networks of these patients that depends on their altered brain rhythms. This knowledge could be used to treat these patients by novel brain stimulation approaches targeting specific altered brain networks in each patient.

In vivo neurometabolic profiling in orthostatic tremor.

The pathogenesis of orthostatic tremor (OT) remains unclear, although some evidence points to dysfunction in the brainstem or cerebellum. We used single voxel proton magnetic resonance spectroscopy (1H-MRS) (3 T) to investigate whether neurochemical changes underlie abnormal cerebellar or cortical function in OT. Fourteen OT patients and 14 healthy controls underwent 1H-MRS studies with voxels placed in midparietal gray matter and cerebellum (vermis and central white matter). Spectral analysis was analyzed using the software package LCModel (version 6.3). The absolute metabolite concentrations and ratios of total N-acetylaspartate + N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamate + glutamine to creatine were calculated. In midparietal gray matter spectra, we found a significant decrease in the absolute concentration of NAA in OT patients versus healthy controls (7.76 ±â€Š0.25 vs 8.11 ±â€Š0.45, P = 0.017). A similar decrease in NAA was seen in the cerebellar vermis (7.33 ±â€Š0.61 vs 8.55 ±â€Š1.54, P = 0.014) and cerebellar white matter (8.54 ±â€Š0.79 vs 9.95 ±â€Š1.57, P = 0.010). No differences in the other metabolites or their ratios were observed. Reductions in both cerebral cortical and cerebellar NAA suggest that there is neuronal damage or loss in OT, raising the intriguing question as to whether OT is a neurodegenerative disease. Along with clinical history and electrophysio0logical examination, 1H-MRS could serve as a useful diagnostic aid for OT.

Resting state functional MRI reveals abnormal network connectivity in orthostatic tremor.

Very little is known about the pathogenesis of orthostatic tremor (OT). We have observed that OT patients might have deficits in specific aspects of neuropsychological function, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests a possible involvement of frontocerebellar circuits. We examined whether resting-state functional magnetic resonance imaging (fMRI) might provide further insights into the pathogenesis on OT. Resting-state fMRI data in 13 OT patients (11 women and 2 men) and 13 matched healthy controls were analyzed using independent component analysis, in combination with a "dual-regression" technique, to identify group differences in several resting-state networks (RSNs). All participants also underwent neuropsychological testing during the same session. Relative to healthy controls, OT patients showed increased connectivity in RSNs involved in cognitive processes (default mode network [DMN] and frontoparietal networks), and decreased connectivity in the cerebellum and sensorimotor networks. Changes in network integrity were associated not only with duration (DMN and medial visual network), but also with cognitive function. Moreover, in at least 2 networks (DMN and medial visual network), increased connectivity was associated with worse performance on different cognitive domains (attention, executive function, visuospatial ability, visual memory, and language). In this exploratory study, we observed selective impairments of RSNs in OT patients. This and other future resting-state fMRI studies might provide a novel method to understand the pathophysiological mechanisms of motor and nonmotor features of OT.

Automated quantification of epicardial adipose tissue in cardiac magnetic resonance imaging.

Cardiovascular disease is one of the leading causes of death worldwide. Epicardial adipose tissue (EAT) has emerged as an independent predictor of high cardiometabolic risk. Cardiovascular MRI has proven to be a feasible and reproducible method to assess EAT quantitatively. We present a novel approach for the automated quantification of EAT using "a priori" anatomical information. We extracted a region of interest (ROI) in the end-diastolic heart phase followed by a GVF-snake algorithm to smooth it. For the EAT and endocardial boundary detection, a Law's texture filter is applied. Left and right ventricle are localized using spatial prior information. Then, thresholding is applied to quantify the cardiac muscle. For the EAT, it is differentiated from the paracardial fat by K-cosine curvature analysis. Results for 10 morbidly obese patients show no significant differences between manual and automatic quantification with a remarkable time and effort saving between them.