Method-comparison study between a watch-like sensor and a cuff-based device for 24-h ambulatory blood pressure monitoring.

The use of 24-h ambulatory blood pressure monitoring (ABPM) has been continuously increasing over the last decades. However, cuff-based devices may cause discomfort, particularly at night, leading to potentially non-representative blood pressure (BP) values. We investigated the feasibility of a cuff-less BP monitoring solution in 67 subjects undergoing conventional 24-h ABPM. A watch-like optical sensor was attached at the upper arm or wrist at the contralateral side of the cuff. Systolic (SBP) and diastolic BP (DBP) values were estimated from the measured optical signals by pulse wave analysis. Average 24-h, daytime and nighttime BP values were compared between the conventional monitor and the cuff-less sensor. The differences between both methods-expressed as mean ± standard deviation (95% limits of agreement)-were of - 1.8 ± 6.2 mmHg (- 13.9, 10.3) on SBP and - 2.3 ± 5.4 mmHg (- 13.0, 8.3) on DBP for 24-h averages, of - 1.5 ± 6.6 mmHg (- 14.4, 11.4) on SBP and - 1.8 ± 5.9 mmHg (- 13.4, 9.9) on DBP for daytime averages, and of 0.4 ± 7.5 mmHg (- 14.4, 15.1) on SBP and - 1.3 ± 6.8 mmHg (- 14.7, 12.0) on DBP for nighttime averages. These results encouragingly suggest that cuff-less 24-h ABPM may soon become a clinical possibility.

Blood pressure monitoring during anesthesia induction using PPG morphology features and machine learning.

Blood pressure (BP) is a crucial biomarker giving valuable information regarding cardiovascular diseases but requires accurate continuous monitoring to maximize its value. In the effort of developing non-invasive, non-occlusive and continuous BP monitoring devices, photoplethysmography (PPG) has recently gained interest. Researchers have attempted to estimate BP based on the analysis of PPG waveform morphology, with promising results, yet often validated on a small number of subjects with moderate BP variations. This work presents an accurate BP estimator based on PPG morphology features. The method first uses a clinically-validated algorithm (oBPM®) to perform signal preprocessing and extraction of physiological features. A subset of features that best reflects BP changes is automatically identified by Lasso regression, and a feature relevance analysis is conducted. Three machine learning (ML) methods are then investigated to translate this subset of features into systolic BP (SBP) and diastolic BP (DBP) estimates; namely Lasso regression, support vector regression and Gaussian process regression. The accuracy of absolute BP estimates and trending ability are evaluated. Such an approach considerably improves the performance for SBP estimation over previous oBPM® technology, with a reduction in the standard deviation of the error of over 20%. Furthermore, rapid BP changes assessed by the PPG-based approach demonstrates concordance rate over 99% with the invasive reference. Altogether, the results confirm that PPG morphology features can be combined with ML methods to accurately track BP variations generated during anesthesia induction. They also reinforce the importance of adding a calibration measure to obtain an absolute BP estimate.

Accuracy of blood pressure measurement across BMI categories using the OptiBP™ mobile application.

PURPOSE: Obesity is a clear risk factor for hypertension. Blood pressure (BP) measurement in obese patients may be biased by cuff size and upper arm shape which may affect the accuracy of measurements. This study aimed to assess the accuracy of the OptiBP smartphone application for three different body mass index (BMI) categories (normal, overweight and obese). MATERIALS AND METHODS: Participants with a wide range of BP and BMI were recruited at Lausanne University Hospital's hypertension clinic in Switzerland. OptiBP estimated BP by recording an optical signal reflecting light from the participants' fingertips into a smartphone camera. Age, sex and BP distribution were collected to fulfil the AAMI/ESH/ISO universal standards. Both auscultatory BP references and OptiBP BP were measured and compared using the simultaneous opposite arms method, as described in the 81060-2:2018 ISO norm. Subgroup analyses were performed for each BMI category. RESULTS: We analyzed 414 recordings from 95 patients: 34 were overweight and 15 were obese. The OptiBP application had a performance acceptance rate of 82%. The mean and standard deviation (SD) differences between the optical BP estimations and the auscultatory reference rates (criterion 1) were respected in all subgroups: SBP mean value was 2.08 (SD 7.58); 1.32 (6.44); -2.29 (5.62) respectively in obese, overweight and normal weight subgroup. For criterion 2, which investigates the precision errors on an individual level, the threshold for systolic BP in the obese group was slightly above the requirement for this criterion. CONCLUSION: This study demonstrated that the OptiBP application is easily applicable to overweight and obese participants. Differences between the reference measure and the OptiBP estimation were within ISO limits (criterion 1). In obese participants, the SD of mean error was outside criterion 2 limits. Whether auscultatory measurement, due to arm morphology or the OptiBP is associated with increasing bias in obese still needs to be studied.

What is the context? • Hypertension and obesity have a major impact on population health and costs. • Obesity is a chronic disease characterized by abnormal or excessive fat accumulation. • Obesity, in combination with other diseases like hypertension, is a major risk factor for cardiovascular and total death. • In Europe, the obesity rate is 21.5% for men and 24.5% for women. • Hypertension, which continues to increase in the population, is a factor that can be modified when well managed. • Blood pressure measurement by the usual method may be complicated in obese patients due to fat accumulation and the shape of the arm and can lead to measurement errors. In addition, the non-invasive blood pressure measurement can be constraining and uncomfortable.What is new? • Smartphone apps are gradually appearing and allow the measurement of blood pressure without a pressure cuff using photoplethysmography. • OptiBP is a smartphone application that provides an estimate of blood pressure that has been evaluated in the general population. • The objective of this study is to assess whether OptiBP is equally effective in obese and overweight patients.What is the impact? • The use of smartphones to estimate BP in overweight and obese patients may be a solution to the known bias associated with cuff measurement. • The acquisition of more and more data with a larger number of patients will allow the continuous improvement of the application's algorithm.

Evaluation of a Wearable System for Fetal ECG Monitoring Using Cooperative Sensors.

Fetal electrocardiography (fECG) has gotten widespread interest in the last years as technology for fetal monitoring. Compared to cardiotocography (CTG), the current state of the art, it can be designed in smaller formfactor and is thus suited for long-term and unsupervised monitoring. In the present study we evaluated a wearable system which is based on CSEM's cooperative sensors, a versatile technology that allows for the measurement of multiple biosignals and an easy integration into a garment or patch. The system was tested on 25 patients with singleton pregnancies and an age of gestation ≥ 37 weeks. To reject unreliable fetal heart rate (fHR) estimations, the signal processing algorithm provides a signal quality index. In 12 out of 21 patients available for analysis, a good performance of fHR estimations was obtained with a mean absolute error < 5 bpm and an acceptance rate >70%. However, the remaining 9 patients showed low acceptance rates and high errors. Besides investigating the source of these high errors, future work includes the investigating improved signal processing algorithms, different body positions and the use of dry electrodes. Clinical Relevance - The aim of this work is to develop a wearable system that can be offered in hospitals as an alternative to cardiotocography, or as a home monitoring tool for at risk fetuses, in the era of evolving telemedicine.

Comparability of a Blood-Pressure-Monitoring Smartphone Application with Conventional Measurements-A Pilot Study.

(1) Background: New cuffless technologies attempting blood-pressure measurements (BPM) offer possibilities to improve hypertension awareness and control. The aim of this study was to compare a smartphone application (app)-based algorithm with office BPM (OBPM). (2) Methods: We included consecutive patients with an indication for ambulatory BPM. The smartphone app (RIVA digital) acquired the pulse wave in the fingers' arterial bed using the phone's camera and estimated BP based on photoplethysmographic (PPG) waveforms. Measurements were alternatingly taken with an oscillometric cuff-based device and smartphone BPM (AppBP) on two consecutive days. AppBP were calibrated to the first OBPM. Each AppBP was compared to its CuffBP (mean of the previous/following OBPM). (3) Results: 50 participants were included, resulting in 50 AppBP values on Day 1 and 33 on Day 2 after exclusion of 225 AppBP due to insufficient quality. The mean ± SD of the differences between AppBP and CuffBP was 0.7 ± 9.4/1.0 ± 4.5 mmHg (p-value 0.739/0.201) on Day 1 and 2.6 ± 8.2/1.3 ± 4.1 mmHg (p-value 0.106/0.091) on Day 2 for systolic/diastolic values, respectively. There were no significant differences between the deviations on Day 1 and Day 2 (p-value 0.297/0.533 for systolic/diastolic values). Overall, there were 10 (12%) systolic measurement pairs differing by >15 mmHg. (4) Conclusions: In this pilot evaluation, the RIVA Digital app shows promising results when compared to oscillometric cuff-based measurements, especially regarding diastolic values. Its differences between AppBP−CuffBP have a good stability one day after calibration. Before clinical use, signal acquisition needs improvement and the algorithm needs to undergo formal validation against a gold-standard BPM method.

Multimodal Investigation of Neuroinflammation in Aviremic Patients With HIV on Antiretroviral Therapy and HIV Elite Controllers.

BACKGROUND AND OBJECTIVES: The presence of HIV in the CNS has been related to chronic immune activation and cognitive dysfunction. The aim of this work was to investigate (1) the presence of neuroinflammation in aviremic people with HIV (PWH) on therapy and in nontreated aviremic PWH (elite controllers [ECs]) using a translocator protein 18 kDa radioligand; (2) the relationship between neuroinflammation and cognitive function in aviremic PWH; and (3) the relationship between [11C]-PBR28 signal and quantitative MRI (qMRI) measures of brain tissue integrity such as T1 and T2 relaxation times (rts). METHODS: [11C]-PBR28 (standard uptake value ratio, SUVR) images were generated in 36 participants (14 PWH, 6 ECs, and 16 healthy controls) using a statistically defined pseudoreference region. Group comparisons of [11C]-PBR28 SUVR were performed using region of interest-based and voxelwise analyses. The relationship between inflammation, qMRI measures, and cognitive function was studied. RESULTS: In region of interest analyses, ECs exhibited significantly lower [11C]-PBR28 signal in the thalamus, putamen, superior temporal gyrus, prefrontal cortex, and cerebellum compared with the PWH. In voxelwise analyses, differences were observed in the thalamus, precuneus cortex, inferior temporal gyrus, occipital cortex, cerebellum, and white matter (WM). [11C]-PBR28 signal in the WM and superior temporal gyrus was related to processing speed and selective attention in PWH. In a subset of PWH (n = 12), [11C]-PBR28 signal in the thalamus and WM regions was related to a decrease in T2 rt and to an increase in T1 rt suggesting a colocalization of increased glial metabolism, decrease in microstructural integrity, and iron accumulation. DISCUSSION: This study casts a new light onto the role of neuroinflammation and related microstructural alterations of HIV infection in the CNS and shows that ECs suppress neuroinflammation more effectively than PWH on therapy.

Feature Learning for Blood Pressure Estimation from Photoplethysmography.

Blood pressure (BP) is an important indicator for prevention and management of cardiovascular diseases. Alongside the improvement in sensors and wearables, photoplethysmography (PPG) appears to be a promising technology for continuous, non-invasive and cuffless BP monitoring. Previous attempts mainly focused on features extracted from the pulse morphology. In this paper, we propose to remove the feature engineering step and automatically generate features from an ensemble average (EA) PPG pulse and its derivatives, using convolutional neural network and a calibration measurement. We used the large VitalDB dataset to accurately evaluate the generalization capability of the proposed model. The model achieved mean errors of -0.24 ± 11.56 mmHg for SBP and -0.5 ± 6.52 mmHg for DBP. We observed a considerable reduction in error standard deviation of above 40% compared to the control case, which assumes no BP variation. Altogether, these results highlight the capability to model the dependency between PPG and BP.

Influence of Measurement Location on Reflectance Pulse Oximetry in Sleep Apnea Patients: Wrist vs. Upper Arm.

Peripheral oxygen saturation (SpO2) plays a key role in diagnosing sleep apnea. It is mainly measured via transmission pulse oximetry at the fingertip, an approach less suited for long-term monitoring over several nights.In this study we tested a more patient-friendly solution via a reflectance pulse oximetry device. Having previously observed issues with pulse oximetry at the wrist, we investigated in this study the influence of the location of our device (upper arm vs. wrist) to measure SpO2. Accuracy was compared against state-of-the-art fingertip SpO2 measurements during a full overnight polysomnography in nine patients with suspected sleep apnea.The upper arm location clearly showed a lower root mean square error ARMS = 1.8% than the wrist ARMS = 2.5% and a lower rate of automatic data rejection (19% vs 25%). Irrespective of the measurement location the accuracies obtained comply with the ISO standard and the FDA guidance for pulse oximeters. In contrast to the wrist, the upper arm location seemed to be more resilient to deteriorating influences such as venous blood.Reflectance pulse oximetry at the wrist remains challenging but the upper arm could provide remedy for more robust SpO2 estimates to reliably screen for sleep apnea and other diseases.Clinical Relevance- The performance of reflectance pulse oximetry measured at the upper arm during sleep is superior to measurements at the wrist which are perturbed by undesired large fluctuations suspected to be caused by venous blood. If confirmed, this could also apply to the optical measurement of other vital signs such as blood pressure.

Ultrahigh field in vivo characterization of microstructural abnormalities in the orbitofrontal cortex and amygdala in autism.

There are currently no biomarkers for autism spectrum disorder (ASD). This neurodevelopmental condition has previously been associated with histopathological findings, including increased neuronal packing density in the amygdala, abnormal laminar cytoarchitecture and increased average neuronal density in the prefrontal cortex. The present study examined whether new brain imaging technologies could reveal in vivo, in adults with ASD, the manifestation of previously described histopathological changes. Using quantitative mapping at ultrahigh field (7 Tesla), we show that we can observe microstructural alterations in the right lateral orbitofrontal cortex and the bilateral amygdala in adult individuals with ASD in vivo. These imaging alterations point to an abnormal laminar cytoarchitecture and to an increased neuronal density, similar to what has been previously described in post-mortem data in ASD. Our data demonstrate that it is possible to visualize, in vivo and at the individual level, alterations of cortical and subcortical microstructure in ASD. Future studies will be needed to extend these findings to a larger group of individuals and evaluate their association with symptomatology as well as their specificity among the different neurodevelopmental disorders.

Smartphone based blood pressure measurement: accuracy of the OptiBP mobile application according to the AAMI/ESH/ISO universal validation protocol.

OBJECTIVE: The aim of this study was to assess the accuracy of the OptiBP mobile application based on an optical signal recorded by placing the patient's fingertip on a smartphone's camera to estimate blood pressure (BP). Measurements were carried out in a general population according to existing standards of the Association for the Advancement of Medical Instrumentation (AAMI), the European Society of Hypertension (ESH) and the International Organization for Standardization (ISO). METHODS: Participants were recruited during a scheduled appointment at the hypertension clinic of Lausanne University Hospital in Switzerland. Age, gender and BP distribution were collected to fulfill AAMI/ESH/ISO universal standards. Both auscultatory BP references and OptiBP were measured and compared using the opposite arm simultaneous method as described in the 81060-2:2018 ISO norm. RESULTS: A total of 353 paired recordings from 91 subjects were analyzed. For validation criterion 1, the mean ± SD between OptiBP and reference BP recordings was respectively 0.5 ± 7.7 mmHg and 0.4 ± 4.6 mmHg for SBP and DBP. For validation criterion 2, the SD of the averaged BP differences between OptiBP and reference BP per subject was 6.3 mmHg and 3.5 mmHg for SBP and DBP. OptiBP acceptance rate was 85%. CONCLUSION: The smartphone embedded OptiBP cuffless mobile application fulfills the validation requirements of AAMI/ESH/ISO universal standards in a general population for the measurement of SBP and DBP.

Machine Learning Approaches For Improved Continuous, Non-occlusive Arterial Pressure Monitoring Using Photoplethysmography.

Arterial pressure (AP) is a crucial biomarker for cardiovascular disease prevention and management. Photoplethysmography (PPG) could provide a novel, paradigm-shifting approach for continuous, non-obtrusive AP monitoring, comfortably integrated in wearable and mobile devices; yet, it still faces challenges in accuracy and robustness. In this work, we sought to integrate machine learning (ML) techniques into a previously established, clinically-validated classical approach (oBPM®) to develop new accurate AP estimation tools based on PPG, and at the same time improve our understanding of the underlying physiological parameters. In this novel approach, oBPM® was used to pre-process PPG signals and robustly extract physiological features, and ML models were trained on these features to estimate systolic AP (SAP). A feature relevance analysis showed that reference (calibration) information, followed by various morphological parameters of the PPG pulse wave, comprised the most important features for SAP estimation. A performance analysis then revealed that LASSO-regularized linear regression, Gaussian process regression and support vector regression are effective for SAP estimation, particularly when operating on reduced feature sets previously obtained with e.g. LASSO. These approaches yielded substantial reductions in error standard deviation of 9-15% relative to conventional oBPM®. Altogether, these results indicate that ML approaches are well-suited, and promising tools to help overcoming the challenges of ubiquitous AP monitoring.

Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes.

Introduction: Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes. Methods: Thirty-two RRMS patients (<5 years disease duration) underwent: (i) 3T MRI for CL/WML detection and clinical assessment at baseline and 2-years follow-up; and (ii) baseline blood test for sNfL. The correlation between the number and volume of CL/WML and sNfL was assessed by using the Spearman's rank correlation coefficient and a generalized linear model (GLM). A GLM was also used to assess the relationship between (i) the number/volume of new, enlarged, resolved, shrunken, stable lesions and (ii) the difference in clinical scores between two time-points. Results: At baseline, sNfL levels correlated with both total CL count/volume (ρ = 0.6/0.7, Corr-P <0.017/Corr-P < 0.001) and with total WML count/volume (ρ = 0.6/0.6, Corr-P < 0.01 for both). Baseline sNfL levels also correlated with new WML count/volume (ρ = 0.6/0.5, Corr-P < 0.01/Corr-P < 0.05) but not with new CL. Longitudinal changes in CL and WML count and volume were significantly associated with (i) sustained attention, auditory information, processing speed and flexibility (p < 0.01), (ii) verbal memory (p < 0.01); (iii) verbal fluency (p < 0.05); and (iv) hand-motor function (p < 0.05). Discussion: Changes in cortical and white matter focal damage in early MS patients correlate with global neuroaxonal damage and is associated to cognitive performances.

Blood pressure measurements with the OptiBP smartphone app validated against reference auscultatory measurements.

Mobile health diagnostics have been shown to be effective and scalable for chronic disease detection and management. By maximizing the smartphones' optics and computational power, they could allow assessment of physiological information from the morphology of pulse waves and thus estimate cuffless blood pressure (BP). We trained the parameters of an existing pulse wave analysis algorithm (oBPM), previously validated in anaesthesia on pulse oximeter signals, by collecting optical signals from 51 patients fingertips via a smartphone while simultaneously acquiring BP measurements through an arterial catheter. We then compared smartphone-based measurements obtained on 50 participants in an ambulatory setting via the OptiBP app against simultaneously acquired auscultatory systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) measurements. Patients were normotensive (70.0% for SBP versus 61.4% for DBP), hypertensive (17.1% vs. 13.6%) or hypotensive (12.9% vs. 25.0%). The difference in BP (mean ± standard deviation) between both methods were within the ISO 81,060-2:2018 standard for SBP (- 0.7 ± 7.7 mmHg), DBP (- 0.4 ± 4.5 mmHg) and MBP (- 0.6 ± 5.2 mmHg). These results demonstrate that BP can be measured with accuracy at the finger using the OptiBP smartphone app. This may become an important tool to detect hypertension in various settings, for example in low-income countries, where the availability of smartphones is high but access to health care is low.

Automated Pulse Oximeter Waveform Analysis to Track Changes in Blood Pressure During Anesthesia Induction: A Proof-of-Concept Study.

BACKGROUND: Intraoperative hypotension is associated with postoperative complications and death. Oscillometric brachial cuffs are used to measure arterial pressure (AP) in most surgical patients but may miss acute changes in AP. We hypothesized that pulse oximeter waveform analysis may help to detect changes in systolic AP (SAP) and mean AP (MAP) during anesthesia induction. METHODS: In 40 patients scheduled for an elective surgery necessitating general anesthesia and invasive AP monitoring, we assessed the performance of a pulse oximeter waveform analysis algorithm (optical blood pressure monitoring [oBPM]) to estimate SAP, MAP, and their changes during the induction of general anesthesia. Acute AP changes (>20%) in SAP and MAP assessed by the reference invasive method and by oBPM were compared using 4-quadrant and polar plots. The tracking ability of the algorithm was evaluated on changes occurring over increasingly larger time spans, from 30 seconds up to 5 minutes. The second objective of the study was to assess the ability of the oBPM algorithm to cope with the Association for the Advancement of Medical Instrumentation (AAMI) standards. The accuracy and precision of oBPM in estimating absolute SAP and MAP values compared to the invasive method was evaluated at various instants after algorithm calibration, from 30 seconds to 5 minutes. RESULTS: Rapid changes (occurring over time spans of ≤60 seconds) in SAP and MAP assessed by oBPM were strongly correlated and showed excellent concordance with changes in invasive AP (worst-case Pearson correlation of 0.94 [0.88, 0.97] [95% confidence interval], concordance rate of 100% [100%, 100%], and angular concordance rate at ±30° of 100% [100%, 100%]). The trending ability tended to decrease progressively as the time span over which the changes occurred increased, reaching 0.89 (0.85, 0.91) (Pearson correlation), 97% (95%, 100%) (concordance rate), and 90% (85%, 94%) (angular concordance rate) in the worst case. Regarding accuracy and precision, oBPM-derived SAP values were shown to comply with AAMI criteria up to 2 minutes after calibration, whereas oBPM-derived MAP values were shown to comply with criteria at all times. CONCLUSIONS: Pulse oximeter waveform analysis was useful to track rapid changes in SAP and MAP during anesthesia induction. A good agreement with reference invasive measurements was observed for MAP up to at least 5 minutes after initial calibration. In the future, this method could be used to track changes in AP between intermittent oscillometric measurements and to automatically trigger brachial cuff inflation when a significant change in AP is detected.

Extra-Axial Inflammatory Signal in Parameninges in Migraine with Visual Aura.

OBJECTIVE: Cortical spreading depression (CSD) underlies the neurobiology of migraine with aura (MWA). Animal studies reveal networks of microvessels linking brain-meninges-bone marrow. CSD activates the trigeminovascular system, evoking a meningeal inflammatory response. Accordingly, this study examines the upregulation of an inflammatory marker in extra-axial tissues in migraine with visual aura. METHODS: We used simultaneously acquired 11 C-PBR28 positron emission tomography/magnetic resonance imaging data of 18kDa translocator protein (an inflammatory marker) in MWA patients (n = 11) who experienced headaches and visual aura in the preceding month. We measured mean tracer uptake (standardized uptake value ratio [SUVR]) in 4 regions of interest comprising the meninges plus the adjacent overlying skull bone (parameningeal tissues [PMT]). These data were compared to healthy controls and patients with pain (chronic low back pain). RESULTS: MWA had significantly higher mean SUVR in PMT overlying occipital cortex than both other groups, although not in the PMT overlying 3 other cortical areas. A positive correlation was also found between the number of visual auras and tracer uptake in occipital PMT. INTERPRETATION: A strong persistent extra-axial inflammatory signal was found in meninges and calvarial bone overlying the occipital lobe in migraine with visual auras. Our findings are reminiscent of CSD-induced meningeal inflammation and provide the first imaging evidence implicating inflammation in the pathophysiology of migraine meningeal symptoms. We suspect that this inflammatory focus results from a signal that migrates from underlying brain and if so, may implicate newly discovered bridging vessels that crosstalk between brain and skull marrow, a finding of potential relevance to migraine and other neuroinflammatory brain disorders. ANN NEUROL 2020;87:939-949.

Quantitative brain relaxation atlases for personalized detection and characterization of brain pathology.

PURPOSE: To exploit the improved comparability and hardware independency of quantitative MRI, databases of MR physical parameters in healthy tissue are required, to which tissue properties of patients can be compared. In this work, normative values for longitudinal and transverse relaxation times in the brain were established and tested in single-subject comparisons for detection of abnormal relaxation times. METHODS: Relaxometry maps of the brain were acquired from 52 healthy volunteers. After spatially normalizing the volumes into a common space, T1 and T2 inter-subject variability within the healthy cohort was modeled voxel-wise. A method for a single-subject comparison against the atlases was developed by computing z-scores with respect to the established healthy norms. The comparison was applied to two multiple sclerosis and one clinically isolated syndrome cases for a proof of concept. RESULTS: The established atlases exhibit a low variation in white matter structures (median RMSE of models equal to 32 ms for T1 and 4 ms for T2 ), indicating that relaxation times are in a narrow range for normal tissues. The proposed method for single-subject comparison detected relaxation time deviations from healthy norms in the example patient data sets. Relaxation times were found to be increased in brain lesions (mean z-scores >5). Moreover, subtle and confluent differences (z-scores ~2-4) were observed in clinically plausible regions (between lesions, corpus callosum). CONCLUSIONS: Brain T1 and T2 quantitative norms were derived voxel-wise with low variability in healthy tissue. Example patient deviation maps demonstrated good sensitivity of the atlases for detecting relaxation time alterations.

Imaging of neuroinflammation in migraine with aura: A [11C]PBR28 PET/MRI study.

OBJECTIVE: To determine if migraine with aura is associated with neuroinflammation, which has been suggested by preclinical models of cortical spreading depression (CSD) as well as imaging of human pain conditions. METHODS: Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [11C]PBR28, a radioligand that binds to the 18 kDa translocator protein, a marker of glial activation. Standardized uptake value ratio (SUVR) was compared between groups, and regressed against clinical variables, using region of interest and whole-brain voxelwise analyses. RESULTS: Compared to healthy controls, migraineurs demonstrated SUVR elevations in nociceptive processing areas (e.g., thalamus and primary/secondary somatosensory and insular cortices) as well as in areas previously shown to be involved in CSD generation (visual cortex). SUVR levels in frontoinsular cortex, primary/secondary somatosensory cortices, and basal ganglia were correlated with frequency of migraine attacks. CONCLUSIONS: These findings demonstrate that migraine with aura is associated with neuroimmune activation/neuroinflammation, and support a possible link between CSD and glial activation, previously observed in animals.

PPG-Based Blood Pressure Monitoring by Pulse Wave Analysis: Calibration Parameters are Stable for Three Months.

The current non-invasive gold standard for the measurement of blood pressure (BP) is the oscillometric cuff at the upper arm, despite its known limitations. In particular, its poor adequacy with continuous monitoring and its measurement incommodity call for the development of simpler and more convenient solutions. Among these, solutions based on pulse wave analysis (PWA) and photoplethysmography (PPG) are of particular interest, due to their low-cost, strong patient compliance, and applicability in and out of clinical settings. In that context, we have recently disclosed a PPG-based PWA algorithm (oBPM™) dedicated to the continuous monitoring of BP in patients undergoing induction of general anesthesia. As is standard with PPG-based BP monitoring techniques, an initial calibration procedure with a reference device is required to allow the estimation of absolute values of BP (in mmHg). However, due to their sensitivity to peripheral effects such as vasomotion, the applicability of PPG-based techniques is often limited by the constant need of re-calibration procedures, sometimes in matters of minutes. In the present study, we evaluated the long-term stability of the calibration for our algorithm by performing PPG measurements at irregular time intervals over a period of 3 months in 13 healthy volunteers. For each measurement, diastolic BP (DBP) was assessed by an oscillometric device and estimated by the oBPM™ algorithm. We found the calibration to remain stable over the entire 3-month period, with estimation errors remaining stable over time and complying with the ISO 81060-2:2018 standard. In addition, we verified - in 11 of our 13 subjects - the sensitivity of the oBPM™ algorithm to changes in DBP. This was done in a protocol involving static leg extension exercises. Excellent trending ability (average per-subject concordance rate of 97.7 ± 5.2 %, and correlation coefficient of 0.98 ± 0.02, p <; 0.001) was found between cuff-derived DBP changes and our estimates. These findings provide a strong added value to the practical usability of the proposed PPG-based PWA approach to BP monitoring, particularly for the clinical management of hypertensive patients in and out of clinics, for whom a simple and comfortable continuous alternative to the oscillometric cuff would be strongly preferred.

Surface-based characteristics of the cerebellar cortex visualized with ultra-high field MRI.

Although having a relatively homogeneous cytoarchitectonic organization, the cerebellar cortex is a heterogeneous region characterized by different amounts of myelin, iron and protein expression profiles. In this study, we used quantitative T1 and T2* mapping at ultra-high field (7T) MRI to investigate the tissue characteristics of the cerebellar gray matter surface and its layers. Detailed subject-specific surfaces were generated at three different cortical depths and averaged across subjects to create averaged T1- and T2*-maps on the cerebellar surface. T1 surfaces showed an alternation of lower and higher T1 values when going from the median to the lateral part of the cerebellar hemispheres. In addition, longer T1 values were observed in the more superficial gray matter layers. T2*-maps showed a similar longitudinal pattern, but no change related to the cortical depths. These patterns are possibly due to variations in the level of myelination, iron and zebrin protein expression.

The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients.

OBJECTIVE: Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. METHODS: Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. RESULTS: In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation times in the pallidum (p < 0.05), which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e-16) and a significant increase in MTR (p-value < 1e-6), suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics-and not changes in lesions or brain volume-were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.