Changes In Blood Volume Research Articles

The Cardiac Caval Index: Improving Noninvasive Assessment of Cardiac Preload.

Inferior vena cava (IVC) pulsatility quantified by the Caval Index (CI) is characterized by poor reliability, also due to the irregular magnitude of spontaneous respiratory activity generating the major pulsatile component. The aim of this study was to test whether the IVC cardiac oscillatory component could provide a more stable index (Cardiac CI-CCI) compared to CI or respiratory CI (RCI). Nine healthy volunteers underwent long-term monitoring in supine position of IVC, followed by 3 minutes passive leg raising (PLR). CI, RCI, and CCI were extracted from video recordings by automated edge-tracking and CCI was averaged over each respiratory cycle (aCCI). Cardiac output (CO), mean arterial pressure (MAP) and heart rate (HR) were also recorded during baseline (1 minutes prior to PLR) and PLR (first minute). In response to PLR, all IVC indices decreased (P < .01), CO increased by 4 ± 4% (P=.055) while HR and MAP did not vary. The Coefficient of Variation (CoV) of aCCI (13 ± 5%) was lower than that of CI (17 ± 5%, P < .01), RCI (26 ± 7%, P < .001) and CCI (25 ± 7%, P < .001). The mutual correlations in time of the indices were 0.81 (CI-RCI), 0.49 (CI-aCCI) and 0.2 (RCI-aCCI). Long-term IVC monitoring by automated edge-tracking allowed us to evidence that 1) respiratory and averaged cardiac pulsatility components are uncorrelated and thus carry different information and 2) the new index aCCI, exhibiting the lowest CoV while maintaining good sensitivity to blood volume changes, may overcome the poor reliability of CI and RCI.

Predictors of changes in cerebral perfusion and oxygenation during obstructive sleep apnea

Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder. Severe OSAS defined as apnea–hypopnea index (AHI) ≥ 30/h is a risk factor for developing cerebro-cardiovascular diseases. The mechanisms of how repetitive sleep apneas/hypopneas damage cerebral hemodynamics are still not well understood. In this study, changes in blood volume (BV) and oxygen saturation (StO2) in the left forehead of 29 newly diagnosed severe OSAS patients were measured by frequency-domain near-infrared spectroscopy during an incremental continuous positive airway pressure (CPAP) titration protocol together with polysomnography. The coefficients of variation of BV (CV-BV) and the decreases of StO2 (de-StO2) of more than 2000 respiratory events were predicted using linear mixed-effect models, respectively. We found that longer events and apneas rather than hypopneas induce larger changes in CV-BV and stronger cerebral desaturation. Respiratory events occurring during higher baseline StO2 before their onsets, during rapid-eye-movement sleep and those associated with higher heart rate induce smaller changes in CV-BV and de-StO2. The stepwise increased CPAP pressures can attenuate these changes. These results suggest that in severe OSAS the length and the type of respiratory event rather than widely used AHI may be better parameters to indicate the severity of cerebral hemodynamic changes.

Development of non-invasive alcohol analyzer using Photoplethysmographytle

Photoplethysmography (PPG) is one of the optical signals commonly used in clinical research for measuring the vital signs. Previously, PPG is often used as an indicator for detecting blood volume changes in the micro-vascular. The advantages of PPG signal mentioned in studies are non-invasive, lower operation cost, and the simplicity of the procedure. Although some the components of the PPG signal are not fully understood, it is generally accepted that it can provide valuable information in clinical study. Thus, it is interesting for finding a relation between PPG signal and blood alcohol concentration. The objective of this study is to classify two groups of ten-volunteer: (1) group of people who consumed alcohol and (2) non-consumed alcohol, by using the difference of PPG signals in these two groups and compared the results with fuel-cell breath alcohol analyzer. A set of PPG reflection data is recorded from optical sensors including the wavelength light of the red light and the infrared light from the fingertip of individuals. In additional, the changes of each signals for distinguishing two groups of volunteers are examined. The set of data is computed and analysed to find the correlation coefficient between significant variables in statistic domain. The analysis techniques are included (1) slope of the signals over time, (2) peak to peak of the heart rate, and (3) deep of waveform valley after rotation for training generalized linear (GLM) classifiers to create classification models. The accuracy of GLM classification can be obtained up to 87.50%. This suggests that PPG technique with our lab prototype has a potential for screening test to classify people who consumed alcohol and non-consumed alcohol.

Do alterations in pulmonary vascular tone result in changes in central blood volumes? An experimental study

BackgroundThe effects of selective pulmonary vascular tone alterations on cardiac preload have not been previously examined. Therefore, we evaluated whether changing pulmonary vascular tone either by hypoxia or the inhalation of aerosolized prostacyclin (PGI2) altered intrathoracic or pulmonary blood volume (ITBV, PBV, respectively), both as surrogate for left ventricular preload. Additionally, the mean systemic filling pressure analogue (Pmsa) and pressure for venous return (Pvr) were calculated as surrogate of right ventricular preload.MethodsIn a randomized controlled animal study in 6 spontaneously breathing dogs, pulmonary vascular tone was increased by controlled moderate hypoxia (FiO2 about 0.10) and decreased by aerosolized PGI2. Also, inhalation of PGI2 was instituted to induce pulmonary vasodilation during normoxia and hypoxia. PBV, ITBV and circulating blood volume (Vdcirc) were measured using transpulmonary thermo-dye dilution. Pmsa and Pvr were calculated post hoc. Either the Wilcoxon-signed rank test or Friedman ANOVA test was performed.ResultsDuring hypoxia, mean pulmonary artery pressure (PAP) increased from median [IQR] 12 [8–15] to 19 [17–25] mmHg (p < 0.05). ITBV, PBV and their ratio with Vdcirc remained unaltered, which was also true for Pmsa, Pvr and cardiac output. PGI2 co-inhalation during hypoxia normalized mean PAP to 13 (12–16) mmHg (p < 0.05), but left cardiac preload surrogates unaltered. PGI2 inhalation during normoxia further decreased mean PAP to 10 (9–13) mmHg (p < 0.05) without changing any of the other investigated hemodynamic variables.ConclusionsIn spontaneously breathing dogs, changes in pulmonary vascular tone altered PAP but had no effect on cardiac output, central blood volumes or their relation to circulating blood volume, nor on Pmsa and Pvr. These observations suggest that cardiac preload is preserved despite substantial alterations in right ventricular afterload.

Brief neuronal afterdischarges in the rat hippocampus lead to transient changes in oscillatory activity and to a very long-lasting decline in BOLD signals without inducing a hypoxic state

The effects of hippocampal neuronal afterdischarges (nAD) on hemodynamic parameters, such as blood-oxygen-level-dependent (BOLD) signals) and local cerebral blood volume (CBV) changes, as well as neuronal activity and metabolic parameters in the dentate gyrus, was investigated in rats by combining in vivo electrophysiology with functional magnetic resonance imaging (fMRI) or 1H-nuclear magnetic resonance spectroscopy (1H-NMRS). Brief electrical high-frequency pulse-burst stimulation of the right perforant pathway triggered nAD, a seizure-like activity, in the right dentate gyrus with a high incidence, a phenomenon that in turn caused a sustained decrease in BOLD signals for more than 30 min. The decrease was associated with a reduction in CBV but not with signs of hypoxic metabolism. nAD also triggered transient changes mainly in the low gamma frequency band that recovered within 20 min, so that the longer-lasting altered hemodynamics reflected a switch in blood supply rather than transient changes in ongoing neuronal activity. Even in the presence of reduced baseline BOLD signals, neurovascular coupling mechanisms remained intact, making long-lasting vasospasm unlikely. Subsequently generated nAD did not further alter the baseline BOLD signals. Similarly, nAD did not alter baseline BOLD signals when acetaminophen was previously administered, because acetaminophen alone had already caused a similar decrease in baseline BOLD signals as observed after the first nAD. Thus, at least two different blood supply states exist for the hippocampus, one low and one high, with both states allowing similar neuronal activity. Both acetaminophen and nAD switch from the high to the low blood supply state. As a result, the hemodynamic response function to an identical stimulus differed after nAD or acetaminophen, although the triggered neuronal activity was similar.

Quantification of cerebral blood volume changes caused by visual stimulation at 3 T using DANTE-prepared dual-echo EPI.

We investigate the influence of moving blood-attenuation effects when using "delay alternating with nutation for tailored excitation" (DANTE) pulses in conjunction with blood oxygen level dependent (BOLD) of functional MRI (fMRI) at 3 T. Based on the effects of including DANTE pulses, we propose quantification of cerebral blood volume (CBV) changes following functional stimulation. Eighteen volunteers in total underwent fMRI scans at 3 T. Seven volunteers were scanned to investigate the effects of DANTE pulses on the fMRI signal. CBV changes in response to visual stimulation were quantified in 11 volunteers using a DANTE-prepared dual-echo EPI sequence. The inflow effects from flowing blood in arteries and draining vein effects from flowing blood in large veins can be suppressed by use of a DANTE preparation module. Using DANTE-prepared dual-echo EPI, we quantitatively measured intravascular-weighted microvascular CBV changes of 25.4%, 29.8%, and 32.6% evoked by 1, 5, and 10 Hz visual stimulation, respectively. The extravascular fraction (∆S/S)extra at TE = 30 ms in total BOLD signal was determined to be 64.8 ± 3.4%, which is in line with previous extravascular component estimation at 3 T. Results show that the microvascular CBV changes are linearly dependent on total BOLD changes at TE = 30 ms with a slope of 0.113, and this relation is independent of stimulation frequency and subject. The DANTE preparation pulses can be incorporated into a standard EPI fMRI sequence for the purpose of minimizing inflow effects and reducing draining veins effects in large vessels. Additionally, the DANTE-prepared dual-echo EPI sequence is a promising fast imaging tool for quantification of intravascular-weighted CBV change in the microvascular space at 3 T.

ITVT-10. Using functional Ultrasound (fUS) for real-time, depth-resolved functional and vascular delineation of brain tumors with micrometer-millisecond precision

Abstract BACKGROUND Neurosurgical practice still relies heavily on pre-operatively acquired images to guide tumor resections, a practice which comes with inherent pitfalls such as registration inaccuracy due to brain shift, and lack of real-time functional or morphological feedback. Here we describe functional Ultrasound (fUS) as a new high-resolution, depth-resolved, MRI/CT-registered imaging technique able to detect functional regions and vascular morphology during awake and anesthesized tumor resections. MATERIALS AND METHODS fUS relies on high-frame-rate (HFR) ultrasound, making the technique sensitive to very small motions caused by vascular dynamics (µDoppler) and allowing measurements of changes in cerebral blood volume (CBV) with micrometer-millisecond precision. This opens up the possibility to 1) detect functional response, as CBV-changes reflect changes in metabolism of activated neurons through neurovascular coupling, and 2) visualize in-vivo vascular morphology of pathological and healthy tissue with high resolution at unprecedented depths. During a range of anesthetized and awake neurosurgical procedures we acquired vascular and functional images of brain and spinal cord using conventional ultrasound probes connected to a research acquisition system. Building on Brainlab’s Intra-Operative Navigation modules, we co-registered our intra-operative Power Doppler Images (PDIs) to patient-registered MRI/CT-data in real-time. RESULTS During meningioma and glioma resections, our co-registered PDIs revealed fUS’ ability to visualize the tumor’s feeding vessels and vascular borders in real-time, with a level of detail unprecedented by conventional MRI-sequences. During awake resections, fUS was able to detect distinct, ESM-confirmed functional areas as activated during conventional motor and language tasks. In all cases, images were acquired with micrometer-millisecond (300 µm, 1.5–2.0 ms) precision at imaging depths exceeding 5 cm. CONCLUSION fUS is a new real-time, high-resolution and depth-resolved imaging technique, combining favorable imaging specifications with characteristics such as mobility and ease of use which are uniquely beneficial for a potential image-guided neurosurgical tool.

Sequential forward mother wavelet selection method for mental workload assessment on N-back task using photoplethysmography signals

The increasing demands of a cognitive task require additional brain resources. This demand, known as mental workload, can lead to deteriorated task performance. Therefore, assessment of mental workload can provide a proper working environment to promote the working efficiency or improve safety in high-risk working environments for a subject. In this study, we present a novel sequential forward mother wavelet selection method for three levels of mental workload assessment on N-back task using photoplethysmography (PPG) signals, which non-invasively measures the blood volume changes in the microvascular bed of tissue from the skin surface with a low-cost opto-electronic technique. The proposed method was successfully applied to a PPG dataset, which was recorded from 22 healthy subjects during an N-back task using a wearable sensor. Instead of using only one mother wavelet, the features were extracted from effective mother wavelet combinations by means of a sequential forward mother wavelet selection method. In this three-class problem, the highest classification accuracy (CA) rates were achieved with 10 s (s) PPG signal segments compared with the 6 s, and 8 s PPG signal segments. For the 10 s PPG signals segments the highest CA was obtained as 76.67% for Subject 20 and the average CA for all subjects was obtained as 65.76%. Furthermore, the proposed method provided 3.59% CA improvement in average. We believed that the proposed method could ensure a great alternative to conventional mental workload assessment techniques.

Photoplethysmographic analysis of retinal videodata based on the Fourier domain approach.

Assessment of retinal blood flow inside the optic nerve head (ONH) and the peripapillary area is an important task in retinal imaging. For this purpose, an experimental binocular video ophthalmoscope that acquires precisely synchronized video sequences of the optic nerve head and peripapillary area from both eyes has been previously developed. It enables to compare specific characteristics of both eyes and efficiently detect the eye asymmetry. In this paper, we describe a novel methodology for the analysis of acquired video data using a photoplethysmographic approach. We describe and calculate the pulsatile attenuation amplitude (PAA) spatial map, which quantifies the maximum relative change of blood volume during a cardiac cycle using a frequency domain approach. We also describe in detail the origin of PAA maps from the fundamental (the first) and the second harmonic component of the pulsatile signal, and we compare the results obtained by time-based and frequency-based approaches. In several cases, we show the advantages and possibilities of this device and the appropriate image analysis approach - fast measurement and comparison of blood flow characteristics of both eyes at a glance, the robustness of this approach, and the possibility of easy detection of asymmetry.

Development of Continuous Blood Pressure Measurement System Using Photoplethysmograph and Pulse Transit Time

It is not only a problem for old age anyone. So, blood pressure is the one provides importance information with vital signs about cardiovascular health using oscillometric method. Unfortunately, this method required inflation and following deflation of the cuff. This method only gives instantaneous blood pressure and continuous measurement is not available. It is not available to the patients that required long term monitoring. To overcome this problem, the development of Continuous Non-Invasive Blood Pressure (NIBP) algorithm based on Pulse Transit Time (PTT) using two channel Photoplethysmograph (PPG) is proposed in this study. PPG is a non-invasive device for detecting blood volume changes can be affected by various physiological factors, analysis of the PPG signal can provide sufficient information on the human health condition; more specifically their cardio-vascular related performance. Literatures show that the PTT has linear relationship with blood pressure. Nevertheless, the determination of the model structure, order and real-time implementation to offer a continuous measurement of the PTT still remains challenging tasks in this area. PTT can be as index to monitor cardiovascular disease. In this project, dynamic model based on pulse transit time will be proposed to continuously monitor blood pressure by using PPG signals. Different kind of resolutions in microcontroller combined with PPG sensor will be used as well. MATLAB software is also been applied for PTT calculation based on two PPG sensors. PPG is method for detect blood volume changes with optical source transmitter send from one end and received the signal from another by receiver through body tissue as medium. MATLAB functions as Digital Signal Processing (DSP) for signals received in computer. Linear Regression technique and Fung's algorithm are applied to obtain the best fit line for all the points in order to systolic and diastolic blood pressure measurement. The results showed that the algorithm based on pulse transit time has been developed for the assessment of blood pressure and justify patient’ condition with 86.34% and 88.20% accuracy. Finally, this technique is a simple, user friendly and operator independent PPG system suitable for long term and wearable blood pressure monitor.

Preserved Cerebral Oxygenation with Worsening Global Myocardial Strain during Pediatric Chronic Hemodialysis.

Cerebral and myocardial hypoperfusion occur during hemodialysis in adults. Pediatric patients receiving chronic hemodialysis have fewer cardiovascular risk factors, yet cardiovascular morbidity remains prominent. We conducted a prospective observational study of pediatric patients receiving chronic hemodialysis to investigate whether intermittent hemodialysis is associated with adverse end organ effects in the heart or with cerebral oxygenation (regional tissue oxyhemoglobin saturation [rSO2]). We assessed intradialytic cardiovascular function and rSO2 using noninvasive echocardiography to determine myocardial strain and continuous noninvasive near-infrared spectroscopy for rSO2. We measured changes in blood volume and measured central venous oxygen saturation (mCVO2) pre-, mid-, and post-hemodialysis. The study included 15 patients (median age, 12 years; median hemodialysis vintage, 13.2 [9-24] months). Patients were asymptomatic. The rSO2 did not change during hemodialysis, whereas mCVO2 decreased significantly, from 73% to 64.8%. Global longitudinal strain of the myocardium worsened significantly by mid-hemodialysis and persisted post-hemodialysis. The ejection fraction remained normal. Lower systolic BP and faster blood volume change were associated with worsening myocardial strain; only blood volume change was significant in multivariate analysis (β-coefficient, -0.3; 95% confidence interval [CI], -0.38 to -0.21; P<0.001). Blood volume change was also associated with a significant decrease in mCVO2 (β-coefficient, 0.42; 95% CI, 0.07 to 0.76; P=0.001). Access, age, hemodialysis vintage, and ultrafiltration volume were not associated with worsening strain. Unchanged rSO2 suggested that cerebral oxygenation was maintained during hemodialysis. However, despite maintained ejection fraction, intradialytic myocardial strain worsened in pediatric hemodialysis and was associated with blood volume change. The effect of hemodialysis on individual organ perfusion in pediatric versus adult patients receiving hemodialysis might differ.

Cerebral and muscle near-infrared spectroscopy during lower-limb muscle activity - volitional and neuromuscular electrical stimulation.

Chronic venous insufficiency (CVI) can lead to blood clotting in the deep veins of the legs, a disease known as deep vein thrombosis. An estimated 40 percent of people in the United States have venous insufficiency that may be ameliorated with neuromuscular electrical stimulation (NMES). Near-infrared spectroscopy (NIRS) is a non-invasive optical imaging method for monitoring hemodynamics. NIRS, being an optical technique has no stimulation artefact, can be combined with NMES for theranostics application. In this study, we combined muscle NIRS (mNIRS) with electromyogram (EMG) of the calf muscles to detect blood volume changes (based on total hemoglobin concentration) in the muscle during volitional tiptoe movements at different frequencies. Also, blood volume changes were measured during NMES (using the geko™ device) at different device settings. In the mNIRS+NMES study, we also measured the cerebral hemodynamics using functional NIRS (fNIRS). The mNIRS was conducted using a frequency domain (FD) method (called FDNIRS) that used a multi-distance method to isolate muscle hemodynamics. FDNIRS-EMG study in ten healthy humans found a statistically significant (p<0.05) effect of the tiptoe frequencies on the EMG magnitude (and power) that increased with tiptoe frequency. Also, the muscle blood volume (standing/rest) decreased (p<0.01) with increasing tiptoe frequency and increasing NMES intensity that was statistically significantly (p<0.05) different between males and females. Moreover, increasing NMES intensity led to a statistically significant (p<0.01) increase in the cerebral blood volume - measured with fNIRS. Therefore, combined mNIRS and fNIRS with NMES can provide a theranostics application for brain+muscle in CVI.

A Non-invasive Radial Arterial Compliance Measuring Method using Bio-Impedance.

Arterial compliance is one of the essential indicators of certain types of cardiovascular disease, with both systematic and local compliance exhibiting significance. Radial arterial compliance (RAC) has been regarded as an important type of local compliance in several long-term pathophysiological studies. Bio-Impedance (Bio-Z) is a non-invasive signal which can be used to unobtrusively monitor blood volume changes, captured using wearable sensors. In this paper, a compliance monitoring technique based on Bio-Z is proposed for long-term RAC measurements. Both the distensibility-blood pressure (BP) relation and compliance-mean artery pressure relation are analyzed to observe interparticipant compliance variations from four healthy participants, by controlling the blood flow in a way similar to the oscillometric method for BP measurement. A Bio-Z based compliance index (DBZI) is proposed that can be leveraged for continuous and unobtrusive sensing paradigms. A consecutive seven-day experiment shows that the mean and standard deviation values of the difference between the median value of the Bio-Z based beat-by-beat calculated compliance and DBZI are 0.17 and 0.20 mOhm/mmHg, respectively. This demonstrates the consistency and repeatability of the measurements. The results show that DBZI can track the Bio-Z based compliance with an error of 9.72% and 11.67%, compared to a gold standard, in terms of mean and standard deviation, respectively.

Complementary Role of Oxytocin and Vasopressin in Cardiovascular Regulation.

The neurons secreting oxytocin (OXY) and vasopressin (AVP) are located mainly in the supraoptic, paraventricular, and suprachiasmatic nucleus of the brain. Oxytocinergic and vasopressinergic projections reach several regions of the brain and the spinal cord. Both peptides are released from axons, soma, and dendrites and modulate the excitability of other neuroregulatory pathways. The synthesis and action of OXY and AVP in the peripheral organs (eye, heart, gastrointestinal system) is being investigated. The secretion of OXY and AVP is influenced by changes in body fluid osmolality, blood volume, blood pressure, hypoxia, and stress. Vasopressin interacts with three subtypes of receptors: V1aR, V1bR, and V2R whereas oxytocin activates its own OXTR and V1aR receptors. AVP and OXY receptors are present in several regions of the brain (cortex, hypothalamus, pons, medulla, and cerebellum) and in the peripheral organs (heart, lungs, carotid bodies, kidneys, adrenal glands, pancreas, gastrointestinal tract, ovaries, uterus, thymus). Hypertension, myocardial infarction, and coexisting factors, such as pain and stress, have a significant impact on the secretion of oxytocin and vasopressin and on the expression of their receptors. The inappropriate regulation of oxytocin and vasopressin secretion during ischemia, hypoxia/hypercapnia, inflammation, pain, and stress may play a significant role in the pathogenesis of cardiovascular diseases.

Quantitate Image Responses in High Risk p16+ Oropharyngeal Cancer Patients Treated With Definitive ChemoRT and Concurrent Nivolumab Compared to ChemoRT Alone

Biomarkers of immunotherapy response are increasingly important in oropharyngeal cancer with the rapid expansion of treatment in the R/M population and many ongoing upfront trials. CPS score is the most commonly used method to quantify immune infiltration and predict response to immunotherapy, although limited by its static nature and sampling error. Previous studies show that pre-RT to mid-treatment changes in MRI-derived blood volume (BV) and apparent diffusion coefficient (ADC) as well as FDG-PET derived metabolic tumor volume (MTV) and total lesion glycolysis (TLG) serve as imaging markers for pattern failure of HNC treated by CRT. The goal of this study is to evaluate changes in image metrics during concurrent immunotherapy and CRT compared to those from CRT.MRI and FDG-PET scans were acquired pre- and mid-treatment (fx 10) from 75 patients with high risk p16+ OPSCC (AJCC stage 3 or "matted nodes") who were treated with definitive concurrent CRT on 2 prospective institutional trials. The patients included: 1) the first 15 patients treated with definitive CRT 70Gy/concurrent carboplatin/taxol and concurrent nivolumab (iCRT) and 2) 60 patients treated with 70-80Gy/concurrent weekly cisplatin/carboplatin (CRT). Changes in quantitative image metrics from pre- to mid-treatment of primary tumors and individual lymph nodes were evaluated: gross tumor volume (GTV), MTV at 50% max SUV, TLG, mean SUV, mean BV and ADC between the two treatment groups using unpaired t test.Clinical characteristics and baseline quantitative image metrics were similar between CRT and iCRT groups, except the iCRT group had a lower BV value of primary tumors and a greater MTV of nodal tumors than CRT group (P = 0.05). However, at mid-treatment, iCRT patients had: 1) significantly greater increases in mean BV and ADC of primary tumors than CRT patients (49% vs. 23% and 21% vs. 12%, P < 0.007 and 0.03, respectively); but 2) less decreases in MTV, TLG and mean SUV of primary tumors than CRT patients, for which 11% of the TLG decrease was significantly different from 43% decrease of CRT group (P < 0.05); and 3) 12% decrease in mean SUV of nodal tumors that was significantly less than 25% in CRT group (P < 0.0001). With a mean follow-up of 11 months in the iCRT group, there has been only 1 DM in a patient with persistent low BV in the primary tumor, consistent with our previous findings in CRT patients.This analysis suggests that high risk p16+ OPSCC patients treated with iCRT had larger increases in BV and ADC and a smaller decrease in TLG in primary tumors mid-treatment compared to CRT group. Increases in BV and ADC have been identified to be associated with improved tumor control by previous studies of CRT. The minimal reduction of FDG metrics of iCRT group may be due to inflammatory response to anti-PD1. These findings warrant further investigation as predictive biomarkers for iCRT response to treatment.

Flexible and Robust 3D a‐SiGe Radial Junction Near‐Infrared Photodetectors for Rapid Sphygmic Signal Monitoring

AbstractFlexible near‐infrared (NIR) photodetectors (PDs) are desired for accurate heart rate monitoring, based directly on arterial‐blood‐volume‐change detection, instead of indirect oximetry technology. In this work, a robust 3D construction of flexible a‐SiGe:H p‐i‐n radial junction (RJ) PDs is explored directly upon soft Al foils, working at NIR wavelength 800 nm, which has the highest skin transparency and the least absorption difference from oxyhemoglobin and deoxyhemoglobin variation. The 3D a‐SiGe:H RJ‐PDs demonstrate excellent flexibility and mechanical stability that can undergo 1000‐times bending to 10 mm radius, with a high responsivity of ≈140 mA W−1@800 nm and rise/fall time scales of 5.4 µs/17.6 µs (3.6 µs/13.2 µs before bending). Successful photoplethysmography (PPG) detection of sphygmic signals is achieved at the wrist with significant arterial blood volume changes, working in reflectance mode and using a single NIR source @800 nm. These unique capabilities, enabled by the a‐SiGe:H RJ, have a promising potential to establish a reliable and convenient PPG detection technology, which can help to extract the heartbeat via solely arterial blood volume change, as a complementary and potentially very useful new diagnostic dimension for efficient and accurate real‐time health monitoring.

Grey-box modeling and hypothesis testing of functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal high-definition tDCS in healthy humans

Transcranial direct current stimulation (tDCS) has been shown to evoke hemodynamics response; however, the mechanisms have not been investigated systematically using systems biology approaches. Our study presents a grey-box linear model that was developed from a physiologically detailed multi-compartmental neurovascular unit model consisting of the vascular smooth muscle, perivascular space, synaptic space, and astrocyte glial cell. Then, model linearization was performed on the physiologically detailed nonlinear model to find appropriate complexity (Akaike information criterion) to fit functional near-infrared spectroscopy (fNIRS) based measure of blood volume changes, called cerebrovascular reactivity (CVR), to high-definition (HD) tDCS. The grey-box linear model was applied on the fNIRS-based CVR during the first 150 seconds of anodal HD-tDCS in eleven healthy humans. The grey-box linear models for each of the four nested pathways starting from tDCS scalp current density that perturbed synaptic potassium released from active neurons for Pathway 1, astrocytic transmembrane current for Pathway 2, perivascular potassium concentration for Pathway 3, and voltage-gated ion channel current on the smooth muscle cell for Pathway 4 were fitted to the total hemoglobin concentration (tHb) changes from optodes in the vicinity of 4x1 HD-tDCS electrodes as well as on the contralateral sensorimotor cortex. We found that the tDCS perturbation Pathway 3 presented the least mean square error (MSE, median <2.5%) and the lowest Akaike information criterion (AIC, median -1.726) from the individual grey-box linear model fitting at the targeted-region. Then, minimal realization transfer function with reduced-order approximations of the grey-box model pathways was fitted to the ensemble average tHb time series. Again, Pathway 3 with nine poles and two zeros (all free parameters), provided the best Goodness of Fit of 0.0078 for Chi-Square difference test of nested pathways. Therefore, our study provided a systems biology approach to investigate the initial transient hemodynamic response to tDCS based on fNIRS tHb data. Future studies need to investigate the steady-state responses, including steady-state oscillations found to be driven by calcium dynamics, where transcranial alternating current stimulation may provide frequency-dependent physiological entrainment for system identification. We postulate that such a mechanistic understanding from system identification of the hemodynamics response to transcranial electrical stimulation can facilitate adequate delivery of the current density to the neurovascular tissue under simultaneous portable imaging in various cerebrovascular diseases.

Techniques of Recording Photoplethysmographic Signals

Abstract The photoplethysmography optically measures blood volume changes within micro vascular tissue. Furthermore, photoplethysmographic signals are used within pulse oximeters in order to calculate the oxygen saturation of the blood. This standard measurement technique is performed as a non-invasive spot check method for human health conditions in hospitals or other health care facilities. Usually at least two light sources are used alternating in order to measure photoplethysmograms at different wavelengths. In this paper we will investigate different methods of optically recording photoplethysmographic signals.

Characterization of cortical hemodynamic changes following sensory, visual, and speech activation by intraoperative optical imaging utilizing phase-based evaluation methods.

Alterations within cerebral hemodynamics are the intrinsic signal source for a wide variety of neuroimaging techniques. Stimulation of specific functions leads due to neurovascular coupling, to changes in regional cerebral blood flow, oxygenation and volume. In this study, we investigated the temporal characteristics of cortical hemodynamic responses following electrical, tactile, visual, and speech activation for different stimulation paradigms using Intraoperative Optical Imaging (IOI). Image datasets from a total of 22 patients that underwent surgical resection of brain tumors were evaluated. The measured reflectance changes at different light wavelength bands, representing alterations in regional cortical blood volume (CBV), and deoxyhemoglobin (HbR) concentration, were assessed by using Fourier‐based evaluation methods. We found a decrease of CBV connected to an increase of HbR within the contralateral primary sensory cortex (SI) in patients that were prolonged (30 s/15 s) electrically stimulated. Additionally, we found differences in amplitude as well as localization of activated areas for different stimulation patterns. Contrary to electrical stimulation, prolonged tactile as well as prolonged visual stimulation are provoking increases in CBV within the corresponding activated areas (SI, visual cortex). The processing of the acquired data from awake patients performing speech tasks reveals areas with increased, as well as areas with decreased CBV. The results lead us to the conclusion, that the CBV decreases in connection with HbR increases in SI are associated to processing of nociceptive stimuli and that stimulation type, as well as paradigm have a nonnegligible impact on the temporal characteristics of the following hemodynamic response.

Comprehensive Physiological Modeling Provides Novel Insights Into Heart Failure With Preserved Ejection Fraction Physiology.

BackgroundAlthough a rapid rise in left atrial pressure during exertion is considered pathognomonic of heart failure with preserved ejection fraction (HFpEF), the fundamental circulatory determinants of this response are not clear, impacting upon the development of more effective therapies. We aimed to comprehensively describe the circulatory mechanics of patients with HFpEF at rest and during exercise in comparison with controls.Methods and ResultsWe performed simultaneous right‐heart catheterization and echocardiography at rest and during exercise in 22 healthy control volunteers and 60 patients with confirmed HFpEF. Using detailed individual patient‐level hemodynamic and left ventricular ejection fraction data we performed computer simulations to evaluate the circulatory parameters including the estimated stressed blood volumethat contribute to the resting and exercise pulmonary capillary pressure. At rest and during exercise, left ventricular stiffness (V30, the end‐diastolic pressure–volume relationship at a filling pressure of 30 mm Hg), left ventricular elastance, and arterial elastance were all significantly greater in HFpEF than in controls. Stressed blood volume was significantly greater in HFpEF (26.9±5.4 versus 20.2±4.7 mL/kg, P<0.001), becoming even more pronounced during exercise (40.9±3.7 versus 27.5±7.0 mL per 70 kg, P<0.001). During exercise, the magnitude of the change in stressed blood volume (r=0.67, P<0.001) and left ventricular stiffness (r=−0.44, P<0.001) were key determinants of the rise in pulmonary capillary wedge pressure. Further detailed modeling studies showed that the hemodynamic response to exercise results from a complex non‐linear interaction between circulatory parameters.ConclusionsThe circulatory determinants of HFpEF physiology are complex. We identified stressed blood volume at rest and during exercise is a novel, key factor, therebyrepresenting an important potential therapeutic target.