Bio-Impedance Measurement Optimization for High-Resolution Carotid Pulse Sensing.

Continuous hemodynamic monitoring is important for long-term cardiovascular healthcare, especially in hypertension. The impedance plethysmography (IPG) based carotid pulse sensing is a non-invasive diagnosis technique for measuring pulse signals and further evaluating the arterial conditions of the patient such as continuous blood pressure (BP) monitoring. To reach the high-resolution IPG-based carotid pulse detection for cardiovascular applications, this study provides an optimized measurement parameter in response to obvious pulsation from the carotid artery. The influence of the frequency of excitation current, electrode cross-sectional area, electrode arrangements, and physiological site of carotid arteries on IPG measurement resolution was thoroughly investigated for optimized parameters. In this study, the IPG system was implemented and installed on the subject's neck above the carotid artery to evaluate the measurement parameters. The measurement results within 6 subjects obtained the arterial impedance variation of 2137 mΩ using the optimized measurement conditions, including excitation frequency of 50 kHz, a smaller area of 2 cm2, electrode spacing of 4 cm and 1.7 cm for excitation and sensing functions, and location on the left side of the neck. The significance of this study demonstrates an optimized measurement methodology of IPG-based carotid pulse sensing that greatly improves the measurement quality in cardiovascular monitoring.

In vivo third-harmonic generation microscopy study on vitiligo patients.

Melanin is known to provide strong third-harmonic generation (THG) contrast in human skin. With a high concentration in basal cell cytoplasm, THG contrast provided by melanin overshadows other THG sources in human skin studies. For better understanding of the THG signals in keratinocytes without the influence of melanin, an in vivo THG microscopy (THGM) study was first conducted on vitiliginous skin. As a result, the THG-brightness ratio between the melanin-lacking cytoplasm of basal cells and collagen fibers is about 1.106 at the dermal-epidermal junctions of vitiliginous skin, indicating high sensitivity of THGM for the presence of melanin. We further applied the in vivo THGM to assist evaluating the therapeutic outcome from the histopathological point of view for those showed no improvement under narrowband ultraviolet B therapy based on the seven-point Physician Global Assessment score. Our clinical study indicates the high potential of THGM to assist the histopathological assessment of the therapeutic efficacy of vitiligo treatments.

Classification of established atopic dermatitis in children with the in vivo imaging methods.

Atopic dermatitis (AD) is a cutaneous disease resulting from a defective barrier and dysregulated immune response. The severity scoring of atopic dermatitis (SCORAD) is used to classify AD. Noninvasive imaging approaches supplementary to SCORAD were investigated. Cr:forsterite laser-based microscopy was employed to analyze endogenous third-harmonic generation (THG) and second-harmonic generation (SHG) signals from skin. Imaging parameters were compared between different AD severities. Three-dimensional reconstruction of imaged skin layers was performed. Finally, statistic models from quantitative imaging parameters were developed for predicting disease severity. Our data demonstrate that THG signal intensity of lesional skin in AD were significantly increased and was positively correlated with AD severity. Characteristic gray level co-occurrence matrix (GLCM) values were observed in more severe AD. In the 3D reconstruction video, individual dermal papilla and obvious fibrosis in the upper papillary dermis were easily identified. Our estimation models could predict the disease severity of AD patients with an accuracy of nearly 85%. The THG signal intensity and characteristic GLCM patterns are associated with AD severity and can serve as quantitative predictive parameters. Our imaging approach can be used to identify the histopathological changes of AD objectively, and to complement the SCORAD index, thus improving the accuracy of classifying AD severity.

Prognostic significance of mechanical biomarkers derived from pulse wave analysis for predicting long-term cardiovascular mortality in two population-based cohorts.

BACKGROUND: Numerous mechanical biomarkers derived from pulse wave analysis (PWA) have been proposed to predict cardiovascular outcomes. However, whether these biomarkers carry independent prognostic value and clinical utility beyond traditional cardiovascular risk factors hasn't been systematically evaluated. We aimed to investigate the additive utility of PWA-derived biomarkers in two independent population-based cohorts. METHODS: PWA on central arterial pressure waveforms obtained from subjects without a prior history of cardiovascular diseases of two studies was conducted based on the wave transmission and reservoir-wave theory: firstly in the Kinmen study (1272 individuals, a median follow-up of 19.8years); and then in the Cardiovascular Disease Risk Factors Two-Township Study (2221 individuals, median follow-up of 10years). The incremental value of the biomarkers was evaluated by net reclassification index (NRI). RESULTS: In multivariate Cox analyses accounting for age, gender, body mass index, systolic blood pressure, fasting glucose, high-density- and low-density-lipoprotein cholesterol, and smoking, only systolic (SC) and diastolic rate constant (DC) of reservoir pressure could independently and consistently predict cardiovascular mortality in both cohorts and the combined cohort (SC: hazard ratio 1.18 [95% confidence interval 1.08-1.28, p<0.001; DC: 1.18 [1.09-1.28], p<0.001]. Risk prediction estimates in traditional risk prediction models were significantly more accurate when incorporating peak of reservoir pressure (NRI=0.049, p=0.0361), SC (NRI=0.043, p=0.0236) and DC (NRI=0.054, p=0.047). CONCLUSIONS: Of all PWA-derived biomarkers, SC and DC were consistently identified as valuable parameters for incremental cardiovascular risk prediction in two large prospective cohorts.

Is Noninvasive Brachial Systolic Blood Pressure an Accurate Estimate of Central Aortic Systolic Blood Pressure?

OBJECTIVES: Noninvasive brachial systolic blood pressure (nSBP-B) usually approaches invasive central systolic blood pressure (iSBP-C) with a high correlation. Whether nSBP-B is an accurate estimate of iSBP-C remained to be investigated. Thus, this study aimed to compare the errors of nSBP-B and noninvasive central systolic blood pressure (nSBP-C) with different techniques in estimating iSBP-C. METHODS: Simultaneous invasive high-fidelity central aortic pressure waveforms and the noninvasive left brachial pulse volume recording (PVR) waveform were recorded in a Generation group ( N = 40) and a Validation group ( N = 100). The accuracy of the noninvasive estimates of iSBP-C obtained from analysis of the calibrated PVR waveform using the generalized transfer function (GTF), pulse waveform analysis (PWA), and N-point moving average (NPMA) methods was examined in the Validation group by calculating the mean absolute error (MAE). RESULTS: In Generation group, the MAE was 4.6±4.1mm Hg between nSBP-B and invasive brachial SBP, and 6.8±5.5mm Hg between nSBP-B and iSBP-C. In comparison, the MAE of between iSBP-C and nSBP-C with PWA, NPMA, and GTF were 5.5±4.5, 5.8±4.9, and 5.9±5.0mm Hg, respectively. In Validation group, the MAE of nSBP-B (6.9±4.6mm Hg) for estimating iSBP-C was significantly greater than that of PWA (5.0±3.4mm Hg) and NPMA (6.1±4.4mm Hg), and GTF (6.1±4.9mm Hg). The percentage of absolute band error ≤5mm Hg was 62% for nSBP-B, 69% for GTF, 83% for PWA, and 69% for NPMA. CONCLUSIONS: The accuracy of nSBP-B was inferior to the n SBP-C measures in estimating iSBP-C.

Near-field sub-THz transmission-type image system for vessel imaging in-vivo.

A THz near-field transmission imaging system was successfully demonstrated to image the vessels inside the ears of nude mice in vivo. Wave-guided illumination and near-field scanning detection with a sub-wavelength aperture were applied. An operating frequency of 340 GHz was chosen to achieve a higher penetration depth in tissues with a reasonable signal-to-noise ratio. The near-field pattern of the power transmittance through the vessel was also numerically simulated and showed good correspondence to the measured results. The capability of the system for long-term monitoring in vivo was also demonstrated.

Quantitative analysis of intrinsic skin aging in dermal papillae by in vivo harmonic generation microscopy.

Chronological skin aging is associated with flattening of the dermal-epidermal junction (DEJ), but to date no quantitative analysis focusing on the aging changes in the dermal papillae (DP) has been performed. The aim of the study is to determine the architectural changes and the collagen density related to chronological aging in the dermal papilla zone (DPZ) by in vivo harmonic generation microscopy (HGM) with a sub-femtoliter spatial resolution. We recruited 48 Asian subjects and obtained in vivo images on the sun-protected volar forearm. Six parameters were defined to quantify 3D morphological changes of the DPZ, which we analyzed both manually and computationally to study their correlation with age. The depth of DPZ, the average height of isolated DP, and the 3D interdigitation index decreased with age, while DP number density, DP volume, and the collagen density in DP remained constant over time. In vivo high-resolution HGM technology has uncovered chronological aging-related variations in DP, and sheds light on real-time quantitative skin fragility assessment and disease diagnostics based on collagen density and morphology.

Application of the N-point moving average method for brachial pressure waveform-derived estimation of central aortic systolic pressure.

The N-point moving average (NPMA) is a mathematical low-pass filter that can smooth peaked noninvasively acquired radial pressure waveforms to estimate central aortic systolic pressure using a common denominator of N/4 (where N=the acquisition sampling frequency). The present study investigated whether the NPMA method can be applied to brachial pressure waveforms. In the derivation group, simultaneously recorded invasive high-fidelity brachial and central aortic pressure waveforms from 40 subjects were analyzed to identify the best common denominator. In the validation group, the NPMA method with the obtained common denominator was applied on noninvasive brachial pressure waveforms of 100 subjects. Validity was tested by comparing the noninvasive with the simultaneously recorded invasive central aortic systolic pressure. Noninvasive brachial pressure waveforms were calibrated to the cuff systolic and diastolic blood pressures. In the derivation study, an optimal denominator of N/6 was identified for NPMA to derive central aortic systolic pressure. The mean difference between the invasively/noninvasively estimated (N/6) and invasively measured central aortic systolic pressure was 0.1±3.5 and -0.6±7.6 mm Hg in the derivation and validation study, respectively. It satisfied the Association for the Advancement of Medical Instrumentation standard of 5±8 mm Hg. In conclusion, this method for estimating central aortic systolic pressure using either invasive or noninvasive brachial pressure waves requires a common denominator of N/6. By integrating the NPMA method into the ordinary oscillometric blood pressure determining process, convenient noninvasive central aortic systolic pressure values could be obtained with acceptable accuracy.

Measurement accuracy of a stand-alone oscillometric central blood pressure monitor: a validation report for Microlife WatchBP Office Central.

BACKGROUND: The superiority of prognostic value of blood pressure (BP) measured at central aorta (CBP) over conventional brachial BP measured by cuff-based BP monitors has reignited the development of new noninvasive techniques for estimating CBP. The present study validated the accuracy of CBP measured by a newly developed stand-alone CBP monitor. METHODS: The CBP monitor provided readings of brachial systolic BP (SBP), brachial diastolic BP (DBP), central SBP, and central pulse pressure (PP). Brachial PP and central DBP were calculated from the relevant readings. The accuracy of the brachial and central SBP, PP, and DBP was validated against the simultaneously recorded invasively measured central aortic SBP, PP, and DBP, according to the invasive standard requirements for the noninvasive brachial BP monitors from the Association for the Advancement of Medical Instrumentation (AAMI) in 85 subjects (255 measurements; age range, 30-93 years). RESULTS: The mean differences of cuff BP with reference to the invasively measured central SBP, PP, and DBP were -2.6 ± 9.0, -8.6 ± 11.2, and 6.1 ± 7.0 mm Hg, respectively, with the former two being obviously underestimated at high CBP and overestimated at low CBP. In contrast, the corresponding differences for the central SBP, PP, and DBP measured by the CBP monitor were -0.6 ± 5.5, -0.4 ± 7.0, and -0.2 ± 6.5 mm Hg, respectively, without obvious systematic bias. The distribution of measurement errors for central SBP, PP, and DBP surpassed the AAMI criteria. CONCLUSION: Central SBP, PP, and DBP can be measured accurately by a stand-alone automatic BP monitor.

Resistance exercise training reduces arterial reservoir pressure in older adults with prehypertension and hypertension.

We examined changes in central blood pressure (BP) following resistance exercise training (RET) in men and women with prehypertension and never-treated hypertension. Both Windkessel theory and wave theory were used to provide a comprehensive examination of hemodynamic modulation with RET. Twenty-one participants (age 61±1 years, n=6 male; average systolic blood pressure (SBP)/diastolic blood pressure (DBP)=138/84 mm Hg) were randomized to either 12 weeks of RET (n=11) or an inactive control group. Central BP and augmentation index (AIx) were derived from radial pressure waveforms using tonometry and a generalized transfer function. A novel reservoir-wave separation technique was used to derive excess wave pressure (related to forward and backward traveling waves) and reservoir pressure (related to the capacitance/Windkessel properties of the arterial tree). Wave separation using traditional impedance analysis and aortic flow triangulation was also applied to derive forward wave pressure (Pf) and backward wave pressure (Pb). There was a group-by-time interaction (P<0.05) for central BP as there was a significant ~6 mm Hg reduction in SBP and ~7 mm Hg reduction in DBP following RET with no change in the control condition. There were also group-by-time interactions (P<0.05) for Pf, excess wave pressure and reservoir pressure attributable to reductions in these parameters in the RET group concomitant with slight increases in the control group. There was no change in AIx or Pb (P>0.05). RET may reduce central BP in older adults with hypertension and prehypertension by lowering Pf and reservoir pressure without affecting pressure from wave reflections.

Virtual spatial overlap modulation microscopy for resolution improvement.

High spatial and temporal resolutions are important advantages of optical imaging over other modalities. The recently developed spatial overlap modulation (SPOM) microscopy enables high resolution imaging by spatial modulation of double-beam overlap. However, SPOM suffers from bad temporal resolution and high system complexity. In this paper, we re-formulate the SPOM resolution theory and develop Virtual SPOM (vSPOM) microscopy. By one-way oversampling and convolution with differential filters, vSPOM not only realizes the same factor of spatial resolution improvement as SPOM, but overcome SPOM's major drawbacks. We demonstrated vSPOM on in vivo clinical images and find that the Gabor filter, which represents two-beam vSPOM, is the most effective among all vSPOM filters. The development of vSPOM enables easy incorporation of SPOM into any imaging system, and extends the use of SPOM to real-time in vivo applications.

Measurement of central aortic pulse pressure: noninvasive brachial cuff-based estimation by a transfer function vs. a novel pulse wave analysis method.

BACKGROUND: The prognostic value of central aortic pulse pressure (PP-C) may have been underestimated due to its measurement inaccuracy. We aimed to investigate the accuracy of noninvasive brachial cuff-based estimation of PP-C by a generalized transfer function (GTF) or a novel pulse wave analysis (PWA) approach to directly estimate PP-C. METHODS: Invasive high-fidelity right brachial and central aortic pressure tracings, and left brachial pulse volume plethysmography (PVP) waveforms from an oscillometric blood pressure (BP) monitor were all digitized simultaneously in 40 patients during cardiac catheterization. An aortic-to-brachial GTF and a PWA multivariate prediction model using the PVP waveforms calibrated to brachial cuff systolic BP (SBP) and diastolic BP(DBP) were constructed. Accuracy of the two methods was examined in another 100 patients against invasively measured PP-C. RESULTS: The error of cuff PP in estimating PP-C was 1.8 ± 12.4 mm Hg. Application of the GTF on noninvasively calibrated PVP waveforms produced reconstructed aortic pressure waves and PP-C estimates with errors of -3.4 ± 11.6 mm Hg (PP-C = reconstructed aortic SBP - aortic DBP) and -2.3 ± 11.4 mm Hg (PP-C = reconstructed aortic SBP - cuff DBP), respectively. The observed systematic errors were proportional to the magnitudes of PP-C. In contrast, the error of the PWA prediction model was 3.0 ± 7.1 mm Hg without obvious proportional systematic error. CONCLUSIONS: Large random and systematic errors are introduced into the PP-C estimates when PP-C is calculated as the difference between the estimated central SBP and central or cuff DBP. The accuracy can be improved substantially with the novel PWA approach.

Measurement of central systolic blood pressure by pulse volume plethysmography with a noninvasive blood pressure monitor.

BACKGROUND: Central systolic blood pressure (SBP) can be estimated by an oscillometric method developed from a pulse volume plethysmography (PVP) device. The present study applied this novel method to a noninvasive blood pressure monitor (NBPM). METHODS: We enrolled 50 patients (37 men, age range 30-84 years) referred for cardiac catheterization. Invasive right brachial and central aortic pressures (using a dual-sensor pressure catheter), and noninvasive left brachial SBP and diastolic blood pressure (DBP), and PVP waveform (using a customized NBPM) were simultaneously recorded. Central SBP was estimated by analysis of the PVP waveform calibrated to the noninvasive SBP and DBP, using both the original (CSBP-O) and the newly generated (CSBP-N) regression equations. The reproducibility of the invasive central SBP by CSBP-O and CSBP-N was examined using the concordance correlation coefficient. RESULTS: Overall, the invasive central aortic SBP ranged 86-176 with a mean of 124 ± 21 mm Hg. The mean differences between the estimated and the invasive central SBP were -1.3 ± 6.7 mm Hg for CSBP-O and 0.0 ± 6.2 mm Hg for CSBP-N, respectively. The concordance correlation coefficients for CSBP-O and CSBP-N were 0.94 (95% confidence interval (CI): 0.93-0.94) and 0.95 (95% CI: 0.95-0.96), and both were significantly better than that for the noninvasive brachial SBP (0.87, 0.84-0.91) indicated by non-overlapping CIs. CONCLUSIONS: The PVP method for noninvasive estimation of central SBP can be applied to a commonly used NBPM. Whether the NBPM-derived central SBP is superior to the noninvasive brachial SBP in the prediction of cardiovascular risks remains to be investigated.

Quantification of the calibration error in the transfer function-derived central aortic blood pressures.

BACKGROUND: The accuracy of the central aortic systolic (SBP-C) and pulse (PP-C) blood pressures estimated noninvasively by a generalized transfer function technique has been questioned. The purpose of the present study was to quantify precisely the impact of the input errors (differences between the oscillometric (SBP-O, DBP-O, PP-O) and invasive (SBP-B, DBP-B, PP-B) brachial systolic, diastolic, and pulse blood pressures) on the output errors (differences between the estimated and invasively measured SBP-C and PP-C). METHODS: Invasive high-fidelity right brachial and central aortic pressure waveforms, and SBP-O, DBP-O, and PP-O (=SBP-O - DBP-O) were obtained simultaneously in 40 patients during cardiac catheterization. A generalized transfer function was applied on the individual brachial pressure waveform to derive predicted SBP-C and PP-C. RESULTS: Observed input errors were -2.3 ± 5.8 mm Hg from SBP-O, 8.1 ± 5.3 mm Hg from DBP-O, and -10.4 ± 7.1 mm Hg from PP-O, respectively. The output errors were -2.2 ± 6.4 mm Hg and -10.3 ± 8.0 mm Hg for SBP-C and PP-C, respectively, when the brachial pressure waveforms were recalibrated using SBP-O and DBP-O. The outputs were determined by the inputs according to the Equation (1): SBP-C error = 0.97 × SBP-O error + 0.03 (r = 0.88, P < 0.01); and the Equation (2): PP-C error = 0.96 × PP-O error - 0.30 (r = 0.86, P < 0.01). CONCLUSIONS: Noninvasive application of the generalized transfer function techniques produces estimates of SBP-C and PP-C with errors equivalent to those of the oscillometric blood pressure monitor in the estimation of SBP-B and PP-B. The output errors can be predicted from input errors of SBP-O and DBP-O.