ResearchPad - blood-flow https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Direct comparison of activation maps during galvanic vestibular stimulation: A hybrid H<sub>2</sub>[<sup>15</sup> O] PET—BOLD MRI activation study]]> https://www.researchpad.co/article/elastic_article_14749 Previous unimodal PET and fMRI studies in humans revealed a reproducible vestibular brain activation pattern, but with variations in its weighting and expansiveness. Hybrid studies minimizing methodological variations at baseline conditions are rare and still lacking for task-based designs. Thus, we applied for the first time hybrid 3T PET-MRI scanning (Siemens mMR) in healthy volunteers using galvanic vestibular stimulation (GVS) in healthy volunteers in order to directly compare H215O-PET and BOLD MRI responses. List mode PET acquisition started with the injection of 750 MBq H215O simultaneously to MRI EPI sequences. Group-level statistical parametric maps were generated for GVS vs. rest contrasts of PET, MR-onset (event-related), and MR-block. All contrasts showed a similar bilateral vestibular activation pattern with remarkable proximity of activation foci. Both BOLD contrasts gave more bilateral wide-spread activation clusters than PET; no area showed contradictory signal responses. PET still confirmed the right-hemispheric lateralization of the vestibular system, whereas BOLD-onset revealed only a tendency. The reciprocal inhibitory visual-vestibular interaction concept was confirmed by PET signal decreases in primary and secondary visual cortices, and BOLD-block decreases in secondary visual areas. In conclusion, MRI activation maps contained a mixture of CBF measured using H215O-PET and additional non-CBF effects, and the activation-deactivation pattern of the BOLD-block appears to be more similar to the H215O-PET than the BOLD-onset.

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<![CDATA[A three-dimensional phase-field model for multiscale modeling of thrombus biomechanics in blood vessels]]> https://www.researchpad.co/article/elastic_article_14644 Thromboembolism is associated with detachment of small thrombus pieces from the bulk in the blood vessel. These detached pieces, also known as emboli, travel through the blood flow and may block other vessels downstream, e.g., they may plug the deep veins of the leg, groin or arm, leading to venous thromboembolism (VTE). VTE is a significant cause of morbidity and mortality and it affects more than 900,000 people in the United States and result in approximately 100,000 deaths every year. Mechanical interaction between flowing blood and a thrombus is crucial in determining the deformation of the thrombus and the possibility of releasing emboli. In this study, we develop a phase-field model that is capable of describing the structural properties of a thrombus and its biomechanical properties under different blood flow conditions. Moreover, we combine this thrombus model with a particle-based model which simulates the initiation of the thrombus. This combined framework is the first computational study to simulate the development of a thrombus from platelet aggregation to its subsequent viscoelastic responses to various shear flows. Informed by clinical data, this framework can be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions.

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<![CDATA[Cerebral Blood Flow Response to Simulated Hypovolemia in Essential Hypertension]]> https://www.researchpad.co/article/N1af6c3db-82a7-481e-93d4-14d77b5755d5

Supplemental Digital Content is available in the text.

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<![CDATA[A novel visual ranking system based on arterial spin labeling perfusion imaging for evaluating perfusion disturbance in patients with ischemic stroke]]> https://www.researchpad.co/article/N32085c18-73a0-407b-8668-9d011597efb2

We developed a visual ranking system by combining the parenchymal perfusion deficits (PPD) and hyperintense vessel signals (HVS) on arterial spin labeling (ASL) imaging. This study aimed to assess the performance of this ranking system by correlating with subtypes classified based on dynamic susceptibility contrast (DSC) imaging for evaluating the perfusion disturbance observed in patients with ischemic stroke. 32 patients with acute or subacute infarcts detected by DSC imaging were reviewed. Each patient’s brain was divided into 12 areas. ASL ranks were defined by the presence (+) or absence (-) of PPD/HVS as follows; I:–/–, II:–/+, III: +/+, and IV: +/–. DSC imaging findings were categorized based on cerebral blood flow (CBF) and time to peak (TTP) as normal (normal CBF/TTP), mismatched (normal CBF/delayed TTP), and matched (decreased CBF/delayed TTP). Two reviewers rated perfusion abnormalities in the total of 384 areas. The four ASL ranks correlated well with the DSC subtypes (Spearman’s r = 0.82). The performance of ASL ranking system was excellent as indicated by the area under the curve value of 0.94 using either matched or mismatched DSC subtype as the gold standard and 0.97 using only the matched DSC subtype as the gold standard. The two methods were in good-to-excellent agreement (maximum κ-values, 0.86). Inter-observer agreement was excellent (κ-value, 0.98). Although the number of patients was small and the number of dropouts was high, our proposed, ASL-based visual ranking system represented by PPD and HVS provides good, graded estimates of perfusion disturbance that agree well with those obtained by DSC perfusion imaging.

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<![CDATA[Exploring magnetohydrodynamic voltage distributions in the human body: Preliminary results]]> https://www.researchpad.co/article/5c89777ed5eed0c4847d2e42

Background

The aim of this study was to noninvasively measure regional contributions of vasculature in the human body using magnetohydrodynamic voltages (VMHD) obtained from electrocardiogram (ECG) recordings performed inside MRI’s static magnetic field (B0). Integrating the regional VMHD over the Swave-Twave segment of the cardiac cycle (Vsegment) provides a non-invasive method for measuring regional blood volumes, which can be rapidly obtained during MRI without incurring additional cost.

Methods

VMHD was extracted from 12-lead ECG traces acquired during gradual introduction into a 3T MRI. Regional contributions were computed utilizing weights based on B0’s strength at specified distances from isocenter. Vsegment mapping was performed in six subjects and validated against MR angiograms (MRA).

Results

Fluctuations in Vsegment, which presented as positive trace deflections, were found to be associated with aortic-arch flow in the thoracic cavity, the main branches of the abdominal aorta, and the bifurcation of the common iliac artery. The largest fluctuation corresponded to the location where the aortic arch was approximately orthogonal to B0. The smallest fluctuations corresponded to areas of vasculature that were parallel to B0. Significant correlations (specifically, Spearman’s ranked correlation coefficients of 0.96 and 0.97 for abdominal and thoracic cavities, respectively) were found between the MRA and Vsegment maps (p < 0.001).

Conclusions

A novel non-invasive method to extract regional blood volumes from ECGs was developed and shown to be a rapid means to quantify peripheral and abdominal blood volumes.

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<![CDATA[Frequency-resolved analysis of coherent oscillations of local cerebral blood volume, measured with near-infrared spectroscopy, and systemic arterial pressure in healthy human subjects]]> https://www.researchpad.co/article/5c6c75b8d5eed0c4843d006b

We report a study on twenty-two healthy human subjects of the dynamic relationship between cerebral hemoglobin concentration ([HbT]), measured with near-infrared spectroscopy (NIRS) in the prefrontal cortex, and systemic arterial blood pressure (ABP), measured with finger plethysmography. [HbT] is a measure of local cerebral blood volume (CBV). We induced hemodynamic oscillations at discrete frequencies in the range 0.04–0.20 Hz with cyclic inflation and deflation of pneumatic cuffs wrapped around the subject’s thighs. We modeled the transfer function of ABP and [HbT] in terms of effective arterial (K(a)) and venous (K(v)) compliances, and a cerebral autoregulation time constant (τ(AR)). The mean values (± standard errors) of these parameters across the twenty-two subjects were K(a) = 0.01 ± 0.01 μM/mmHg, K(v) = 0.09 ± 0.05 μM/mmHg, and τ(AR) = 2.2 ± 1.3 s. Spatially resolved measurements in a subset of eight subjects reveal a spatial variability of these parameters that may exceed the inter-subject variability at a set location. This study sheds some light onto the role that ABP and cerebral blood flow (CBF) play in the dynamics of [HbT] measured with NIRS, and paves the way for new non-invasive optical studies of cerebral blood flow and cerebral autoregulation.

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<![CDATA[Association of small fiber neuropathy and post treatment Lyme disease syndrome]]> https://www.researchpad.co/article/5c6c75a6d5eed0c4843cff72

Objectives

To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction.

Methods

This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored.

Results

10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv.

Conclusions

SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

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<![CDATA[Reproducibility and validity of a novel invasive method of assessing peripheral microvascular vasomotor function]]> https://www.researchpad.co/article/5c57e6ddd5eed0c484ef3ffe

In healthy arteries, blood flow is regulated by microvascular tone assessed by changes in blood flow volume and vascular resistance to endothelium-dependent and -independent vasodilators. We developed a novel method of using intravascular ultrasound (IVUS) and a Doppler flow wire to measure changes in blood flow volume and vascular resistance of the profunda arterial bed. We assessed the variability over 6 months in measuring microvascular endothelium-dependent dilation to acetylcholine and endothelium-independent dilation to adenosine in 20 subjects who were part of a larger study of Gulf War Illness without obstructive peripheral artery disease. Vasomotor function was assessed by Infusions of control (dextrose), acetylcholine (10-6M), adenosine (50μg), and nitroglycerin (25μg/ml). 400 IVUS and 240 flow velocity images were measured a mean 6 (SD = 2) months apart blind to measurement and infusion stage. The mean (SD) baseline profunda flow was 227 (172) ml/min and vascular resistance 4.6 x 104 (2.4 x 104) dynes-s/cm5. The intraclass correlation coefficients for 6-month variability for vascular function were excellent (range 0.827–0.995). Bland-Altman analyses showed mean differences of less than 2% for microvascular endothelium-dependent function (flow volume and resistance) and less than 1% for macrovascular endothelium-dependent function with acceptable limits of agreement. In 49 subjects assessing concurrent validity of the technique against atherosclerosis risk factors, we observed greater impairment in microvascular endothelium-dependent function per year of age (flow volume = -1.4% (p = 0.018), vascular resistance = 1.5% (p = 0.015)) and current smoking (flow volume = -36.7% (p = .006), vascular resistance = 50.0% (p<0.001)). This novel method of assessing microvascular vasomotor function had acceptable measurement reproducibility and validity.

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<![CDATA[An optimized low-pressure tourniquet murine hind limb ischemia reperfusion model: Inducing acute ischemia reperfusion injury in C57BL/6 wild type mice]]> https://www.researchpad.co/article/5c536bb5d5eed0c484a49072

Acute ischemia reperfusion injury in skeletal muscle remains an important issue in several fields of regenerative medicine. Thus, a valid model is essential to gain deeper insights into pathophysiological relations and evaluate possible treatment options. While the vascular anatomy of mice regularly prevents sufficient vessel occlusion by invasive methods, there is a multitude of existing models to induce ischemia reperfusion injury without surgical procedures. Since there is no consensus on which model to prefer, this study aims to develop and evaluate a novel, optimized low-pressure tourniquet model. C57BL/6 mice underwent an ischemic procedure by either tourniquet or invasive artery clamping. A sham group served as control. With exception of the sham group, mice underwent 2 hours of ischemia followed by 4 hours of reperfusion. Groups were compared using microcirculatory and spectroscopic measurements, distinctions in tissue edema, histological and immunohistochemical analyses. Both procedures led to a significant decrease in tissue blood flow (- 97% vs. - 86%) and oxygenation (- 87% vs. - 75%) with a superiority of the low-pressure tourniquet. Tissue edema in the tourniquet cohort was significantly increased (+ 59%), while the increase in the clamping cohort was non-significant (+ 7%). Haematoxylin Eosin staining showed significantly more impaired muscle fibers in the tourniquet group (+ 77 p.p. vs. + 11 p.p.) and increased neutrophil infiltration/ROI (+ 51 vs. + 8). Immunofluorescence demonstrated an equal increase of p38 in both groups (7-fold vs. 8-fold), while the increase in apoptotic markers (Caspase-3, 3-Nitrotyrosine, 4-Hydroxynonenal) was significantly higher in the tourniquet group. The low-pressure tourniquet has been proven to produce reproducible and thus reliable ischemia reperfusion injury. In addition, significantly less force was needed than previously stated. It is therefore an important instrument for studying the pathophysiology of ischemia reperfusion injury and for the development of prophylactic as well as therapeutic interventions.

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<![CDATA[Variations in pulsatile flow around stenosed microchannel depending on viscosity]]> https://www.researchpad.co/article/5c5369aed5eed0c484a463f8

In studying blood flow in the vessels, the characteristics of non-Newtonian fluid are important, considering the role of viscosity in rheology. Stenosis, which is an abnormal narrowing of the vessel, has an influence on flow behavior. Therefore, analysis of blood flow in stenosed vessels is essential. However, most of them exist as simulation outcomes. In this study, non-Newtonian fluid was observed in stenosed microchannels under the pulsatile flow condition. A polydimethylsiloxane channel with 60% stenosis was fabricated by combining an optic fiber and a petri dish, resembling a mold. Three types of samples were prepared by changing the concentrations of xanthan gum, which induces a shear thinning effect (phosphate buffered saline (PBS) solution as the Newtonian fluid and two non-Newtonian fluids mimicking normal blood and highly viscous blood analog). The viscosity of the samples was measured using a Y-shaped microfluidic viscometer. Thereafter, velocity profiles were analyzed under the pulsatile flow condition using the micro-particle image velocimetry (PIV) method. For the Newtonian fluid, the streamline was skewed more to the wall of the channel. The velocity profile of the non-Newtonian fluid was generally blunter than that of the Newtonian fluid. A highly oscillating wall shear stress (WSS) during the pulsatile phase may be attributed to such a bluntness of flow under the same wall shear rate condition with the Newtonian fluid. In addition, a highly viscous flow contributes to the variation in the WSS after passing through the stenosed structures. A similar tendency was observed in simulation results. Such a variation in the WSS was associated with plaque instability or rupture and damage of the tissue layer. These results, related to the influence on the damage to the endothelium or stenotic lesion, may help clinicians understand relevant mechanisms.

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<![CDATA[Submaximal exercise cardiac output is increased by 4 weeks of sprint interval training in young healthy males with low initial Q̇-V̇O2: Importance of cardiac response phenotype]]> https://www.researchpad.co/article/5c521807d5eed0c484796650

Cardiovascular adaptations to exercise, particularly at the individual level, remain poorly understood. Previous group level research suggests the relationship between cardiac output and oxygen consumption (Q˙-V˙O2) is unaffected by training as submaximal Q˙ is unchanged. We recently identified substantial inter-individual variation in the exercise Q˙-V˙O2 relationship that was correlated to stroke volume (SV) as opposed to arterial oxygen content. Therefore we explored the effects of sprint interval training (SIT) on modulating Q˙-V˙O2 given an individual’s specific Q˙-V˙O2 relationship. 22 (21±2 yrs) healthy, recreationally active males participated in a 4-week SIT (8, 20 second sprints; 4x/week, 170% of the work rate at V˙O2 peak) study with progressive exercise tests (PET) until exhaustion. Cardiac output (Q˙ L/min; inert gas rebreathe, Finometer Modelflow™), oxygen consumption (V˙O2 L/min; breath-by-breath pulmonary gas exchange), quadriceps oxygenation (near infrared spectroscopy) and exercise tolerance (6–20; Borg Scale RPE) were measured throughout PET both before and after training. Data are mean Δ from bsl±SD. Higher Q˙ (HQ˙) and lower Q˙ (LQ˙) responders were identified post hoc (n = 8/group). SIT increased the Q˙-V˙O2 post-training in LQ˙ (3.8±0.2 vs. 4.7±0.2; P = 0.02) while HQ˙ was unaffected (5.8±0.1 vs. 5.3±0.6; P = 0.5). ΔQ˙ was elevated beyond 80 watts in LQ˙ due to a greater increase in SV (all P<0.04). Peak V˙O2 (ml/kg/min) was increased in LQ˙ (39.7±6.7 vs. 44.5±7.3; P = 0.015) and HQ˙ (47.2±4.4 vs. 52.4±6.0; P = 0.009) following SIT, with HQ˙ having a greater peak V˙O2 both pre (P = 0.02) and post (P = 0.03) training. Quadriceps muscle oxygenation and RPE were not different between groups (all P>0.1). In contrast to HQ˙, LQ˙ responders are capable of improving submaximal Q˙-V˙O2 in response to SIT via increased SV. However, the increased submaximal exercise Q˙ does not benefit exercising muscle oxygenation.

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<![CDATA[Intervention against hypertension in the next generation programmed by developmental hypoxia]]> https://www.researchpad.co/article/5c50c477d5eed0c4845e87d3

Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy and increased cardiovascular disease in the adult offspring. However, translational studies isolating mechanisms to design intervention are lacking. Sheep and humans share similar precocial developmental milestones in cardiovascular anatomy and physiology. We tested the hypothesis in sheep that maternal treatment with antioxidants protects against fetal growth restriction and programmed hypertension in adulthood in gestation complicated by chronic fetal hypoxia, the most common adverse consequence in human pregnancy. Using bespoke isobaric chambers, chronically catheterized sheep carrying singletons underwent normoxia or hypoxia (10% oxygen [O2]) ± vitamin C treatment (maternal 200 mg.kg−1 IV daily) for the last third of gestation. In one cohort, the maternal arterial blood gas status, the value at which 50% of the maternal hemoglobin is saturated with oxygen (P50), nitric oxide (NO) bioavailability, oxidative stress, and antioxidant capacity were determined. In another, naturally delivered offspring were raised under normoxia until early adulthood (9 months). Lambs were chronically instrumented and cardiovascular function tested in vivo. Following euthanasia, femoral arterial segments were isolated and endothelial function determined by wire myography. Hypoxic pregnancy induced fetal growth restriction and fetal oxidative stress. At adulthood, it programmed hypertension by enhancing vasoconstrictor reactivity and impairing NO-independent endothelial function. Maternal vitamin C in hypoxic pregnancy improved transplacental oxygenation and enhanced fetal antioxidant capacity while increasing NO bioavailability, offsetting constrictor hyper-reactivity and replenishing endothelial function in the adult offspring. These discoveries provide novel insight into mechanisms and interventions against fetal growth restriction and adult-onset programmed hypertension in an animal model of complicated pregnancy in a species of similar temporal developmental milestones to humans.

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<![CDATA[Relationship between FFR, CFR and coronary microvascular resistance – Practical implications for FFR-guided percutaneous coronary intervention]]> https://www.researchpad.co/article/5c3d017ad5eed0c48403bbb1

Objective

The aim was threefold: 1) expound the independent physiological parameters that drive FFR, 2) elucidate contradictory conclusions between fractional flow reserve (FFR) and coronary flow reserve (CFR), and 3) highlight the need of both FFR and CFR in clinical decision making. Simple explicit theoretical models were supported by coronary data analyzed retrospectively.

Methodology

FFR was expressed as a function of pressure loss coefficient, aortic pressure and hyperemic coronary microvascular resistance. The FFR-CFR relationship was also demonstrated mathematically and was shown to be exclusively dependent upon the coronary microvascular resistances. The equations were validated in a first series of 199 lesions whose pressures and distal velocities were monitored. A second dataset of 75 lesions with pre- and post-PCI measures of FFR and CFR was also analyzed to investigate the clinical impact of our hemodynamic reasoning.

Results

Hyperemic coronary microvascular resistance and pressure loss coefficient had comparable impacts (45% and 49%) on FFR. There was a good concordance (y = 0.96 x − 0.02, r2 = 0.97) between measured CFR and CFR predicted by FFR and coronary resistances. In patients with CFR < 2 and CFR/FFR ≥ 2, post-PCI CFR was significantly >2 (p < 0.001), whereas it was not (p = 0.94) in patients with CFR < 2 and CFR/FFR < 2.

Conclusion

The FFR behavior and FFR-CFR relationship are predictable from basic hemodynamics. Conflicting conclusions between FFR and CFR are explained from coronary vascular resistances. As confirmed by our results, FFR and CFR are complementary; they could jointly contribute to better PCI guidance through the CFR-to-FFR ratio in patients with coronary artery disease.

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<![CDATA[Psychosomatic symptoms during South East Asian haze crisis are related to changes in cerebral hemodynamics]]> https://www.researchpad.co/article/5c3d0122d5eed0c4840389a2

Objectives

Forest fires in South Asia lead to widespread haze, where many healthy individuals develop psychosomatic symptoms. We investigated the effects of haze exposure on cerebral hemodynamics and new symptoms. We hypothesised that vasoactive substances present in the haze, would lead to vasodilation of cerebral vasculature, thereby altering cerebral hemodynamics, which in turn may account for new psychosomatic symptoms.

Methods

Seventy-four healthy volunteers were recruited, and serial transcranial Doppler (TCD) ultrasonography was performed to record blood flow parameters of bilateral middle cerebral arteries (MCA). The first TCD was performed in an air-conditioned environment. It was repeated outdoors after the participants spent 30-minutes in the haze environment. The prevailing level of pollutant standards index (PSI) was recorded. Appropriate statistical analyses were performed to compare cerebral hemodynamics at baseline and after haze exposure in all participants. Subgroup analyses were then employed to compare the findings between symptomatic and asymptomatic participants.

Results

Study participants’ median age was 30 years (IQR 26–34), and new psychosomatic symptoms were reported by 35 (47.3%). There was a modest but significant decrease in pulsatility index (PI) and resistivity index (RI) in the left MCA after haze exposure (PI: p = 0.026; RI: p = 0.021). When compared to baseline parameters, haze exposure resulted in significantly lower mean PI (p = 0.001) and RI (p = 0.001) in symptomatic patients, but this difference was not present in asymptomatic patients (PI: p = 0.919; RI: p = 0.970).

Conclusion

Haze causes significant alterations in cerebral hemodynamics in susceptible individuals, probably responsible for various psychosomatic symptoms. The prognostic implications and health effects of haze require evaluation in a larger study.

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<![CDATA[Poincaré plot analysis of cerebral blood flow signals: Feature extraction and classification methods for apnea detection]]> https://www.researchpad.co/article/5c141ee1d5eed0c484d28a77

Objective

Rheoencephalography is a simple and inexpensive technique for cerebral blood flow assessment, however, it is not used in clinical practice since its correlation to clinical conditions has not yet been extensively proved. The present study investigates the ability of Poincaré Plot descriptors from rheoencephalography signals to detect apneas in volunteers.

Methods

A group of 16 subjects participated in the study. Rheoencephalography data from baseline and apnea periods were recorded and Poincaré Plot descriptors were extracted from the reconstructed attractors with different time lags (τ). Among the set of extracted features, those presenting significant differences between baseline and apnea recordings were used as inputs to four different classifiers to optimize the apnea detection.

Results

Three features showed significant differences between apnea and baseline signals: the Poincaré Plot ratio (SDratio), its correlation (R) and the Complex Correlation Measure (CCM). Those differences were optimized for time lags smaller than those recommended in previous works for other biomedical signals, all of them being lower than the threshold established by the position of the inflection point in the CCM curves. The classifier showing the best performance was the classification tree, with 81% accuracy and an area under the curve of the receiver operating characteristic of 0.927. This performance was obtained using a single input parameter, either SDratio or R.

Conclusions

Poincaré Plot features extracted from the attractors of rheoencephalographic signals were able to track cerebral blood flow changes provoked by breath holding. Even though further validation with independent datasets is needed, those results suggest that nonlinear analysis of rheoencephalography might be a useful approach to assess the correlation of cerebral impedance with clinical changes.

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<![CDATA[Towards quantitative perfusion MRI of the lung in COPD: The problem of short-term repeatability]]> https://www.researchpad.co/article/5c18138dd5eed0c48477538a

Purpose

4D perfusion magnetic resonance imaging (MRI) with intravenous injection of contrast agent allows for a radiation-free assessment of regional lung function. It is therefore a valuable method to monitor response to treatment in patients with chronic obstructive pulmonary disease (COPD). This study was designed to evaluate its potential for monitoring short-term response to hyperoxia in COPD patients.

Materials and methods

19 prospectively enrolled COPD patients (median age 66y) underwent paired dynamic contrast-enhanced 4D perfusion MRI within 35min, first breathing 100% oxygen (injection 1, O2) and then room air (injection 2, RA), which was repeated on two consecutive days (day 1 and 2). Post-processing software was employed to calculate mean transit time (MTT), pulmonary blood volume (PBV) and pulmonary blood flow (PBF), based on the indicator dilution theory, for the automatically segmented whole lung and 12 regions of equal volume.

Results

Comparing O2 with RA conditions, PBF and PBV were found to be significantly lower at O2, consistently on both days (p<10–8). Comparing day 2 to day 1, MTT was shorter by 0.59±0.63 s (p<10–8), PBF was higher by 22±80 ml/min/100ml (p<3·10–4), and PBV tended to be lower by 0.2±7.2 ml/100ml (p = 0.159) at both, RA and O2, conditions.

Conclusion

The second injection (RA) yielded higher PBF and PBV, which apparently contradicts the established hypothesis that hyperoxia increases lung perfusion. Quantification of 4D perfusion MRI by current software approaches may thus be limited by residual circulating contrast agent in the short-term and even the next day.

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<![CDATA[Relationship between hemodynamic parameters and severity of ischemia-induced left ventricular wall thickening during cardiopulmonary resuscitation of consistent quality]]> https://www.researchpad.co/article/5c0841e9d5eed0c484fcb218

Ischemia-induced left ventricular (LV) wall thickening compromises the hemodynamic effectiveness of cardiopulmonary resuscitation (CPR). However, accurate assessment of the severity of ischemia-induced LV wall thickening during CPR is challenging. We investigated, in a swine model, whether hemodynamic parameters, including end-tidal carbon dioxide (ETCO2) level, are linearly associated with the severity of ischemia-induced LV wall thickening during CPR of consistent quality. We retrospectively analyzed 96 datasets for ETCO2 level, arterial pressure, LV wall thickness, and the percent of measured end-diastolic volume (%EDV) relative to EDV at the onset of ventricular fibrillation from eight pigs. Animals underwent advanced cardiovascular life support based on resuscitation guidelines. During CPR, LV wall thickness progressively increased while %EDV progressively decreased. Systolic and diastolic arterial pressure and ETCO2 level were significantly correlated with LV wall thickness and %EDV. Linear mixed effect models revealed that, after adjustment for significant covariates, systolic and diastolic arterial pressure were not associated with LV wall thickness or %EDV. ETCO2 level had a significant linear relationship with %EDV (P = 0.004). However, it could explain only 28.2% of the total variance of %EDV in our model. In conclusion, none of the hemodynamic parameters examined in this study appeared to provide sufficient information on the severity of ischemia-induced LV wall thickening.

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<![CDATA[Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex]]> https://www.researchpad.co/article/5bfc6221d5eed0c484ec6b80

Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the entire brain. Because of the potential significance of blood flow and oxygen supply simulations for illuminating spatiotemporal regulation inside the cortical microanatomy, there is a need to create mathematical models of the entire cerebral circulation with realistic anatomical detail. Our hypothesis is that an anatomically accurate reconstruction of the cerebrocirculatory architecture will inform about possible regulatory mechanisms of the neurovascular interface. In this article, we introduce large-scale networks of the murine cerebral circulation spanning the Circle of Willis, main cerebral arteries connected to the pial network down to the microcirculation in the capillary bed. Several multiscale models were generated from state-of-the-art neuroimaging data. Using a vascular network construction algorithm, the entire circulation of the middle cerebral artery was synthesized. Blood flow simulations indicate a consistent trend of higher hematocrit in deeper cortical layers, while surface layers with shorter vascular path lengths seem to carry comparatively lower red blood cell (RBC) concentrations. Moreover, the variability of RBC flux decreases with cortical depth. These results support the notion that plasma skimming serves a self-regulating function for maintaining uniform oxygen perfusion to neurons irrespective of their location in the blood supply hierarchy. Our computations also demonstrate the practicality of simulating blood flow for large portions of the mouse brain with existing computer resources. The efficient simulation of blood flow throughout the entire middle cerebral artery (MCA) territory is a promising milestone towards the final aim of predicting blood flow patterns for the entire brain.

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<![CDATA[Cerebral blood flow variability in fibromyalgia syndrome: Relationships with emotional, clinical and functional variables]]> https://www.researchpad.co/article/5c0e9898d5eed0c484eaae27

Objective

This study analyzed variability in cerebral blood flow velocity (CBFV) and its association with emotional, clinical and functional variables and medication use in fibromyalgia syndrome (FMS).

Methods

Using transcranial Doppler sonography, CBFV were bilaterally recorded in the anterior (ACA) and middle (MCA) cerebral arteries of 44 FMS patients and 31 healthy individuals during a 5-min resting period. Participants also completed questionnaires assessing pain, fatigue, insomnia, anxiety, depression and health-related quality of life (HRQoL).

Results

Fast Fourier transformation revealed a spectral profile with four components: (1) a first very low frequency (VLF) component with the highest amplitude at 0.0024 Hz; (2) a second VLF component around 0.01-to-0.025 Hz; (3) a low frequency (LF) component from 0.075-to-0.11 Hz; and (4) a high frequency (HF) component with the lowest amplitude from 0.25-to-0.35 Hz. Compared to controls, FMS patients exhibited lower LF and HF CBFV variability in the MCAs (p < .005) and right ACA (p = .03), but higher variability at the first right MCA (p = .04) and left ACA (p = .005) VLF components. Emotional, clinical and functional variables were inversely related to LF and HF CBFV variability (r≥-.24, p≤.05). However, associations for the first VLF component were positive (r≥.28, p≤.05). While patients´ medication use was associated with lower CBFV variability, comorbid depression and anxiety disorders were unrelated to variability.

Conclusions

Lower CBFV variability in the LF and HF ranges were observed in FMS, suggesting impaired coordination of cerebral regulatory systems. CBFV variability was differentially associated with clinical variables as a function of time-scale, with short-term variability being related to better clinical outcomes. CBFV variability analysis may be a promising tool to characterize FMS pathology and it impact on facets of HRQoL.

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<![CDATA[Comparison between optical coherence tomography angiography and immunolabeling for evaluation of laser-induced choroidal neovascularization]]> https://www.researchpad.co/article/5c0c04e2d5eed0c48481ce98

This study aimed to investigate the differences between images obtained by optical coherence tomography angiography (OCTA) with those from immunohistochemical labeling of laser-induced choroidal neovascularization (CNV) in a mouse model. CNV was induced by laser photocoagulation (GYC-2000, NIDEK; wavelength 532 nm) in the left eyes of 10 female C57BL/6J mice aged 6 weeks. The laser parameters included a 100-μm spot, 100-ms pulse duration and 200-mW incident power to rupture Bruch’s membrane. OCT and OCTA CNV images were obtained using the RS-3000 Advance (NIDEK) 5 days post-laser photocoagulation. After OCTA imaging, the isolated choroid/retinal pigment epithelium complexes were fluorescently labeled with CD31 (an endothelial cell marker), platelet-derived growth factor receptor β (PDGFRβ, a pericyte-like scaffold marker), α-smooth muscle actin (α-SMA) and collagen I. Area measurements of the lesions obtained by enface OCTA were compared with immunolabeled CD31+ CNV lesions in choroid flat-mounts. We also examined structural correlations between the PDGFRβ+ pericyte-like scaffold and OCTA images. Laser-induced CNV was clearly detected by enface OCTA, appearing as a hyperflow lesion surrounded by a dark halo. Area measurements of the CNV lesion by immunolabeling were significantly larger than those obtained by enface OCTA (p = 0.006). The CNV lesion beneath the periphery of the pericyte-like scaffold was not clearly visible by enface OCTA due to the dark halo; however, the lesion was detectable as blood flow by cross-sectional OCTA and was also highly labeled by CD31. The periphery of the pericyte-like scaffold appeared to develop into subretinal fibrosis and this region was rich in myofibroblasts. Enface OCTA was unable to detect the entire area of laser-induced CNV in mice, with an undetectable portion located beneath the fibrotic periphery of the pericyte-like scaffold. Due to this OCTA fibrosis artifact, OCTA imaging has limited potential for accurately estimating CNV lesions.

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