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Objective: in the experiment, to investigate the effect of Quercetin on the NO-dependent reactions of isolated vessels involving endothelium and perivascular adipose tissue (PVAT) after a single X-ray irradiation of rats at a sublethal dose. In a clinical study, to investigate the effect of long-term use of Quercetin on the functional state of themicrovascular endothelium in the elderly patients with metabolic syndrome (MS)., Material and Methods: Experimental studies were performed on vascular fragments obtained from adult male rats(7-8 months) of the control group, in animals exposed to a single R-irradiation at a dose of 7 Gy and animals irradiated in the same dose, which received Quercetin orally for 14 days three times a week based on 10 mg/kg bodyweight. Fragments of the thoracic aorta (TA) and mesenteric artery (MA) were cleaned of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+), and then were cut into rings (up to 2 mm). The amplitude of the contractionof the rings TA and MA under the influence of phenylephrine (PE, 3 x 10-6 M), the amplitude of the contraction of therings TA and MA in the presence of a competitive blocker of NO-synthase methyl ester of N-nitro-L-arginine(L-NAME, 10-5 M), the amplitude of relaxation of the rings TA and MA in the presence of N-acetylcysteine (NAC, 10-4 M)were measured. The clinical study examined 110 patients with MS criteria in accordance with ATP III (2001).Patients in the main group for 3 months received Quercetin from the same manufacturer, 80 mg three times a day,patients in the control group received placebo., Results: Single R-irradiation disrupts the regulation of the contractile function of TA and MA, which is evidenced bychanges in the contractile reactions of isolated fragments of these vessels as a response to the action of vasoactivecompounds. Course use of Quercetin in irradiated rats leads to the normalization of contractile and dilatory vascular responses due to partial correction of NO metabolism in the endothelium and PVAT. For the majority of patients(69 %) who received Quercetin, a post-occlusive hyperemia test showed a statistically significant increase of maximal volumetric velocity of the skin blood flow rate and duration of the recovery period to the baseline, which indicates about improvement of vasomotor vascular endothelial function., Conclusions: Course use of Quercetin improves the functional state of the microvascular endothelium among theelderly people with MS, normalizes contractile and dilatory vascular responses in irradiated rats due to partial correction of NO metabolism in the endothelium and PVAT., (O. V. Korkushko, E. M. Gorban, O. V. Bondarenko, I. A. Antonyuk-Shcheglova, S. S. Naskalova, O. V. Parshykov, N. O. Utko, A. V. Gavalko, V. B. Shatilo, G. V. Duzhak.)

Background: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has recently emerged as a novel and accurate non-invasive measure of left ventricular (LV) filling pressure. This systematic review and meta-analysis aimed to give an overview of the possible clinical implications of E/e'sr., Methods: We conducted a systematic review and meta-analysis of all studies involving E/e'sr. Of 598 identified studies, 16 met our inclusion criteria. Studies involving E/e'sr either investigated its prognostic value (n = 9) or its correlation with invasively measured LV filling pressure (n = 7)., Results: The pooled meta-analysis showed a significant correlation between E/e'sr and pulmonary capillary wedge pressure (PCWP) measured invasively across the studies assessing this relationship (Cohen's d = 3.90 95% CI [2.38-6.39], p < 0.001) and between E/e'sr and left ventricle end-diastolic pressure (LVEDP) measured invasively across the studies assessing this relationship (Cohen's d = 5.30 95% CI [2.83-9.96], p < 0.001). The pooled analysis of the prognostic studies showed that E/e'sr was a significant predictor of adverse outcomes after multivariable adjustment across the different study populations in a random effects model (overall estimated HR: 1.58 95% CI [1.28-1.96], p < 0.001, per 1 m increase)., Conclusion: E/e'sr correlates well with invasive measures of LV filling pressure. In addition, E/e'sr provides significant prognostic information across various patient populations. Further studies are needed to test if E/e'sr has an advantage to E/e'.

New Findings: What is the central question of this study? Are ultraviolet radiation (UVR)-induced increases in skin blood flow independent of skin erythema? Does broad-spectrum UVR exposure attenuate NO-mediated cutaneous vasodilatation, and does sunscreen or sweat modulate this response? What are the main findings and their importance? Erythema and vascular responses to UVR are temporally distinct, and sunscreen prevents both responses. Exposure to UVR attenuates NO-mediated vasodilatation in the cutaneous microvasculature; sunscreen or simulated sweat on the skin attenuates this response. Sun over-exposure may elicit deleterious effects on human skin that are separate from sunburn, and sunscreen or sweat on the skin may provide protection., Abstract: Exposure to ultraviolet radiation (UVR) may result in cutaneous vascular dysfunction independent of erythema (skin reddening). Two studies were designed to differentiate changes in erythema from skin vasodilatation throughout the 8 h after acute broad-spectrum UVR exposure with (+SS) or without SPF-50 sunscreen (study 1) and to examine NO-mediated cutaneous vasodilatation after acute broad-spectrum UVR exposure with or without +SS or simulated sweat (+SW) on the skin (study 2). In both studies, laser-Doppler flowmetry was used to measure red cell flux, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure). In study 1, in 14 healthy adults (24 ± 4 years old; seven men and seven women), the skin erythema index and CVC were measured over two forearm sites (UVR only and UVR+SS) before, immediately after and every 2 h for 8 h post-exposure (750 mJ cm -2 ). The erythema index began to increase immediately post-UVR (P < 0.05 at 4, 6 and 8 h), but CVC did not increase above baseline for the first 4-6 h (P ≤ 0.01 at 6 and 8 h); +SS prevented both responses. In study 2, in 13 healthy adults (24 ± 4 years old; six men and seven women), three intradermal microdialysis fibres were placed in the ventral skin of the forearm [randomly assigned to UVR (450 mJ cm -2 ), UVR+SS or UVR+SW], and one fibre (non-exposed control; CON) was placed in the contralateral forearm. After UVR, a standardized local heating (42°C) protocol quantified the percentage of NO-mediated vasodilatation (%NO). The UVR attenuated %NO compared with CON (P = 0.01). The diminished %NO was prevented by +SS (P < 0.01) and +SW (P < 0.01). Acute broad-spectrum UVR attenuates NO-dependent dilatation in the cutaneous microvasculature, independent of erythema. Sunscreen protects against both inflammatory and heating-induced endothelial dysfunction, and sweat might prevent UVR-induced reductions in NO-dependent dilatation., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Purpose: We assess the increase in total retinal blood flow (TRBF) induced by flicker stimulation of the human retina in vivo and investigate the flicker induced hyperemia by means of a vascular flow model of the retinal circulation to study neurovascular coupling (NC)., Methods: In six healthy subjects, TRBF was measured before and during stimulation with diffuse luminance flicker. Blood flow velocities in retinal vessels were measured via dual-beam bidirectional Doppler Fourier-domain optical coherence tomography (FD-OCT), retinal vessel diameters were assessed based on FD-OCT phase data. This allowed for the calculation of TRBF before and during visual stimulation. Additionally, a mathematical flow model for the retinal vasculature was adapted to study the implications of diameter variations on retinal perfusion. Measured and simulated perfusion was compared to draw conclusions on the diameter variations in different layers of the vascular tree., Results: The measured mean baseline flow was 36.4 ± 6.5 μl/min while the mean flow during flicker stimulation was 53.4% ± 8.3 μl/min. The individual increase in TRBF during flicker stimulation ranged between 34% and 66%. The average increase in TRBF over all measured subjects was 47.6% ± 12.6%., Conclusions: Dual-beam bidirectional Doppler FD-OCT allowed quantifying NC in the human retina in vivo and may be a promising method for monitoring alterations in NC caused by various pathologies. The comparison of the measured data with the results obtained in the simulated vasculature indicates that the vasodilation induced by NC is more pronounced in smaller vessels.

The feasibility of implementing magnetic struts into drug-eluting stents (DESs) to mitigate the adverse hemodynamics which precipitate stent thrombosis is examined. These adverse hemodynamics include platelet-activating high wall shear stresses (WSS) and endothelial dysfunction-inducing low wall shear stresses. By magnetizing the stent struts, two forces are induced on the surrounding blood: (1) magnetization forces which reorient red blood cells to align with the magnetic field and (2) Lorentz forces which oppose the motion of the conducting fluid. The aim of this study was to investigate whether these forces can be used to locally alter blood flow in a manner that alleviates the thrombogenicity of stented vessels. Two-dimensional steady-state computational fluid dynamics (CFD) simulations were used to numerically model blood flow over a single magnetic drug-eluting stent strut with a square cross section. The effects of magnet orientation and magnetic flux density on the hemodynamics of the stented vessel were elucidated in vessels transporting oxygenated and deoxygenated blood. The simulations are compared in terms of the size of separated flow regions. The results indicate that unrealistically strong magnets would be required to achieve even modest hemodynamic improvements and that the magnetic strut concept is ill-suited to mitigate stent thrombosis.

Purpose: To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy., Methods and Materials: We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration associated with radiation therapy of 5 daily fractions (7.5, 9, or 13.5 Gy/d) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiation therapy. Oxygen saturation and total hemoglobin concentration were computed using an inverse Monte Carlo model., Results: First, oxygenation kinetics during and after radiation therapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiation therapy (days 12-15) compared with tumors that recurred locally. Second, within the group of tumors that recurred, faster increases in oxygenation during radiation therapy (day 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operating characteristic curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. Third, the rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/d did not initiate an increase in oxygenation, whereas 13.5 Gy/d triggered significant increases in oxygenation during and after radiation therapy., Conclusions: Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiation therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the effects of different therapeutic 1-MHz ultrasound waveforms on endothelial function before and after cyclooxygenase (COX) inhibition. Forty-two healthy volunteers aged 27.2 ± 3.8 y underwent interventions and an evaluation for endothelial function (n = 15; with COX inhibition, n = 15; duration of the vasodilator effect, n = 12) by technique flow-mediated dilation. Continuous ultrasound therapy (0.4 W/cm(2 SATA)), pulsed ultrasound therapy (20% duty cycle, 0.08 W/cm(2 SATA)) or placebo (equipment power off) was randomly applied over the brachial artery for 5 min. COX inhibition (aspirin) was carried out 30 min before treatments. In relation to the placebo, flow-mediated dilation increased by 4.8% using continuous ultrasound and by 3.4% using pulsed ultrasound. After COX, flow-mediated dilation was enhanced by 2.1% by continuous ultrasound and 2.6% by pulsed ultrasound. This vasodilation persisted for 20 min. Continuous and pulsed therapeutic 1-MHz ultrasound waveforms improved endothelial function in humans, which provided them with anti-inflammatory vascular effects., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

In this study, we looked at the possible effects of low-level laser therapy (LLLT) on blood flow velocity, and serotonin (5-HT) and cholinesterase levels in patients with chronic headache associated with temporomandibular disorders (TMD). LLLT has been clinically applied over the past years with positive results in analgesia and without the report of any side effects. The understanding of biological mechanisms of action may improve clinical results and facilitate its indication. Ten patients presenting headache associated with TMD completed the study. An 830-nm infrared diode laser with power of 100 mW, exposure time of 34 s, and energy of 3.4 J was applied on the tender points of masseter and temporal muscle. Blood flow velocity was determined via ultrasound Doppler velocimetry before and after laser irradiation. The whole blood 5-HT and cholinesterase levels were evaluated three days before, immediately, and three days after laser irradiation. Pain score after treatment decreased to a score of 5.8 corresponding to 64% of pain reduction (P < 0.05). LLLT promoted a decrease in the blood flow velocity (P < 0.05). In addition, the 5-HT levels were significantly increased three days after LLLT (P < 0.05). The cholinesterase levels remained unchanged at the analyzed time points (P > 0.05). Our findings indicated that LLLT regulates blood flow in the temporal artery after irradiation and might control 5-HT levels in patients suffering with tension-type headache associated to TMD contributing to pain relief., (© 2016 by the Society for Experimental Biology and Medicine.)

Unlabelled: The aim of this study was to objectively assess the impact of low level laser therapy on skin blood flow, in terms of two of its components - the flow and trophic and therapeutic effect., Material and Methods: Nineteen children aged 3-15 years have been included in the study (seven boys and twelve girls) with a diagnosis of meningomyelocele in the lumbosacral area. In nine of them (47.3%) bedsores were found in the area of paresis location. Studies of skin blood flow were performed using xenon 133 clearance in the Department of Nuclear Medicine of the Children's Memorial Health Institute. Xenon 133 radioisotope in saline with intrinsic activity 74 MBq in 1 ml was used as the marker. Laser application was performed immediately prior to the application of the marker with a tag shower 60 mW probe, emitting 680 nm red light with surface power density of 0.5 J/cm2., Results: Within the tested children the laser application resulted in a significantly increased skin blood flow. Average results in tested group before LLLT are 7.47 ml/100 g/min, after LLLT 11.08 ml/100 g/min., Conclusions: 1. LLLT significantly increases the perfusion of the skin. 2. The effect of the increased perfusion as the result of laserotherapy in the most evident in children with skin trophic abnormalities. 3. Results confirmed by clinical observation indicate, that perfusion increase in relation to LLLT takes place with participation of trophic component of skin blood circulation.

Background: Extracorporeal shock wave treatment (ESWT) has proven its clinical benefits in different fields of medicine. Tissue regeneration and healing is improved after shock wave treatment. Even in the case of burn wounds angiogenesis and re-epithelialization is accelerated, but ESWT in extensive burn wounds is impracticable., Hypothesis: High energy ESWT influences cutaneous microcirculation at body regions remote from application site., Methods: Eighteen Sprague Dawley rats were randomly assigned to two groups and received either high energy ESWT (Group A: total 1000 impulses, 10 J) or placebo shock wave treatment (Group B: 0 impulses, 0 J), applied to the dorsal lower leg of the hind limb. Ten minutes later microcirculatory effects were assessed at the contralateral lower leg of the hind limb (remote body region) by combined Laser-Doppler-Imaging and Photospectrometry., Results: In Group A cutaneous capillary blood velocity was significantly increased by 152.8% vs. placebo ESWT at the remote body location (p = 0.01). Postcapillary venous filling pressure remained statistically unchanged (p > 0.05), while cutaneous tissue oxygen saturation increased by 12.7% in Group A (p = 0.220)., Conclusion: High energy ESWT affects cutaneous hemodynamics in body regions remote from application site in a standard rat model. The results of this preliminary study indicate that ESWT might be beneficial even in disseminated and extensive burn wounds by remote shock wave effects and should therefore be subject to further scientific evaluation., (Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the extent and consequences of histotripsy-induced hemolysis in vivo., Materials and Methods: Porcine femoral venous blood was treated with histotripsy in 11 animals with systemic heparinization and 11 without heparin. Serum and hemodynamic measurements were obtained at 0, 2, 5, 10, 15, and 30 minutes and 48-72 hours after the procedure. Fisher exact test was used to determine differences in mortality between heparinized and nonheparinized groups. A linear mixed effects model was used to test for differences in blood analytes and hemodynamic variables over time., Results: Of 11 animals in the nonheparinized group, 5 died during or immediately after histotripsy (45% nonheparin mortality vs 0% heparin mortality, P = .035). Serum hematocrit, free hemoglobin, lactate dehydrogenase (LDH), and right ventricular systolic pressure changed significantly (P < .001) over the treatment time. Serum hematocrit decreased slightly (from 32.5% ± 3.6% to 29.4% ± 4.2%), whereas increases were seen in free hemoglobin (from 6.2 mg/dL ± 4.6 to 348 mg/dL ± 100), LDH (from 365 U/L ± 67.8 ± to 722 U/L ± 84.7), and right ventricular systolic pressure (from 23.2 mm Hg ± 7.2 to 39.7 mm Hg ± 12.3). After 48-72 hours, hematocrit remained slightly decreased (P = .005), whereas LDH and free hemoglobin remained slightly increased compared with baseline (both P < .001)., Conclusions: Intravascular histotripsy applied to free-flowing venous blood is safe with systemic heparinization, causing only transient hemodynamic and metabolic disturbances, supporting its use as a future noninvasive thrombolytic therapy modality., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Background: In a previous study it is shown that for topically applied ALA-PDT, PpIX concentration correlates with vascular changes including vasoconstriction and/or vascular leakage of small vessels and arterioles in the mouse epidermis and dermis. In this study we report on vascular responses induced by ALA-PDT for different fluence rates, including both changes in vessel diameter and dynamics in RBC velocity in arterioles, imaged using intra-vital confocal microscopy in skinfold chambers in hairless mice. Our interest is in the dynamics of vascular changes in the early stages of illumination., Methods: We have determined the total PDT dose to be relatively low, 13 J cm(-2), and fluence rates of 26, 65 and 130 mW cm(-2) were investigated. Local vascular effects occurred very soon after the start of the therapeutic illumination in ALA-PDT., Results: In this study, we did not find a significant difference between fluence rates. Arterioles were particularly sensitive to vasoconstriction during low dose PDT, often resulting in complete vasoconstriction. When we observed complete vasoconstriction, this coincided with changes in RBC velocity., Conclusion: Since the therapeutic effects of PDT are dependent on a fine balance between the need for oxygen during illumination and disruption of the vasculature, the results of the present study add to our understanding of acute vascular effects during ALA-PDT and aid our efforts to optimize PDT using porphyrin pre-cursors., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background and Purpose: Prior work aimed at improving our understanding of human cerebral autoregulation has explored individual physiological mechanisms of autoregulation in isolation, but none has attempted to consolidate the individual roles of these mechanisms into a comprehensive model of the overall cerebral pressure-flow relationship., Methods: We retrospectively analyzed this relationship before and after pharmacological blockade of α-adrenergic-, muscarinic-, and calcium channel-mediated mechanisms in 43 healthy volunteers to determine the relative contributions of the sympathetic, cholinergic, and myogenic controllers to cerebral autoregulation. Projection pursuit regression was used to assess the effect of pharmacological blockade on the cerebral pressure-flow relationship. Subsequently, ANCOVA decomposition was used to determine the cumulative effect of these 3 mechanisms on cerebral autoregulation and whether they can fully explain it., Results: Sympathetic, cholinergic, and myogenic mechanisms together accounted for 62% of the cerebral pressure-flow relationship (P<0.05), with significant and distinct contributions from each of the 3 effectors. ANCOVA decomposition demonstrated that myogenic effectors were the largest determinant of the cerebral pressure-flow relationship, but their effect was outside of the autoregulatory region where neurogenic control appeared prepotent., Conclusions: Our results suggest that myogenic effects occur outside the active region of autoregulation, whereas neurogenic influences are largely responsible for cerebral blood flow control within it. However, our model of cerebral autoregulation left 38% of the cerebral pressure-flow relationship unexplained, suggesting that there are other physiological mechanisms that contribute to cerebral autoregulation., (© 2014 American Heart Association, Inc.)

The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-N(ω)-nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N(6)-(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage.

Aim: To evaluate the effect of ageing on the retinal vascular responsiveness to flicker light in glaucoma and ocular hypertension (OHT)., Methods: Retinal vascular response to flicker was measured with the retinal vessel analyser in 56 healthy subjects (59 ± 9 years), 50 primary open-angle glaucoma (POAG) (60 ± 10 years) and 46 OHT patients (62 ± 9 years). In the glaucoma group, the less damaged eye; in the OHT group, the eye with the higher intraocular pressure; and in healthy controls, one randomly selected eye was considered. Parametric and non-parametric linear regression analysis, as well as a model of covariance analysis (ANCOVA) was used to evaluate the effect of age on the vascular response., Results: In all three groups (N=152) absolute (Pearson R: -0.19, p<0.019; Spearman R: -0.22, p<0.006) and relative change (Pearson R: -0.18, p<0.027; Spearman R: -0.21, p<0.010) were statistically associated with age. The ANCOVA showed no difference between the three groups in this regard (absolute change: p=0.43; relative change: p=0.51)., Conclusions: Vascular responsiveness to flicker light decreases with age in healthy individuals, in glaucoma patients and in OHT patients. This effect seems to be comparable between the tested groups, and age-related change in vascular responsiveness to flicker light seems an unlikely risk factor for glaucoma.

Purpose: Abnormalities in single photon emission computed tomography (SPECT) perfusion within the lung and heart are often detected following radiation for tumors in∕around the thorax (e.g., lung cancer or left-sided breast cancer). The presence of SPECT perfusion defects is determined by comparing pre- and post-RT SPECT images. However, RT may increase the density of the soft tissue surrounding the lung∕heart (e.g., chest wall∕breast) that could possibly lead to an "apparent" SPECT perfusion defect due to increased attenuation of emitted photons. Further, increases in tissue effective depth will also increase SPECT photon attenuation and may lead to "apparent" SPECT perfusion defects. The authors herein quantitatively assess the degree of density changes and effective depth in soft tissues following radiation in a series of patients on a prospective clinical study., Methods: Patients receiving thoracic RT were enrolled on a prospective clinical study including pre- and post-RT thoracic computed tomography (CT) scans. Using image registration, changes in tissue density and effective depth within the soft tissues were quantified (as absolute change in average CT Hounsfield units, HU, or tissue thickness, cm). Changes in HU and tissue effective depth were considered as a continuous variable. The potential impact of these tissue changes on SPECT images was estimated using simulation data from a female SPECT thorax phantom with varying tissue densities., Results: Pre- and serial post-RT CT images were quantitatively studied in 23 patients (4 breast cancer, 19 lung cancer). Data were generated from soft tissue regions receiving doses of 20-50 Gy. The average increase in density of the chest was 5 HU (range 46 to -69). The average change in breast density was a decrease of -1 HU (range 13 to -13). There was no apparent dose response in neither the dichotomous nor the continuous analysis. Seventy seven soft tissue contours were created for 19 lung cancer patients. The average change in tissue effective depth was +0.2 cm (range -1.9 to 2.2 cm). The changes in HU represent a <2% average change in tissue density. Based on simulation, the small degree of density and tissue effective depth change is unlikely to yield meaningful changes in either SPECT lung or heart perfusion., Conclusions: RT doses of 20-50 Gy can cause up to a 46 HU increase in soft tissue density 6 months post-RT. Post-RT soft tissue effective depth may increase by 2.0 cm. These modest increases in soft tissue density and effective depth are unlikely to be responsible for the perfusion changes seen on post-RT SPECT lung or heart scans. Further, there was no clear dose response of the soft tissue density changes. Ultimately, the authors findings suggest that prior perfusion reports do reflect changes in the physiology of the lungs and heart.

Objectives: Ultrasound has various biological effects in the human body. The effects of continuous monitoring with ultrasound (sonolysis) on vasodilatation of the radial artery were described recently. We wanted to ascertain whether similar changes in the blood flow velocity during sonolysis could also be detected in the middle cerebral artery., Methods: Fifteen healthy volunteers (6 male and 9 female; age range, 23-68 years; mean ± SD, 47.1 ± 15.1 years) were subjected to 1 hour of middle cerebral artery sonolysis using a diagnostic transcranial probe with a 2-MHz Doppler frequency and measurement of the blood flow velocity at 2-minute intervals. During a second session, a flow curve was recorded for 10 seconds at 2-minute intervals. The peak systolic velocity, end-diastolic velocity, mean flow velocity, pulsatility index, and resistive index were recorded during both measurements., Results: Irregular changes in the measured blood flow parameters were recorded during both sessions. Changes in particular hemodynamic parameters during both measurements were similar. The changes in the peak systolic velocity, end-diastolic velocity, mean flow velocity, pulsatility index, and resistive index were not significantly different between the two measurements (P < .05 in all cases)., Conclusions: As opposed to sonolysis of the radial artery, sonolysis of the middle cerebral artery using a diagnostic 2-MHz frequency in healthy volunteers did not lead to changes in the flow curve or peripheral vasodilatation.

The spleen is a solid organ in which splenomegaly frequently develops and to which abdominal blunt trauma occurs. In this study, we demonstrated the potential therapeutic effect of microbubble-enhanced ultrasound (MEUS) combined with prothrombin to disrupt splenic circulation. A high-pressure-amplitude therapeutic ultrasound (TUS) device was used to treat 36 surgically exposed spleens in healthy New Zealand rabbits. Eighteen spleens were treated with either MEUS (n = 9) or MEUS combined with prothrombin (n = 9). The other 18 spleens were treated with TUS only or sham ultrasound exposure and served as the controls. The TUS was operated at a frequency of 831 kHz and a peak negative pressure of 4.8 MPa. Prothrombin was administered intravenously at 20 IU/kg. Contrast-enhanced ultrasound (CEUS) and acoustic quantification were performed to assess splenic blood perfusion. We found significant blood perfusion slowdown and drop-off in the MEUS-treated spleens. The peak intensity dropped from 20.2 ± 2.70 dB to 11.6 ± 4.58 dB immediately after treatment. The spleens treated with the combination of MEUS and prothrombin showed consistently poor perfusion within 1 h. In histologic examination of the MEUS-treated spleens, we found significant dilatation of splenic sinuses, hemorrhage, interstitial edema and thrombosis. This study demonstrated that the vascular effects induced by microbubble-enhanced, high-pressure ultrasound can slow down or block blood perfusion in the rabbit spleen. Prothrombin helps to enhance and extend the effects for up to 1 h., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: Transcutaneous cranial electrical stimulation (TCES) delivers a high-frequency (166 kHz) pulsed biphasic balanced current with a pulse repetition frequency of 100 Hz with 40% duty cycle through a negative electrode and two positive electrodes over the skull. TCES has a proven ability to potentiate anesthesia and analgesia, although the physiological mechanisms of this effect remain unclear. We hypothesized that the mechanism is a modulation of CBF in the central endogenous opioid system. This study aimed at determining the effects of TCES on CBF to elucidate its physiological mechanism., Methods: Thirty-six healthy volunteers were randomly assigned to active or placebo TCES, and all assessments were double blind. TCES was performed using the Anesthelec™ device. In the stimulated group, an active cable was used, and in the control group (sham), the cable was inactive. CBF was measured by XeCT™ before and after two hours of TCES., Results: Globally, CBF was unchanged by TCES. However, locally, TCES induced a significant CBF decrease in the brainstem and thalamus, which are structures involved in pain and anxiety (TCES and control CBF decrease were 18.5 and 11.9 mL/100g brain tissue/min, respectively)., Conclusion: TCES can modulate local CBF but it has no effect on overall CBF. [Clinical Trials. gov number: NCT00273663]., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

A head exposure setup for efficient and precisely defined exposure of human subjects equipped with a near-infrared imaging (NIRI) sensor is presented. In a partially shielded anechoic chamber the subjects were exposed to Universal Mobile Telecommunications System (UMTS)-like electromagnetic fields (EMF) by using a patch antenna at a distance of 4 cm from the head. The non-contact design of the exposure setup enabled NIRI sensors to easily attach to the head. Moreover, different regions of the head were chosen for localised exposure and simultaneous NIRI investigation. The control software enabled the simple adaptation of the test parameters during exploratory testing as well as the performance of controlled, randomised, crossover and double-blind provocation studies. Four different signals with a carrier frequency of 1900 MHz were chosen for the exposure: a simple continuous wave signal and three different UMTS signals. Furthermore, three exposure doses were available: sham, low (spatial peak specific absorption rate (SAR) = 0.18 W/kg averaged over 10 g) and high (spatial peak SAR = 1.8 W/kg averaged over 10 g). The SAR assessment was performed by measurement and simulation. Direct comparison of measurement and numerical results showed good agreement in terms of spatial peak SAR and SAR distribution. The variability analysis of the spatial peak SAR over 10 g was assessed by numerical simulations. Maximal deviations of -22% and +32% from the nominal situation were observed. Compared to other exposure setups, the present setup allows for low exposure uncertainty, combined with high SAR efficiency, easy access for the NIRI sensor and minimal impairment of test subjects., (Copyright © 2011 Wiley Periodicals, Inc.)

The purpose of this study was to investigate the vascular effects of microbubble-enhanced pulsed high-pressure ultrasound on liver blood perfusion. In the presence of circulating lipid-shell microbubbles, a focused ultrasound transducer was used to transcutaneously treat eight livers of healthy rabbits for perfusion analysis and to treat three livers with the abdomen open for histologic analysis. Twenty-two livers treated with the ultrasound only (n = 11) or microbubbles only (n = 11) served as the controls. The focused ultrasound was operated at a frequency of 1.22 MHz with a peak negative pressure of 4.6 MPa. The liver blood perfusion was estimated by performing contrast-enhanced ultrasound and gray-scale quantification on the livers before and after treatment. A temporary, nonenhanced region occurred in all of the experimental livers. The regional contrast gray-scale values of the experimental group dropped significantly from 88.4 before treatment to 2.7 after treatment. The liver perfusion also demonstrated a gradual recovery over a 60-min period. The liver perfusion of the control groups remained the same after treatment. We found microvascular rupture, hemorrhage and swelling hepatocytes upon histologic examination of the experimental group. Regional liver blood perfusion can be temporarily blocked by microbubble-enhanced focused ultrasound with high-pressure amplitude. These vascular effects can be explained as acute microvascular injury of the liver and may have clinical implications., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the effects of electromagnetic pulses (EMP) on associative learning in mice and test a preliminary mechanism for these effects., Materials and Methods: A tapered parallel plate gigahertz transverse electromagnetic (GTEM) cell with a flared rectangular coaxial transmission line was used to expose male BALB/c mice to EMP (peak-intensity 400 kV/m, rise-time 10 ns, pulse-width 350 ns, 0.5 Hz and total 200 pulses). Concurrent sham-exposed mice were used as a control. Associative learning, oxidative stress in the brain, serum chemistry and the protective action of tocopherol monoglucoside (TMG) in mice were measured, respectively., Results: (1) Twelve hour and 1 day post EMP exposure associative learning was reduced significantly compared with sham control (p<0.05) but recovered at 2 d post EMP exposure. (2) Compared with the sham control, lipid peroxidation of brain tissue and chemiluminescence (CL) intensity increased significantly (p<0.05), while the activity of the antioxidant enzymes Superoxide Dismutase [SOD], Glutathione [GSH], Glutathione Peroxidase [GSH-Px], Catalase [CAT]) decreased significantly (p<0.05) at 3 h, 6 h, 12 h and 1 d post EMP exposure. All these parameters recovered at 2 d post EMP exposure. (3) No significant differences between the sham control group and EMP exposed group were observed in serum cholesterol and triglycerides. (4) Pretreatment of mice with TMG showed protective effects to EMP exposure., Conclusions: EMP exposure significantly decreased associative learning in mice and TMG acted as an effective protective agent from EMP exposure. This mechanism could involve an increase of oxidative stress in brain by EMP exposure.

We studied the influence of preventive irradiation with terahertz electromagnetic waves at frequencies corresponding to nitric oxide emission and absorption molecular spectrum (150,176-150,664 GHz) on hemodynamic parameters in arteries of albino rats upon acute immobilization stress. We showed that exposure to the specified frequencies can produce adaptogenic effect manifesting in the absence of post-stress changes in the linear, systolic, and diastolic blood flow velocities and pressure gradient in various blood vessels of experimental animals.

Doppler optical coherence tomography (DOCT) provides a novel method to measure blood flow velocity in vessels with diameter at micrometer scale. In this study, a developed spectral domain DOCT system is applied to monitor cerebral blood flow velocity changes in a rat. An animal model with a cranial window is used, and by application of a drug, light, and electric stimulations, changes in blood flow velocity of the pial artery in sensory cortex are measured in real time. The results show significant differences in blood flow velocity before and after drug administration or light and electric stimulations, demonstrating the feasibility of DOCT in cerebral microcirculation study. Given its noninvasive nature, high spatial resolution, high velocity sensitivity, and high imaging speed, DOCT shows great promise in brain research by imaging blood flow changes at micrometer scale vessels, which helps to understand the pathogenesis of cerebral diseases and neurodegenerative diseases.

A marked neovascularity has been demonstrated in tendinopathies, due to the inflammatory-degenerative process. The aim of this study was to assess the effect of extracorporeal shock wave therapy (ESWT) on tissue perfusion in the treatment of tendinopathy. An observational clinical study was made of 30 patients undergoing ESWT for tendinopathy of the rotator cuff. A clinical improvement was obtained in 65.6% of patients at 2 and 6 months. This was associated with a statistically significant reduction in the oxygen tissue saturation, measured by oxymetry that was apparent already during treatment, as well as at subsequent follow-up visits. The reduced perfusion achieved with ESWT supports the hypothesis that this treatment can regulate the inflammatory process and offset increased vascularization, restoring physiologic tendon conditions., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Our previous study has shown that prenatal exposure to X-ray irradiation causes cerebral hypo-perfusion during the postnatal development of central nervous system (CNS). However, the source of the hypo-perfusion and its impact on the CNS development remains unclear. The present study developed an automatic analysis method to determine the mean red blood cell (RBC) speed through single microvessels imaged with two-photon microscopy in the cerebral cortex of rats prenatally exposed to X-ray irradiation (1.5 Gy)., Methodology/principal Findings: We obtained a mean RBC speed (0.9±0.6 mm/sec) that ranged from 0.2 to 4.4 mm/sec from 121 vessels in the radiation-exposed rats, which was about 40% lower than that of normal rats that were not exposed. These results were then compared with the conventional method for monitoring microvascular perfusion using the arteriovenous transit time (AVTT) determined by tracking fluorescent markers. A significant increase in the AVTT was observed in the exposed rats (1.9±0.6 sec) as compared to the age-matched non-exposed rats (1.2±0.3 sec). The results indicate that parenchyma capillary blood velocity in the exposed rats was approximately 37% lower than in non-exposed rats., Conclusions/significance: The algorithm presented is simple and robust relative to monitoring individual RBC speeds, which is superior in terms of noise tolerance and computation time. The demonstrative results show that the method developed in this study for determining the mean RBC speed in the spatial frequency domain was consistent with the conventional transit time method.

The purpose of this study was to quantify the changes of tumor blood flow (BF) in cervical cancer after radiation therapy by using perfusion computed tomography (CT), and to examine the difference between maximum slope (MS) and single-input one-compartment model (SOCM) methods. Fourteen consecutive patients who received definitive radiation therapy for cervical cancer from October 2009 to February 2010 were enrolled in this study. Blood flow (BF) analyses were performed using both MS and SOCM methods. Quantitative BF maps were created using Body Perfusion (Toshiba Medical Systems, Co. Tokyo, Japan). Perfusion color maps were successfully created by the two analytical methods. BF of the tumors was clearly higher than that of normal cervix, making it possible to distinguish tumor tissue from normal cervical tissue. BF of the tumors after 20 Gy of radiation therapy calculated by the MS method was significantly larger than that before treatment (126.9 vs. 72.2 ml/min/100 ml, median; p < 0.05). Although BF calculated by the MS and SOCM methods showed a positive linear correlation (p < 0.001, r = 0.981), BF calculated by the MS method was lower than that obtained by the SOCM method (103.7 vs. 115.1 ml/min/100 ml, p < 0.01). The change of tumor BF in cervical cancer before and after radiation therapy can be monitored by conducting blood flow analysis using perfusion CT. BF by the MS method was lower than that by the SOCM method, but the two analytical methods correlated well. Perfusion CT may have potential in noninvasive monitoring of vascular and oxygenation status and for guiding adaptive therapy.

Objectives: Based on well-established physiological theories, we studied correlations between changes in brachial-ankle pulse wave velocity (baPWV) relative to blood pressure (BP) elevation (elasticity of large-to-medium-sized arteries), and coronary artery disease (CAD)., Methods: The baPWV (in centimeters/second) and BP (in millimeters of mercury) were determined in 101 patients before, during, and/or after a cold pressor test using a volume-plethysmographic system., Results: Significantly higher rates of increase in PWV relative to changes in BP were observed in the CAD(+) group than in the CAD(-) group when mean BP [median (25th-75th percentiles): 14.8 (8.3-24.9) vs. 8.6 (5.7-11.4) cm/s/mmHg, P<0.0001], and systolic [10.1 (6.0-17.5) vs. 6.4 (4.4-10.6) cm/s/mmHg, P=0.0023] and diastolic BP [21.0 (14.0-34.4) vs. 10.8 (6.8-16.1) cm/s/mmHg, P<0.0001] were used as BP indices. Similarly, the rates of increase in baPWV showed a significant correlation with the extent of CAD. The rate of increase in baPWV obtained using the mean, systolic and diastolic BP as indices showed an area under the receiver operating characteristic curve of 0.68-0.76, sensitivity of 65-75%, and specificity of 65-75% for the detection of CAD. The area under the receiver operating characteristic curve, sensitivity, and specificity for the rate of increase were slightly higher than those for baseline baPWV and baseline baPWV/baseline BP ratio, but not to a significant degree., Conclusion: The rate of increase in baPWV relative to BP elevation determined by cold pressor test is significantly and moderately correlated with CAD. To identify patients with CAD, the rate of increase in baPWV relative to changes in BP can provide considerable, but limited, information.

Purpose: We used computed tomography (CT) perfusion to evaluate the acute and late effect of radiation therapy (RT) on spinal cord (SC) hemodynamics in patients without symptoms of myelopathy. We hypothesized that SC perfusion could be acutely altered during RT., Methods and Materials: We analyzed neck CT perfusion studies of 36 head-and-neck cancer patients (N1), 16 of whom had previously undergone RT. In a separate group of 6 patients (N2), CT perfusion studies were obtained before RT, after 40 Gy, and after treatment completion., Results: In the N1 group, SC blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability (CP) maps were not significantly different between RT-treated and RT-naive patients. In the N2 group, BF and CP were significantly increased during treatment compared with the baseline and post-RT studies., Conclusions: Radiation therapy of the head and neck may cause transient perturbations of SC perfusion that seem to reverse after treatment. There are no definite chronic effects of RT on SC perfusion observeable at the typical doses administered during treatment of head and neck malignancies., ((c) 2010 Elsevier Inc. All rights reserved.)

Background: Antiangiogenic and anti-vascular therapies present intriguing alternatives to cancer therapy. However, despite promising preclinical results and significant delays in tumor progression, none have demonstrated long-term curative features to date. Here, we show that a single treatment session of Tookad-based vascular targeted photodynamic therapy (VTP) promotes permanent arrest of tumor blood supply by rapid occlusion of the tumor feeding arteries (FA) and draining veins (DV), leading to tumor necrosis and eradication within 24-48 h., Methodology/principal Findings: A mouse earlobe MADB106 tumor model was subjected to Tookad-VTP and monitored by three complementary, non-invasive online imaging techniques: Fluorescent intravital microscopy, Dynamic Light Scattering Imaging and photosensitized MRI. Tookad-VTP led to prompt tumor FA vasodilatation (a mean volume increase of 70%) with a transient increase (60%) in blood-flow rate. Rapid vasoconstriction, simultaneous blood clotting, vessel permeabilization and a sharp decline in the flow rates then followed, culminating in FA occlusion at 63.2 sec+/-1.5SEM. This blockage was deemed irreversible after 10 minutes of VTP treatment. A decrease in DV blood flow was demonstrated, with a slight lag from FA response, accompanied by frequent changes in flow direction before reaching a complete standstill. In contrast, neighboring, healthy tissue vessels of similar sizes remained intact and functional after Tookad-VTP., Conclusion/significance: Tookad-VTP selectively targets the tumor feeding and draining vessels. To the best of our knowledge, this is the first mono-therapeutic modality that primarily aims at the larger tumor vessels and leads to high cure rates, both in the preclinical and clinical arenas.

Single and double examinations of normal males and females in the course of 11-year solar cycle with the use of oscillovasometry and occlusive plethysmography established a direct correlation between the effective diastolic radius of the brachial artery and solar activity characteristics on the day of examination, i.e. number of solar spots and intensity of radiation with the 10.7 cm wavelength. Other blood flow parameters demonstrated opposite correlations with the factors in males and females. As solar activity increased, females displayed linear decrements of arterial elasticity and regional peripheral resistance and growth of the volumetric blood flow velocity equally at rest and at the peak of post-occlusion reactive hyperemia. In males, the correlations had the reversed sign. Besides, males were noted to reduce venous reserve and venous outflow from antebrachial muscles proportionally to the increase of Wolf number. It is inferred that elevated solar activity may be responsible for impairment of the feeling of well-being of people with reduced cardiovascular reserve, particularly in space tight or at high altitudes in the absence of or under weak protection of the geomagnetic field and ozone layer.

This study sought to find out whether the femoral artery of rabbit could be occluded after microbubbles mediated intermitten ultrasound exposure. One hundred and eight rabbits were randomly divided into 3 groups subjected to 3 different factors, namely ultrasound, HIFU combined with Microbubble (the intermitten mode and the continuous mode). After exposure, HE staining was used for visual inspection of the histopathologic change of femoral artery. Electron microscope was used for observation of the ultramicrostructural change; digital subtraction radiography (DSA) was used for inspections of the change in blood flow. There were thrombi formed in the femoral artery and the blood flow was occluded; the endarterium of the femoral artery of rabbits was damaged, and there was cavitation observed in the intermitten exposure group. In the other two groups, there was no change in the the femoral artery of rabbits. Thrombus could be formed in the femoral artery, and blood flow was occluded after exposure to microbubbles-mediated intermitten HIFU.

Purpose: Hyperthermia treatment might increase tumour oxygenation and perfusion, as has been reported for experimental tumours. The present study was performed to investigate this hypothesis in patients undergoing regional hyperthermia treatment., Methods: Thirteen patients with primary or recurrent pelvic tumours were included in this study. Prior to and up to one hour after regional hyperthermia, perfusion was quantitatively determined by H(2)(15)O-PET. The fused CT-PET images were used to extract tumour time-activity curves and to identify the catheter position. Perfusion was calculated from the total tumour time-activity curves and for the time-activity curves at the catheter site. Additionally, perfusion was calculated from the temperature-time curves measured using temperature probes., Results: Perfusion values calculated using H(2)(15)O-PET and those deduced from temperature probe measurements are significantly correlated with a correlation coefficient, R = 0.21. The perfusion values deduced from the temperature measured in a body cavity do not provide information about average tumour perfusion. Perfusion values deduced from the temperature are overestimated for very poorly perfused tissues and underestimated for highly perfused tissues., Conclusions: Temperature measurement during hyperthermia may allow only determination of intermediate perfusion values.

The aim of Magnetic Drug Targeting (MDT) is to concentrate drugs, attached to magnetic particles, in a specific part of the human body by applying a magnetic field. Computational simulations are performed of blood flow and magnetic particle motion in a left coronary artery and a carotid artery, using the properties of presently available magnetic carriers and strong superconducting magnets (up to B approximately 2 T). For simple tube geometries it is deduced theoretically that the particle capture efficiency scales as [see text], with Mn (p) the characteristic ratio of the particle magnetization force and the drag force. This relation is found to hold quite well for the carotid artery. For the coronary artery, the presence of side branches and domain curvature causes deviations from this scaling rule, viz. eta approximately Mn (p) (beta) , with beta > 1/2. The simulations demonstrate that approximately a quarter of the inserted 4 microm particles can be captured from the bloodstream of the left coronary artery, when the magnet is placed at a distance of 4.25 cm. When the same magnet is placed at a distance of 1 cm from a carotid artery, almost all of the inserted 4 microm particles are captured. The performed simulations, therefore, reveal significant potential for the application of MDT to the treatment of atherosclerosis.

Continuous high-intensity focused ultrasound (HIFU) at various intensities has been shown to induce functional changes in arteries. The objective of the current study was to investigate the functional changes in arteries when pulsed HIFU is used at various acoustic power levels. Sonication was applied at an ultrasound frequency of 1 MHz with a burst length of 50 ms and a repetition frequency of 1 Hz. The duration of the whole sonication was 6 s. The femoral arteries and abdominal aortas of Sprague-Dawley rats were surgically exposed and sonicated with pulsed HIFU; the pulsed-HIFU beam was aimed using color images of the blood flow. The peak systolic velocity (PSV) of the blood flow, as measured by Doppler velocimetry, increased in the arteries to which pulsed HIFU had been applied at acoustic powers of 15, 30, and 45 W. The increase in PSV was correlated with the acoustic power of the pulsed HIFU. The temperatures recorded by the thermocouples placed above and below the aorta surfaces did not change significantly during the sonication. Furthermore, no histological changes were found and the vessel wall showed no obvious temperature rise. Therefore, our results indicate that the functional changes induced by pulsed-HIFU exposure are mainly due to mechanical effects.

This comparative study was designed to evaluate effect of low-intensity speckle laser radiation in the green and red wavelengths on intraocular hemodynamics in 202 patients (202 eyes) with retinal vascular problems and without them. Irradiation was performed using "Izumrud" and "Rubin" adapters for an AMO-ATOS unit. Peak systolic velocity and peripheral resistance index in posterior short ciliary arteries and central retinal artery were measured. It was shown for the first time that green speckle laser radiation (wavelength 535 nm) has more pronounced (compared with the red light) effect on intraocular hemodynamics; thereby, it makes a greater contribution to the improvement of the visual function (e.g. in the case of glaucoma) and to the widening of the fields of vision.

Use of the third generation mobile phone system is increasing worldwide. This is the first study to investigate the effects of the third generation system on regional cerebral blood flow (rCBF) in humans. We compared effects of the electromagnetic field (EMF) emitted from the Wideband Code Division Multiple Access (W-CDMA) cellular system versus sham control exposure on rCBF in humans. Nine healthy male volunteers participated in this study. Positron emission tomography (PET) scans were obtained before, during, and after unilateral 30 min EMF exposure. The subtraction analysis revealed no significant rCBF changes caused by the EMF conditions compared with the sham exposure, suggesting that EMF emitted by a third generation mobile phone does not affect rCBF in humans.

Recently we showed that the Pennes bioheat transfer equation was not adequate to quantify mm wave heating of the skin at high blood flow rates. To do so, it is necessary to incorporate an "effective" thermal conductivity to obtain a hybrid bioheat equation (HBHE). The main aim of this study was to determine the relationship between non-specific tissue blood flow in a homogeneous unilayer model and dermal blood flow in multilayer models providing that the skin surface temperatures before and following mm wave exposure were the same. This knowledge could be used to develop multilayer models based on the fitting parameters obtained with the homogeneous tissue models. We tested four tissue models consisting of 1-4 layers and applied the one-dimensional steady-state HBHE. To understand the role of the epidermis in skin models we added to the one- and three-layer models an external thin epidermal layer with no blood flow. Only the combination of models containing the epidermal layer was appropriate for determination of the relationship between non-specific tissue and dermal blood flows giving the same skin surface temperatures. In this case we obtained a linear relationship between non-specific tissue and dermal blood flows. The presence of the fat layer resulted in the appearance of a significant temperature gradient between the dermis and muscle layer which increased with the fat layer thickness., ((c) 2008 Wiley-Liss, Inc.)

Venous malformations of the skin and subcutaneous tissue are compressible, blue-purple tumors that are present at birth. According to the location and symptoms caused, venous malformations can be treated with surgery, sclerotherapy, or a combination of both. Laser therapy can also be used, especially when surgery is contraindicated. We report the case of a 24-year-old man who presented with a venous malformation on the upper and lower left eyelids, which provoked a mechanical ptosis. Treatment with sequential pulsed-dye neodymium yttrium aluminum garnet (PDL-Nd:YAG) laser was performed. After 2 treatments, a marked reduction of volume and blanching of the venous malformation was observed, with satisfactory cosmetic results. The sequential PDL-Nd:YAG laser seems to be an effective and safe therapy for the treatment of cutaneous venous malformations. It penetrates deeper than pulsed-dye laser alone, and because it allows the use of lower fluencies than Nd:YAG laser alone, it reduces the risk of adverse effects.

In MRI, the flow of blood in the patient is subjected to a strong static magnetic field (B(0)). The movement of charge carriers in a magnetic field causes a magnetofluid dynamic (MFD) effect that induces a voltage across the artery. This induced voltage distorts the ECG signal of the patient and appears as an elevation of the T-wave of the ECG signal. Flow of blood through the aortic arch is perpendicular to the magnetic field and coincides with the occurrence of the T-wave of the ECG. Based on these facts, it is proposed that the elevation in the T-wave occurs because of the voltage induced across the aortic arch. In this paper, the elevation is computed mathematically using the equations of MFD. A method is developed to measure this induced voltage based on discretization of the aortic arch and measuring the blood flow profile in the aorta. The results are compared to the ECG signals measured in humans in the bore of 1.5 T imaging magnet. The computed ECG signals at the 12 leads are very similar to the measured values.

Purpose: Several studies have recently shown that a transition from light to dark is associated with a reduction in choroidal blood flow. The mechanism underlying this effect is unclear but may be related to changes in neural input. In the present study, the authors hypothesized that either the alpha-receptor agonist phenylephrine or the nitric oxide synthase (NOS) inhibitor L-NMMA may alter the choroidal blood flow response during a transition from light to dark., Methods: In 15 healthy male nonsmoking subjects, the response of choroidal perfusion was studied in a randomized placebo-controlled three-way crossover study. Phenylephrine, L-NMMA or placebo was administered on different study days, and the effect of a light/dark transition on choroidal perfusion parameters was studied. Subfoveal choroidal blood flow and fundus pulsation amplitude were assessed with laser Doppler flowmetry and laser interferometry, respectively., Results: Before drug administration, a transition from light to dark reduced both choroidal hemodynamic parameters by 11% to 20%. Neither phenylephrine nor placebo altered basal choroidal blood flow or choroidal blood flow responses to the light/dark transitions. By contrast, the NOS inhibitor L-NMMA significantly reduced basal choroidal blood flow by 20.5% +/- 5.9% (P < 0.001) and basal fundus pulsation amplitude by 21.5% +/- 4.8% (P < 0.001). In addition, the response of subfoveal choroidal blood flow (-6.2% +/- 3.2%; P = 0.008) and fundus pulsation amplitude (-4.2% +/- 2.4%; P < 0.001) to the light/dark transition was significantly diminished., Conclusions: The present study indicates that NO plays a role in the choroidal blood flow decrease during a transition from light to dark. Given that L-NMMA is a nonspecific inhibitor of NOS, the present study does not clarify whether this NO is from endothelial or neural sources.

Unlabelled: THE AIM of this study was to investigate whether repeated exposure to radio frequency electromagnetic field (RF-EMF) of 1439 MHz affects the cerebral microcirculation, including blood-brain barrier function, in a rat brain., Materials and Methods: The head of the rat was exposed for four weeks (60 min/day, 5 days/week) to RF-EMF at 2.4 W/kg of brain averaged specific absorption rate (BASAR). Three microcirculatory parameters: blood-brain barrier permeability, leukocyte behavior and plasma velocity were measured before and after RF-EMF exposure using a closed cranial window method., Results: No extravasation of intravenously injected dyes from pial venules was found at any BASAR level. No significant changes in the number of endothelial-adhering leukocytes after exposure were found. The plasma velocity remained constant within the physiological range through each exposure., Conclusion: These findings suggest that there were no effects on the cerebral microcirculation under the given RF-EMF exposure conditions.

Unlabelled: THE AIM of this study was to determine the potential of radio-frequency electromagnetic fields (RF-EMF) to affect cerebral microcirculation, including blood-brain barrier function, in rat brain., Materials and Methods: The head of the rat was exposed for 10 min to 1439 MHz RF-EMF having three intensity doses: 0.6, 2.4, 4.8 W/kg of brain averaged specific absorption rate (BASAR). Four microcirculatory parameters: blood-brain barrier permeability, leukocyte behavior, plasma velocity, and vessel diameter were measured before and after RF-EMF exposure using a closed cranial window method., Results: No extravasation of intravenously injected dyes from pial venules was found at any BASAR level. No significant changes in the number of endothelial-adhering leukocytes after exposure were found. The hemodynamics indicated that the plasma velocities and vessel diameters remained constant within the physiological range throughout each exposure., Conclusion: These findings suggest that there were no effects on the cerebral microcirculation under the given RF-EMF exposure conditions.

Purpose: To investigate the effects of exposure to electromagnetic pulses (EMP) on functional indices of the cardiovascular system in male Sprague-Dawley rats., Materials and Methods: A tapered parallel plate Gigahertz Transverse Electromagnetic cell (GTEM cell) with a flared rectangular coaxial transmission line was used to expose the rats to EMP (0.5 pps, total 200 pulses and whole-body averaged specific absorption rate 50 mW/kg at 200 kV/m or 75 mW/kg at 400 kV/m). Concurrent sham-exposed animals were used as controls. Cardiovascular functions, namely, heart rate, and systolic, mean and diastolic blood pressures were measured immediately and up to 4 weeks post-exposure using a non-invasive tail-cuff photoelectric sensor sphygmomanometer., Results: The heart rates in sham- and EMP-exposed rats were not significantly changed. In the exposed rats, increased systolic blood pressure (SBP) occurred at 0 h and decreased SBP occurred at 1 day and 3 days after exposure. Significantly higher diastolic blood pressure (DBP) was found at 0 h and significantly lower DBP was found at 12 h, 1 day, and 1 month after exposure. Significantly higher mean arterial pressure (MAP) was noted at 0 h and significantly lower MAP was noted at 1 day., Conclusions: Significant alterations in arterial blood pressure were observed in rats exposed to EMP exposure while heart rate was not altered.

The aim of this study is to evaluate the effect of pulsatile blood flow in thermally significant blood vessels on the thermal lesion region during thermal therapy of tumor. A sinusoidally pulsatile velocity profile for blood flow was employed to simulate the cyclic effect of the heart beat on the blood flow. The evolution of temperature field was governed by the energy transport equation for blood flow together with Pennes' bioheat equation for perfused tissue encircling the blood vessel. The governing equations were numerically solved by a novel multi-block Chebyshev pseudospectral method and the accumulated thermal dose in tissue was computed. Numerical results show that pulsatile velocity profile, with various combinations of pulsatile amplitude and frequency, has little difference in effect on the thermal lesion region of tissue compared with uniform or parabolic velocity profile. However, some minor differences on the thermal lesion region of blood vessel is observed for middle-sized blood vessel. This consequence suggests that, in this kind of problem, we may as well do the simulation simply by a steady uniform velocity profile for blood flow.

The authors applied near-infrared low-level laser irradiation (LLLI) directed to the stellate ganglion (SG) and to the common carotid artery (CCA), and compared the effects on central retinal artery blood flow using color pulse Doppler sonography. In 10 healthy volunteers, LLLI (0.92 W, 1 : 1 duty cycle, 10 min) to both the SG and CCA significantly increased peak systolic blood velocity in the ophthalmic artery (p<0.001, each) and central retinal artery (p<0.001, each) without changes in vessel resistance. Irradiation to the CCA produced a stronger effect than that to the SG in the ophthalmic artery (p=0.007) and central retinal artery (p=0.031). These data suggest that LLLI to the SG or to the CCA is a useful therapy for increasing the retrobulbar blood flow, with irradiation directed to the CCA being more effective than that directed to the SG in clinical settings.

The effect of magnetic field (MF) exposure on microcirculation and microvasculature is not clear or widely explored. In the limited body of data that exists, there are contradictions as to the effects of MFs on blood perfusion and pressure. Approximately half of the cited studies indicate a vasodilatory effect of MFs; the remaining half indicate that MFs could trigger either vasodilation or vasoconstriction depending on initial vessel tone. Few studies indicate that MFs cause a decrease in perfusion or no effect. There is a further lack of investigation into the cellular effects of MFs on microcirculation and microvasculature. The role of nitric oxide (NO) in mediating microcirculatory MF effects has been minimally explored and results are mixed, with four studies supporting an increase in NO activity, one supporting a biphasic effect, and five indicating no effect. MF effects on angiogenesis are also reported: seven studies supporting an increase and two a decrease. Possible reasons for these contradictions are explored. This review also considers the effects of magnetic resonance imaging (MRI) and anesthetics on microcirculation. Recommendations for future work include studies aimed at the cellular/mechanistic level, studies involving perfusion measurements both during and post-exposure, studies testing the effect of MFs on anesthetics, and investigation into the microcirculatory effects of MRI.

A decrease in cerebral blood flow (CBF) and brain metabolic activity are well-known complications of stroke. Spinal cord stimulation (SCS) is successfully being used for the treatment of several low-perfusion syndromes. The aim of this chapter is to describe the data that support the effect of SCS on CBF and the use of SCS in the treatment of stroke and cerebral low perfusion syndromes. In addition, we present our relevant studies. Since April 1995, we have assessed 49 non-stroke patients. The following parameters were measured pre- and post-stroke: (1) CBF in healthy contralateral tissue by single photon emission computed tomography (SPECT), (2) systolic and diastolic velocity in the middle cerebral artery (MCA) by transcranial Doppler, (3) blood flow quantification in the common carotid artery (CCA) by color Doppler, and (4) glucose metabolism in healthy contralateral tissue by positron emission tomography (PET). Our results showed that during cervical SCS there was a significant (p < 0.001) increase in systolic (> or =21%) and diastolic (>26%) velocity in the MCA, and CCA blood flow (> or =51%) as well as glucose metabolism (44%). We concluded that cervical SCS (cSCS) can modify CBF and brain metabolism. Its potential role in the management of stroke and low-perfusion syndromes is further investigated by experimental studies and reports describing clinical experience. Appropriate clinical trials are warranted.

Ischemia-reperfusion injuries, such as those suffered from various types of cardiovascular disease, are major causes of death and disability. For relatively short periods of ischemia, much of the damage is potentially reversible and in fact, does not occur until the influx of oxygen during the reperfusion stage. Because of this, there is a window of opportunity to protect the ischemic tissue. Here, we review several mechanisms of protection, such as heat shock proteins, opioids, collateral blood flow, and nitric oxide induction, and the evidence indicating that magnetic fields may be used as a means of providing protection via each of these mechanisms. While there are few studies demonstrating direct protection with magnetic field therapies, there are a number of published reports indicating that electromagnetic fields may be able to influence some of the biochemical systems with protective applications.

This study sought to establish the photothrombotic 'ring' stroke model with late spontaneous reperfusion in adult mice. By applying a 3.0-mm diameter laser ring-beam (514 nm, 0.21 mm thick, 0.65 W/cm2) onto the exposed skull for 60 secs with concurrent erythrosin B (4.25 mg/kg) intravenous infusion for 15 secs, the centrally located cortical region within the ring locus was progressively encroached by an annular ring-shaped perfusion deficit. In this region, local cerebral blood flow (lCBF) measured by laser-Doppler flowmetry declined promptly after irradiation to 43% of the baseline value at 30 mins poststroke. Using double tracer autoradiography, quantitative lCBF measured with [14C]iodoantipyrine was 46 to 17 to 58 ml/100 g/mins at 4 h to 48 h to 7 days postischemia in this area. Cerebral protein synthesis (CPS), as detected by [3H]leucine incorporation into protein, transiently decreased to 57% to 38% to 112% at 4 h to 48 h to 7 days postischemia in the center region. Morphologically, some neurons in the center region appeared swollen at 4 h. At 48 h, the majority of neurons were severely swollen with eosinophilia and pyknosis, whereas at 7 days poststroke' the tissue morphology became partly restored. The center within the mouse photothrombotic ring lesion thus exhibits reversible alterations of local CBF, CPS and tissue morphology that are reminiscent of the cortical penumbra in other models of focal cerebral ischemia.