Local Blood Volume Research Articles

Pinacidil induces vascular dilation and hyperemia in vivo and does not impact biophysical properties of neurons and astrocytes in vitro

Vascular and neural systems are highly interdependent, as evidenced by the wealth of intrinsic modulators shared by the two systems. We tested the hypothesis that pinacidil, a selective agonist for the SUR2B receptor found on smooth muscles, could serve as an independent means of inducing vasodilation and increased local blood volume to emulate functional hyperemia. Application of pinacidil induced vasodilation and increased blood volume in the in vivo neocortex in anesthetized rats and awake mice. Direct application of this agent to the in vitro neocortical slice had no direct impact on biophysical properties of neurons or astrocytes assessed with whole-cell recording. These findings suggest that pinacidil provides an effective and selective means for inducing hyperemia in vivo, and may provide a useful tool in directly testing the impact of hemodynamics on neural activity, as recently predicted by the hemo-neural hypothesis.

Concentric resistance training increases muscle strength without affecting microcirculation

Purpose While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. Materials and methods Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54 ± 9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50 min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. Results The significant ( P < 0.001) increase in CSA (60 ± 16 before vs. 64 ± 15 cm 2 after training) and in absolute muscle strength (isometric, 146 ± 44 vs. 174 ± 50 Nm; isokinetic, 151 ± 53 vs. 174 ± 62 Nm) demonstrated successful training. Neither capillary density ex vivo (351 ± 75 vs. 326 ± 62) nor ultrasonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2 ± 1.2 vs. 1.1 ± 1.1 ml/min/100 g; blood flow velocity, 0.49 ± 0.44 vs. 0.52 ± 0.74 mm s −1). Also, the intensities of high-energy phosphates phosphocreatine and β-adenosintriphosphate were not different after training within the skeletal muscle at rest (β-ATP/phosphocreatine, 0.29 ± 0.06 vs. 0.28 ± 0.04). Conclusion The significant increase in muscle size and strength in response to concentric isokinetic and isometric resistance training occurs without an increase in the in vivo microcirculation of the skeletal muscles at rest.

Caffeine's effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism

The blood-oxygenation-level-dependent (BOLD) signal is dependent on multiple physiological factors such as cerebral blood flow (CBF), local oxygen metabolism (CMRO2) and cerebral blood volume (CBV). Since caffeine affects both CBF and neural activity, its effects on BOLD remain controversial. The calibrated BOLD approach is an excellent tool to study caffeine because it combines CBF and BOLD measures to estimate changes in CMRO2. The present study used the calibrated BOLD approach with 5% CO2 to determine if a 2.5 mg/kg intravenous injection of caffeine changes the coupling between CBF and CMRO2 during motor and visual tasks. The results show that caffeine decreases n, the CBF:CMRO2 coupling ratio, from 2.58 to 2.33 in motor (p=0.006) and from 2.45 to 2.23 in visual (p=0.002) areas respectively. The current study also demonstrated that caffeine does not alter cerebrovascular reactivity to CO2. These results highlight the importance of the calibrated BOLD approach in improving interpretation of the BOLD signal in the presence of substances like caffeine.

50 INTRAVENOUS LASER BLOOD IRRADIATION IN A PARTICULAR CASE OF JUVENILE POLYARTHRITIS

Laser therapy by low light doses shows promising results in the modulation of some cell functions. Various clinical studies indicate that laser therapy is a valuable method for pain treatment and the acceleration of wound healing. However, the mechanism behind it is still not completely understood. To explore the effect of a low-power diode laser (λ=780 nm) on normal skin tissue, time-dependent contrast enhancement has been determined by magnetic resonance imaging (MRI). In the examinations, six healthy volunteers (four male and two female) have been irradiated on their right planta pedis (sole of foot) with 5 J/cm2 at a fluence rate of 100 mW/cm2. T1-weighted magnetic resonance imaging is used to quantify the time-dependent local accumulation of Gadolinium-DPTA, its actual content in the local current blood volume as well as its distribution to the extracellular space. Images are obtained before and after the application of laser light. When laser light is applied the signal to noise ratio increases by more than 0.35±0.15 (range 0.23–0.63) after irradiation according to contrast-enhanced MRI. It can be observed that, after biomodulation with light of low energy and low power, wound healing improves and pain is reduced. This effect might be explained by an increased blood flow in this area. Therefore, the use of this kind of laser treatment might improve the outcome of other therapeutic modalities such as tumour ionizing radiation therapy and local chemotherapy.

Quantitative evaluation of local myocardial blood volume in contrast echocardiography

Myocardial perfusion is usually assessed by Single Photon Emission Computed Tomography (SPECT) imaging. Information about myocardial perfusion is sometimes deduced from angiography or Computed Tomography (CT) angiography, which detect coronary artery stenosis. Contrast echocardiography can be used for that purpose as well. However, the currently available data acquisition and analysis methods are difficult to manage in the clinical environment. This paper presents a novel contrast echo data acquisition protocol and parameter extraction procedure, providing an automatic quantitative evaluation of the local myocardial blood volume for the entire left ventricular myocardium. This information is indicative of local perfusion. Our method evaluates the myocardial blood volume according to the local gray level intensity, as measured during a single heartbeat, when there is a distinct myocardial opacification (based on visual estimation). The echocardiographic image analysis is based on a new attenuation correction technique, which compensates for the ultrasonic signal attenuation in both the tissue and the contrast agent. In comparison, the existing contrast echo based methods utilize the long-term temporal variability of the gray level to extract information regarding the local myocardial blood flow velocity. Our technique has been tested on 17 cine-loops of 15 different patients. We have found a high correlation between abnormal segments, detected automatically by our technique, and segments that have been clinically diagnosed as ischemic (at rest) or infarcted. For that purpose, we have defined ischemic segments as segments fed by coronary arteries with severe stenosis, as determined by angiography, and infarcted segments as segments after Acute Myocardial Infarction, as detected by electrocardiography. Furthermore, we have found a high correlation between the automatically calculated myocardial blood volume levels and the clinical evaluation of segmental contractility, based on echocardiographic imaging.

Respiratory muscle unloading improves leg muscle oxygenation during exercise in patients with COPD

Background:Respiratory muscle unloading during exercise could improve locomotor muscle oxygenation by increasing oxygen delivery (higher cardiac output and/or arterial oxygen content) in patients with chronic obstructive pulmonary disease (COPD).Methods:Sixteen non-hypoxaemic...

Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure

Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 +/- 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation (P < 0.05). There were no significant effects of RM unloading on systemic O2 delivery as QT and SpO2 at submaximal exercise and at Tlim did not differ between PAV and sham ventilation (P > 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Delta[O2Hb]% and Delta[HbTOT]%, respectively (P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.

Effects of probe contact pressure on in vivo optical spectroscopy

The short- and long-term effects of probe contact pressure on in vivo diffuse reflectance and fluorescence spectroscopy were investigated using an animal model. Elevation in probe contact pressure induced major profile alterations in the diffuse reflectance spectra between 400 and 650 nm, and led to significant intensity increases in the fluorescence spectra. The pressure threshold that was required to induce statistically significant spectral alterations was dependent upon the type of tissue. The observed spectral alterations may be attributed to decreases in local blood volume, blood oxygenation, and tissue metabolism, resulting from high probe contact pressure.

Vascular Space Occupancy Weighted Imaging With Control of Residual Blood Signal and Higher Contrast-to-Noise Ratio

It has been recently proposed that the local cerebral blood volume change during brain activation can be measured by a series of images whose contrast is dependent on vascular space occupancy (VASO). VASO takes advantage of the inversion recovery sequence to acquire images when the longitudinal magnetization (Mz) of blood is relaxing through zero. The degree of blood suppression, however, is not always well controlled as a consequence of spatial variations in inversion efficiency and blood T1. Furthermore, while blood is eliminated, the Mz of other tissues is also small, which makes the contrast-to-noise ratio inherently low in VASO. In this paper, diffusion gradients were applied to demonstrate residual intravascular signal in the original VASO. An alternative VASO-weighted imaging was then proposed using a longer inversion time at which the Mz difference between blood and gray matter was optimized. A global saturation immediately after image acquisition was employed to eliminate the Mz disparity between inflowing blood and the residual in-plane blood from previous acquisition. Feasibility was evaluated by numerical simulation and functional experiments. In human visual cortex, the fractional VASO signal and cerebral blood volume changes were found to be -0.6% and 44%, respectively (voxel size = 3.4 x 3.4 x 5.0 mm3). As compared to the original VASO, the presented method provided a largely comparable activation map and hemodynamic curve but was not confounded by the existence of blood. Results also demonstrated its advantages of 1.6-fold higher CNR and insensitivity to variant tissue/blood T1 as well as inversion efficiency.

Assessment of Metabolism and Microcirculation of Healthy Skeletal Muscles by Magnetic Resonance and Ultrasound Techniques

To assess metabolism and microcirculation of healthy skeletal muscle by magnetic resonance (MR) and ultrasound techniques and to compare these data with muscle histology, and anthropometric and blood parameters. Thirty-four healthy volunteers were selected such that their measured aerobic capacity (VO2max) per body weight ranged between 23 and 66 mL/minute/kg to render a large variability of skeletal muscle capillarization as a result of their different physical activity. We analyzed body composition, blood parameters, and skeletal muscle fiber size and capillarization in biopsies of the vastus lateralis muscle. These data were compared with knee extensor cross-sectional area (CSA) obtained by MR imaging, microcirculation of the vastus lateralis muscle by contrast-enhanced ultrasound (CEUS), and its energy and lipid metabolism measured with 31P and 1H MR spectroscopy. Statistical analysis was performed using Pearson's correlation coefficient and significance was tested at a level of .5%. The variable physical activity was reflected in a large variability of vastus lateralis muscle perfusion and metabolism at rest with highest histologic capillarization and CEUS-perfusion values observed in the best-trained volunteers. Levels of high-energy phosphates, such as phosphocreatine, were positively correlated with CSA (r= .5) and histologic fiber size (r= .6 for type IIA and IIX fibers), while phosphocreatine concentration was significantly negatively correlated to myocellular lipids (r=-.6) and trimethyl ammonium containing compounds (r=-.8). Local blood volume measured in vivo with CEUS was positively correlated with several histologic capillarization parameters. Dedicated MR- and CEUS-methods deliver (patho-)physiologic information about capillarization and fiber characteristics of skeletal muscles in vivo and hence establish a useful diagnostic tool for muscular diseases.

High-concentration contrast media in neurological multidetector-row CT applications: implications for improved patient management in neurology and neurosurgery

Dynamic CT scanning after intravenous injection of iodine contrast medium (CM) was proposed in the very early days of CT. The goal was to characterize tissue by extracting information from the temporal course of enhancement. In the early 1980s, modeling algorithms were already described in the literature for the quantitative calculation of cerebral blood flow (CBF). However, cerebral applications suffered from the insufficient temporal resolution available at that time and the central nervous system was already seen primarily as an MRI domain. The renaissance of dynamic CT in neurological applications came in the middle of the 1990s with the introduction of thrombolytic therapy in acute stroke. With CT being the primary imaging modality, getting additional hemodynamic information from the same device without having to move the patient appeared attractive. Multimodal CT protocols allow a comprehensive diagnosis of the emergency stroke patient in less than 15 minutes by combining nonenhanced CT (NECT), perfusion CT (PCT) and CT angiography (CTA). Dynamic PCT can also render important information in patients with intraaxial brain tumors, allowing differentiation not only between lymphoma and glioma but also between low-grade and high-grade glioma by quantifying local cerebral blood volume (CBV) and permeability of the blood-brain barrier (BBB). However, even if a shorter imaging time permits a reduction in volume of CM, adequate total iodine levels must be preserved for dynamic CT applications. Increased concentrations of iodine are therefore helpful to obtain adequate total iodine levels for imaging.

A Direct Method for Measuring Mouse Capillary Cortical Blood Volume Using Multiphoton Laser Scanning Microscopy

Knowledge of the blood volume per unit volume of brain tissue is important for understanding brain function in health and disease. We describe a direct method using two-photon laser scanning microscopy to obtain in vivo the local capillary blood volume in the cortex of anesthetized mouse. We infused fluorescent dyes in the circulating blood and imaged the blood vessels, including the capillaries, to a depth of 600 microm below the dura at the brain surface. Capillary cortical blood volume (CCBV) was calculated without any form recognition and segmentation, by normalizing the total fluorescence measured at each depth and integrating the collected intensities all over the stack. Theoretical justifications are presented and numerical simulations were performed to validate this method which was weakly sensitive to background noise. Then, CCBV had been estimated on seven healthy mice between 2%+/-0.3% and 2.4%+/-0.4%. We showed that this measure of CCBV is reproductible and that this method is highly sensitive to the explored zones in the cortex (vessel density and size). This method, which dispenses with form recognition, is rapid and would allow to study in vivo temporal and highly resolute spatial variations of CCBV under different conditions or stimulations.

Retrobulbar Blood Flow in Idiopathic Dilated Episcleral Veins and Glaucoma

Dilated episcleral veins may occur in the presence of orbital tumors, carotid cavernous sinus fistula and other orbital obstructive lesions. A 39-year-old man had a history of a red left eye for two years. The visual acuity was 20/20, episcleral and conjunctival veins were dilated, and both the intraocular (24 mmHg) and episcleral venous (18 mmHg) pressures were increased. The canal of Schlemm was filled with blood, and glaucomatous damage was pronounced in the optic nerve head and the visual field of the left eye. The retrobulbar blood flow in the left eye was normal in the ophthalmic and central retinal arteries, but markedly decreased in the central retinal vein. There were no signs of fistula or shunts. The right eye was without any pathology. MR and catheter angiography of the head and orbit were both normal. Following trabeculectomy, the intraocular and episcleral venous pressures dropped to 9 mmHg and 8 mmHg, respectively, at 6 months follow-up. The episcleral and conjunctival venous congestion regressed, and the blood flow in the central retinal vein increased. The reason for the observed clinical picture (Radius-Maumenee syndrome) and haemodynamic improvement after reduction of the intraocular pressure is not clear. We outline a hypothesis involving an increase of the vascular resistance in the vortex veins and the superior ophthalmic vein with a shift in local blood volume and vascular pressure due to high intraocular pressure.

Autofluorescence endoscopy for the gastrointestinal tract

This review focuses on our basic study results and clinical experience of fluorescence endoscopy for the gastrointestinal (GI) tract. Collagen, which fluoresces in the green wavelength range, is one of the major sources of tissue autofluorescence (AF) and AF imaging systems are now available. With their use, however, it is important to take into account tissue changes other than, or in addition to, changes in gross tissue morphology. These may include alterations in the local blood volume, tissue metabolic activity, and relative fluorophore concentrations. New AF imaging systems are very easy to use, because white light endoscopy can be changed to AF at the push of a button, and hold great promise for diagnosis of early carcinomas and premalignant lesions in the GI tract. In particular, AF endoscopy has potential for identification of small or flat tumors, tumor margins and premalignant lesions in Barrett's esophagus, as well as for assessing tumor grade and response to therapy. However, large-scale studies are needed to clarify the clinical impact of this new diagnostic approach.

Contrast-enhanced Ultrasound in Dermatomyositis- and Polymyositis

To evaluate prospectively contrast-enhanced ultrasound (CEUS) in patients suspected of having dermatomyositis or polymyositis. In 35 patients (23 women, 12 men; mean age, 51 years+/-16 years) who were suspected of having dermatomyositis or polymyositis, perfusion in clinically affected skeletal muscles was quantified with contrast-enhanced intermittent power Doppler ultrasound. By applying a modified model that analyzed the replenishment kinetics of microbubbles, the perfusion-related parameters blood flow, local blood volume and blood flow velocity were measured. Findings were compared with muscle biopsy appearances and with the results of MRI that was performed with a 1.5-Tesla unit. Receiver operating characteristic analysis was performed and optimum thresholds for diagnosis of myositis were determined. Eleven patients had histologically confirmed dermatomyositis or polymyositis and showed significantly higher blood flow velocity (P=.01 for dermato- and P<.001 for polymyositis), blood flow (P<.001 for dermato- and polymyositis), and blood volume (P=.007 for dermato- and P<.001 for polymyositis) on contrast-enhanced ultrasound than those who did not have myositis. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis. MRI had a sensitivity, specificity, positive (PPV), and negative predicting values (NPV) of 100%, 88%, 77%, and 100% for diagnosis of myositis, respectively. CEUS blood flow was the best ultrasound measure for diagnosis of dermato- or polymyositis with sensitivity, specificity, PPV, and NPV of 73%, 91%, 80%, and 88%, respectively. Increased skeletal muscle perfusion measured by CEUS could serve as an additional measurer for the diagnosis of an inflammatory myopathy.

Osteosarcoma

We sought to evaluate diffusion and perfusion weighted 1.5 T magnetic resonance imaging (MRI) in detecting tumor necrosis with histologic correlation after preoperative chemotherapy. Eight patients (ages 11-19 years) with histologic proven osteosarcoma of the limbs underwent T1- and fat-suppressed T2-weighted spin echo and diffusion-weighted EPI sequences (b value = 700) after 5 cycles of standard chemotherapy. Tumor volume and apparent diffusion coefficients (ADC) were calculated. Tumor signal intensities were measured in dynamic contrast enhanced T1-weighted fast gradient echo-sequences obtained every 3 seconds after an intravenous injection of gadolinium-DTPA. Perfusion parameters of first-pass tracing of contrast medium (time-to-peak, slope of contrast enhancement curve) were calculated, and perfusion maps were established. After MRI, all patients underwent limb resection, and the specimens were investigated macroscopically and histologically. The degree of tumor necrosis was assessed using the histologic Salzer-Kuntschik classification (grades 1-6) after chemotherapy. Necrotic areas, which were confirmed by macroscopic/histologic examination, showed ADC values up to 2.7 (mean, 2.3 +/- 0.2). Viable tumor areas revealed lower apparent diffusion coefficients (mean, 0.8 +/- 0.3). The differences in ADC between viable and necrotic tumor were highly significant (paired t test; P = 0.01). Slopes of necrotic areas ranged from 0.1 up to 5.2%/min (mean, 1.5%/min) and those of viable tumor areas from 2.8 to 31.5%/min (mean, 16.1%/min). The time-to-peak-values (TTPs) ranged from 40 to 210 seconds (mean, 131 seconds, SD 60 seconds) in necrotic tumors and from 30 to 96 seconds (mean, 55 seconds, SD 21) in viable areas of sarcomas. The differences in slope and TTP between viable and necrotic tumor were highly significant. In necrotic areas, the linear correlation between slope (%/min) and ADC (mm/s) and between TTP (s) and ADC were weak, respectively. Both dynamic contrast-enhanced MRI and diffusion-weighted MRI permit recognition of tumor necrosis induced by chemotherapy in osteosarcomas. We hypothesized that diffusion-weighted imaging is correlated directly with tumor necrosis. Perfusion-weighted imaging is correlated with microvessel density, vascular permeability, local blood volume, and flow. Therefore, perfusion weighed MRI depicts areas of tumor cell necrosis indirectly.

Relationship of Skeletal Muscle Perfusion Measured by Contrast-Enhanced Ultrasonography to Histologic Microvascular Density

The purpose of this study was to compare skeletal muscle perfusion measured by contrast-enhanced ultrasonography (CEUS) with microvascular density in muscle biopsies. Power Doppler sonography after intravenous bolus injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by analyzing replenishment kinetics. CEUS perfusion was compared with vascularization of biopsy samples from vastus lateralis muscle. Subjects were selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per body weight ranged between 23 and 66 mL . min(-1) . kg(-1) to render a large variability of skeletal muscle capillarization. Moreover, subjects' venous blood hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume fraction (1-Hkt=PVF) in which the microbubbles can distribute. Median capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO(2)max (r=0.59; P<.01). Among CEUS parameters, B showed the closest correlation to CFC (r=0.53; P<.01). When CFC was normalized for PVF, correlation of B to CFC was r=0.64 (P<.01). CEUS could depict the physiologic large variability of vastus lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3] approximately mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] approximately mL . min(-1) . 100 g tissue(-1)). B is significantly related to fiber-adjacent capillarization and may represent physiologic capillary recruitment (eg, through metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion quantification.

TREATMENT OF FEMALE INFERTILITY INCORPORATING LOW-REACTIVE LASER THERAPY (LLLT): AN INITIAL REPORT

Infertility is a major physiological and psychological problem for women, and can also put strain on the husband-wife relationship. A number of approaches have been developed for the infertile woman with a fertile husband, such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and artificial insemination with the husband’s (or partner’s) sperm (AIH). Although the success rate with these approaches is good, some women remain refractorily infertile. Low incident levels of laser energy, known as low reactive-level laser therapy (LLLT), have been proved useful in a variety of clinical fields, including the enhancement of local blood flow rate and volume. The present study evaluated the adjunctive application of an 830 nm diode LLLT system (60 mW in continuous wave, 5 min/point, approx. 300 J/cm2) in combination with artificial reproductive technology (ART). Twenty-four patients (ages ranging from 30-48 yrs) received LLLT, among whom there were 8 pregnancies (33.3%) and 3 miscarriages (12.5%), with greater efficacy seen in the younger age groups. Of the 24, 19 underwent ICSI plus LLLT with 7 pregnancies (pregnancy rate of 36.8%). On the other hand, in twenty-one ICSI patients during the same period who did not receive LLLT, only 4 pregnancies occurred (pregnancy rate of 19%). However, the series is too small to state definitively that LLLT significantly contributed to improvement in the rate of pregnancy among refractorily infertile women, but based on our experience we feel that LLLT improved the blood supply to the ovum and womb, thereby increasing the pregnancy rate. Furthermore, LLLT is safe, painless, easy to deliver and well tolerated. We will certainly continue using LLLT in infertile women, and larger studies are planned for the future to confirm the interesting results of the present study.

Assessment of Skeletal Muscle Perfusion Using Contrast-Enhanced Ultrasonography

The purpose of this study was to develop a clinically applicable examination method to assess perfusion of the skeletal muscle using contrast-enhanced ultrasonography (CEUS) analyzing replenishment kinetics of microbubbles. Power Doppler sonography (7 MHz) after intravenous bolus injection of 10 mL of a microbubble contrast agent was used to repeatedly examine the perfusion of the right biceps muscle at rest and after defined exercise in 10 healthy volunteers. Parameters of perfusion, such as local blood volume, blood flow velocity, and perfusion, were calculated by a modified analysis of replenishment kinetics. For validation, CEUS was correlated with venous occlusion plethysmography (VOP) examining the right forearm flexor muscles at rest and after defined exercise. The CEUS examination was easily feasible and was able to depict the physiologic large variability of the right biceps muscle perfusion at rest (mean +/- SD, 3.0 +/- 2.3 [approximately mL/s x 100 mg]) compared with the results after exercise (22.9 +/- 11.0 [approximately mL/s x 100 mg]). The perfusion calculated with VOP significantly correlated with the CEUS parameters perfusion (r = 0.81; P < .001) and blood volume (r = 0.82; P < .001). The calculated mean blood flow velocity in the right forearm flexor muscles raised from 0.41 +/- 0.24 mm/s at rest to 0.64 +/- 0.39 mm/s after exercise, showing a significant correlation with the CEUS perfusion (r = 0.72; P < .001). Muscle perfusion can be easily and quantitatively assessed with CEUS. Compared with VOP, CEUS allows for a separate analysis of different muscle groups, unaffected by skin perfusion. Its application may be of particular interest in the diagnosis and monitoring of pathologic microvascularization in myositis or diabetic obstructive disease.

Initial Oligemia with Capillary Flow Stop Followed by Hyperemia during K+-Induced Cortical Spreading Depression in Rats

Local cerebral blood volume (CBV) and capillary flow changes in regions of depolarizing neurons during K(+)-induced cortical spreading depression (CSD) in the cerebral cortex of alpha-chloralose-urethane-anesthetized rats were examined employing a transillumination (550 nm) video system. Capillary flow was calculated as the reciprocal of mean transit times of blood in pixels of 40 microm x 40 microm, each of which contains a few capillaries. Potassium microinjection into the cortex evoked repetitive wave-ring spreads of oligemia at a speed of ca. 2.33 +/- 0.48 mm/min. During the spread of CSD, tracer (either saline or carbon black) was injected into the internal carotid artery. Colocated with the oligemic wave, we detected capillary flow stop as evidenced by disappearance of the hemodilution curves. At any location in the region of interest within the cerebral cortex, we observed cyclic changes of capillary flow stop/hyperperfusion in synchrony with oligemia/hyperemia fluctuations. The initial flow stop and oligemia were ascribed to capillary compression by astroglial cell swelling, presumably at the pericapillary endfeet, since the oligemia occurred before larger vessel changes. We conclude that local depolarizing neurons can decrease adjacent capillary flow directly and immediately, most likely via astroglial cell swelling, and that the flow stop triggers upstream arteriolar dilatation for capillary hyperperfusion.