A sensitivity analysis of the step-temperature technique for measurement of local tissue blood perfusion

The step-temperature technique is a thermal technique that uses a small thermistor probe for measuring blood perfusion of tissue. The blood perfusion is derived from temperature and power measurements using equations that describe heat transfer in the integrated probe/tissue system. A numerical experiment is used to analyse the theoretical error caused by the assumptions used in the technique. The effects of the bead parameters, tissue parameters and measurement parameters are investigated. The study results are in accordance with experimental phenomena described previously. An optimal measurement time window is found to be 4-10 s, dependent mainly on the thermal conductivity and blood perfusion of tissue measured. This research will lead to reduce perfusion measurement errors.     

A novel model of the pulse decay method for measurement of local tissue blood perfusion

The blood perfusion of biological tissue is a basic parameter of physiology and medical engineering. A novel average temperature model (ATM) is presented in this paper to measure the blood perfusion of tissue based on the thermal pulse-decay method. Differing from the existing point source model (PSM) and spherical source model (SSM), the probe bead average temperature analytical solution is derived and used to estimate the blood perfusion. The blood perfusion prediction errors caused by the approximate assumptions used in each model are studied using the numerical experiment method. Contributions of the tissue parameters, probe thermistor bead parameters, and measurement parameters, such as tissue thermal conductivity, tissue thermal diffusivity, blood perfusion rate, bead thermal conductivity, bead radius, measurement time, and thermal pulse length are discussed. The predicting accuracy of the ATM model is compared with the PSM model and SSM model. The results show that, for all the cases tested, the ATM model is better than the other two.     

Continuous blood density measurement for hemodynamic monitoring: An analysis of its accuracy and sensitivity

Continuous measurement of arterial blood density after bolus injection of fluids of different density into the right atrium has been used to measure cardiac output and mean transit time through the central circulation. The transit time distribution for density, however, differs from that for plasma-phase tracers such as indocyanine green. This difference may yield important information about red cell transit times through the microcirculation. We analyzed the potential of the density technique to resolve small changes in transit time distributions. Rayleigh's Method was used to calculate the relationship between density distribution within the U-tube and frequency of oscillation. Fourier integral transformation of a functional representation of indocyanine green dye curves provided an estimate of amplitude versus frequency for likely input density signals. We found that the ability of the densitometer to accurately follow blood density changes depends upon physiologic parameters associated with the experimental animal and upon the physical characteristics of the densitometer itself. Even for small animals, such as a rabbit, the densitometer theoretically has the ability to accurately follow rapid density changes over time.     

A new thermode perfusion system for local temperature manipulation

A thermode perfusion system incorporating a miniature heater was used to alter the local temperature in the brain of the marmot and of the cat. In the marmot, local temperature has been changed or clamped over a range of 35–39°C at the rate of 0.4°C/W. In the cat, local temperature has been increased by 1.5°C and decreased by 2°C at the rate of 0.15°C/W.     

家兔体外血浆灌流实验方法的建立

目的建立兔体外血浆灌流的动物实验方法,用于评价一种体外血浆脂类吸附过滤器。方法以高脂血症大耳白兔为模型动物,先后使用了2种不同面积的中空纤维型血浆分离器,通过5mL真空采血管离心和100mL生理盐水袋离心等方法,将血浆与血细胞分离,通过蠕动泵在体外建立血浆循环。结果0．3m2的血浆分离器能够将血浆与血细胞有效分离,顺利进行血浆循环;但是,由于该型号的血浆分离器的容积过大,动物失血过多,因肺水肿等原因导致动物死亡。0．1m2的小型血浆分离器不能将高脂血症动物血浆与血细胞分离;而使用采血管,采血速度不能控制,操作时间长,血细胞损失过多,动物死亡率高。利用100mL生理盐水袋作为离心分离容器,分批采血,采用15％的枸橼酸钠溶液抗凝,离心分离血浆与血细胞,血浆进行体外循环;同时严格控制采血速度、回输速度以及抗凝条件,成功地建立了兔体外血浆灌流实验方法和方案,操作简单,动物存活率高。结论利用100mL生理盐水袋分批采血,离：0法分离血浆与血细胞,建立血浆体外循环。操作简单,比膜血浆分离器费用低,动物存活率高,是进行血液净化相关材料评价的理想的兔体外血浆灌流模型。     

The continuous high-precision measurement of the density of flowing blood

Summary The mechanical oscillator technique for the measurement of the density of fluids is based on the influence of mass on the natural frequency of a mechanical oscillator. The practical application of this principle was worked out by Kratky et al. (1969) and Leopold (1970). It is demonstrated in this study that the method permits the continuous high-precision measurement of the density of flowing blood in anesthetized animals. The accuracy is 10^–5 g/ml, the maximum sampling rate 20/min.As found in rabbits and cats during the control state, physiological blood density changes related to spontaneous blood pressure variations are up to 2·10^–4 g/ml. The method can be combined with i.v. injections of isotonic and iso-oncotic solutions to determine cardiac output and blood volume on the basis of a density dilution principle. Since the density of the interstitial fluid is lower than that of blood, fluid shifts through the capillary walls can be detected. The effects of hypertonic glucose and of hyperoncotic dextran have been examined. Changes in the density of the arterial blood appear within 10 s after i.v. injection of these fluids. Similarly, density changes result from hemorrhage and reinfusion. During and after i.v. administration of vasoactive drugs (noradrenaline, angiotensin II, acetylcholine), marked transient changes in blood density are seen which obviously reflect the effects of fluid shifts through the capillary walls. During hemorrhagic hypotension we found periodic variations in the blood density synchronous with spontaneously occurring Mayer waves. The new method seems to be a promising tool for investigations on physiological and pathological capillary fluid dynamics.     

Steady-state analysis and evaluation of a new thermal sensor for surface measurements of tissue perfusion

The steady-state response and operating characteristics of a new thermal sensor for surface measurements of local tissue perfusion have been analyzed theoretically and evaluated in vivo. The flow measurement system incorporates an electrically isolated thin-film thermal sensor, which is maintained at a fixed temperature by high frequency response electronic circuitry. The sensor rests on the tissue surface, and the power required to maintain a fixed probe to tissue temperature elevation is measured and related to tissue blood flow. A theoretical analysis of the steady-state probe response to flow changes was carried out employing the bio-heat-transfer equation and a solution based on Fourier series to describe the temperature distribution within the tissue domain. A comparison of steady-state theory to results obtained from initial experimental tests on the surface of the dog heart, over a perfusion range 0.51 to 2.00 ml/min/g, shows close agreement. The probe demonstrates good sensitivity to flow changes, provides stable and continuous measurements, and appears promising for both research and clinical applications.     

A new thermal sensor for surface-based measurement of local myocardial perfusion

The transient response of a new thermal sensor for continuous surface-based measurement of local tissue blood flow was evaluated in the beating dog heart. The sensor is 2.5 mm square, tests on the heart, and responds to flow changes only within a region of tissue 3-4 mm below its location on the epicardial surface. Initial studies demonstrate excellent sensitivity, good frequency response with a time constant of the order of 10-11 s, and an ability to continuously monitor changes in local myocardial blood flow during a variety of well-understood interventions, including coronary artery occlusion, reactive hyperemia, and intravenous administration of nitroglycerin and dipyridamole.     

Parametric studies on the phase shift method to measure the blood perfusion of biological bodies

To better understand the phase shift method to non-invasively measure the blood perfusion of living tissues in vivo, the dual reciprocity boundary element method (DRBEM) was applied to numerically solve the transient and non-linear two-dimensional bio-heat transfer in biological bodies subject to a sinusoidal heat flux at the skin surface. The influences of the heating flux, the heating oscillation magnitude, the heating frequency, the blood vessel underneath the skin, and the space or temperature dependent blood perfusion to the temperature response and the phase shift between the heat flux and the temperature response at the skin surface were comprehensively examined. The effects of the heating area to the temperature response were also investigated. And a better understanding on the heat transfer behavior of biological bodies under sinusoidal heating was thus obtained. These results are expected to be valuable for constructing the practical instrumentation to non-invasively measure the blood perfusion of biological bodies.     

A servo-controlled roller pump for constant flow or constant pressure blood perfusion under normal pulsatile or non-pulsatile conditions

This paper describes the design of a servo-controlled precision roller pump applicable for constant blood flow or constant blood pressure perfusion in research on the peripheral circulation. The pump, and its feed-back control, can simulate normal cardiac induced autoperfusion by reproducing the arterial pulse pressure configuration with high fidelity. Its design is such as to minimize damage of the red blood cells and consequent release of vasoactive substances, a problem encountered with most conventional pumps. The present pump principle may also find a use in heart-lung machines and dialysis equipment and can be used as a precision infusion pump.     

单微颗粒在血管内运动状态的力学分析

目的分析单个微颗粒在血管内的受力情况及影响其运动状态的因素。方法以靶向给药中血管流体中的微颗粒为研究对象,将血管模型简化成平行平板流动腔内的泊肃叶流动,依次分析单个微颗粒在流场中所受各个力的具体计算方法,通过力与力矩平衡条件列出微颗粒运动状态的方程,利用数值计算方法得到微颗粒所受力与颗粒粒径、流体流量之间的关系以及临界运动状态时粒径与流量的关系。结果流量增加和微颗粒粒径越大,微颗粒越容易滚动、滑移和上升;在流量和粒径关系图上,上升运动的临界线要高于滑移运动的临界线,而滚动运动临界线处于最下方。结论对于人体血液流量,微颗粒不会做上升运动。随着流量减少,一定粒径的颗粒可以从滑移运动过渡到纯滚动运动,在有弹性变形的情形下会出现完全静止。恰当选择颗粒的粒径及颗粒的表面黏附度对药物颗粒通过血液输送到达标靶位置至关重要。     

Theoretical analysis of the transient thermal clearance method for regional blood flow measurement

In the noninvasive transient thermal clearance method a metal plate at room temperature is attached to the investigated skin. The plate is thermally insulated from the environment, and so the tissue temperature, after an initial decrease, is increased at a rate which depends both on heat convection by blood and on tissue thermal conductivity. The corresponding bioheat conductivity equation is solved and the dependence of plate temperature on time and on blood flow discussed. It is shown that, for an appropriate choice of metal and plate thickness, regional blood flow can be derived from temperature/time curves.     

The influence of Sildenafil citrate on uterine tissue perfusion and the cardiovascular system during the luteal phase of the ovarian cycle in cows

The aim of the study was to evaluate the influence of the Sildenafil citrate on the blood flow in the uterus of cows during dioestrus. Uterine blood flow was examined in five, healthy, adult cows. Between day 6–8 of the ovarian cycle, each cow received 200 mg of sildenafil diluted in 10 ml of warm saline into the body of the uterus. Analysis of the blood pressure, ECG and the maximum velocity in m/s (V max) in the aorta was performed and selected parameters of the blood flow (PI, pulsatile index; RI, resistance index; SPV, systolic peak velocity; EDV, end diastolic velocity; FVI, flow velocity integral; SV/DV, systolic peak velocity: end-diastolic velocity ratio) were measured in the uterine artery (Arteria uterine) before and after sildenafil infusion. In addition, Color Doppler examination of the uterine wall perfusion was analyzed. A significant decrease of values of PI and SV/DV ratio as well as an increase of end diastolic velocity and time averaged maximum velocity was noted. With the use of color coded sonography, the increased intensity of the blood flow in the uterine wall was observed. It was concluded that intrauterine administration of sildenafil during dioestrus can increase uterine tissue perfusion.     

Thermal method for continuous measurement of cerebral perfusion

A new thermal system using constant heating power for continuous measurement of cerebral perfusion is presented. It is designed and implemented for optimal perfusion sensitivity and dynamic response based on heat-transfer analysis of perfused brain tissue with thermistors on the cortical surface. Two matched thermistors are used, one to serve as a perfusion sensor and the other to compensate for the base-line temperature changes. To improve the signal-to-noise ratio of the measurement system, lock-in amplifiers are used to minimise long-term drift and low-frequency noise. Errors in the measurement caused by electrical and thermal fluctuations are tested and analysed. In vitro tests show that the measurement accuracy of temperature change is better than 10⁻³°C, and the temperature resolution is even greater. In vivo evaluation confirms that the system is responsive to cerebral perfusion changes associated with sudden changes in mean arterial blood pressure caused by bolus injection of norepinephrine, blood withdrawal and blood infusion. The dynamic response of the system is sufficient to detect the autoregulatory perfusion changes in response to arterial blood pressure alteration and the oscillations of cerebral blood flow.     

Design of scaffolds for blood vessel tissue engineering using a multi-layering electrospinning technique

Aiming to develop a scaffold architecture mimicking morphological and mechanically that of a blood vessel, a sequential multi-layering electrospinning (ME) was performed on a rotating mandrel-type collector. A bi-layered tubular scaffold composed of a stiff and oriented PLA outside fibrous layer and a pliable and randomly oriented PCL fibrous inner layer (PLA/PCL) was fabricated. Control over the level of fibre orientation of the different layers was achieved through the rotation speed of the collector. The structural and mechanical properties of the scaffolds were examined using scanning electron microscopy (SEM) and tensile testing. To assess their capability to support cell attachment, proliferation and migration, 3T3 mouse fibroblasts and later human venous myofibroblasts (HVS) were cultured, expanded and seeded on the scaffolds. In both cases, the cell-polymer constructs were cultured under static conditions for up to 4 weeks. Environmental-scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), histological examination and biochemical assays for cell proliferation (DNA) and extracellular matrix production (collagen and glycosaminoglycans) were performed. The findings suggest the feasibility of ME to design scaffolds with a hierarchical organization through a layer-by-layer process and control over fibre orientation. The resulting scaffolds achieved the desirable levels of pliability (elastic up to 10% strain) and proved to be capable to promote cell growth and proliferation. The electrospun PLA/PCL bi-layered tube presents appropriate characteristics to be considered a candidate scaffold for blood vessel tissue engineering.     

A technique for improved blood sampling during sleep studies

Research protocols often require that blood samples be drawn during sleep. This study compares the efficacy of obtaining nocturnal blood samples using a standard heparinized intravenous setup versus the same intravenous setup used in conjunction with a small chemical heating pad. The chemical heating pad significantly improved the number of blood samples obtained and the maintenance of intravenous patency. The use of a chemical heating pad is an economical way to resolve the frustration of lost blood samples while maintaining a reasonable environment to monitor sleep.     

数字图像分析技术在鸡胚卵黄囊膜血管形成模型中的应用

目的应用数字图像处理技术客观、准确和快速地对鸡胚卵黄囊膜(chick embryo yolk sac membrane,YSM)血管图像进行定量分析,为促血管和抗血管生成药物的评价和筛选提供有效可靠的技术支持。方法应用OPTPRO2007图像采集系统和Image-proplus6.0图像分析软件对鸡胚卵黄囊膜血管图像背景处理和血管面积及血管密度等参数进行客观、准确地测量。结果建立了有效的鸡胚卵黄囊膜数字图像血管自动分析方法和步骤并通过药物实验对鸡胚卵黄囊膜血管图像进行了参数检测和统计分析。结论应用OPTPRO2007图像采集系统和Image-proplus6.0图像处理分析软件对鸡胚卵黄囊膜图像血管进行自动分析的方法不仅操作简便而且可较准确、快速、客观地反映鸡胚血管新生情况,优于鸡胚尿囊膜血管发生模型的常规人工目测血管计数方法。     

Techniques for continous measurement of local cerebral blood flow,PaO2,PaCO2 and blood pressure in the non-anesthetized animal

Summary Techniques have been developed for the study of cerebral blood flow (CBF) in non-anesthetized, non-curarized animals. Continuous recording of one or several local CBF in subcortical structures can be made, simultaneously with continous recordings of cerebral temperature,PaO₂,PaCO₂, arterial pressure and the E.Co.G. The CBF measurements, obtained by a thermal clearance method, are semi-quantitative.PaO₂ andPaCO₂ are measured quantitatively directly in the aorta by mass spectrography. Conventional techniques are used for the arterial pressure and the E.Co.G. recordings. The main advantage of the techniques described is the possibility of undertaking repeated long-duration recordings of the principal cerebro-vascular variables on animals not affected by operation stress or by drugs capable of modifying the regulation of CBF.     

Evaluation of the thermodilution technique for measuring coronary sinus blood flow

Summary In hydraulic non-occlusive models, mixing effects were studied with slug-injection and constant-infusion techniques. Measurements were accomplished by means of catheters specially constructed with thermistors. Constant-rate infusion of 5 ml/min of saline at room temperature showed homogeneity of mixing. Good correlation (r=0.936) was found between metered flow ranging from 50–450 ml/min and reciprocal temperature changes.In anesthetized open chest dogs reciprocal temperature changes during constant-infusion thermodilution was compared with coronary sinus flow metered by graduated cylinder and stop-watch. For this purpose all the coronary sinus blood was directed through a tubing system with a Y-connector into the jugular vein. In the range of 50–450 ml/min the metered coronary sinus blood flow and the reciprocal of the observed changes in temperature showed a linear correlation (r=0.949). The reproducibility of the thermodilution method is fairly good. Therefore it is believed that this technique will allow accurate measurement of coronary sinus blood flow.This work was supported by a grant of the Swiss National Fund for Scientific Research.