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Temperature uniformity during hyperthermia: the impact of large vessels.

During hyperthermia the presence of a large vessel entering the heated volume and carrying blood at the systemic temperature can be an important source of temperature non-uniformity and possible underdosage. The minimal tumour temperature near a large vessel is determined by the vessel wall temperature: a number of factors influencing the vessel wall temperature are considered--effective tissue conductivity, flow type, vessel size, entrance effects and counter-current flow. In some specific cases, especially when tissue perfusion is high, the vessel wall temperature may reach therapeutic levels when the mean blood temperature is still low. In general, well perfused tumours have a better chance of being heated uniformly. Regional heating improves temperature uniformity by reducing entrance and equilibration effects as blood is heated before entering the tumour. Raising the core temperature also reduces temperature inhomogeneity. Spatial SAR resolution should preferably be of the order of magnitude of a centimetre or better.

Blood Vessels↗

Accuracy of geometrical modelling of heat transfer from tissue to blood vessels.

We have developed a thermal model in which blood vessels are described as geometrical objects, 3D curves with associated diameters. Here the behaviour of the model is examined for low resolutions compared with the vessel diameter and for strongly curved vessels. The tests include a single straight vessel and vessels describing the path of a helix embedded in square tissue blocks. The tests show the excellent behaviour of our discrete vessel implementation.

Blood Vessels↗

Tests of the geometrical description of blood vessels in a thermal model using counter-current geometries.

We have developed a thermal model, for use in hyperthermia treatment planning, in which blood vessels are described as geometrical objects; 3D curves with associated diameters. For the calculation of the heat exchange with the tissue an analytic result is used. To arrive at this result some assumptions were made. One of these assumptions is a cylindrically symmetric temperature distribution. In this paper the behaviour of the model is examined for counter-current vessel geometries for which this assumption is not valid. Counter-current vessel pairs intersecting a circular tissue slice are tested. For these 2D geometries vessel spacing, tissue radius and resolution are varied, as well as the position of the vessel pair with respect to the discretized tissue grid. The simulation results are evaluated by comparison of the different heat flow rates with analytical predictions. The tests show that for a fixed vessel configuration the accuracy is not a simple decreasing function of the voxel dimensions, but is also sensitive to the position of the configuration with respect to the discretized tissue grid.

Blood Vessels↗

Theoretical analysis of the heat convection coefficient in large vessels and the significance for thermal ablative therapies.

Ablative therapies such as radio-frequency (RF) ablation are increasingly used for treatment of tumours in liver and other organs. Often large vessels limit the extent of the thermal lesion, and cancer cells close to the vessel survive resulting in local tumour recurrence. Accurate estimates of the heat convection coefficient h for large vessels will help improve ablation techniques, and are required for estimation of thermal lesion dimensions in simulations. Previous estimates of h did not consider that only part of the vessel is heated, and assumed uniform temperature distribution at the vessel wall. An analytical relationship between the heat convection coefficient, blood velocity and temperature is formulated. The heat convection coefficient evaluated will assist both simulations and design of proper protocols for in vivo measurements. The mathematical model developed in this work describes the exchange of heat between a solid surface and a moving fluid and it is based on energy and motion equations for Navier-Stokes fluids. A particular case of a laminar blood flow in the portal vein is studied when a portion of its surface is heated. The results show that heating a larger portion of the vessels reduces convective heat loss, which may result in more effective ablation strategies.

Blood Flow Velocity↗

Comparison of diffusion approximation and Monte Carlo based finite element models for simulating thermal responses to laser irradiation in discrete vessels.

Both diffusion approximation (DA) and Monte Carlo (MC) models have been used to simulate light distribution in multilayered human skin with or without discrete blood vessels. However, no detailed comparison of the light distribution, heat generation and induced thermal damage between these two models has been done for discrete vessels. Three models were constructed: (1) MC-based finite element method (FEM) model, referred to as MC-FEM; (2) DA-based FEM with simple scaling factors according to chromophore concentrations (SFCC) in the epidermis and vessels, referred to as DA-FEM-SFCC; and (3) DA-FEM with improved scaling factors (ISF) obtained by equalizing the total light energy depositions that are solved from the DA and MC models in the epidermis and vessels, respectively, referred to as DA-FEM-ISF. The results show that DA-FEM-SFCC underestimates the light energy deposition in the epidermis and vessels when compared to MC-FEM. The difference is nonlinearly dependent on wavelength, dermal blood volume fraction, vessel size and depth, etc. Thus, the temperature and damage profiles are also dramatically different. DA-FEM-ISF achieves much better results in calculating heat generation and induced thermal damage when compared to MC-FEM, and has the advantages of both calculation speed and accuracy. The disadvantage is that a multidimensional ISF table is needed for DA-FEM-ISF to be a practical modelling tool.

Blood Vessels↗

Resonance frequency of microbubbles in small blood vessels: a numerical study.

Microbubbles are currently used as ultrasound contrast agents. Their potential therapeutic applications are also under investigation. This work is designed to provide some insight into the mechanisms of energy absorption and deposition by a preformed gas bubble in the microvasculature to optimize its efficacy. In the linear regime, the most favourable condition for the transfer of energy from an ultrasonic field to a gas bubble occurs when the centre frequency of the ultrasonic field equals the resonance frequency of the bubble. The resonance frequency of gas microbubbles has been investigated up to now mainly in unbounded liquids; however when bubbles are confined in small regions, their resonance frequency is strongly affected by the surrounding boundaries. A parametric study on how the resonance frequency of microbubbles in blood vessels is affected by the bubble radius, vessel radius and the bubble position in the vessel is presented. The resonance frequency decreases below its free value with decreasing vessel radius for vessels smaller than 200-300 microm depending on the bubble size. This model suggests the possibility of using ultrasound in a range of frequencies that are, in general, lower than the ones used now for therapeutic and diagnostic applications of ultrasound (a few MHz). When microbubbles oscillate at their resonance frequency they absorb and therefore emit more energy. This energy may allow specific blood vessels to be targeted for both diagnostic and therapeutic applications of ultrasound.

Blood Vessels↗

Effect of experimental tooth movement on nerve fibres immunoreactive to calcitonin gene-related peptide, protein gene product 9.5, and blood vessel density and distribution in rats.

The effect of experimental tooth movement on nerve fibers immunoreactive to calcitonin gene-related peptide (CGRP) and to protein gene product (PGP) 9.5 were studied, as well as the coincidence of these responses with changes in blood vessel density and distribution in the periodontal ligament (PDL) and pulp of young Wistar rats. The first right maxillary molar was moved mesially by an orthodontic appliance for 3, 7, 14 and 21 days. Sagittal and horizontal serial sections were incubated alternately with antibodies to CGRP, PGP 9.5 and laminin. Nerve and blood vessel density and distribution between the experimental and control sides were compared in the apical and cervical PDL, and in root and coronal pulp. The most pronounced changes occurred in the 7 day group. CGRP and PGP 9.5 immunoreactive nerves in the apical PDL showed increased density, being distributed towards the alveolar bone and frequently found in bone resorption lacunae. Numerous nerve fibres were often present adjacent to hyalinized tissue, but were never found near or within root resorption lacunae. Nerve sprouting was also present both in the root and coronal pulp. Increased nerve and blood vessel density generally coincided with each other. At day 14, periodontal nerves and blood vessels were still disorganized compared with the controls. Tissues near cellular cementum and root resorption lacunae were consistently devoid of nerve fibres. After 21 days, PDL nerve and blood vessel density and distribution were nearly at control level. However, nerve fibres were regularly found inside root resorption areas. In conclusion, experimental tooth movement induces dynamic changes in density and distribution of periodontal and pulpal nerve fibres, indicating their involvement in both early stages of periodontal remodelling and later in the regenerative processes of the PDL, generally occurring in concerted action with modulation of blood vessels.

Alveolar Process↗

Blood vessel response to pan-endothelium (RECA-1) antibody in normal and tooth loaded rat periodontal ligament.

Immunolabelling of the normal rat molar periodontal ligament (PDL) with RECA-1 antibody, an endothelial cell surface marker, demonstrated the endothelium in the different categories of blood vessels. The intensity of immunolabelling was similar for venous capillaries (VC), post-capillary-sized venules (PCV), and collecting venules (CV). Arterial capillaries (AC) and terminal arterioles (TA) showed a different response, both having a high intensity of endothelium and smooth muscle cell labelling, whether they were located in the PDL or alveolar bone. An experimental, continuous loading of approximately 100 g was applied unilaterally to the mandibular molars for 10 minutes. In the PDL apical compression zone this load resulted in a loss of RECA-1 immunolabelling of the VC, PCV, and CV. Adjacent to the alveolar crest, where shear and tension loads were judged to have occurred, there was enhanced immunoreactivity of VC, PCV, and CV. In the loaded PDL, the AC and TA, irrespective of their location in the ligament or bone, showed strong immunofluorescence of their endothelium and the enveloping smooth muscle layer. Vessel and PDL immunofluorescence were analysed with standardized grey scale densitometry, and the data subjected to ANOVA. Comparison between individual vessel means showed significant differences (P < 0.05). Control teeth showed no immunostaining difference between the coronal and apical region vessels, whereas in the loaded teeth the overall cervical vessel endothelium had a significantly higher value than the apical vessel endothelium (P < 0.001). These findings demonstrate that the endothelium of this microvascular bed can undergo significant immunoreactivity changes when exposed to short-term, continuous, tooth loading.

Alveolar Process↗

Reproducibility of 3D free-breathing magnetic resonance coronary vessel wall imaging.

AIMS: Although the coronary artery vessel wall can be imaged non-invasively using magnetic resonance imaging (MRI), the in vivo reproducibility of wall thickness measures has not been previously investigated. Using a refined magnetization preparation scheme, we sought to assess the reproducibility of three-dimensional (3D) free-breathing black-blood coronary MRI in vivo. METHODS AND RESULTS: MRI vessel wall scans parallel to the right coronary artery (RCA) were obtained in 18 healthy individuals (age range 25-43, six women), with no known history of coronary artery disease, using a 3D dual-inversion navigator-gated black-blood spiral imaging sequence. Vessel wall scans were repeated 1 month later in eight subjects. The visible vessel wall segment and the wall thickness were quantitatively assessed using a semi-automatic tool and the intra-observer, inter-observer, and inter-scan reproducibilities were determined. The average imaged length of the RCA vessel wall was 44.5+/-7 mm. The average wall thickness was 1.6+/-0.2 mm. There was a highly significant intra-observer (r=0.97), inter-observer (r=0.94), and inter-scan (r=0.90) correlation for wall thickness (all P<0.001). There was also a significant agreement for intra-observer, inter-observer, and inter-scan measurements on Bland-Altman analysis. The intra-class correlation coefficients for intra-observer (r=0.97), inter-observer (r=0.92), and inter-scan (r=0.86) analyses were also excellent. CONCLUSION: The use of black-blood free-breathing 3D MRI in conjunction with semi-automated analysis software allows for reproducible measurements of right coronary arterial vessel-wall thickness. This technique may be well-suited for non-invasive longitudinal studies of coronary atherosclerosis.

Adult↗

Coronary angioplasty of the unstable angina related vessel in patients with multivessel disease.

This study is a retrospective analysis of the efficacy of percutaneous transluminal coronary angioplasty of the ischaemia-related vessel in patients with unstable angina. Forty-three patients had multivessel disease with dilatation of the ischaemia-related vessel only (group I; partial revascularization) while 111 patients had single vessel disease only (group II; total revascularization). The initial success rate in both groups was identical (88 versus 88%). The need for emergency coronary artery bypass surgery was similar in the two groups (group I 12% versus group II 9%; NS). The total post PTCA myocardial infarction rate (despite urgent CABG) was also similar in the two groups (group I 9% versus group II 10%; NS). The results of electrocardiographic exercise testing and Thallium-201 scintigraphy provide objective evidence for incomplete revascularization in group I. The maximum workload achieved was lower, and the frequency of exercise induced angina, ST-segment depression and reversible perfusion defect was higher than in group II. Moreover, at 6 months follow-up the recurrence rate of angina pectoris rate was higher in group I than in group II (29% versus 16% P less than 0.05). It is concluded that dilatation of the ischaemia related vessel only in patients with unstable angina and multivessel disease is as effective in the management of the acute phase of unstable angina as is dilatation of the ischaemia related vessel in patients with single vessel disease. However, due to only partial revascularization the recurrence rate of angina pectoris is higher.

Adult↗

The effect of high-dose medium- and long- term progestogen exposure on endometrial vessels.

A total of 19 paraffin-embedded endometrial tissue blocks were obtained from high-dose progestogen-exposed patients. A labelled streptavidin-biotin-alkaline phosphatase method was used with antibodies against von Willebrand factor (vWF) and CD34. The density of CD34 and vWF positive (CD34+ and vWF+) vessels in progestogen-exposed endometria (103 +/- 9.6/mm2 and 106 +/- 8.7/mm2) was significantly lower than in endometria from women with normal cycles (169 +/- 9.3/mm2 and 136 +/- 8.0/mm2) (P < 0.05). In women with normal menstrual cycles the concentration of CD34+ vessels was significantly higher than the number of vWF+ vessels (P = 0.0001). By comparison, the concentration of CD34+ vessels was similar to the concentration of vWF+ vessels in progestogen-exposed endometria. The ratios of vascular density as determined by vWF+ and CD34+ staining the control and progestogen groups were 0.81 and 1.05 respectively (P = 0.0001). Dilated venules were seen in the progestogen group. This study has demonstrated firstly that CD34 antibody detected the endothelial cells in a higher proportion of small endometrial vessels than vWF, and secondly that high-dose progestogen exposure significantly decreased the density of microvessels and increased the number of dilated venules in endometrium.

Antigens, CD↗

Additional evidence that the sympathetic nervous system regulates the vessel wall release of tissue plasminogen activator.

It is established that sympathetic neurons can synthesize, transport and store tissue plasminogen activator (t-PA) within axon terminals in the smooth muscle of vessel walls. Moreover, sympathetic excitations (e.g. physical and mental stress) are known to induce an acute release of t-PA into the circulation. However, relatively little is known about the nature and extent of sympathetic nervous system involvement in the release process. We inquired whether a chemical sympathectomy will alter the release of t-PA into the blood, and the intrinsic release of stored t-PA from isolated whole vessel explants. A long-term sympathectomy was induced in adult Sprague-Dawley rats by injection of guanethidine during a 5-week course. The destruction of ganglion neurons and vessel wall axons was verified immunohistochemically. t-PA release was assayed as the free activity in hind limb plasma and explant culture medium. Following sympathectomy: (i) the basal t-PA activity in plasma was 70% less than controls (2.92 +/- 1.96 versus 9.33 +/- 1.72 IU/ml; </= 0.001); (ii) the acute release from isolated vessels induced by bradykinin or phenylephrine was comparably reduced; and (iii) the greatest reductions occurred in densely innervated small vessel explants. The results provide new support for an autonomic regulation of neural t-PA release into the vessel wall matrix and blood of densely innervated thin-walled microvessels.

Animals↗

Accurate analysis of blood vessel sizes and stenotic lesions using stereoscopic DSA system.

We have developed a technique to determine accurately the magnification factor and three-dimensional orientation of a vessel segment from a stereoscopic pair of digital subtraction angiograms (DSA). Our DSA system includes a stereoscopic x-ray tube with a 25-mm focal spot shift. The magnification and orientation of a selected vessel segment are determined from the distance and direction of the focal spot shift and the stereoscopic discrepancy in image positions for that segment. Our results indicate that the accuracies of determining the magnification and orientation are less than 1% and approximately 5 degrees, respectively. After the magnification and orientation are determined accurately, an iterative deconvolution technique for the measurement of vessel image size is applied to the selected vessel segment. This iterative deconvolution technique provides the best estimate of vessel image size by taking into account the unsharpness of the digital system. With this technique, the vessel image size can be determined to an accuracy of approximately 1.0 mm, which corresponds to one third the pixel size of our DSA system. Information derived from stereoscopic analysis and iterative deconvolution thus allows accurate calculation of actual vascular dimensions from DSA images.

Angiography↗

Measurement of distensibility of blood vessels using cineangiograms.

We developed a new, cineangiographic method to accurately measure the dynamic changes in the internal diameter of human arteries in vivo. Cine films were digitized at a spatial resolution of 4 microns/pixel, using a line image sensor. The vessel edges, with a Gaussian fit to a unilateral profile curve of the vessel, were determined with the aid of a computer program. We measured contrast-filled cylinder vessel models (2 to 7 mm in diameter) and evaluated precision, accuracy and linearity of the diameter measurement. A pulsatile vessel model of about 3.9 mm in internal diameter was used to examine the reliability of our method for detecting arterial wall motion. If the coefficient of variation of the vessel diameter determined cineangiographically was less than 2.2% we considered the cineangiograms sufficiently accurate to determine the internal vessel diameter and evaluate arterial distensibility.

Adult↗

Cine phase-contrast MR flow measurements: improved precision using an automated method of vessel detection.

OBJECTIVE: The purpose of this study was to construct a method of vessel edge detection that correctly identifies vessel pixels and to compare the interuser variability of cine phase contrast MR volumetric flow rates obtained with the conventional manual method and an automated method. MATERIALS AND METHODS: The automated method was developed based on a magnitude image threshold value and compared with the manual method in a flow phantom (three users) and in velocity images of the portal vein (five users). The threshold value determined from the magnitude image was applied to a region of interest surrounding the vessel of interest on the magnitude image to construct a vessel edge detection mask m(x,y). The velocity images were then multiplied by the mask m(x,y) and volumetric flow rates determined using the identified vessel pixels. RESULTS: In the flow phantom, flow measurements with the magnitude threshold method had significantly less interuser variability compared with the manual method (p < 0.01) and were within 10% (mean 6.0%) of the actual flow versus 35% (mean 18.6%) with the manual method. Regarding flow measurements in the portal vein of six volunteers, the magnitude threshold method was significantly more precise (p < 0.01) than the manual method with a mean standard deviation between the five users of 40.4 +/- 12.9 ml/min (range 22-60 ml/min) and 110.4 +/- 32.7 ml/min (range 70-155 ml/min), respectively. CONCLUSION: The magnitude threshold method of vessel edge detection developed in this study yields flow measurements that are accurate in the model system and have significantly less interuser variability than the manual method. This method shows promise for improving the precision of cine phase contrast flow measurements.

Adult↗

Initial platelet deposition at the human microvascular anastomosis: effect on downstream platelet deposition to intact and injured vessels.

Initial platelet deposition (PD) in and around the region of a small-vessel anastomosis may set the stage for thrombosis and tissue loss. To study this problem, a human vessel model (human placental artery, HPA) has been designed to mimic the vascular injuries attendant on clinical microsurgery. To perform these studies, dissected lengths of human placental artery were treated to provide the following four types of injury: group I: control, dissected but otherwise uninjured (N = 5); group II: distal portion of vessel endothelium removed (N = 5); group III: central anastomosis, distal endothelium intact (N = 7); and group IV: central anastomosis, distal endothelium removed (N = 4). Vessels were perfused with 25 ml human whole blood for 17 +/- 5 s at an average shear rate of 536 s-1. Vessels in groups I to IV were segmented at 2-cm intervals, and the number of 111In-labeled platelets was measured. Data from the following groups of exposure zones were pooled and analyzed: endothelium intact, endothelium absent, anastomosis present, postanastomosis with endothelium intact, and postanastomosis with endothelium absent. Significant numbers of platelets were found to attach to intact endothelium, indicating that ischemia and microsurgical handling may augment platelet deposition to otherwise uninjured vessels. A similar degree of platelet deposition was measured after exposure of the subendothelium and perfusion, indicating that superficial subendothelial exposure in the absence of an additional prothrombotic stimulus may lead to no greater platelet deposition than occurs on slightly injured endothelium alone. Platelet deposition at anastomoses was strikingly elevated, although the anastomosis had no additive effect on platelet deposition to downstream endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

Computerized measurement of retinal blood vessel calibre: description, validation and use to determine the influence of ageing and hypertension.

OBJECTIVE: To validate a computer-based method for measuring the calibre of retinal blood vessels, and use it to determine the effects of ageing and arterial hypertension on the calibres of these vessels and on their ratio. METHODS: Digital eye fundus images covering a 50 degrees field and centred on the optic disc were obtained using a 540 nm filter. The boundaries of blood vessels crossing a series of circles concentric with the optic disc were located by an image analysis program; the calibres of vessels crossing the circles perpendicularly were determined automatically, the average arteriole and average vein calibres were calculated, and the arteriovenous ratio (AVR) was calculated as the ratio of these averages. The within-operator, between-operator and within-eye reliability of this method was investigated using images of 30 or 40 eyes; the effects of ageing on average vessel calibres and AVR using both eyes of each of 120 normotensive volunteers aged 10-69 years (60 males, 60 females); and the effects of arterial hypertension using a group of 54 hypertensive patients aged 50.9 +/- 13.9 years. RESULTS: Within-operator, between-operator and within-eye correlation coefficients for AVR were all better than 0.95, and the corresponding coefficients of variation were all better than 3%. The results of Bland Altman approach show a very good agreement. There were no significant differences between right and left eyes or between the sexes in either the normotensive or the hypertensive group. In the normotensive group, vein calibre was almost constant (111 +/- 6 microm), but arteriole calibre and AVR fell significantly from 96 +/- 6 microm and 0.870 +/- 0.046, respectively, in the second decade of life to 85 +/- 4 microm and 0.761 +/- 0.044 in the seventh decade. Arterial hypertension was not associated with changes in vein calibre, but was associated with decreases in arteriole calibre (from 91 +/- 7 microm among normotensive individuals to 84 +/- 2 microm) and AVR (from 0.816 +/- 0.056 to 0.755 +/- 0.027). Age significantly modulated the AVR-reducing influence of hypertension (P = 0.003). CONCLUSION: The proposed method of measuring retinal blood vessel calibres is reliable and precise (especially for the AVR). In this study, its results confirmed that increasing age and arterial hypertension are both associated with reductions in retinal arteriole calibre and AVR.

Adolescent↗

Detection of optic disc in retinal images by means of a geometrical model of vessel structure.

We present here a new method to identify the position of the optic disc (OD) in retinal fundus images. The method is based on the preliminary detection of the main retinal vessels. All retinal vessels originate from the OD and their path follows a similar directional pattern (parabolic course) in all images. To describe the general direction of retinal vessels at any given position in the image, a geometrical parametric model was proposed, where two of the model parameters are the coordinates of the OD center. Using as experimental data samples of vessel centerline points and corresponding vessel directions, provided by any vessel identification procedure, model parameters were identified by means of a simulated annealing optimization technique. These estimated values provide the coordinates of the center of OD. A Matlab prototype implementing this method was developed. An evaluation of the proposed procedure was performed using the set of 81 images from the STARE project, containing images from both normal and pathological subjects. The OD position was correctly identified in 79 out of 81 images (98%), even in rather difficult pathological situations.

Algorithms↗