Tissue-growth-based synthetic tree generation and perfusion simulation

Biological tissues receive oxygen and nutrients from blood vessels by developing an indispensable supply and demand relationship with the blood vessels. We implemented a synthetic tree generation algorithm by considering the interactions between the tissues and blood vessels. We first segment major arteries using medical image data and synthetic trees are generated originating from these segmented arteries. They grow into extensive networks of small vessels to fill the supplied tissues and satisfy the metabolic demand of them. Further, the algorithm is optimized to be executed in parallel without affecting the generated tree volumes. The generated vascular trees are used to simulate blood perfusion in the tissues by performing multiscale blood flow simulations. One-dimensional blood flow equations were used to solve for blood flow and pressure in the generated vascular trees and Darcy flow equations were solved for blood perfusion in the tissues using a porous model assumption. Both equations are coupled at terminal segments explicitly. The proposed methods were applied to idealized models with different tree resolutions and metabolic demands for validation. The methods demonstrated that realistic synthetic trees were generated with significantly less computational expense compared to that of a constrained constructive optimization method. The methods were then applied to cerebrovascular arteries supplying a human brain and coronary arteries supplying the left and right ventricles to demonstrate the capabilities of the proposed methods. The proposed methods can be utilized to quantify tissue perfusion and predict areas prone to ischemia in patient-specific geometries.

     

Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues

Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the density of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.     

Inducing occlusion effect in Y-shaped vessels using high-intensity focused ultrasound: finite element analysis and phantom validation

High-intensity focused ultrasound (HIFU) surgery offers a truly non-invasive treatment method with no skin incision, but precise targeting of tumour tissues for thermotherapy. Clinical experience reveals that the efficacy of tumour destruction not only involves in coagulating necrosis, but also involves in damaging the tumour vessels, which play an important role in tumour progression. These vessels take the elevated temperature away by perfusion, resulting in uncertainty of the occlusion effect during HIFU treatment. In this study, a Y-shaped vessel model comprising common and tumour vessels and an indirect fabrication method are proposed. The physical properties of the fabricated vessel phantom are measured and compared with human tissue. Simulation is performed using finite element modelling according to the tissue parameter, perfusion rate of the tumour vessel and treatment parameters including power intensity and exposure duration. The phantom experiments are carried out with perfusion of egg white to validate the threshold time prediction obtained from the simulation results. Our findings reveal that the threshold time obtained from experiments is consistent with the simulated one.     

Superiority of the deep circumflex iliac vessels as the supply for free groin flaps. Clinical work.

In this paper we present 16 cases of free transfer of compound flaps from the groin, 11 using the deep circumflex iliac vessels as a stem and 5 using the superficial circumflex iliac vessels as a stem. We found the deep vessels superior in many ways to the superficial vessels for this purpose; they are larger, permitting greater ease in anastomoses and providing more reliable blood flow. We believe that larger osteocutaneous or myocutaneous flaps can be transferred on the deep vessels than on the superficial ones-and that the deep circumflex iliac flap may supplant the conventional free going flap in most situations. The method evolved in response to patient need, not for surgical éclat.     

The timing and nature of neovascularization of jejunal free flaps: an experimental study in a large animal model.

The present study was designed (1) to determine whether a free jejunal transfer in a large animal model can develop collateral circulation that is adequate to maintain viability after division of the pedicle and (2) to determine the earliest time pedicle ligation is safe after transplantation. A 15-cm jejunal segment was transferred to the necks of 18 dogs weighing 25 to 35 kg. The bowel segment was inset longitudinally under the skin on one side of the neck, partially covered by the neck muscles, and the mesenteric vessels were anastomosed to recipient vessels in the neck. The proximal and distal bowel stomas were exteriorized through skin openings 12 cm apart and matured. The dogs were subjected to ligation of the vascular pedicle at different intervals: postoperative day 7 (group I, n = 3), day 14 (group II, n = 5), day 21 (group III, n = 5), and day 28 (group IV, n = 5). Blood perfusion was measured in the proximal and distal bowel stomas before pedicle division (control) and 24 hours later using hydrogen gas clearance and fluorescein dye. Bowel necrosis was analyzed using planimetry. The bowel was also stained with hematoxylin and eosin and factor VIII, and new blood vessels were counted. Mean values (+/- standard deviation) were compared with control values for each test and with normal values in the intact bowel using analysis of variance with Neumann-Keuls post-hoc test for multiple comparisons. No jejunal free flaps survived when the vascular pedicle was divided 1 week postoperatively. Bowel survival was 60 percent at 2 weeks, 83 percent at 3 weeks, and 100 percent at 4 weeks. Hydrogen gas clearance values (ml/min/100 g) were 49.6 +/- 8.7 in the mucosa of the intraabdominal jejunum and 37.9 +/- 9.4 in the jejunum that was transferred to the neck before division of the pedicle. Twenty-four hours after pedicle division, hydrogen gas clearance values were 2.8 +/- 6.4 in group I (p < 0.05), 22.4 +/- 12.4 in group II, 23.9 +/- 9.3 in group III, and 34.2 +/- 7.5 in group IV. FluoroScan readings in the transferred jejunum were 201 +/- 7.2 in the control group, 9.3 +/- 2.8 in group I (p < 0.05), 79.1 +/- 10.6 in group II, 66.2 +/- 7.3 in group III, and 164 +/- 11.9 in group IV. New vessel formation as identified by factor VIII staining correlated with increasing bowel perfusion and flap survival rate. Bowel neovascularization, perfusion, and survival increased progressively 1 week after transfer. Significant portions of the transferred bowel will neovascularize and survive as early as 2 weeks postoperatively. However, a minimum of 4 weeks before ligation of the pedicle is necessary to maximize flap perfusion and guarantee survival.     

Vasomotion in critically perfused muscle protects adjacent tissues from capillary perfusion failure

We analyzed the incidence and interaction of arteriolar vasomotion and capillary flow motion during critical perfusion conditions in neighboring peripheral tissues using intravital fluorescence microscopy. The gracilis and semitendinosus muscles and adjacent periosteum, subcutis, and skin of the left hindlimb of Sprague-Dawley rats were isolated at the femoral vessels. Critical perfusion conditions, achieved by stepwise reduction of femoral artery blood flow, induced capillary flow motion in muscle, but not in the periosteum, subcutis, and skin. Strikingly, blood flow within individual capillaries was decreased (P < 0.05) in muscle but was not affected in the periosteum, subcutis, and skin. However, despite the flow motion-induced reduction of muscle capillary blood flow during the critical perfusion conditions, functional capillary density remained preserved in all tissues analyzed, including the skeletal muscle. Abrogation of vasomotion in the muscle arterioles by the calcium channel blocker felodipine resulted in a redistribution of blood flow within individual capillaries from cutaneous, subcutaneous, and periosteal tissues toward skeletal muscle. As a consequence, shutdown of perfusion of individual capillaries was observed that resulted in a significant reduction (P < 0.05) of capillary density not only in the neighboring tissues but also in the muscle itself. We conclude that during critical perfusion conditions, vasomotion and flow motion in skeletal muscle preserve nutritive perfusion (functional capillary density) not only in the muscle itself but also in the neighboring tissues, which are not capable of developing this protective regulatory mechanism by themselves.     

CT灌注评价高碳酸血症模型下正常大鼠脑组织血流动力学变化

目的探讨CT灌注评价高碳酸血症模型下正常大鼠脑组织血流动力学变化的可行性;研究大鼠CT灌注参数变化率与α-SMA表达之间的相关性。方法 10只雄性SD大鼠,体质量250～300g,在吸入空气和吸入高浓度CO2混合气体(10%CO2和90%空气组成)后15min,分别使用GE16层Light Speed CT扫描仪对大鼠脑尾状核层面进行CT灌注扫描,原始图像经GE ADW4.2工作站Perfusion3.0脑部灌注软件处理后产生灌注曲线及伪彩图像,两次扫描前均测定大鼠的血液CO2分压、pH值等血气分析指标。检查结束后24h内,大鼠取脑固定,在尾状核中心层面切片,进行脑组织HE染色及鼠特异性SMA抗体免疫组化染色。应用SPSS11.5统计学软件进行分析:采用配对t检验,比较正常大鼠右侧尾状核在吸入空气和吸入高浓度CO2混合气体后CT灌注参数脑血容量(CBV)、脑血流量(CBF)、血管表面通透性(PS)和平均透过时间(MTT)的变化有无差异;采用Pearson相关分析分别检测大鼠右侧尾状核的SMA阳性血管染色计数与灌注参数CBV和CBF在CO2分压升高前后的变化率相关性。结果所有大鼠在吸入含10%CO2和90%空气的混合气体15min后,动脉血CO2分压均明显升高(t=9.39,P0.001),血浆pH值降低(t=13.49,P0.001)。正常SD大鼠右侧基底节区CBV、CBF、PS每100g组织分别为(10.28±4.01)mL、(304.95±88.77)mL/min、(0.26±0.37)mL/min,MTT值为(1.48±0.07)s;吸入10%CO2和90%空气的混合气体后右侧基底节区CBV、CBF值明显增加,每100g组织分别为(19.25±8.42)mL(t=4.92,P=0.001)和(507.33±167.94)mL/min(t=6.75,P0.001);吸入混合气体前后CBV、CBF增加百分比分别为(87.14±46.45)%、(65.75±22.05)%;PS及MTT变化不显著(P均0.05)。大鼠脑组织α-SMA阳性染色血管计数为(12.7±3.23)条/高倍视野。Pearson相关分析显示,正常脑组织的CBV和CBF变化率与其α-SMA阳性计数之间呈显著相关(r分别为0.652和0.890,P均0.05)。结论 CT灌注技术在改变血液CO2分压的条件下可以反映脑组织血流动力学变化;大鼠正常脑组织高碳酸血症前后CT灌注参数变化率与成熟血管数量相关。     

Assessing potential errors of MRI-based measurements of pulmonary blood flow using a detailed network flow model

MRI images of pulmonary blood flow using arterial spin labeling (ASL) measure the delivery of magnetically tagged blood to an image plane during one systolic ejection period. However, the method potentially suffers from two problems, each of which may depend on the imaging plane location: 1) the inversion plane is thicker than the imaging plane, resulting in a gap that blood must cross to be detected in the image; and 2) ASL includes signal contributions from tagged blood in conduit vessels (arterial and venous). By using an in silico model of the pulmonary circulation we found the gap reduced the ASL signal to 64-74% of that in the absence of a gap in the sagittal plane and 53-84% in the coronal. The contribution of the conduit vessels varied markedly as a function of image plane ranging from ～90% of the overall signal in image planes that encompass the central hilar vessels to <20% in peripheral image planes. A threshold cutoff removing voxels with intensities >35% of maximum reduced the conduit vessel contribution to the total ASL signal to ～20% on average; however, planes with large contributions from conduit vessels underestimate acinar flow due to a high proportion of in-plane flow, making ASL measurements of perfusion impractical. In other image planes, perfusion dominated the resulting ASL images with good agreement between ASL and acinar flow. Similarly, heterogeneity of the ASL signal as measured by relative dispersion is a reliable measure of heterogeneity of the acinar flow distribution in the same image planes.     

Functional and morphological characteristics of coronary vessels in varying degree of coronary perfusion]

Limitation of coronary perfusion of different degree induces inhomogeneous changes in resistance of vessels in the hypoperfusing zone: an adequate dilatory regulatory reaction may be followed by an increase in resistance of the coronary vessels. An active component of diastolic coronary resistance used to analyze vascular reactions, rate and character of changes in resistance under conditions of coronary perfusion as well as histological and electron-microscopic estimation of the vascular wall state testify to reversibility and active character of the observed changes in coronary resistance including its increase. This increase is pathogenetically significant as it may induce further development of the coronary perfusion disorder.     

Whole bone marrow transplantation induces angiogenesis following acute ischemia

Several recent studies have shown that purified subsets of bone marrow (BM) cells can differentiate into endothelial, cardiac, and other cell types. During coronary artery bypass graft (CABG) surgery, sternal BM is routinely discarded. To determine if this BM can be used to induce angiogenesis and augment perfusion of the cardiac tissues after CABG, a simplified and more practical approach of using whole BM extract was tried to determine whether it would be adequate for the induction of BM-derived angiogenesis in experimental acute limb ischemia. BM was prepared from FVB/N-TgN(TIE2 lacZ)182 Sato (Tie2-lacZ) or B6.129S7-Gtrosa 26 (Rosa 26) mice that express beta-galactosidase (beta-gal) in endothelial cells and most adult tissues, respectively. Acute limb ischemia was induced in either C57BL6/J or FVB/N mice by double ligation of the left femoral artery just distal to the profunda femoral artery branch. Occlusion of the ligated artery was verified by angiography. The study group (n = 31) received an intramuscular injection of 50 micro l containing 1 x 10(6) BM cells, 5 mm proximal to the site of ligation. Experimental controls (n = 21) had an intramuscular injection of 50 micro l of saline. Angiogenesis in the mice was assessed by histological analysis. BM-derived beta-gal(+) cells were observed to aggregate in the vicinity of the ligated artery and not in the injected musculature BM-derived endothelial cells were incorporated within capillaries and small size blood vessels near the site of ligation. Generation of BM-derived blood vessels in experimental acute limb ischemia does not require purification of specific subset of cells. The elimination of cell purification will enhance the ease of using BM transplantation in generating blood vessels.     

Histologic change of arteriovenous malformations of the face and scalp after free flap transfer

In three patients with long-standing vascular malformations of the face and scalp, radial forearm free flaps were transferred after a near-total excision of the lesion. All patients had typical high-flow malformations with thrill and bruit. The onset and progression of the malformations were analyzed through clinical and histologic studies. After free flap transfer, the vascular malformations were followed up grossly and histologically for between 4 and 9 years. There was no recurrence of arteriovenous malformation after free flap transfer. The portion of the residual lesion adjacent to the transferred free flap disappeared, and the remaining discoloration also vanished grossly. Histologic comparison of immediate postoperative and 4-month postoperative specimens from the margin and residual lesion using Victoria blue staining showed that the typical preoperative findings for arteriovenous malformation-an intermingling of thick-walled vessels with abundant elastic fibers and thin-walled vessels without elastic fibers-had undergone change, resulting in the disappearance of the thick-walled vessels and leaving only homogeneous, thin-walled vasculature. The highly vascularized free flap, which does not contain abnormal fistulas, impacted the histologic change of the arteriovenous malformation by blocking the vicious cycle of ischemia and anatomic replacement of disfigured skin and subcutaneous tissues.     

Improved measurements of intracellular nitric oxide in intact microvessels using 4,5-diaminofluorescein diacetate

4,5-Diaminofluorescein diacetate (DAF-2 DA) has been widely used for the measurement of nitric oxide (NO) in living cells and tissues. We previously established a method that demonstrated platelet activating factor (PAF)-induced endothelial NO production in intact venules using DAF-2 DA. In previous applications, the loading dye was removed from the extracellular space before NO measurements. However, in high permeability vessels, endothelial cells quickly released the accumulated intracellular DAF-2 after the washout, which compromises the NO measurement. The objective of this study was to investigate if the presence of DAF-2 DA during NO measurements could overcome the dye retention problem and enhance the sensitivity of NO detection. Experiments were conducted in individually perfused rat venules, and endothelial NO was measured using fluorescence imaging under basal and stimulated conditions with continuous perfusion of DAF-2 DA. Continuous dye perfusion was found to promote a relatively constant endothelial dye concentration in both normal and high permeability vessels throughout the experiment. With the use of this method, the basal and stimulated NO was quantified after endothelial DAF-2 concentrations reached a steady state. Our results showed enhanced sensitivity of detecting PAF-stimulated NO compared with a previous method. We also found that the hydrolyzed intracellular DAF-2, the precursor of DAF-2 triazole, contributed significantly to the measured fluorescence and that an appropriate subtraction of non-NO-dependent intracellular DAF-2 fluorescence is critical for the assessment of NO in living tissues. This method overcame the dye leakage problem, enhanced the sensitivity of NO detection, and improved NO quantification, demonstrating significant advantages over existing methodologies using DAF-2.     

Application of the cross-bridge microvascular anastomosis when no recipient vessels are available for anastomosis: 85 cases

The purpose of this article is to introduce the results of free tissue transfers using the technique of the cross-bridge microvascular anastomosis when the recipient lacks suitable vessels for anastomosis. Between May of 1982 and June of 2002, a series of 85 patients underwent this procedure. The transferred tissues were the free latissimus dorsi myocutaneous flap, the free vascularized fibula, the free fibular osteocutaneous flap, and the free iliac osteocutaneous flap, alone or in combination. The donor vessels were the anterior tibial artery and great saphenous vein, the posterior tibial artery and its venae comitantes, and the radial artery and cephalic vein. Good results were achieved. The success rate reached 95.29 percent. The authors believe this procedure can be performed in the event of serious tissue defect where the vessels are unsuitable for anastomosis.     

A perfusion method of incubation to demonstrate horseradish peroxidase in bone

Summary A perfusion method of incubation to show horseradish peroxidase in the bone of young mice is presented. After perfusion fixation, the incubation medium is perfused from the descending aorta into the entire lower half of the animal. From the vessels there is good penetration of the medium into all tissues. This allows the preparation of any one perfused bone to ground-, semithin-, and ultrathin sections.Differences in peroxidase distribution in the entire bone suggest regional differences in vascular supply.The tracer enzyme diffuses freely from the vessels into the extracellular fluid of bone. 3 min after injection, peroxidase is found between all bone lining cells and in osteocyte lacunae.     

Transfer of molecules from ejaculate to females in Drosophila melanogaster and Drosophila pseudoobscura

Methionine in the form of free amino acids, small peptides and several proteins is transferred from ejaculate to females in Drosophila melanogaster and D. pseudoobscura. The male contribution is found mostly in the ovary and the sizes of the polypeptides transferred have been established. Some components of the ejaculate are rapidly transferred to the somatic tissues outside the ovary and reproductive system where they co-migrate with the yolk polypeptides. The incorporation of free methionine into polypeptides in non-reproductive tissues is higher in females that have been deprived of a source of protein prior to mating. The molecules transferred from ejaculate may have roles in regulating reproductive behaviour and may also be used as a nutrient source. We suggest that free amino acids in the ejaculate are rapidly utilised in protein synthesis in the somatic tissues outside the ovary and could provide a boost to yolk protein and hence egg production in females in nature, where nutrients may be in limited supply.     

An advanced computational bioheat transfer model for a human body with an embedded systemic circulation

In the present work, an elaborate one-dimensional thermofluid model for a human body is presented. By contrast to the existing pure conduction-/perfusion-based models, the proposed methodology couples the arterial fluid dynamics of a human body with a multi-segmental bioheat model of surrounding solid tissues. In the present configuration, arterial flow is included through a network of elastic vessels. More than a dozen solid segments are employed to represent the heat conduction in the surrounding tissues, and each segment is constituted by a multilayered circular cylinder. Such multi-layers allow flexible delineation of the geometry and incorporation of properties of different tissue types. The coupling of solid tissue and fluid models requires subdivision of the arterial circulation into large and small arteries. The heat exchange between tissues and arterial wall occurs by convection in large vessels and by perfusion in small arteries. The core region, including the heart, provides the inlet conditions for the fluid equations. In the proposed model, shivering, sweating, and perfusion changes constitute the basis of the thermoregulatory system. The equations governing flow and heat transfer in the circulatory system are solved using a locally conservative Galerkin approach, and the heat conduction in the surrounding tissues is solved using a standard implicit backward Euler method. To investigate the effectiveness of the proposed model, temperature field evolutions are monitored at different points of the arterial tree and in the surrounding tissue layers. To study the differences due to flow-induced convection effects on thermal balance, the results of the current model are compared against those of the widely used modelling methodologies. The results show that the convection significantly influences the temperature distribution of the solid tissues in the vicinity of the arteries. Thus, the inner convection has a more predominant role in the human body heat balance than previously thought. To demonstrate its capabilities, the proposed new model is used to study different scenarios, including thermoregulation inactivity and variation in surrounding atmospheric conditions.     

Cell-specific subcellular localization of soluble epoxide hydrolase in human tissues.

Soluble epoxide hydrolase (sEH) is a phase-I xenobiotic metabolizing enzyme having both an N-terminal phosphatase activity and a C-terminal epoxide hydrolase activity. Endogenous hydrolase substrates include arachidonic acid epoxides, which have been involved in regulating blood pressure and inflammation. The subcellular localization of sEH has been controversial. Earlier studies using mouse and rat liver suggested that sEH may be cytosolic and/or peroxisomal. In this study we applied immunofluorescence and confocal microscopy using markers for different subcellular compartments to evaluate sEH colocalization in an array of human tissues. Results showed that sEH is both cytosolic and peroxisomal in human hepatocytes and renal proximal tubules and exclusively cytosolic in other sEH-containing tissues such as pancreatic islet cells, intestinal epithelium, anterior pituitary cells, adrenal gland, endometrium, lymphoid follicles, prostate ductal epithelium, alveolar wall, and blood vessels. sEH was not exclusively peroxisomal in any of the tissues evaluated. Our data suggest that human sEH subcellular localization is tissue dependent, and that sEH may have tissue- or cell-type-specific functionality. To our knowledge, this is the first report showing the subcellular localization of sEH in a wide array of human tissues.     

A New Fixation Procedure for Study of the Histaminergic Neurons by Immunoelectron Microscopy using the Direct Antiserum against Histamine

A new perfusion protocol was developed to detect histaminc-like immunoreactive neurons at the electron microscopic level. By stepwise perfusion of 1-ethyl-3(3-diamethylaminopropyl)-carbodiimide and paraformaldchyde solutions, the brain block could be cut with a vibratome and the immunoreactivity could be detected using the avidin-biotin-peroxidase-complex method. We used this method to study the ultrastructure and synaptic relations of the histaminergic neurons in the postmanunillary caudal magnocellular nucleus of the rat hypothalamus. This method should also be useful for examination of histaminergic neurons in other tissues and the synaptic relations of histaminergic neurons with other neurotnunsmitter-containing neurons by double immunostaining.     

Endothelial cell proliferation in male reproductive organs of adult rat is high and regulated by testicular factors

Endothelial cells in the intact adult are, apart from those in the female reproductive organs, believed to be quiescent. Systematic examination of endothelial cell proliferation in male reproductive organs has not been performed and was therefore the aim of the present study. Intact adult rats were either pulse labeled or long-term labeled with bromodeoxyuridine to label proliferating cells. The roles of Leydig cells and testosterone were examined after castration or treatment with the Leydig cell toxin ethane dimethane sulfonate (EDS) and testosterone substitution. After perfusion fixation, all blood vessels remained open and were easily identified. In all male reproductive organs studied, particularly in the testis and epididymis, endothelial cell proliferation was considerably higher than in other tissues such as the liver, brain, and muscle. Proliferating endothelial cells were observed in all types of blood vessels in male reproductive organs, but other characteristics of new blood vessel formation were not seen. High endothelial cell proliferation may reflect a continuous high turnover of endothelial cells rather than classical angiogenesis. In the epididymis, the ventral and dorsolateral prostate lobes, and the seminal vesicles, endothelial cell proliferation decreased after testosterone withdrawal and increased following testosterone treatment. In the testis, endothelial cell proliferation was decreased after Leydig cell depletion but remained low after testosterone substitution. High, hormonally regulated endothelial cell proliferation is not unique to the female but is also seen in the male reproductive organs.     

A new fundamental bioheat equation for muscle tissue--part II: Temperature of SAV vessels

In this study, a new theoretical framework was developed to investigate temperature variations along countercurrent SAV blood vessels from 300 to 1000 microm diameter in skeletal muscle. Vessels of this size lie outside the range of validity of the Weinbaum-Jiji bioheat equation and, heretofore, have been treated using discrete numerical methods. A new tissue cylinder surrounding these vessel pairs is defined based on vascular anatomy, Murray's law, and the assumption of uniform perfusion. The thermal interaction between the blood vessel pair and surrounding tissue is investigated for two vascular branching patterns, pure branching and pure perfusion. It is shown that temperature variations along these large vessel pairs strongly depend on the branching pattern and the local blood perfusion rate. The arterial supply temperature in different vessel generations was evaluated to estimate the arterial inlet temperature in the modified perfusion source term for the s vessels in Part I of this study. In addition, results from the current research enable one to explore the relative contribution of the SAV vessels and the s vessels to the overall thermal equilibration between blood and tissue.