Canine Aorta Research Articles

Experimental and theoretical investigation of aortic wall tissue in tensile tests.

Understanding the mechanical properties of aortic tissue is essential for developing numerical computation tools and assessing the risk of aortic aneurysm fractures. Tensile tests using aortic wall specimens allow for the determination of stress and strain depending on the location and direction of the sample. The aim of this study was to perform a mechanical tensile test using canine aorta samples and create a numerical model of aortic tissue tension from the processed data. Dogbone-shaped samples were dissected from canine aortic segments. The initial measurements were made at zero tension and the tensile tests were conducted at 10 mm/min until rupture. Force and stretch data were used to obtain engineering and true stress-strain curves. The true stress-strain curves were taken until the maximum strength was obtained, after which they were smoothed and fitted using a logistic function with three coefficients. These curves were then used as material mechanical properties for a numerical model of the aortic tissue tension. A simplified rectangle form was used to mimic the middle of the dogbone-shaped portion of the tissue specimen. Experimental displacement data were collected for the boundary conditions of the finite element 3D model. The experimental data processing revealed that the logistic function described the nonlinear behaviour of the aorta soft tissue with an accuracy of 95% from the start of the tension to the media layer rupture. By applying numerical simulations, we obtained a correspondence of the load curve with an RMSE = 0.069 for the theoretical and experimental external tension data. The numerical investigation confirmed that the non-linear soft tissue was validated by applying a logistic function approach to the mechanical properties of the aortic wall.

Animal study on adjustable pre - fenestration aortic stent - graft.

To isolate aortic arch pathologies and keep the branches superior in arch patent, it always need physicians to do in-vivo fenestration or in-situ fenestration when performing the thoracic endovascular aortic repair (TEVAR). However, both of those fenestration techniques need structure modification of the stent-graft, which may affect their long-term stability. We designed an adjustable pre-fenestration aortic stent-graft to treat pathologies in this area and obtained a patent branch arteries. This study used this new designed stent-graft to perform fenestrated-TEVAR (f-TEVAR) in canine aorta. This study aims to identify its feasibility and safety through animal experiments, which might provide preliminary data for potential human implantation. A total of 8 Labrador Retrievers were underwent f-TEVAR by using the new devices. Digital subtraction angiography was performed before and after f-TEVAR to evaluate the success of the procedures. All the canines were divided into a 4-week group (feeding for 4 weeks after operation) and a 12-week group (feeding for 12 weeks after operation). Computed tomography angiography (CTA) were performed before euthanasia. The success rate of operation was 100%. During the operation, there was no accident of major bleeding or failure to be released by fenestration. Adjustable fenestration worked well. No stent-graft migration was found in CTA at 4 weeks and 12 weeks after the operation. All branch arteries kept by the adjustable fenestration were patent. The result of feasibility and safety of the new designed adjustable pre-fenestration aortic stent-graft in f-TEVAR of canine is acceptable. This study provides a reference for further optimization of this stent and human f-TEVAR implantation involving aortic arch lesions.

Computational Investigation and Histopathological Validation of Interaction Between Stent Graft and Aorta in Retrograde Type A Dissection After TEVAR in Canine Models

Purpose: Retrograde type A dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) has been a major drawback of endovascular treatment. To our knowledge, no studies have simulated and validated aortic injuries caused by stent grafts (SGs) in animal models. Therefore, the aim of this study was to evaluate and quantify the SG–aorta interaction through computational simulations and to investigate the underlying mechanism through histopathological examinations. Methods: Two custom-made Fabulous® (DiNovA Meditech, Hang Zhou, China) SGs were implanted in 2 canine aortas with a 5-mm difference in the distance in landing locations. The aortic geometries were extracted from RTAD and non-RTAD cases. A computational SG model was assembled based on the implanted SG using the software Pro-ENGINEER Wildfire 5.0 (PTC Corporation, Needham, Mass). TEVAR simulations were performed 7 times for each canine model using Abaqus software (Providence, RI, USA), and the maximum aortic stress (MAS) was calculated and compared among the groups. Three months after SG implantation, the canine aortas were harvested, and were examined using hematoxylin and eosin staining and Elastica Van Gieson (EVG) staining to evaluate histopathological changes. Results: In the computational models for both canines, MAS was observed at the proximal bare stent (PBS) at aortic greater curve. The PBS generated higher stress toward the aortic wall than other SG parts did. Moreover, the MAS was significantly higher in canine No.1 than in canine No.2 (0.415±0.210 versus 0.200±0.160 MPa) (p<0.01). Notably, in canine No.1, an RTAD developed at the MAS segment, and histopathological examinations of the segment showed an intimal flap, a false lumen, elastin changes, and medial necrosis. RTAD was not observed in canine No.2. In both SG-covered aortas, medial necrosis, elastic fiber stretching, and inflammatory infiltration were seen. Conclusion: The characteristic MAS distribution remained at the location where the apex of the PBS interacted with the aortic wall at greater curve. RTAD histopathological examinations showed intimal damage and medial necrosis at the proximal landing zone, at the same MAS location in computational simulations. The in vivo results were consistent with the computational simulations, suggesting the MAS at greater curve may cause RTAD, and the potential application of computational simulation in the mechanism study of RTAD.

Age-Related Changes in the Canine Aorta.

Degenerative changes in the aorta are commonly observed in both dogs and humans, and those changes that occur with age morphologically overlap with those observed in genetic or degenerative diseases. Therefore, recognition of age-related aortic changes is important for diagnosticians, as such histologic findings should be distinguished from lesions of specific diseases. The aortas from 37 dogs without clinical cardiovascular disease ranging in age from 2 months to 15 years were divided into 3 cohorts to assess age-relatedness, and evaluated histologically using standardized nomenclature and diagnostic criteria adapted and modified from the human literature. We found that the histopathologic severity scores for intimal thickening, translamellar medial fibrosis, loss of smooth muscle cell nuclei, and medial microcalcification were higher in older dogs, whereas the scores for both intralamellar and translamellar mucoid extracellular matrix accumulation ("cystic medial necrosis") were not different among age groups. Dogs with translamellar medial fibrosis and aortic medial microcalcification were significantly older compared with dogs without these findings, while the presence of aortic medial chondro-osseous metaplasia was not related to age. Taken together, we demonstrate a range of age-related aortic histologic changes in dogs without clinical cardiovascular disease and suggest that integration of signalment and clinical data can aid in the differentiation of such findings from non-age-related disease processes.

Energy-based constitutive modelling of local material properties of canine aortas.

This study aims at determining the in vitro anisotropic mechanical behaviour of canine aortic tissue. We specifically focused on spatial variations of these properties along the axis of the vessel. We performed uniaxial stretch tests on canine aortic samples in both circumferential and longitudinal directions, as well as histological examinations to derive the tissue's fibre orientations. We subsequently characterized a constitutive model that incorporates both phenomenological and structural elements to account for macroscopic and microstructural behaviour of the tissue. We showed the two fibre families were oriented at similar angles with respect to the aorta's axis. We also found significant changes in mechanical behaviour of the tissue as a function of axial position from proximal to distal direction: the fibres become more aligned with the aortic axis from 46° to 30°. Also, the linear shear modulus of media decreased as we moved distally along the aortic axis from 139 to 64 kPa. These changes derived from the parameters in the nonlinear constitutive model agreed well with the changes in tissue structure. In addition, we showed that isotropic contribution, carried by elastic lamellae, to the total stress induced in the tissue decreases at higher stretch ratios, whereas anisotropic stress, carried by collagen fibres, increases. The constitutive models can be readily used to design computational models of tissue deformation during physiological loading cycles. The findings of this study extend the understanding of local mechanical properties that could lead to region-specific diagnostics and treatment of arterial diseases.

Performance assessment of pulse wave imaging using conventional ultrasound in canine aortas ex vivo and normal human arteries in vivo

The propagation behavior of the arterial pulse wave may provide valuable diagnostic information for cardiovascular pathology. pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique capable of mapping multiple wall motion waveforms along a short arterial segment over a single cardiac cycle, allowing for the regional pulse wave velocity (PWV) and propagation uniformity to be evaluated. The purpose of this study was to improve the clinical utility of PWI using a conventional ultrasound system. The tradeoff between PWI spatial and temporal resolution was evaluated using an ex vivo canine aorta (n = 2) setup to assess the effects of varying image acquisition and signal processing parameters on the measurement of the PWV and the pulse wave propagation uniformity r2. PWI was also performed on the carotid arteries and abdominal aortas of 10 healthy volunteers (24.8 ± 3.3 y.o.) to determine the waveform tracking feature that would yield the most precise PWV measurements and highest r2 values in vivo. The ex vivo results indicated that the highest precision for measuring PWVs ∼2.5–3.5 m/s was achieved using 24–48 scan lines within a 38 mm image plane width (i.e. 0.63–1.26 lines/mm). The in vivo results indicated that tracking the 50% upstroke of the waveform would consistently yield the most precise PWV measurements and minimize the error in the propagation uniformity measurement. Such findings may help establish the optimal image acquisition and signal processing parameters that may improve the reliability of PWI as a clinical measurement tool.

Reservoir and reservoir-less pressure effects on arterial waves in the canine aorta.

A time-domain approach to couple the Windkessel effect and wave propagation has been recently introduced. The technique assumes that the measured pressure in the aorta (P) is the sum of a reservoir pressure (Pr), due to the storage of blood, and an excess pressure (Pe), due to the waves. Since the subtraction of Pr from P results in a smaller component of Pe, we hypothesized that using the reservoir-wave approach would produce smaller values of wave speed and intensities. Therefore, the aim of this study is to quantify the differences in wave speed and intensity using P, wave-only, and Pe, reservoir-wave techniques. Pressure and flow were measured in the canine aorta in the control condition and during total occlusion at four sites. Wave speed was determined using the PU-loop (c) and PeU-loop (ce) methods, and wave intensity analysis was performed using P and separately using Pe; the magnitude and time of the main waves and the reflection index were calculated. Both analyses produced similar wave intensity analysis curves, and no significant differences in the timing of the waves, except onset of the forward expansion wave, indicated that distal occlusions have little effect on haemodynamics in the ascending aorta. We consistently found lower values of wave speed and intensities when the reservoir-wave model was applied. In particular, the magnitude of the backward waves was markedly smaller, even during proximal occlusions. In the absence of other independent techniques or evidence, it is not currently possible to decide which of the two models is more correct.

President’s address of the 65th annual scientific meeting of the Japanese Association for Thoracic Surgery: challenges for advanced esophageal cancer

Advanced esophageal tumors have been a challenge for surgery since the very beginning, and these challenges continue still today. In the early period of three-field lymphadenectomy (late 1980s), there was no special attention paid to tracheal necrosis after such an extended operation. In 1988, we reported functional mediastinal dissection preserving the right bronchial artery to prevent such complications. In 1993, we reported that the survival after three-field lymphadenectomy was better than that after en-bloc esophagectomy, and then the lymph node compartment classification based on the metastatic rate and the survival rate. This concept was introduced into the 9th edition of the Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus published in 1999. In early 1980s, combined resection of the neighboring organs was initiated for a locally advanced esophageal cancer. Almost all patients who underwent such an operation, however, died of metastasis in the short-term after surgery without any additional treatment. In 1987, we reported several types of tracheal repair using the latissimus dorsi muscle flap, as a less-invasive surgery that enabled adjuvant or additive therapy, after resection of the trachea involved by cancer. Then in 2004, we demonstrated that the canine aorta could be resected even immediately after aortic stenting. This suggests that an esophageal cancer involving the aorta can be resected using a new technique. To meet the challenges posed by advanced esophageal cancer, the help of other specialized fields besides esophageal surgery is needed: "The specialist must know everything of something, something of everything."

Spatially discrete thermal drawing of biodegradable microneedles for vascular drug delivery

Spatially discrete thermal drawing is introduced as a novel method for the fabrication of biodegradable microneedles with ultra-sharp tip ends. This method provides the enhanced control of microneedle shapes by spatially controlling the temperature of drawn polymer as well as drawing steps and speeds. Particular focus is given on the formation of sharp tip ends of microneedles at the end of thermal drawing. Previous works relied on the fracture of polymer neck by fast drawing that often causes uncontrolled shapes of microneedle tips. Instead, this approach utilizes the surface energy of heated polymer to form ultra-sharp tip ends. We have investigated the effect of such temperature control, drawing speed, and drawing steps in thermal drawing process on the final shape of microneedles using biodegradable polymers. XRD analysis was performed to analyze the effect of thermal cycle on the biodegradable polymer. Load–displacement measurement also showed the dependency of mechanical strengths of microneedles on the microneedle shapes. Ex vivo vascular tissue insertion and drug delivery demonstrated microneedle insertion to tunica media layer of canine aorta and drug distribution in the tissue layer.

Pulse-Wave Propagation in Straight-Geometry Vessels for Stiffness Estimation: Theory, Simulations, Phantoms and In Vitro Findings

Pulse wave imaging (PWI) is an ultrasound-based method for noninvasive characterization of arterial stiffness based on pulse wave propagation. Reliable numerical models of pulse wave propagation in normal and pathological aortas could serve as powerful tools for local pulse wave analysis and a guideline for PWI measurements in vivo. The objectives of this paper are to (1) apply a fluid-structure interaction (FSI) simulation of a straight-geometry aorta to confirm the Moens-Korteweg relationship between the pulse wave velocity (PWV) and the wall modulus, and (2) validate the simulation findings against phantom and in vitro results. PWI depicted and tracked the pulse wave propagation along the abdominal wall of canine aorta in vitro in sequential Radio-Frequency (RF) ultrasound frames and estimates the PWV in the imaged wall. The same system was also used to image multiple polyacrylamide phantoms, mimicking the canine measurements as well as modeling softer and stiffer walls. Finally, the model parameters from the canine and phantom studies were used to perform 3D two-way coupled FSI simulations of pulse wave propagation and estimate the PWV. The simulation results were found to correlate well with the corresponding Moens-Korteweg equation. A high linear correlation was also established between PWV² and E measurements using the combined simulation and experimental findings (R² = 0.98) confirming the relationship established by the aforementioned equation.

Alterations in Aortic Wave Reflection With Vasodilation and Vasoconstriction in Anaesthetized Dogs

BackgroundUsing the reservoir-wave approach, we studied wave propagation, reflection, and re-reflection in the canine aorta with administrations of sodium nitroprusside (NP) and methoxamine (Mtx). MethodsIn 8 anaesthetized dogs, excess pressures were calculated from pressure and flow measurements at 4 locations along the aorta; wave intensity analysis was employed to identify wavefronts and the type of waves. ResultsNP (intravenous; 14 μg/min) decreased mean aortic pressure from 80 ± 3 mm Hg to 48 ± 1 mm Hg; Mtx (intravenous; 10 μg/min) increased mean pressure from 80 ± 3 mm Hg to 104 ± 4 mm Hg. NP increased negative reflection near the kidneys (reflection coefficient: −0.33 vs −0.18; P < 0.01) and produced new negatively reflecting sites just beyond the arch and in the proximal femoral arteries, consistent with a vasodilating effects of nitrates on conducting arteries. Mtx negated negative reflection from near the kidneys (−0.02 vs −0.17; P < 0.01) and increased positive femoral reflection (0.38 vs 0.26; P < 0.01). The large reflected compression wave was re-reflected from the closed aortic valve to produce a prominent increase in middiastolic pressure in the distal aorta. ConclusionsThe reservoir-wave approach explains decreasing diastolic pressure without positing waves that travel at near-infinite velocities and reveals the pressure changes that are uniquely due to wave motion.

Variations in local elastic modulus along the length of the aorta as observed by use of a scanning haptic microscope (SHM)

Variations in microscopic elastic structures along the entire length of canine aorta were evaluated by use of a scanning haptic microscope (SHM). The total aorta from the aortic arch to the abdominal aorta was divided into 6 approximately equal segments. After embedding the aorta in agar, it was cut into horizontal circumferential segments to obtain disk-like agar portions containing ring-like samples of aorta with flat surfaces (thickness, approximately 1 mm). The elastic modulus and topography of the samples under no-load conditions were simultaneously measured along the entire thickness of the wall by SHM by using a probe with a diameter of 5 μm and a spatial resolution of 2 μm at a rate of 0.3 s/point. The elastic modulus of the wall was the highest on the side of the luminal surface and decreased gradually toward the adventitial side. This tendency was similar to that of the change in the elastin fiber content. During the evaluation of the mid-portion of each tunica media segment, the highest elastic modulus (40.8 ± 3.5 kPa) was identified at the thoracic section of the aorta that had the highest density of elastic fibers. Under no-load conditions, portions of the aorta with high elastin density have a high elastic modulus.

Wave Propagation and Reflection in the Canine Aorta: Analysis Using a Reservoir-Wave Approach

Background Our objective was to demonstrate wave propagation and reflection in the canine aorta. Recently we proposed that aortic pressure is the instantaneous sum of wave-related or “excess” pressure and reservoir or windkessel pressure. Accordingly, in this research we calculated reservoir pressure and subtracted it from measured pressure to identify the change in pressure due to forward- or backward-travelling waves. Methods In 8 anesthetized dogs, excess pressures were calculated from pressure and flow measurements at 4 locations along the aorta; wave intensity analysis was employed to identify wavefronts and the type of waves. Results We found that forward compression and decompression waves generated by the left ventricle are reflected, first, from a negative or “open-end” reflection site near the renal arteries (32.0 ± 0.8 cm [SEM] from the aortic root) and, second, from a positive site in the femoral arteries (65.3 ± 2.8 cm or 54.9 ± 2.1 cm, based on 2 alternative extrapolation techniques). Conclusions Aortic wave propagation and reflection can be demonstrated clearly and directly by wave intensity analysis after volume-related changes–changes in reservoir or windkessel pressure–in aortic pressure are accounted for.

Five Types of Polyurethane Vascular Grafts in Dogs: The Importance of Structural Design and Material Selection

Five polyurethane vascular grafts with three different chemistries were investigated in terms of device function, healing characteristics and material stability in a canine abdominal aorta model for prescheduled periods of 1 and 6 months. Corvita®-reinforced grafts, with walls made of poly(carbonate urethane) (PCU) filaments, displayed a relatively thin, uniform and partially endothelialized inner capsule with good tissue in-growth. The external polyester mesh separated from the underlying PCU wall due to the degradation of the melt adhesive between these two layers. Three types of Thoratec® access graft exhibited a high degree of thrombus and little tissue in-growth, and were non-adhesive to both the inner and external capsules as the solid layer beneath their lumens completely blocked any transmural communication. The microporous poly(ether urethane urea) degraded extensively. Pulse-Tec® grafts at one month also demonstrated non-adhesive properties because the external skin served as a barrier to tissue in-growth. At 6 months, its poly(ether urethane) wall displayed the most severe degradation, damaging graft structural integrity and causing significant tissue deposition in the degradation areas. This study shows the importance of multiple factors in vascular prosthesis design and demonstrates that collective and comprehensive thinking will be key in the future development of creative and novel approaches.

Cardiovascular Effects of Right Ventricle-Pulmonary Artery Valved Conduit Implantation in Experimental Pulmonic Stenosis

Right ventricle (RV)-pulmonary artery (PA) valved conduit (RPVC) implantation decreases RV systolic pressure in pulmonic stenosis (PS) by forming a bypass route between the RV and the PA. The present study evaluates valved conduits derived from canine aortae in a canine model of PS produced by pulmonary artery banding (PAB). Pulmonary stenosis was elicited using PAB in 10 conditioned beagles aged 8 months. Twelve weeks after PAB, the dogs were assigned to one group that did not undergo surgical intervention and another that underwent RPVC using denacol-treated canine aortic valved grafts (PAB+RPVC). Twelve weeks later, the rate of change in the RV-PA systolic pressure gradient was significantly decreased in the PAB+RPVC, compared with the PAB group (60.5 +/- 16.7% vs. 108.9 +/- 22.9%; p<0.01). In addition, the end-diastolic RV free wall thickness (RVFWd) was significantly reduced in the PAB+RPVC, compared with the PAB group (8.2 +/- 0.2 vs. 9.4 +/- 0.7 mm; p<0.05). Thereafter, regurgitation was not evident beyond the conduit valve and the decrease in RV pressure overload induced by RPVC was confirmed. The present results indicate that RPVC can be performed under a beating heart without cardiopulmonary bypass and adapted to dogs with various types of PS, including "supra valvular" PS or PS accompanied by dysplasia of the pulmonary valve. Therefore, we consider that this method is useful for treating PS in small animals.

Finite element Galerkin's scheme for flow in blood vessels with magnetic effects

In this paper, a finite element solution of the Navier?Stokes equations for steady flow under the magnetic effects through a double branch two-dimensional section of a three-dimensional model of a canine aorta is discussed. The equations have been solved using Galerkin' finite element scheme. The fluid is chosen to be Newtonian and incompressible and flow is assumed in the region of arterial vessel system. The steady flow, branch flow and shear stress under the magnetic effects have been discussed in detail. The numerical solutions are then compared with the experimental results. The effects of a magnetic field have been used to control the flow, which may be useful in certain pulmonary edima cases, etc.

Basic fibroblast growth factor slow release stent graft for endovascular aortic aneurysm repair: A canine model experiment

Persistent endoleak and endotension, complications after endovascular aortic repair, may be caused by an unorganized thrombus inside the aneurysm. The experimental study was designed to evaluate the effectiveness of stent grafts (S/Gs) with slow release of basic fibroblast growth factor (bFGF) for the organization. The S/Gs were constructed of self-expanding Z stent covered with expanded polytetra fluoroethylene graft, and coated with elastin to be able to bind and slowly release bFGF. Five elastin-coated S/Gs with bFGF (bFGF-S/Gs) and without bFGF (C-S/Gs) were placed in the normal canine aorta respectively. The thoracic aortic aneurysm models were surgically created with a jugular vein patch in 12 beagles. S/Gs with six holes, for creating endoleaks, were used in the experiment of aneurysmal repair. The bFGF-S/Gs (n = 6) and C-S/Gs (n = 6) were implanted. The beagles were sacrificed at two weeks after the endovascular procedure and examined histologically. The bFGF-S/Gs induced six times the intimal proliferation of the C-S/Gs in normal aorta. Twelve animals had successfully created aneurysms, and had endoleaks just after the endovascular procedure. At two weeks after the endovascular procedure, the percentage of fibrous area in the aneurysmal cavity treated with bFGF-S/G (35.7 +/- 4.3%) was significantly greater than C-S/G (13.6 +/- 2.2%) (P < .01). bFGF-S/Gs are effective for accelerating organization of the aneurysm cavity and developing neointima. Further research on bFGF-S/Gs would clarify the association of endoleaks.

Novel tissue-engineered vascular patches based on decellularized canine aortas and their recellularization in vitro

Decellularized allo- or xenogeneic vascular grafts have been found to give more promising results than some biodegradable synthetic polymers. However, owing to absence of well-organized cells, especially confluent endothelial cells, their long-term patency is limited. Seeding vessel-originated cells on these grafts may overcome the deficiency. In this study, canine aortas were decellularized and cross-linked. 4′,6-Diamidino-2-phenylindole (DAPI) and Masson’ trichrome staining showed complete removal of cell debris, while structure integrity of extracellular matrix (ECM) was remained. Human umbilical vein endothelial cells (HUVECs) and human umbilical artery smooth muscle cells (HUASMCs) were seeded on these decellularized aorta patches in three manners, ECs alone (EC/O), SMCs alone (SMC/O) and ECs on SMCs layer (EC/SMC). In EC/O and SMC/O, scanning electron microscopy (SEM) examination indicated both cells could form confluent layers on the decellularized patches when seeded at high density, but their morphology and alignment changed with seeding density. In EC/SMC, ECs could grow well on SMCs layer, but their morphology, alignment, and confluence degree were deeply influenced by the density of SMCs beneath.

Vascular endothelial growth factor gene therapy induces early re-establishment of canine bronchial circulation☆☆☆

To evaluate the usefulness of gene therapy with human vascular endothelial growth factor 165 (phVEGF(165)) to promote the early re-establishment of systemic arterial perfusion in canine bronchi deprived of bronchial circulation. To disrupt bronchial circulation, dogs were submitted to transversal bronchotomy dividing the left mainstem bronchus into a proximal and a distal portion. phVEGF(165) (VEGF group, n=8) or physiologic saline solution (control group, n=8) were then delivered to the left distal bronchus. After that, the airway was reconstituted with interrupted suture. On day 3, nine dogs (four VEGF and five controls) were euthanized and their left distal bronchi were harvested to evaluate VEGF(165) gene expression by reverse transcription-polymerase chain reaction. In the other dogs (four VEGF and three controls), a microvascular dye was injected through the canine aorta to verify the re-establishment of arterial blood supply to the distal bronchus. Additionally, VEGF immunohistochemistry was performed in distal airway specimens. Microvascular dye was observed in 100% of specimens transfected with phVEGF(165) compared to none in controls. VEGF gene expression (p<0.01) and VEGF protein expression (p<0.05) were higher in VEGF(165)-treated bronchi. Local transfection with phVEGF(165) promoted the early re-establishment of systemic arterial perfusion to bronchi previously deprived of bronchial circulation. Gene therapy with phVEGF(165) may be a useful tool to restore bronchial circulation by promoting early airway angiogenesis.

Arterial Vulnerable Plaque Characterization Using Ultrasound-Induced Thermal Strain Imaging (TSI)

Thermal strain imaging (TSI) is demonstrated in two model systems mimicking two potential clinical applications. First, a custom ultrasound (US) microscope produced high-resolution TSI images of an excised porcine coronary artery. Samples were placed in a temperature-controlled water chamber and scanned transversely and longitudinally. Phase-sensitive, correlation-based speckle tracking was applied to map the spatial distribution of temporal strain across the sample. TSI differentiated fatty tissue from water-based arterial wall and muscle with high contrast and a spatial resolution of 60 microm for a 50-MHz transducer. Both transverse and longitudinal TSI images compared well with B-scans of arterial wall structures, including intima, media, adventitia, and overlying fatty tissue. A second model system was used to test the hypothesis that US can produce the heating pattern required for TSI of internal structures. A 2-D phased array with independent drive electronics was combined with a conventional US scanner (iU22, Philips, Bothell, WA) for these studies. This 513-element array, originally designed for the US therapy, acted as the US heat source. To quantify the temporal strain induced by this system, TSI was performed on a homogeneous rubber phantom. TSI temperature estimates were within 3% error for a 3.2 degrees C temperature rise produced within 2 s using a specially designed beamformer and pulse sequencer. The system was then used to produce TSI scanning of an excised kidney containing an intact piece of fat below the collecting system. These images were validated using an magnetic resonance imaging (MRI) pulse sequence designed for lipid quantification. TSI scans matched well MRI scans and histology both anatomically and quantitatively. Finally, to test the potential of US-induced TSI for a significant clinical problem, images were obtained on an excised canine aorta with fatty tissue inside the lumen. Both longitudinal and transversal TSI agreed well with anatomy. These in vitro results demonstrate the potential of high-resolution US-induced TSI with a small temperature change (<1 degrees C) for plaque characterization.