Characterization of 3-Dimensional Printing and Casting Materials for use in Magnetic Resonance Imaging Phantoms at 3 T.

Imaging phantoms are used to calibrate and validate the performance of magnetic resonance imaging (MRI) systems. Many new materials have been developed for additive manufacturing (three-dimensional [3D] printing) processes that may be useful in the direct printing or casting of dimensionally accurate, anatomically accurate, patient-specific, and/or biomimetic MRI phantoms. The T1, T2, and T2* spin relaxation times of polymer samples were tested to discover materials for use as tissue mimics and structures in MRI phantoms. This study included a cohort of polymer compounds that was tested in cured form. The cohort consisted of 101 standardized polymer samples fabricated from: two-part silicones and polyurethanes used in commercial casting processes; one-part optically cured polyurethanes used in 3D printing; and fused deposition thermoplastics used in 3D printing. The testing was performed at 3 T using inversion recovery, spin echo, and gradient echo sequences for T1, T2, and T2*, respectively. T1, T2, and T2* values were plotted with error bars to allow the reader to assess how well a polymer matches a tissue for a specific application. A correlation was performed between T1, T2, T2* values and material density, elongation, tensile strength, and hardness. Two silicones, SI_XP-643 and SI_P-45, may be usable mimics for reported liver values; one silicone, SI_XP-643, may be a useful mimic for muscle; one silicone, SI_XP-738, may be a useful mimic for white matter; and four silicones, SI_P-15, SI_GI-1000, SI_GI-1040, and SI_GI-1110, may be usable mimics for spinal cord. Elongation correlated to T2 (p = 0.0007), tensile strength correlated to T1 (p = 0.002), T2 (p = 0.0003), and T2* (p = 0.003). The 80 samples not providing measurable signal with T1, T2, T2* relaxation values too short to measure with the standard sequences, may be useful for MRI-invisible fixturing and medical devices at 3 T.

Cytotoxicity and thermomechanical behavior of biomedical shape-memory polymer networks post-sterilization.

Shape-memory polymers (SMPs) are being increasingly proposed for use in biomedical devices. This paper investigates the cytotoxicity, surface characteristics and thermomechanics of two acrylate-based SMP networks as a function of sterilization using a minimal essential media elution test, FTIR-ATR and dynamic mechanical analysis (DMA). Networks sterilized by low-temperature plasma elicited a cytotoxic response and are shown to completely destroy the cell monolayer. FTIR-ATR analysis showed evidence of surface oxidation with an increase and broadening of the absorbance peak from approximately 3500 to 3100 cm(-1), which is associated with an increase in hydroxyl groups. DMA revealed small, but statistically significant, differences in reduction of the glass transition temperatures of both networks when sterilized with gamma irradiation. One network showed an increase in rubbery modulus, which is an indication of crosslink density, after gamma irradiation. Lastly, practical sterilization concerns of SMP devices are discussed in light of the different methods.

Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension.

Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries.

Comparison of mechanical behavior among the extrapulmonary arteries from rats.

Results of comparative tests on pulmonary arteries from untreated Long-Evans rats are presented from three sections of the artery: the trunk, and the right and left main extrapulmonary arteries. Analyses were conducted looking for mechanical differences between the flow (longitudinal) and circumferential directions, between the right and left main arteries, and between each of the mains and the trunk. The mechanical properties of rat pulmonary arteries were obtained with a bubble inflation technique. A flat disk of rat pulmonary artery was constrained at the periphery and inflated, and the geometry of the resulting bubble of material recorded from six different angles. To analyze the data, the area under the stress-strain curve was calculated for each test and orientation. This area, related to the strain-energy density, was calculated at stress equal to 200kPa, for the purpose of statistical comparison. The mean values for the area show that the trunk is less compliant than the main arteries; this difference is supported by histological evidence. When comparing the circumferential and longitudinal properties of the arteries, differences are found for the trunk and left main arteries, but with opposite orientations being more compliant. The mean values for the two orientations for the right main artery are statistically identical. There was indication of significant difference in mechanical properties between the trunk and the main arteries. The left main artery in the circumferential orientation is highly compliant and appears to strongly influence the likelihood that significant differences will exist when included in a statistical population. These data show that each section of the extrapulmonary arterial system should not be expected to behave identically, and they provide the baseline mechanical behavior of the pulmonary artery from normotensive rats.

Bubble-test method for synthetic and bovine vascular material.

A measurement system has been designed and constructed at NIST for the study of the mechanical properties of synthetic and bovine vascular materials. The measurement technique was validated on latex, where good agreement was found with the Neo-Hookean model. Measurements were also made on expanded polytetrafluoroethylene, which is commonly used for vascular grafts. The measurements of this material were carried out over a pressure range greater than would be seen in vivo. However, the strains were still small enough to effectively apply the Neo-Hookean model to these data.

A model study of capacitive micromachined ultrasonic transducers fabricated using atomic layer deposition process.

In this paper, we present the model study of capacitive micromachined ultrasonic transducers (CMUTs) fabricated by atomic layer deposition (ALD) technology, which uses a self-limiting binary reaction process to produce ultra-thin membranes. Advantages of ALD include precise control of membrane thickness, lower cost due to a reduction in the number of fabrication steps, the potential to use a large variety of materials, and increased reliability due to the enhanced surface quality of the membranes. These capabilities promise fabrication of transducers with superior operating characteristics. However, no study has yet documented sensitivity and power requirements for CMUTs created using ALD. We present here a first-order mechanical and equivalent circuit analysis along with a fabrication process to create and characterize CMUTs using ALD. Simulation results show that these systems have the potential for excellent sensitivity and decreased power requirements. Work to test the fabricated elements is currently underway.

Comparison of strength properties of normotensive and hypertensive rat pulmonary arteries.

A series of tests were conducted to quantify the difference in the mechanical properties of normo- and hypertensive pulmonary arteries. A bubble-test design was employed to measure the biaxial properties of a segment of artery. The test results compare the properties at multiple orientations of the trunk, right, and left pulmonary arteries from normal (Control) and monocrotaline-treated male Long-Evans wild rats that ranged in age from 8 to 17 weeks old, along with some preliminary results from hypoxic Long-Evans knock-out rats. Data show little difference between the stress-strain relationship of the control pulmonary arteries and that of the monocrotaline-treated pulmonary arteries. However, the preliminary results from the hypoxic pulmonary arteries show that the arterial material strains less before the onset of strain-stiffening behavior. The longitudinal orientation exhibits strain stiffening at lower strains than does the circumferential orientation. The differences between the left and right main arteries are minor. The trunk consistently demonstrates less stiffening in the region of larger strains for all conditions.

Development and validation of implantable sensors for monitoring function of prosthetic heart valves: in vitro studies.

The development of a 'smart' heart valve prosthesis, with the intrinsic ability to monitor thrombus formation, mechanical failure and local haemodynamics and to relay this information externally, would be of significant help to clinicians. The first step towards such a valve is development of the sensors and examination of whether sensor output provides predictive information on function. Custom-made piezo-electric sensors were mounted onto the housing of mechanical valves with various layers of simulated thrombus and bioprosthetic valves with normal and stiffened leaflets. Sensor output was examined using joint time-frequency analysis. Sensors were able to detect leaflet opening and closing with high fidelity for all types of valve. The frequency content of the closing sounds for the mechanical valves contained several peaks between 100 Hz and 10 kHz, whereas closing sounds for the bioprosthetic valve contained energy in a lower frequency range (<1 kHz). A frequency peak of 47 +/- 15 Hz was seen for the normal bioprosthetic valve; this peak increased to 115 +/- 12 Hz for the valve with visibly stiffened leaflets. Total low-frequency (80-3500 Hz) energy content diminished predictably with increasing levels of thrombus for the mechanical valves. Lastly, closing sound intensity correlated well with closing pressure dynamics (dp/dt) (y = 190x - 443; r = 0.90), indicating that the sensors also provide information on haemodynamics. These studies provide initial evidence regarding the use of embedded sensors to detect prosthetic valve function. Efforts to encapsulate these sensors with telemetry into a custom valve are currently underway.

An Experimental Method for Measuring Mechanical Properties of Rat Pulmonary Arteries Verified With Latex.

This paper describes a test method for measuring the mechanical properties of small, nonlinear membrane samples from a rat model for pulmonary hypertension. The size and nonlinearity of the pulmonary artery samples poses a challenge for developing a test method that will generate quality, reproducible data in the pressure range experienced by the hypertensive pulmonary artery. The experimental method described here has sufficient precision to yield a combined relative standard uncertainty of 4 %. The method is calibrated against 75 µm thick latex and the data agree well with the neo-Hookian model.

Effect of vessel size on the flow efficiency of the total cavopulmonary connection: in vitro studies.

The total cavopulmonary connection (TCPC) creates a passive system of blood flow into the pulmonary circulation. We hypothesize that the efficiency differences found in models with superior vena cava-inferior vena cava (SVC-IVC) offsets is dependent on vessel size, with flow efficiency improving with larger size vessels. Two sets of in vitro TCPC models (TCPC-3 and TCPC-15) were constructed corresponding to average vessel diameters of 3- and 15-year-old patients. The model with full SVC-IVC offset was the most efficient in TCPC-3 models. There was no significant difference between geometric arrangements in TCPC-15 models; however, the average efficiencies were significantly higher. Among the models representing vessel sizes of the younger age group, the model with the full-diameter SVC-IVC offset was the most efficient. The models representing vessel sizes of the older age group showed marked improvement in efficiencies throughout without obvious differences between various geometric arrangements. This suggests that geometric considerations in TCPC surgical techniques may be of lower than expected significance over the life span of a patient. More important, after balancing the effects of improved flow efficiency with larger vessels against the effects of chronic volume overload, the trend of performing the Fontan surgery on increasingly younger patients may need to be reconsidered after further studies.

Development of a noninvasive ultrasound color M-mode means of estimating pulmonary vascular resistance in pediatric pulmonary hypertension: mathematical analysis, in vitro validation, and preliminary clinical studies.

BACKGROUND: Accurate determination of pulmonary vascular resistance (PVR) is an important component in the evaluation and treatment of pediatric patients with pulmonary hypertension. We developed a novel technique, based on the concept of flow propagation, to estimate PVR noninvasively. The hypothesis is that changes in PVR cause changes in the velocity propagation (Vel(prop)) within the main pulmonary artery and that Vel(prop) can be quantified using color M-mode imaging. METHODS AND RESULTS: We tested the hypothesis using mathematical modeling, in vitro experiments, and preliminary clinical studies. The mathematical model showed that pressure and velocity tracings are closely correlated in time and that 6 to 18 ms time resolution was needed to resolve propagation times within typical main pulmonary artery lengths (2 to 5 cm). The in vitro experiments demonstrated that it was feasible to use color M-mode to measure Vel(prop) and that Vel(prop) correlated well with downstream resistance [y=(-1.01x)+22.77; R=0.96]. The method was then evaluated on patients undergoing acute pulmonary reactivity testing (n=22 measurements). Good correlation between Vel(prop) and PVR was found [y=(-1.71x)+26.0; R=0.90; SEE=2.41]. CONCLUSION: This newly developed method promises to be useful in the noninvasive evaluation of adults and children with pulmonary hypertension.

A general method for estimating deformation and forces imposed in vivo on bioprosthetic heart valves with flexible annuli: in vitro and animal validation studies.

BACKGROUND AND AIM OF THE STUDY: The use of flexible structures within cardiovascular prostheses such as valves, stents and vascular grafts has been proposed as a means of more closely modeling native mechanics, and thereby reducing the biomechanical problems associated with rigid materials. However, the design of such materials has been hampered by the paucity of quantitative information on the in-vivo behavior of such structures. The aim of this study was to explore the use of 3D ultrasound imaging coupled with finite element analysis (FEA) as a tool to estimate deformation and forces imposed in vivo on a novel bioprosthetic valve design. METHODS: The method was first tested using in-vitro static loading conditions, where good agreement between displacements seen on video and those obtained from application of the identical force within the finite element program was seen. The method was then tested in a porcine model with valves implanted in the mitral position. Images of the deforming annular ring were obtained over the cardiac cycle using 3D intravascular ultrasound; these images were fed into the FEA program for calculation of reaction forces. RESULTS: Results in vitro showed that a force of 2.7-8.0 Newtons (N) was required to produce a deformation of between 1.0 and 3.0 mm in the radial direction. A time history of deformation and force around the ring of the valve stent could be obtained for the in-vivo conditions. These results revealed a maximum deformation of 0.5-1.7 mm along the short axis (anteroposterior) of the mitral valve. Coupled to this, a peak reaction force of 4.4-13.9 N was found at the points corresponding to maximal deflection. Both deformation and reaction force reached maximum during atrial contraction. CONCLUSION: This method provides an accurate means of estimating deformation and corresponding forces imposed in vivo on intracardiac prostheses. The results provide information on the dynamic behavior of the mitral valve annulus. Such information should be useful in the design of flexible cardiovascular prostheses.

Artificial neural network-based method of screening heart murmurs in children.

BACKGROUND: Early recognition of heart disease is an important goal in pediatrics. Efforts in developing an inexpensive screening device that can assist in the differentiation between innocent and pathological heart murmurs have met with limited success. Artificial neural networks (ANNs) are valuable tools used in complex pattern recognition and classification tasks. The aim of the present study was to train an ANN to distinguish between innocent and pathological murmurs effectively. METHODS AND RESULTS: Using an electronic stethoscope, heart sounds were recorded from 69 patients (37 pathological and 32 innocent murmurs). Sound samples were processed using digital signal analysis and fed into a custom ANN. With optimal settings, sensitivities and specificities of 100% were obtained on the data collected with the ANN classification system developed. For future unknowns, our results suggest the generalization would improve with better representation of all classes in the training data. CONCLUSION: We demonstrated that ANNs show significant potential in their use as an accurate diagnostic tool for the classification of heart sound data into innocent and pathological classes. This technology offers great promise for the development of a device for high-volume screening of children for heart disease.

Accuracy of the Bernoulli equation for estimation of pressure gradient across stenotic Blalock-Taussig shunts: an in vitro and numerical study.

Accurate assessment of the pressure gradient (PG) across a modified Blalock-Taussig (mBT) shunt is important in planning for staging to a cavopulmonary anastomosis for many patients with cyanotic congenital heart disease. The mBT shunt Doppler velocity has been used in the simplified echo Bernoulli equation to predict this PG with variable results. The purpose of this investigation is to provide analysis of the flow dynamics through stenotic mBT shunts and to assess the accuracy of Doppler techniques in determining PGs and the presence and location of stenosis. Three-dimensional models of mBT shunts were created, with and without stenosis. In vitro and computational fluid dynamic flow experiments were carried out. In vitro experiments demonstrated that the Doppler-measured PG underestimated catheter-measured PG in the mBT shunt with diffuse stenosis. In nonstenotic mBT and those that had outlet and inlet stenosis, the Doppler-measured PG showed underestimation of catheter PG at low PG and generally improved estimation at higher PG. In the mBT shunt model with inlet stenosis, there was slight overestimation at higher PG. Numerical simulations provide an "observation window" into events occurring in and around mBT shunts showing that the hemodynamics vary significantly. Changing hemodynamic processes are at work through stenotic mBT shunts causing variations in overestimation and underestimation of catheter-measured PG using the simplified echo Bernoulli equation. Our results have relevance to the assessment of patients with mBT shunts, helping to explain some of the discrepancies that investigators have found in the past.

A method for determining the reference effective flow areas for mechanical heart valve prostheses: in vitro validation studies.

BACKGROUND: The anatomic opening area (AOA) is usually reported as the primary index of mechanical heart valve function. Because flow contracts immediately distal to an orifice as a result of the vena contracta effect, AOA may not be a good measure of true effective flow area. METHODS AND RESULTS: Laser flow imaging was used to visualize the contraction in the jet flow stream as it passed through bileaflet mechanical valves under steady and pulsatile conditions. Such visualization allowed clear measurement of the individual vena contracta areas (VCAs) of the 3 valve orifices. VCAs for side orifices were larger (94+/-2% of AOA) than those through the central orifice (34+/-8%). Formation of large radial vortices around the leaflet tips constricted the central orifice flow stream and appeared to be the main reason for smaller central VCA. Total VCA remained constant until approximately 0.5 orifice diameters ( approximately 1.0 cm) downstream, beyond which cross-sectional area increased as a result of entrainment of receiving chamber flow. Total VCA was larger for steady flow (89.6+/-2.7% of AOA) than for pulsatile flow (76.3+/-5.0% of AOA). CONCLUSIONS: This study further clarifies flow dynamics through bileaflet mechanical valves and provides previously unavailable reference information on VCAs for these valves. Such information should aid clinicians in explaining Doppler-derived and catheter-measured pressure discrepancies, validating clinical techniques for quantifying effective flow areas, and optimizing valve size for implantation. The method should also be useful for comparative studies of different valve designs.

Utility of the proximal jet width in the assessment of regurgitant and stenotic orifices--effect of low velocity filter and comparison to actual vena contracta width: an in vitro and numerical study.

AIM: The colour Doppler proximal jet width (CDPJW) has been shown to be directly related to the severity of regurgitant and stenotic valve lesions. It is generally assumed that the CDPJW is equivalent to the vena contracta width (VCW). The purpose of this numerical and in vitro study was to evaluate how changing low velocity filter (LVF) settings on colour Doppler imaging devices may affect the CDPJW and its estimate of the VCW. METHODS: Computational fluid dynamic software was used to create models of round orifices (0.785, 1.13, 1.76, 3.14 cm2) at set flow rates (0.37-25 1/min). In vitro experiments were performed with round orifices (0.2, 0.95 and 1.76 cm2) with set flow rates (1.8-3.6 1/min). Laser flow visualization was used to obtain gold standard vena contracta widths for comparison to CDPJW for various LVF settings (4-24 cm/s). RESULTS: With the LVF set 'too low', overestimation errors occur. In contrast, with the LVF set 'too high', underestimation errors occur. Optimal LVF settings are required to avoid over- and underestimation errors of up to 280%. SUMMARY: The VCW is related to regurgitant or stenotic lesion severity, and the CDPJW is an approximation of the VCW. The CDPJW closely resembles the actual VCW only at optimally chosen LVF settings. LVF settings can have a significant impact on the accuracy of the CDPJW. Inter mediate filter settings remove unnecessary background noise while maintaining actual flow regions, thereby providing the best agreement between the CDPJW and the VCW. If treatment decisions are to be based on these measurements, understanding such dependencies becomes quite important.

Real-time 3-dimensional volumetric ultrasound imaging of the vena contracta for stenotic valves with the use of echocardiographic contrast imaging: in vitro pulsatile flow studies.

The purpose of our study was to investigate the utility of real-time 3-dimensional volumetric ultrasound coupled with echo contrast imaging to visualize and quantify effective flow areas for stenotic valves in vitro. Real-time 3-dimensional ultrasound imaging has recently emerged as a promising method for increasing the quantitative accuracy of echocardiography. Since the technique currently does not process Doppler information, its use for quantifying flow has not been studied. However, the use of contrast agents to visualize cardiac flows with the use of echocardiography should allow determination of mass-dependent flow parameters such as effective flow area (vena contracta area) for stenotic lesions. We used real-time 3-dimensional imaging in an in vitro stenotic valve model (areas 0.785 to 1.767 cm2) under pulsatile flow conditions (60 bpm; 40 to 80 mL/beat). An echo contrast agent was used to visualize the distal jet. Real-time 3-dimensional imaging provides simultaneous views of long-axis and short-axis (C-scan) image planes of the jet. The vena contracta was identified and measured by placing the C-scan line immediately distal to the orifice and measuring the cross-sectional flow area. System gain and postprocessing curve shape affected 3-dimensional areas; minimal gain and a custom curve produced best agreement to actual vena contracta areas measured with a previously validated laser method (y = 0.939x + 0.089; r = 0.98; standard error of estimate = 0.158 cm2). We conclude that real-time 3-dimensional ultrasound imaging coupled with a contrast agent can be used as an accurate yet simple clinical means of measuring effective flow areas for stenotic valves.

Insights into catheter/Doppler discrepancies in congenital aortic stenosis.

Despite inherent discrepancies between Doppler and catheter gradients in aortic stenosis, the simplified Bernoulli equation is still the accepted noninvasive technique to quantitate severity. The Reynolds number is a dimensionless parameter that characterizes the nature of flow as being viscous, turbulent, or transitional. Recently, in vivo and animal studies have successfully used a Reynolds number-based approach to reconcile Doppler-estimated and catheter-measured discrepancies. At the midrange of Reynolds number, pressure recovery effects are most evident, resulting in "overestimation" of catheter gradients by Doppler. At the lower range of the Reynolds number viscous effects are important, whereas at a higher range, turbulent factors are dominant; both result in a tendency toward agreement. We recorded 18 peak instantaneous gradients from dual left ventricular catheters (15 to 95 mm Hg), while simultaneously recording Doppler velocities before and after intervention in 11 pediatric patients (ages 0.5 to 16 years, mean 4.5). Doppler correlated but overestimated catheter-measured peak instantaneous gradients (y = 0.84x + 18.4, r = 0.8, SEE +/- 15.2 mm Hg, mean percent difference 29.9 +/- 36) over the range of catheter gradients measured. Accounting for the Reynolds number successfully collapsed data onto a single curve. Our study confirms in a clinical setting the importance of applying fluid dynamic principles such as the Reynolds number to explain apparent discrepancies between catheter and Doppler gradients. These principles provide a foundation for developing clinically appropriate correction factors.