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Biomedical and Biotechnology Engineering

2007;():1-7. doi:10.1115/IMECE2007-41153.

Nanoparticle-based drug delivery is a promising cancer treatment method due to the ability to target tumor sites by preferential extravasation and to deliver higher loads of therapeutics. Although nanoparticle penetration in tumor tissue is limited due to diffusional restrictions, delivery can be improved by enzymatic degradation of extracellular matrix proteins at the tumor site. Here, a mathematical model describing transport of nanoparticles in non-uniformly porous spheroids is developed, accounting for binding of particles with cells and endocytosis. Results of parametric simulations for nanoparticle concentration inside spheroids highlight the influence of various system parameters. Preliminary experimental data show qualitative agreement with the theory. These results are useful for understanding nanoparticle delivery and for designing drug delivery strategies.

Commentary by Dr. Valentin Fuster
2007;():9-16. doi:10.1115/IMECE2007-41295.

The objective of this paper is to analyze the temperature distributions and heat affected zone in skin tissue medium when irradiated with either a collimated or a focused laser beam from a short pulse laser source. Single-layer and three-layer tissue phantoms containing embedded inhomogeneities are used as a model of human skin tissue having subsurface tumor. Q-switched Nd:YAG laser is used in this study. Experimental measurements of axial and radial temperature distribution in the tissue phantom are compared with the numerical modeling results. For numerical modeling, the transient radiative transport equation is first solved using discrete ordinates method for obtaining the intensity distribution and radiative heat flux inside the tissue medium. Then the temperature distribution is obtained by coupling the bio-heat transfer equation with either hyperbolic non-Fourier or parabolic Fourier heat conduction model. The hyperbolic heat conduction equation is solved using MacCormack’s scheme with error terms correction. It is observed that experimentally measured temperature distribution is in good agreement with that predicted by hyperbolic heat conduction model. The experimental measurements also demonstrate that converging laser beam focused directly at the subsurface location can produce desired high temperature at that location as compared to that produced by collimated laser beam for the same laser parameters.

Commentary by Dr. Valentin Fuster
2007;():17-21. doi:10.1115/IMECE2007-41305.

We report in this work our observations from detailed atomistic investigations of the interactions between solutions containing 11.3 mol% of dimethylsulfoxide (DMSO) and three fully hydrated bilayers of lipid molecules, (BLMs). The BLMs considered were: dipalmitoyl-phosphatidylcholine (DPPC), palmitoyloleoyl-phosphatidylcholine (POPC) and dimyristoylphosphatidylcholine (DMPC); all in the fluid phase and under equilibrium conditions at 323K and 298K, respectively. All of our simulations were performed over 100 ns total simulation time and in the absence of any externally applied stress to the membranes. In all three systems investigated, in the presence of DMSO, we observed that small hydrophobic pores start to open across the membranes at various times during the simulations ranging from 10 ns for the DMPC, 45ns for POPC to 50ns for DPPC membrane. By carefully analyzing the membranes structures we concluded that hydrophobic pores open and close continuously during the simulation beyond the above mentioned time marks. Interestingly, as there is no external stress applied to the membranes these hydrophobic pores are presumably nucleated by thermal fluctuations. In all three systems we also observe that after some time after the first hydrophobic pore nucleation the pore starts to grow and transforms into a hydrophilic pore which continue to grow at an even higher rate. Our MD simulation studies of various BLMs indicate that the presence of DMSO may lower the pore edge line tension leading to pore nucleation and growth due to only thermal fluctuations.

Commentary by Dr. Valentin Fuster
2007;():23-27. doi:10.1115/IMECE2007-41308.

Injury to biological cells during the freezing-thawing process of a cryopreservation protocol is related to the thermodynamic state of the intracellular water. The two primary biophysical phenomena are water transport and intracellular ice formation (IIF). Unfortunately, there is no technique currently available to measure IIF in the cells of opaque tissue sections. In this proceeding we report the use of a calorimeter to assess IIF in two different cell suspensions, adult stem cells and pacific oyster embryos. The close agreement between the IIF data obtained using the calorimetric data with corresponding data obtained using a well-established cryomicroscopy technique validated the calorimetric method. Since, the calorimetric measurements are independent of shape and size, it is ideally suited to measure IIF in opaque tissue sections; the focus of future studies.

Topics: Ice
Commentary by Dr. Valentin Fuster
2007;():29-36. doi:10.1115/IMECE2007-41796.

Intracranial blood flow simulations for studying brain aneurysms are based on many assumptions including the Womersley profile for the inlet boundary condition. Moreover, computational domains seem to be more or less arbitrarily chosen. Previous studies have shown that long inlet vessels lead to more realistic flow just upstream of the aneurysm. In order to guide our studies of cerebral aneurysms, using the high-order spectral/hp element method, we systematically investigated the geometric sensitivity of wall shear stress (WSS) on aneurysms; specifically, the effect of parent vessel geometry on the WSS in aneurysms was considered. Using datasets of two patients with different type of aneurysms, five different geometric models were generated. With the aneurysm geometries fixed, the length or turning angles of inlet parent vessel were varied one at a time. This study demonstrates that the turning angle of upstream blood vessel, the type of aneurysm, and its location with respect to the parent vessel affect the distribution of WSS in the aneurysm. In the fusiform aneurysm with sharp turns, the inlet length makes a substantial difference on impinging location, magnitude, and direction of WSS. On the other hand, the saccular type aneurysm with a smoother parent vessel does not show any significant change. Therefore, the computational domain should be determined based on the geometry of parent vessels and the type of aneurysm.

Commentary by Dr. Valentin Fuster
2007;():37-40. doi:10.1115/IMECE2007-42370.

This paper presents an immunoassay capable of detecting an antigen without labeling or immobilization. By measuring a change in fluid resistance, the immunoassay successfully differentiates a positive control from a negative control. The same device can also act as a particle counter due to its high sensitivity. It is capable of detecting differences in concentrations as low as 104 particles per milliliter. An analytical model is developed to analyze the measured signal.

Commentary by Dr. Valentin Fuster
2007;():41-45. doi:10.1115/IMECE2007-42376.

This paper describes the fabrication and actuation of bio-mimetic cilia for fluid manipulation. High aspect ratio cilia made of polydimethylsiloxane (PDMS) were successfully assembled in a microfluidic device by our novel fabrication method. This method was to release the PDMS cilia from a Si mold and assemble the cilia in a device. All the process was performed under water in order to avoid the stiction and pairing of the PDMS cilia. The underwater assembly method enabled a high aspect ratio PDMS structure assembly in a fluidic device. The PDMS cilia were actuated in air and water by lead-zirconate-titanate (PZT) microstage. In the fabricated device, the maximum displacement of the cilia was observed at 120Hz in air and at 50Hz in de-ionized (DI) water with our experimental condition. The actuated cilia in a solution produced convective and propulsive fluid flow near the cilia structure. The developed device can be used for precise handling of small volume sample (e.g., 1 μL).

Topics: Fluids , Biomimetics
Commentary by Dr. Valentin Fuster
2007;():47-53. doi:10.1115/IMECE2007-42765.

The aim of the present study is to obtain the stress distribution pattern on the different domains of the tooth in the oral cavity, taking into account non linear properties of the periodontal ligaments (PDL)surrounding the tooth. The stresses and deformation under the action of chewing forces are studied to estimate the risk of tooth fractures. Initially, linear stress and deformation analysis is carried out with three posts different in constitution. However, considering the role of periodontal ligaments, which ensures uniform stress distribution in tooth structure, due to its elastic and non-linear properties, it is felt necessary to simulate the model for non linear analysis. The study reveals that non-linear analysis gives more realistic results as compared to linear analysis. It is observed that under similar loading conditions, the stresses are approximately 25% less in case of non linear analysis and the deformation is 50% more as compared to linear static analysis for an endodontically treated maxillary central incisor. The Dentist can do selection of optimum post core system with better accuracy.

Commentary by Dr. Valentin Fuster
2007;():55-62. doi:10.1115/IMECE2007-43055.

Polymerase Chain Reaction (PCR) is an enzymatic process that has dramatically advanced many fields of life sciences, where it is an indispensable tool in a burgeoning range of applications, including diagnostic medicine, molecular biology, forensics and food testing. Recent increased demand for extremely high throughput PCR systems has led to the development of miniaturised continuous flow microfluidic PCR devices, which may have extremely high throughput compared to standard commercial PCR thermal cyclers. A novel continuous flow microfluidic PCR device has been designed and fabricated, consisting of two thermal zones maintained on aluminium thermal blocks providing the precise temperatures required for denaturation and annealing/extension. Polycarbonate sideplates retain the denaturation thermal block vertically above the annealing/extension thermal block while allowing for a variable air gap to be maintained between them. Heating of the denaturation thermal block is achieved using a Labview controlled Thermofoil heater, while the annealing/extension thermal block is maintained at temperature by optimised heat transfer from the denaturation block. Flow-through capillary tubing is positioned into a grooved serpentine channel machined into these thermal blocks. This serpentine channel passes through each thermal block fifty times, providing fifty PCR thermal cycles. Contamination free high throughput continuous flow PCR necessitates that the samples be encapsulated in an immiscible carrier fluid to eradicate cross contamination between samples and suppress the likelihood of the sample contacting the capillary leading to sample degradation. Encapsulation of the PCR reaction mixture is achieved upstream of the thermal cycler through segmentation of the sample into droplets entrained within an immiscible carrier fluid, which are then cycled through the thermal cycler. High throughput DNA amplification of two genes, GAPDH and LEF1, from the REH cell line has been successfully demonstrated on this microfluidic platform without any detectable contamination between samples. The PCR droplet reactors were approximately 250nl which is two orders of magnitude less than the standard sample size for most commercial PCR thermal cyclers.

Commentary by Dr. Valentin Fuster
2007;():63-69. doi:10.1115/IMECE2007-43058.

Real-time quantitative Polymerase Chain Reaction (PCR) is an extremely sensitive and reliable method for quantifying gene expression, allowing subtle shifts in gene expression to be easily monitored. Currently, stationary real-time PCR is readily achieved using fluorescent labels which increase in fluorescence as the DNA is exponentially amplified. Quantitative PCR is used in a myriad of applications. However currently most commercial real-time PCR devices are batch process stationary well based systems, limiting their throughput. Continuous flow microfluidic PCR devices have allowed for advancement in terms of improved PCR throughput and reduced reagent usage. As part of an overall total analysis system a device integrating all the functional steps of continuous flow realtime quantitative PCR has been designed and fabricated. Initially the PCR reaction mixture is segmented into nano-litre PCR reactors which are then thermally cycled on a two temperature fifty cycle flow-through PCR device, which allows laser induced fluorescent imaging of the nanoreactors. Previous studies into continuous flow PCR have demonstrated endpoint fluorescent measurements, however this research allows PCR nanoreactors to be fluorescently monitored after every PCR thermal cycle. Fluorescent optical monitoring is achieved through laser excitation of the nanoreactors while a Charged Coupled Device (CCD) camera is used to record the fluorescent emissions from the nanoreactors. Intensity analysis of the recorded images is then preformed using MATLAB to accurately determine the fluorescence intensity level, thereby allowing real-time quantitative amplification curves to be generated. This has major advantages over existing continuous flow PCR devices which use endpoint fluorescence and capillary electrophoresis, as the amplification curves allow far more information to be gleaned and allow the initial DNA template concentration to be accurately determined.

Topics: Flow (Dynamics) , Chain , DNA
Commentary by Dr. Valentin Fuster
2007;():71-77. doi:10.1115/IMECE2007-43443.

Magnetic nanoparticle hyperthermia attracts growing research interest aiming to develop a localized heating approach for malignant tumors treatment. In this method, magnetic nanoparticles delivered to the tissue or blood vessels induce localized heating when exposed to alternating magnetic field, leading to irreversible thermal damage to the tumor. Controlling the heat distribution and temperature elevation in such treatment is still an immense challenge in clinical applications. In this study, we inject nanofluid into agarose gel to study nanofluid transport in the extracellular space of biological tissue. Nanofluid distribution in the gel is examined via digital images of the nanofluid spreading in the gel. By adjusting gel concentrations and injection flow rates, we expect to identify an idealized particle delivery strategy for achieving spherical shaped nanoparticle dispersion. Thermocouples are then inserted into the gel to measure the initial temperature rises at various locations in the gel to obtain the specific absorption rate (SAR). The preliminary results have demonstrated that a spherical shaped particle deposition is possible with a relatively low injection rate of the nanofluid and a technique that minimizes the air gap surrounding the injection needle. The distribution of energy absorption (SAR) implies that the nanoparticle distribution in the gel is not uniform. High concentration of nanoparticles is observed close to the center of the injection site. Based on the particle deposition pattern, a theoretical model will be developed in the future to simulate the temperature distribution in tissue during nanoparticle hyperthermia treatment. The simulated results will help provide guidance for designing a better treatment protocol in future clinical application.

Topics: Nanoparticles , Cancer
Commentary by Dr. Valentin Fuster
2007;():79-85. doi:10.1115/IMECE2007-43764.

Recent experimental studies on human and bovine cortical bone shows that fracture strength of a cortical bone cannot be characterized by a single value of fracture toughness, but rather by variable crack growth resistance values. The mechanism of resistance of a crack extension in a bone is generally defined by R-curve behavior, which can be expressed as the relation between crack growth resistance values and crack extension. Crack bridging stress in front of a crack has been shown to be the main source of this resistance of the bone crack extension. The calculation of this bridging stress is important for predicting fracture stress in cortical bone material. In this study, a theoretical model based on weight function was developed to evaluate the bridging stress in front of a cortical bone crack tip. The main goal of this research was to investigate the role of specimen orientation on bridging stress. The hypothesis used was that specimen orientation has significant influence on the bridging stress. Two specific aims are developed to support this hypothesis: determination of the bridging stress along a crack length and investigation of the orientation effect on bridging stress. A weight function formulation was used to calculate crack opening displacements. The bridging stress along a crack can be found by minimizing the experimental and calculated crack opening displacements using a least square formulation. Finally, the bridging stress variation along a crack extension was examined in the specimen along two different orientations. The developed analytical model produces a gradually increasing trend of bridging stress with crack extension which depends on the orientation of the specimen extraction.

Commentary by Dr. Valentin Fuster
2007;():87-94. doi:10.1115/IMECE2007-43916.

Cryosurgery is a minimally invasive clinical technique with controlled destruction of target tissues through a specifically administrated freezing procedure. This method has now been used in a wide variety of clinical situations such as treatment of skin cancers, glaucoma, lung and prostate tumor etc. However, there still exist many bottle necks to impede the success of a cryosurgery. A most critical factor has been that insufficient or inappropriate freezing will not completely destroy the target tumor tissues, which as a result may lead to tumor regenesis and thus failure of treatment. Meanwhile, the surrounding healthy tissues may suffer from serious freeze injury due to unavoidable release of a large amount of cold from the freezing probe. To resolve this difficulty, we proposed an innovative strategy, termed as nano-cryosurgery, to significantly improve freezing efficiency of a conventional cryosurgical procedure. The basic principle of this protocol is to inject functional solution with nano particles into the target tissues, which then serves as either to maximize the freezing heat transfer process, regulate freezing scale, modify ice-ball formation orientation or prevent the surrounding healthy tissues from being frozen. Meanwhile, introduction of nanoparticles during cryosurgery could also help better image the edge of a tumor as well as the margin of the iceball. Along this direction, several progresses have been made on mechanism interpretation, theoretical modeling, numerical prediction, conceptual experimental demonstration and treatment planning etc. in the authors’ lab. This study is dedicated to present a preliminary outline on the nano-cryosurgery by summing up the aspects as mentioned above. The evident merits and shortcomings of the nano cryosurgery will be illustrated. Some potential feasibility, versatile applications and possible challenges when nanotechnology meets cryosurgery will be pointed out. It is expected that the concepts of nano-cryosurgery may suggest new opportunities for realizing a highly safe, targeted and accurate freezing therapy in future tumor clinics.

Topics: Freezing , Tumors
Commentary by Dr. Valentin Fuster
2007;():95-96. doi:10.1115/IMECE2007-43920.

Recently, a minimally invasive probe system capable of performing both cryosurgery and hyperthermia treatment for deep tumor was developed. With the increasing applications of such combined system, it becomes apparent that without optimal configuration of the multiple probes during multiple freeze/heat cycles, it is difficult produce a conformal lesion in the tumor tissue, which may lead to either insufficient or excessive freezing/heating and consequently, to tumor recurrence or to destruction of healthy tissue. In this study, a comprehensive three-dimensional numerical investigation is performed to design optimal configurations of the multiple probes used in the combined cryosurgical and hyperthermic treatment. The results presented in this study will be useful for treatment planning of the combined cryosurgical and hyperthermic treatment.

Topics: Probes , Tumors
Commentary by Dr. Valentin Fuster
2007;():97-101. doi:10.1115/IMECE2007-43921.

To perform a cryosurgical procedure successfully, it is important to carefully design the optimal freezing parameters (such as the number of cryoprobes, the locations, the insertion paths and depths of cryoprobes) before cryosurgery. Failure to do so accurately could lead to either insufficient or excessive freezing. Due to the irregularly shaped tumors commonly encountered in clinics, multiple cryoprobes are often needed, which makes the parameter optimization rather difficult. Computerized planning tools would help to alleviate this difficulty. In this study, a three-dimensional cryosurgery planning tool is developed, based on the numerical algorithm presented in our recent works. This tool is developed with general purpose and applicable for the treatment planning of tumor with complex geometry. For demonstration purposes, several examples for typical cryosurgery cases using multiple cryoprobes are given and interpreted.

Topics: Geometry , Probes , Tumors
Commentary by Dr. Valentin Fuster
2007;():103-111. doi:10.1115/IMECE2007-41344.

Osteoarthritis (OA) is a degenerative disease of articular cartilage that may lead to pain, limited mobility and joint deformation. It has been reported that abnormal stresses and irregular stress distribution may lead to the initiation and progression of OA. Body weight and the frontal plane tibiofemoral angle are two biomechanical factors which could lead to abnormal stresses and irregular stress distribution at the knee. The tibiofemoral angle is defined as the angle made by the intersection of the mechanical axis of the tibia with the mechanical axis of the femur in the frontal plane. In this study, reflective markers were placed on the subjects’ lower extremity bony landmarks and tracked using motion analysis. Motion analysis data and force platform data were collected together during single-leg stance, double-leg stance and walking gait from three healthy subjects with no history of osteoarthritis (OA), one with normal tibiofemoral angle (7.67°), one with varus (bow-legged) angle (0.20°) and one with valgus (knocked-knee) angle (10.34°). The resultant moment and forces in the knee were derived from the data of the motion analysis and force platform experiments using inverse dynamics. The results showed that Subject 1 (0.20° valgus) had a varus moment of 0.38 N-m/kg, during single-leg stance, a varus moment of 0.036 N-m/kg during static double-leg stance and a maximum varus moment of 0.49 N-m/kg during the stance phase of the gait cycle. Subject 2 (7.67° valgus tibiofemoral angle) had a varus moment of 0.31 N-m/kg, during single-leg stance, a valgus moment of 0.046 N-m/kg during static double-leg stance and a maximum varus moment of 0.37 N-m/kg during the stance phase of the gait cycle. Subject 3 (10.34° valgus tibiofemoral angle) had a varus moment of 0.30 N-m/kg, during single-leg stance, a valgus moment of 0.040 N-m/kg during static double-leg stance and a maximum varus moment of 0.34 N-m/kg during the stance phase of the gait cycle. In general, the results show that the varus moment at the knee joint increased with varus knee alignment in static single-leg stance and gait. The results of the motion analysis were used to obtain the knee joint contact stress by finite element analysis (FEA). Three-dimensional (3-D) knee models were constructed with sagittal view MRI of the knee. The knee model included the bony geometry of the knee, the femoral and tibial articular cartilage, the lateral and medial menisci and the cruciate and the collateral ligaments. In initial FEA simulations, bones were modeled as rigid, articular cartilage was modeled as isotropic elastic, menisci were modeled as transversely isotopic elastic, and the ligaments were modeled as 1-D nonlinear springs. The material properties of the different knee components were taken from previously published literature of validated FEA models. The results showed that applying the axial load and varus moment determined from the motion analysis to the FEA model Subject 1 had a Von Mises stress of 1.71 MPa at the tibial cartilage while Subjects 2 and 3 both had Von Mises stresses of approximately 1.191 MPa. The results show that individuals with varus alignment at the knee will be exposed to greater stress at the medial compartment of the articular cartilage of the tibia due to the increased varus moment that occurs during single leg support.

Topics: Weight (Mass) , Stress , Knee
Commentary by Dr. Valentin Fuster
2007;():113-119. doi:10.1115/IMECE2007-41873.

One approach to enhance nerve and spinal cord regeneration following injury is to implant a biomaterial scaffold to ”bridge” the gap of the injury. Structural/mechanical anisotropy has been suggested as a means of orienting this growth axially. We have spatially varied the mechanical properties of a 3D collagen gel to direct growth axially and unidirectionally. Gradients of mechanical properties were generated in collagen gels by exposing the collagen to a 0–1mM gradient of genipin, a cell-tolerated crosslinking agent, for 12hrs via microfluidics. The gradient of stiffness was confirmed via a gradient of genipin-induced fluorescence intensity, which we have previously correlated to the storage modulus of collagen gels. The growth of neurites from isolated chick embryo dorsal root ganglia (DRG) in the presence of these gradients was evaluated after 5 days in culture. In control cases, neurites grew into the collagen gel and up either side of the cross-channel to approximately equal lengths. A 20% difference in differential growth was observed in control experiments. In contrast, when presented a gradient of shear modulus from ∼365Pa – 60Pa, neurites elected to grow down the gradient of stiffness to the compliant side, with an almost 300% difference. Interestingly, the length of neurites in gels with gradients was significantly greater than the length of those grown in gels with uniform, untreated gels with high compliance. Control of neurite growth, cell migration, and other aspects of cell behavior in 3D scaffolds via mechanical properties offers vast potential for tissue engineering and other regenerative therapies.

Topics: Stiffness
Commentary by Dr. Valentin Fuster
2007;():121-125. doi:10.1115/IMECE2007-42013.

We have developed a solid mechanics model of nearly incompressible, viscoelastic soft tissue for finite element analysis (FEA) in MATLAB 7.2. Newmark’s method was used to solve the finite element equations of motion for our model. The solution to our dynamic problem was validated with a transient dynamic analysis in ANSYS 10.0. We further demonstrated that our MATLAB FEA qualitatively agrees with those results observed with acoustic radiation force methods on soft tissues and tissue-mimicking materials. We showed that changes in Young’s modulus and the damping coefficient affect the displacement amplitude and phase shift of the response data in the same manner: An increase in Young’s modulus or damping coefficient decreases both the displacement amplitude and response lag. Future work on this project will involve frequency analysis on response data and studying the initial transient region to help uncouple the effects of Young’s modulus and damping coefficient on response characteristics. This will get us one step closer to being able to explicitly determine Young’s modulus and the damping coefficient from the temporal response data of acoustic radiation force methods, which is the ultimate goal of our project.

Commentary by Dr. Valentin Fuster
2007;():127-133. doi:10.1115/IMECE2007-42294.

Mechanical changes in breast tissues as a result of cancer are usually detected through palpation by the physician and/or self examination. However, physicians are unable to palpate most masses under 1 cm in diameter and microscopic diseases. The goal of our study is to introduce the application of the Harmonic Motion Imaging (HMI), an acoustic radiation force technique, for reliable sensitive tumor detection and real-time monitoring of tumor ablation. Here, we applied the HMI technique using a single-element Focused Ultrasound (FUS) transducer. Due to the highly localized and harmonic nature of the response, the motion characteristics can be directly linked to the regional tissue modulus. In this experiment, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) probe, was used. The FUS beam was further modulated by a low AM continuous wave at 25 Hz. A pulser/receiver was used to drive the pulse-echo transducer at a Pulse Repetition Frequency (PRF) of 5.4 kHz. The radio-frequency (RF) signals were acquired using a standard pulse echo technique. The intensity amplitudes of the FUS beam at the focus (Ispta ) were 231 W/cm2 for tumor detection and 1086 W/cm2 for FUS ablation. An analog bandpass filter was used to remove the spectrum of the FUS beam prior to displacement estimation. The resulting axial tissue displacement (i.e., HMI displacement) was estimated using an RF-based speckle tracking technique based on 1D cross-correlation. For tumor mapping, a harmonic radiation force was applied using a 2D raster-scan technique. The 3D HMI image was obtained by combining multiple 2D planes at different depths. The 2D and 3D HMI images in ex vivo breast tissues could detect a benign tumor (2×5×5mm3 ) surrounded by normal tissue, and a malignant tumor (8×7×5mm3 ) embedded in glandular and fat tissues. For FUS therapy, temperature measurements and RF signals were acquired during thermal ablation. HMI images during FUS ablation showed lower displacements, indicating thus tissue hardening due to lesion formation at temperatures higher than 50°C. A finite-element model (FEM) simulation was also used to analyze the findings of the experimental results. In conclusion, this technique demonstrates feasibility of the HMI technique for tumor detection and characterization, as well as real-time monitoring of tissue ablation based on the associated tissue elasticity changes.

Commentary by Dr. Valentin Fuster
2007;():135-143. doi:10.1115/IMECE2007-42530.

In this work, the spreading properties of biomaterials, while a counter-rotating roller is used in rapid prototyping machines, are modeled and characterized. For modeling, the slab method is used in which biomaterial geometrical properties are incorporated into the model. A pressure dependent plasticity model is used as a constitutive model for biomaterial powders. In addition, the coulomb friction law for the powder-roller interface boundary is incorporated into the model. Size and shape of powder particles as well as roller rotational and linear velocities are considered within the friction coefficient. Powder bed parameters such as compaction pressure, stress distribution and relative density are predicted using the simulation.

Commentary by Dr. Valentin Fuster
2007;():145-151. doi:10.1115/IMECE2007-42975.

This study utilizes novel characterization techniques nanoindentation and nanoscratch for testing both the human enamel and dentine together with two biocompatible dental filling materials; epoxy nanocomposite and silver amalgam. Nanoindentation tests were performed to obtain accurate hardness and reduced modulus values for the enamel, dentin and two different fillers. We utilized Nano-scratch tests to obtain critical load in scratch test and resistance to sliding wear. Testing showed the silver amalgam filling has a higher modulus of elasticity, hardness and wear resistance compared to the nanocomposite. The novel mechanical characterization techniques utilized might assist in better understanding the mechanical behavior of the dental fillers and thus facilitate the design of robust fillers with excellent mechanical properties.

Commentary by Dr. Valentin Fuster
2007;():153-159. doi:10.1115/IMECE2007-43001.

This work is concerned with the 3D finite element modeling of porous implants in which the pore characteristics and distribution are taken into account. The analysis is conducted for scaffolds composed of various biocompatible materials such as Hydroxyapatite, PMMA, PEEK, Ti-6Al-4V, Silicon Nitride, Zirconia and Alumina. Furthermore, the potential of bone growth within the scaffolds is investigated using principal strain histograms of loaded scaffolds. The results show that the histogram of the principal strain resembles a top hat distribution while the porosity (void fraction) decreases. For a specific porosity, the principal strain distribution falls within the desired region (for optimal bone growth) by selecting materials with some particular Poisson’s ratio, although stress-shielding possibility rises due to an increase in the apparent stiffness of the scaffold. The increase in the apparent stiffness is a result of high Young modulus of the above-mentioned materials. The model will provide a platform for designers to adjust internal architecture features (e.g., the porosity level, shape/size/orientation of pores and the material properties) based on the host bone data prior to the scaffold fabrication.

Topics: Biomechanics , Bone
Commentary by Dr. Valentin Fuster
2007;():161-169. doi:10.1115/IMECE2007-42266.

In this article, we describe the design of a shape memory alloy-based system to stretch cells cultured on top of a flexible membrane in multi-directions (longitudinal and transverse). Mechanical cues (such as strain and force) can affect the state and behavior of cells, such as, morphology, the differentiation process, and apoptosis. Therefore, a thorough understanding of the effects of mechanical perturbations on cells/tissues will have a deep impact in the biological sciences. The proposed design allows application of anisotropic (multi-axial) strain with high-precision. Certain cells, for example endothelial cells that line the inside of blood vessels, experience multi-axial (circumferential and longitudinal) stresses and strains. A cell stretching device that enables controlled application of biaxial strain will allow for systematic and accurate studies of the effects of externally applied mechanical perturbation throughout the cell, tissue, or organ. A preliminary design is proposed that exploits the strain recovery property of the shape memory alloy (SMA) actuators. We describe the design of the mechanical system and show experimental results to demonstrate stretching of a thin PDMS membrane in the longitudinal and transverse directions. To account for the inherent nonlinearity of the SMA, a feedback controller is implemented to achieve high-precision control of the stretching process. Additionally, the design can be integrated with an atomic force microscope (AFM) for high spatial and temporal resolution studies.

Commentary by Dr. Valentin Fuster
2007;():171-178. doi:10.1115/IMECE2007-42399.

Adaptive optics (AO) systems make use of active optical elements namely wavefront correctors to improve the quality of imaging through dynamically varying media. Vision science is an area of application of these systems where they have been used to enhance the resolution of imaging of internal parts of the human eye. However, their widespread use in clinical devices is limited due to the insufficient performance and high costs of the currently available wavefront correctors. Recently, magnetic fluid deformable mirrors (MFDM) have been proposed as a type of wavefront correctors that can sufficiently overcome the problems associated with the existing wavefront correctors. The practical implementation of this new type of deformable mirrors is contingent on the development of effective methods to model and control the shape of their deformable surface. To help meet this critical requirement, this paper presents an analytical model of a circular MFDM in cylindrical geometry. The resulting model can be used in the design of control systems for ophthalmic adaptive optics systems. Preliminary results of an experimental investigation aimed at validation of the analytical model are also presented.

Commentary by Dr. Valentin Fuster
2007;():179-180. doi:10.1115/IMECE2007-42493.

We investigate multiple-annular-ring CMUT array configuration for forward-looking intravascular ultrasound (FL-IVUS) imaging. This configuration has the potential for independent optimization of each ring and uses the silicon area more effectively without any particular drawback. We designed and fabricated a sample 1mm diameter dual annular ring CMUT test array which consists of 24 transmit and 32 receive elements. For imaging experiments, we designed IC chips that contain 8 transimpedance amplifiers, a multiplexer and a buffer. The real time-pulse echo experiments obtained with designed IC electronics show 26dB Signal to Noise Ratio (SNR) from a 3.5 mm away aluminum reflector in oil. This paper presents our first efforts in obtaining real time imaging with designed IC chips which is one step before CMUT on CMOS implementation.

Commentary by Dr. Valentin Fuster
2007;():181-182. doi:10.1115/IMECE2007-43524.

A number of designs for microneedles have recently been developed to facilitate the painless injection of medications, such as insulin, into the human body [1–6]. The injections are painless because the needles penetrate the skin predominantly in the epidermal layer of skin which contains no nerve endings. Some microneedles do not contain inner channels and are simply coated with medication, the intent being that the transdermal drug delivery will take place through absorption over time. A more effective method of medicinal transfer is to equip the microneedles with an inner channel to facilitate rapid delivery of the medication to the skin.

Commentary by Dr. Valentin Fuster
2007;():183-185. doi:10.1115/IMECE2007-41102.

Cavitation – the growth and collapse of mostly empty bubbles — is commonly attributed to large scale or very rapid flows, e.g. at ship propellors or at fuel injection nozzles. Cavitation is very aggressive to materials and one reason is its ability to focus fluid flows to very small scales; the bubbles concentrate the energy from the fluid during their shrinkage. Only recently the attention from largely free cavitation bubbles has shifted towards the study of more confined bubbles [1–5]. Here we report on an experiment to exploit cavitation in microfluidic systems or so called lab-on-a-chip devices for flow handling and biological cell manipulation. In microfluidics generally due to the small scales low Reynolds number flows are observed. Yet, cavitation bubble-induced flows allow to reach a high Reynolds number regime also on these small scales. By exploiting this rarely studied flow regime new techniques for liquid and cell handling become feasible. Here, we will report first on the effect of a channel wall on the bubble dynamics and then present an application for cell handling and membrane poration.

Commentary by Dr. Valentin Fuster
2007;():187-190. doi:10.1115/IMECE2007-41280.

Coronary heart disease is the single leading cause of death in America today. Annually, an estimated 1.2 million Americans suffer from a new or recurrent coronary attack. Coronary heart disease is caused by atherosclerosis, the narrowing of the coronary arteries due to fatty build ups of plaque. It’s likely to produce angina pectoris (chest pain), heart attack or both. The placement of a stent in the artery is used to prevent the collapse of the balloon treated artery. However the struts can introduce the excessive stresses on the artery wall and cause the artery to be re-blocked after weeks or months (in-stent restenosis). This study will quantify how key parameters of a stent such as mesh design, strut thickness, and plaque geometry affect the restenosis conditions. Results will identify the desirable properties necessary for the development of effective therapeutic strategy for reducing in-stent restenosis.

Commentary by Dr. Valentin Fuster
2007;():191-200. doi:10.1115/IMECE2007-41387.

Stone breakage in shock wave lithotripsy is improved by slowing the rate of shock wave (SW) delivery. Previous studies have shown that increased cavitation at fast pulse repetition frequency (PRF) reduces the tensile phase of the SW, while the leading positive wave is virtually unaffected. Since the tensile component of the SW drives cavitation, and since cavitation at the stone contributes to breakage, it seems likely that increased cavitation along the path to the stone affects cavitation at the stone. Here we present preliminary data suggesting that PRF influences bubble dynamics at the stone. High-speed imaging showed that as PRF increased, bubble density of cavitation clouds increased, and the size of individual bubbles decreased. A new method to measure stresses generated by cavitation was used to show that locally induced stresses from bubble collapse can be greater than the incident SW, and were higher at 0.5Hz than at 2Hz PRF.

Commentary by Dr. Valentin Fuster
2007;():201-204. doi:10.1115/IMECE2007-41562.

Endodontic therapy, better known as root canal treatment, is a procedure performed to remove damaged and/or infected tissue from the inner canals of teeth and seal the canals to prevent the teeth from being a source of infection. Each year more than 24 million teeth receive endodontic treatment in the United States. A typical procedure includes access preparation (opening crown with drills), root canal shaping and cleaning, and then root canal filling. This treatment is expensive, time-consuming, and prone to human error. The outcome relies on the clinician’s skill, which is gained through years of training and practice. The success quotient of this treatment is 60–65% for general dentists and 90% for specialists (endodontists). There is a need for advanced endodontic technology innovation. This paper will describe the process of mechanical design of computer-controlled micro machine, which will perform the automatic probing, drilling, cleaning, and filling of the root canal. The paper will also discuss the innovations involved from the traditional way endodonticsts treat root canal to science and technology based automation.

Commentary by Dr. Valentin Fuster
2007;():205-210. doi:10.1115/IMECE2007-41600.

Inexpensive models of the radius with and without an internal fixation system for a mid-shaft fracture are developed and analyzed using the Finite Element Method (FEM). FE models are based on geometry obtained from simple yet effective manufacturing methods. Median trabecular and cortical bone mechanical properties for a healthy adult male are used in the FEM model. These models are used to quantify the changes in bone stresses that occur when internal fixation devices are retained after the fracture has healed. The linear static responses to tensile and torsional loads with and without bone plates are examined. The static response trends obtained agree reasonably well with current literature where more expensive modeling techniques were used. A fatigue analysis is also performed based on the FE static results coupled with S-N curves for the plate and bone material in order to predict the combined mechanical response of the bone plate system over time. Recommendations are suggested which may be used as additional guidelines to consider for bone plate system selection and determination of hardware removal.

Commentary by Dr. Valentin Fuster
2007;():211-220. doi:10.1115/IMECE2007-41629.

This paper presents a methodology for predicting the mechanical damage inflicted on the brain by a high explosive (HE) detonation and leading to traumatic brain injury (TBI). A brain model, with its complexity, is used in the computational procedure. The processes of HE detonation and shock propagation in the air, as well as their interaction with the head, are modeled by an Arbitrary Lagrangian Eulerian (ALE) multi-material formulation, together with a penalty-based fluid/structure interaction algorithm. This methodology provides intracranial pressure and maximum shear stress within the microscale time frame for this highly dynamic phenomenon. Two scenarios are simulated. In one scenario, the brain is in close proximity to a 1lb trinitrotoluene (TNT) explosion, and the other to a 0.5lb explosion. The resulting countercoup intracranial pressure-time histories, from the 1 lb TNT explosive scenario, demonstrates that pressure falls below −100 kPa. This can cause cavitation bubbles and damage to the brain tissue. The simulations also predict that the areas of high pressure and shear stress concentration are consistent with those of clinical observations. These resulted intracranial pressure and shear stress responses are the parameters to examine against injury criterions thresholds.

Topics: Simulation , Brain , Wounds
Commentary by Dr. Valentin Fuster
2007;():221-227. doi:10.1115/IMECE2007-41772.

The simulation capability for intraoperative brain tissue deformation by the surgical procedures using computational Finite Element analysis is demonstrated in this paper. Our research group has been developing the patient-specific three-dimensional Finite Element brain deformation model consisting of precise anatomical structures, i.e., brain parenchyma with both gyri and sulci on the surface, falx cerebri, and tentorium, in order to evaluate brain shift during navigation surgery without additional acquisition of intraoperative imaging. In this study, both gray and white matters of the brain tissues were modeled as homogeneous nonlinear hyper-viscoelastic material. The falx cerebri with tentorium was modeled as linear elastic material which is much stiffer than the brain tissue. The skull was modeled as a rigid body. In the numerical simulation, the computation of the intraoperative cerebellum tissue deformation due to retraction by spatula for posterior fossa surgery was conducted by ABAQUS/Explicit. The illustrative results successfully demonstrate the interaction between brain tissue and spatula.

Commentary by Dr. Valentin Fuster
2007;():229-236. doi:10.1115/IMECE2007-41797.

Bone formation is subject in vivo to mechanical stimulation. Although many researches for bone cells of osteoblastic lineage sensing and responding to mechanical stimulation have been reported mainly in the biochemical field, effects of mechanical stimulation on bone cells are not well understood. In this study, in order to clarify effects of acceleration amplitude and frequency of mechanical stimulation on MC3T3-E1, which is an osteoblast-like cell line derived from mouse calvaria, in the sense of mechanical vibrations, their cell proliferation, cell morphology, bone matrix generation and gene expression of alkaline phosphatase (ALP) were investigated when sinusoidal inertia force was applied to the cells. After the cells were cultured in culture plates in a CO2 incubator for one day and adhered on the cultured plane, vibrating groups of the culture plates were set on an aluminum plate attached to a exciter and cultured under sinusoidal excitation in another incubator separated from non-vibrating groups of the culture plates. Acceleration amplitude and frequency were set to several kinds of conditions. The time evolution of cell density was obtained by counting the number of cells with a hemocytometer. The cell morphology was observed with a phase contrast microscope. Calcium salts generated by the cells were observed by being stained with alizarin red S solution and their images were captured with a CCD camera. The vibrating groups for the cell proliferation and the calcium salts staining were sinusoidally excited for 24 hours a day during 28-day cultivation. Gene expression of ALP was measured by a real-time reverse transcription polymerase chain reaction (real-time RT-PCR) method. After the vibrating groups for the PCR were excited for 7 days, the total RNAs were extracted. After reverse transcription, real-time RT-PCR was performed. Gene expression for ALP and a housekeeping gene were determined simultaneously for each sample. ALP gene level in each sample was normalized to the measured housekeeping gene level. The results to be obtained are as follows. In the range from 12.5 to 200 Hz, saturation cell density for the cell proliferation shows tendency of increase as frequency decreases and ALP gene expression shows a peak to frequency at 50 Hz. Among 0, 0.25 and 0.5 G, saturation cell density and ALP gene expression show tendency of increase as acceleration amplitude increases.

Commentary by Dr. Valentin Fuster
2007;():237-240. doi:10.1115/IMECE2007-42342.

In order to better rehabilitate lower limb amputees, prostheses need to provide torsional control in the transverse plane to facilitate turning. When designing prostheses, it is helpful to create mechanical models of biological behavior. This paper presented a model of transverse plane ankle function during turn initiation, the first step of a multi-step turning sequence. Motion capture data was collected from ten subjects performing left turns. Four states of stance phase were chosen based on distinct events in the power curve. Passive elements were chosen to model the ankle in each state for turn initiation. The ankle was observed to act as a quadratic torsional spring and a linear torsional damper in State 1 and as linear torsional springs in States 2–4. Damping was found only in State 4 where it was modeled as a linear torsional damper. Turn initiation stiffness coefficients were similar to straight walking in State 1 and 2, but differed in States 3 and 4. This indicates that the turn begins in the middle of stance phase when viewed in terms of transverse plane ankle function. The results of this study should assist with the mechanical design and control of a biomimetic torsional prosthesis by suggesting a finite state control system and by providing the stiffness and damping coefficients to be controlled.

Commentary by Dr. Valentin Fuster
2007;():241-249. doi:10.1115/IMECE2007-42391.

This paper presents the design of an Adaptive Optics (AO) system for retinal imaging applications. The development of retinal imaging systems allows for early diagnosis of eye diseases. Such systems can increase the quality of life of patients as well as curtail increasing health care costs through early eye disease detection and treatment. Until recently, AO systems have been prohibitively expensive and cumbersome. This has been mainly due to the size and cost of flexible membrane mirrors normally used as the aberration correction device. Recent developments in the technology of Microelectromechanical System (MEMS) based actuators allow the implementation of AO systems which would have been difficult to implement a few years ago due to exorbitant costs. The aim of this paper is to present the design of a compact and flexible low cost AO system using off the shelf components to measure and compensate for the aberrations of the eye. The design is based around the system’s main components which include a 52 channel magnetically actuated deformable membrane mirror, a Shack Hartmann wavefront sensor and a control system which runs on a single processor personal computer. All the components are commercially available. The use of the MEMS-based magnetically actuated mirror allows for increased resolution and force compared to conventional membrane mirrors designed mainly for use in astronomical applications. The performance of the closed-loop system is evaluated through experiments. Although designed as a diagnostic tool for eye diseases, such a system will find a number of applications in basic research in the visual sciences, including the study of microscopic structures in the living retina that could not be seen before. Optometrists, retinal surgeons, and ophthalmologists will also benefit from using such a system, through potential improvements on commonly used instruments such as phoropters and fundus cameras.

Commentary by Dr. Valentin Fuster
2007;():251-261. doi:10.1115/IMECE2007-42573.

Ponseti technique is a common non-surgical treatment based on serial manipulation and casting for idiopathic infant clubfoot. We have used three dimensional MRI throughout the treatment, to investigate the effect of the casts on the clubfoot of a one week old (at the beginning of treatment) male with unilateral right idiopathic congenital clubfoot deformity. A total of 21 MRI scans were obtained during weekly serial manipulation and corrective casting. Changes in shape, volume, ossification, and positional relationships of the hind foot anlagen were studied. We found that immediate shape changes occur following casting, particularly in the talus and the navicular, and when after one week the cast is removed the anlagen do not elastically return to their original shape and position prior to casting. Furthermore, the growth rate of some of the clubfoot anlagen, in particular the talus, was faster than normal. A faster ossification was observed in the calcaneus and cuboid. Results also showed correction in parallelism of calcaneus and talus in the anteroposterior plane, minor correction of this parallelism in the lateral view necessitating a heel cord tenotomy, and correction of the medial rotation of calcaneus. Under this treatment changes in talar neck angle yielded a decreasing trend. The navicular moved with respect to the head of the talus from a medial to a lateral position. Relative to the talar body it shifted laterally. Also the geometrical center of talus ossific nucleus was noted to move towards the center of the whole anlagen suggesting that the ossification extends in the opposite direction from the head of the talus. It was concluded that the mechanism of adaptation to the casting loads was quick deformation immediately upon cast application followed by adaptation to the new shape in the cast. These were qualitative findings. It was also concluded that most of the correction occurred during the initial treatment period, primarily during the first and second weeks (1). On the quantitative end, it was confirmed that MRI and computer techniques can be utilized to ascertain and quantify the abnormalities which were impossible to well identify otherwise. MRI based studies have powerful potential to provide helpful information on the choice of treatment as well as guidance throughout. For instance, it may therefore be possible in the present case to shorten the treatment time without adverse effects on the outcome.

Commentary by Dr. Valentin Fuster
2007;():263-270. doi:10.1115/IMECE2007-42692.

One of the leading causes for death after heart diseases and cancer in all over the world is still stroke. Most strokes happen because an artery carrying blood from the heart to the brain is clogged. Most of the time, as with heart attacks, the problem is atherosclerosis, hardening of the arteries, calcified build up of fatty deposits on the vessel wall. The primary troublemaker is the carotid artery, one on each side of the neck, the main thoroughfare for blood to the brain. In this study, the fluid dynamic simulations were done in the carotid bifurcation artery for studying the formation of atherosclerosis, and shear thinning behavior of blood as well as Newtonian comportment was studied. Under the steady flow conditions, Reynolds numbers representing the steady flow were under 1700. A comparison between rheological models for investigation each non-Newtonian model was carried out, velocity and wall shear stress distributions and its effect on developing atherosclerosis was studied; also the effect of non-Newtonian entrance length through this problem was exhibited.

Commentary by Dr. Valentin Fuster
2007;():271-280. doi:10.1115/IMECE2007-42928.

The hazard caused by inhaled particles depends on the site at which they deposit within the respiratory system. Knowledge of respiratory aerosol deposition rates and locations is necessary to (1) evaluate potential health effects and establish critical exposure limits and (2) design effective inhaled medications that target specific lung regions. Particles smaller than 10 μm in diameter can be breathed into lungs and are known as inhalable particles, while most of larger particles settle in mouth and nose. Inhalable particles settle in different regions of the lungs and the settling regions depends on the particle size. The motion of a particle is mainly affected by the inertia of the particle and by the particle’s aerodynamic drag. The most important dimensionless parameters in the prediction of particle motion are the flow Reynolds number and the Stoke number, which combines the effects of particle diameter, particle density, shape factor and slip factor. The purpose of this study is to investigate the airflows in human respiratory airways. The influence of particle size on transport and deposition patterns in the 3-D lung model of the human airways is the primary concern of this research. The lung model developed for this research extends from the trachea to the segmental bronchi and it is based on Weibel’s model. The velocity field of air is studied and particle transport and deposition are compared for particles in the diameter range of 1 μm – 100 μm (G0 to G2) and 0.1 μm – 10 μm (G3 to G5) at airflow rates of 6.0, 16.7, and 30.0 L/min, which represent breathing at rest, light activity, and heavy activity, respectively. The investigation is carried out by computational fluid dynamics (CFD) using the software Fluent 6.2. Three-dimensional, steady, incompressible, laminar flow is simulated to obtain the flow field. The discrete phase model (DPM) is then employed to predict the particle trajectories and the deposition efficiency by considering drag and gravity forces. In the present study, the Reynolds number in the range of 200 – 2000 and the Stoke number in the range of 10−5 – 0.12 are investigated. For particle size over 10 μm, deposition mainly occurs by inertial impaction, where deposition generally increases with increases in particle size and flow rate. Most of the larger micron sized particles are captured at the bifurcations, while submicron sized particles flow with the fluid into the lung lower airways. The trajectories of submicron sized particles are strongly influenced by the secondary flow in daughter branches. The present results of particle deposition efficiency in the human upper airways compared well with data in the literature.

Commentary by Dr. Valentin Fuster
2007;():281-284. doi:10.1115/IMECE2007-43061.

Clinical experience has demonstrated that the performance of the 2nd and 3rd generation shock wave lithotripters in terms of stone comminution has become inferior to the 1st generation Dornier HM-3 lithotripter. A primary change in the design of the newer generation lithotripters is the enlarged aperture of the shock source, leading to a higher peak pressure with a smaller focal area. To evaluate the effect of beam size on stone comminution in the same lithotripter, we developed a reflector insert for the HM-3 that can substantially increase the peak pressure while concomitantly tightening the beam size of the lithotripter field. Using a light spot hydrophone, we have characterized the acoustic fields produced by the two reflector configurations at 20 kV. The peak positive pressure and the −6dB beam size were found to be 87 MPa and 4 mm for the HM-3 with the reflector insert, which are significantly different than the corresponding values (51 MPa and 13 mm) for the original reflector. In contrast, the peak tensile pressure and the total acoustic energy of the lithotripter pulse were found to be similar (−12 MPa and 59 mJ with the reflector insert, −11 MPa and 52 mJ for the original reflector). Stone comminution was evaluated in four different holders in order to determine the effect of lateral spreading of residual fragments on lithotripsy outcome. After 250 shocks, the results of stone comminution in a mesh holder of D = 15 mm (63% vs. 61%) were similar. However, the corresponding values produced by the HM-3 with reflector insert in a finger cot of D = 15 mm (45%) and in a membrane holder of D = 30 mm (14%) were significantly lower than those produced by the original reflector (56% and 26%). Further, the efficiencies of stone comminution in both the mesh holder and the finger cot were much higher than that in the membrane holder. These results suggest that a wide beam size in the original HM-3 may increase stone comminution efficiency when the fragments are spread out to a large area during lithotripsy. In contrast, when the fragments are confined during lithotripsy the beam size may not influence significantly the treatment outcome.

Commentary by Dr. Valentin Fuster
2007;():285-294. doi:10.1115/IMECE2007-43156.

In order to better understand the contribution of bubble collapse to stone comminution in shockwave lithotripsy, the shock-induced and Rayleigh collapse of a spherical air bubble is investigated using numerical simulations, and the free-field collapse of a cavitation bubble is studied experimentally. In shock-induced collapse near a wall, it is found that the presence of the bubble greatly amplifies the pressure recorded at the stone surface; the functional dependence of the wall pressure on the initial standoff distance and the amplitude are presented. In Rayleigh collapse near a solid surface, the proximity of the wall retards the flow and leads to a more prominent jet. Experiments show that re-entrant jets form in the collapse of cavitation bubbles excited by lithotripter shockwaves in a fashion comparable to previous studies of collapse near a solid surface.

Commentary by Dr. Valentin Fuster
2007;():295-299. doi:10.1115/IMECE2007-43319.

The human spine is a mechanically complex system of joints crucial for stable posture and movement. The ultimate goal of a vertebral body replacement following a spinal injury that necessitates such a procedure is to have the replacement strut fully incorporate into the spine. This incorporation process is known as bony “fusion”, which facilitates the restoration of stability. Bone graft and metallic implants have been used for vertebral body replacement procedures. Both methods have been associated with failure of fusion and recurrence of instability. The development and rationale of the mechanical testing procedures implemented to best differentiate the stability afforded by bone graft versus expandable titanium cage is presented.

Commentary by Dr. Valentin Fuster
2007;():301-302. doi:10.1115/IMECE2007-43380.

Predicting cardiac alternans is a crucial step toward detection and prevention of ventricular fibrillation, a heart rhythm disorder that kills hundreds of thousands of people in the US each year. According to the theory of dynamical systems, cardiac alternans is mediated by a period-doubling bifurcation, which is associated with variations in a characteristic eigenvalue. Thus, knowing the eigenvalues would allow one to predict the onset of alternans. The existing criteria for alternans either adopt unrealistically simple assumptions and thus produce erroneous predictions or rely on complicated intrinsic functions, which are not possible to measure experimentally. In this work, we present a model-independent technique to estimate a system’s eigenvalues without requirements on the knowledge of the underlying dynamic model. The method is based on principal components analysis of a pseudo-state space; therefore, it allows one to compute the dominant eigenvalues of a system using the time history of a single measurable variable, e.g. the transmembrane voltage or the intracellular calcium concentration in cardiac experiments. Numerical examples based on a cardiac model verify the accuracy of the method. Thus, the technique provides a promising tool for predicting alternans in real-time experiments.

Topics: Eigenvalues
Commentary by Dr. Valentin Fuster
2007;():303-305. doi:10.1115/IMECE2007-43582.

Despite recent innovations in lithotripter design and technology, the first generation Dornier HM-3 electrohydraulic lithotripter remains the most effective clinical, non-invasive modality for comminuting stones. Understanding the fundamental differences between the HM-3 and more clinically practicable lithotripters is critical to achieving meaningful improvements in future models. This study aims to further clarify the role of the second, weaker pulse of the HM-3 in stone comminution by introducing a similar pulse in the pressure profile of an electromagnetic lithotripter. Additionally, this study investigates the potential for this tandem shock technique to improve comminution in electromagnetic lithotripters through optimization of the interpulse delay time.

Commentary by Dr. Valentin Fuster
2007;():307-308. doi:10.1115/IMECE2007-43585.

Electroporation, in which strong electric pulses create transient pores in the cell membrane, is commonly used as a method for delivering molecules into cells. One of the pulsing protocols used in practice, a two-pulse protocol, creates a certain number of pores (Num) with a short, large electric pulse, and then controls the pore size with a second, smaller electric pulse of strength V0 . This study uses nonlinear analysis of an electroporation model to determine guidelines for the magnitude of V0 and Num that will produce pores of a desired radius (r). Analysis reveals that for Num between 85 and 3190, number and type of fixed points (FPs) depend on Num and V0 . For this range of Num, there exist two stable FPs and one unstable FP, and increasing V0 beyond a certain threshold (V0 th ) drives the system to the FP with larger r. V0 th can be fit to a function that is linearly dependent on Num. This study shows that for a given Num created by the first pulse, choice of V0 will allow the experimenter to optimize pore size for a specific application.

Topics: Electroporation
Commentary by Dr. Valentin Fuster
2007;():309-319. doi:10.1115/IMECE2007-43955.

Blunt traumatic rupture of the carotid artery is a rare but life threatening injury. The histology of the artery is key to understanding the aetiology of this injury. The carotid artery is composed of three layers known as the tunica intima, media, and adventitia, with distinct biomechanical properties. In order to examine the behaviour of the carotid artery under external load we have developed a three layer finite element model of this vessel. A rubber-like material model from LS-DYNA was selected for the FE model. The Arbitrary-Lagrangian Eulerian (ALE) approach was adopted to simulate the interaction between the fluid (blood) and the structure (carotid). To verify the FE model, the impact bending tests are simulated using this FE model. Simulation results agree with tests results well. Furthermore, the mechanical behaviour of carotid artery tissues under impact loading were revealed by the simulations. The results provide a basis for a more in-depth investigation of the carotid artery in vehicle crashes. In addition, it provides a basis for further work on aortic tissue finite element modeling.

Commentary by Dr. Valentin Fuster
2007;():321-322. doi:10.1115/IMECE2007-43991.

Understanding the dynamics of bubble oscillation in tissue-constrained media such as within blood vessels is important for many current and potential therapeutic ultrasound applications. Cavitation is a primary mechanism responsible for vessel rupture and tissue injury in shock wave lithotripsy [1]. In sonoporation cavitation can be used to increase permeability of biological membranes. Particularly, ultrasound contrast agents are widely used for imaging of blood vessels and for enhancement of ultrasound-mediated gene delivery [2]. Modeling of non-linear oscillations of bubbles in acrylic capillaries in a high-intensity focused ultrasound field revealed a clear dependence of bubble displacement and fragmentation on tube diameter [3]. However, the effect of elastic boundary on bubble dynamics may differ significantly from that of a rigid boundary [4, 5]. In this study, experimental investigation of the dynamics of bubble oscillation in an elastic tube was performed and preliminary results from tubes of different inner diameters are presented.

Commentary by Dr. Valentin Fuster
2007;():323-324. doi:10.1115/IMECE2007-43996.

The synergistic integration of high intensity focused ultrasound (HIFU) thermal ablation and HIFU-induced gene therapy represents a promising approach in improving the overall efficacy and quality of cancer therapy. Previous studies have demonstrated that HIFU can induce GFP gene activation under the control of hsp70B promoter in a murine tumor model [1]. Thermal stress has been identified as the primary mechanism to regulate the gene expression. However, the natural heterogeneity and opacity of solid tumors has hindered direct correlation of site-specific gene expression level with in situ thermal dosimetry. We have developed a homogeneous and transparent cell-embedded tissue mimicking phantom as an alternative for simultaneous assessment of temperature distribution, HIFU lesion formation, and gene expression.

Commentary by Dr. Valentin Fuster
2007;():327-329. doi:10.1115/IMECE2007-41179.

A modified fading memory model is introduced in this work to describe the behavior of airway smooth muscle dynamics. The model is used to simulate two biophysical cases: a finite duration for the step change in length and a case for external longitudinal oscillations. For both cases, the model describes the cross-bridge behaviour well and indicates that the muscle length change is the most important factor to determine the degree of cross-bridge detachment. However, the frequency of oscillation represents the velocity of the length change, which affects the cross-bridge cycling rate as reflected in the lower frequency range. The model is intended to interpret certain biophysical processes and not to accurately model the biophysical events underlying muscle contraction.

Commentary by Dr. Valentin Fuster
2007;():331-332. doi:10.1115/IMECE2007-41193.

Exploratory clinical studies use ovine neonates to study the efficacy of new respiratory support treatments for human neonates with respiratory distress syndrome. A mathematical model of the ovine neonatal respiratory system is developed to understand the mechanisms of respiratory improvement noticed in clinical trials. Simulating the ovine lung as a five-lobe branched system, the model aims to simulate the behaviour of the individual lobes, pleural compartment, chest wall and the branching structure of the first few bifurcations of airways. Results from the model are correlated with published data from ovine neonates.

Topics: Oscillations , Pressure , Lung
Commentary by Dr. Valentin Fuster
2007;():333-335. doi:10.1115/IMECE2007-41456.

During phonation, the vocal folds collision in the glottal closure is considered as a risk factor for pathology development. Based on the finite element model using the software ABAQUS™, the impact stresses between the vocal folds are studied.

Commentary by Dr. Valentin Fuster
2007;():337-340. doi:10.1115/IMECE2007-42289.

This work investigates the use of frequency spectrum analysis of waveguide propagation in multi-layered anisotropic piezoelectric transducers. A semi-analytical finite-element analysis (SAFE) is used to model the transducer as a piezoelectric infinite plate. Dispersion curves, group velocities and displacement frequency spectra can be obtained for any multilayered piezoelectric plate. Stress-free boundary conditions were assumed for all analyses. Results for open and closed circuit boundary conditions were analyzed. Zero-Group-Velocity (ZGV) frequencies of high-order waveguide modes were observed to provide multi-resonant displacement frequency spectrum. Comparison of numerical and experimental results shows a good agreement between peak and off-peak values of the displacement spectrum. Results showed that optimization of layered structure may provide an efficient means for generating multi-thickness (ZGV) waveguide modes, thus increasing the bandwidth of harmonic ultrasound transducers for contrast imaging.

Commentary by Dr. Valentin Fuster
2007;():341-347. doi:10.1115/IMECE2007-42358.

Whole body vibration (WBV) has been identified as a risk factor for low back musculoskeletal disorders and injuries. One potential mechanism by which WBV may lead to low back injury is through stimulation of muscle spindle organs and repetitive activation of the stretch-reflex neuromotor response. Such repetitive activation could lead to muscular fatigue and/or neuromotor adaptation. Understanding mechanical transmission of vibration to the neuromotor system and the resulting neuromotor activation is critical to understanding these mechanisms. In this study, it was theorized that activation of the extensor musculature of the low back is a response to the lengthening and shortening of the extensor musculature. This lengthening and shortening of the extensor musculature may be the result of flexion-extension rotation in the lumbar spine. By measuring lumbar flexion and extension, the amplitude and phase of this lengthening and shortening were assessed. Using electromyographic data from the erector spinae muscle groups at the L2/L3 lumbar level, the cyclic activation of the extensor musculature was also measured. Neuromotor transmission was observed over a frequency range of 3–20 Hz and vibration magnitudes of 1 and 2 m/s^2 RMS. Resonance peaks in lumbar flexion-extension and the integrated electromyographic data were observed at 4 Hz and 10–12 Hz. A lumbar belt was used to reduce transmission of axial seat-pan vibration to lumbar flexion-extension and to observe the changes in cyclic electromyographic activity. The lumbar belt was found to decrease both lumbar flexion-extension and paraspinal muscle activity demonstrating a link between axial seatpan vibration, lumbar flexion-extension and the cyclic activation of the neuromotor system. These results provide information on the neuromotor effects of WBV and may be used to design better low back injury prevention methods.

Topics: Vibration , Belts
Commentary by Dr. Valentin Fuster
2007;():349-350. doi:10.1115/IMECE2007-42480.

We designed and fabricated a 64 element 1-D linear dual electrode Capacitive Micromachined Ultrasonic Transducer (CMUT) array operating at 9.5 MHz for Intracardiac Echocardiography (ICE). The dual electrode CMUT structure increases the overall sensitivity by 12.6dB (6.2dB in receive sensitivity; 6.4dB in output pressure) when compared to optimized single electrode CMUT. We report peak output pressure of 2.3MPa on the CMUT surface when 170V AC and 180V DC is applied. This significant performance increase makes the CMUT more competitive with their piezoelectric counterparts.

Commentary by Dr. Valentin Fuster
2007;():351-353. doi:10.1115/IMECE2007-43283.

To understand how the input impedance determined at the throat correlates with changes in the dynamic characteristics of the airways, a simplified 5-lobe model is developed and simulated. The model takes into account some realistic conditions such as varying cross-sectional areas, flexible wall properties and branching. The lobe terminal impedances are implemented in the model to predict the input impedance at the throat. The effects of airway constrictions and wall eleatance variations on this impedance are determined for a range of frequencies. It is concluded that the developed model is capable of predicting various physiological changes in the airway passages.

Commentary by Dr. Valentin Fuster
2007;():355-356. doi:10.1115/IMECE2007-43370.

Pulse wave velocity (PWV) is widely used for estimating the stiffness of an artery. PWV is measured by the time of travel of the “foot” of the pressure wave over a known distance. This technique has a low time resolution and is an average measurement of artery stiffness between the two measuring positions. In this paper an arterial wave is generated non-invasively in the vessel wall by the radiation force of ultrasound. The wave velocity in the vessel is measured non-invasively by ultrasound with high time resolution over a short distance of a few millimeters.

Topics: Waves , Ultrasound
Commentary by Dr. Valentin Fuster

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