Finite-Element Analysis of Ex Vivo and In Vivo Hepatic Cryoablation

Cryoablation is a widely used method for the treatment of nonresectable primary and metastatic liver tumors. A model that can accurately predict the size of a cryolesion may allow more effective treatment of tumor, while sparing normal liver tissue. We generated a computer model of tissue cryoablation using the finite-element method (FEM). In our model, we considered the heat transfer mechanism inside the cryoprobe and also cryoprobe surfaces so our model could incorporate the effect of heat transfer along the cryoprobe from the environment at room temperature. The modeling of the phase shift from liquid to solid was a key factor in the accurate development of this model. The model was verified initially in an ex vivo liver model. Temperature history at three locations around one cryoprobe and between two cryoprobes was measured. The comparison between the ex vivo result and the FEM modeling result at each location showed a good match, where the maximum difference was within the error range acquired in the experiment (< 5 degC). The FEM model prediction of the lesion size was within 0.7 mm of experimental results. We then validated our FEM in an in vivo experimental porcine model. We considered blood perfusion in conjunction with blood viscosity depending on temperature. The in vivo iceball size was smaller than the ex vivo iceball size due to blood perfusion as predicted in our model. The FEM results predicted this size within 0.1-mm error. The FEM model we report can accurately predict the extent of cryoablation in the liver.     

In Vivo Impedance Imaging With Total Variation Regularization

We show that electrical impedance tomography (EIT) image reconstruction algorithms with regularization based on the total variation (TV) functional are suitable for in vivo imaging of physiological data. This reconstruction approach helps to preserve discontinuities in reconstructed profiles, such as step changes in electrical properties at interorgan boundaries, which are typically smoothed by traditional reconstruction algorithms. The use of the TV functional for regularization leads to the minimization of a nondifferentiable objective function in the inverse formulation. This cannot be efficiently solved with traditional optimization techniques such as the Newton method. We explore two implementations methods for regularization with the TV functional: the lagged diffusivity method and the primal dual–interior point method (PD-IPM). First we clarify the implementation details of these algorithms for EIT reconstruction. Next, we analyze the performance of these algorithms on noisy simulated data. Finally, we show reconstructed EIT images of in vivo data for ventilation and gastric emptying studies. In comparison to traditional quadratic regularization, TV regulariza tion shows improved ability to reconstruct sharp contrasts.      

In Vivo Electrical Impedance Spectroscopy of Tissue Reaction to Microelectrode Arrays

The goal of this experiment was to determine the electrical properties of the tissue reaction to implanted microelectrode arrays. We describe a new method of analyzing electrical impedance spectroscopy data to determine the complex impedance of the tissue reaction as a function of postimplantation time. A model is used to extract electrical model parameters of the electrode-tissue interface, and is used to isolate the impedance of the tissue immediately surrounding the microelectrode. The microelectrode arrays consist of microfabricated polyimide probes, incorporating four 50-mum-diameter platinum microelectrodes. The devices were implanted in the primary motor cortex of adult rats, and measurements were performed for 12 weeks. Histology was performed on implants at three time points in one month. Results demonstrate that the tissue reaction causes a rapid increase in bioimpedance over the first 20 days, and then stabilizes. This result is supported by histological data.     

Vision and Task Assistance Using Modular Wireless In Vivo Surgical Robots

Minimally invasive abdominal surgery (laparoscopy) results in superior patient outcomes compared to conventional open surgery. However, the difficulty of manipulating traditional laparoscopic tools from outside the body of the patient generally limits these benefits to patients undergoing relatively low complexity procedures. The use of tools that fit entirely inside the peritoneal cavity represents a novel approach to laparoscopic surgery. Our previous work demonstrated that miniature mobile and fixed-based in vivo robots using tethers for power and data transmission can successfully operate within the abdominal cavity. This paper describes the development of a modular wireless mobile platform for in vivo sensing and manipulation applications. Design details and results of ex vivo and in vivo tests of robots with biopsy grasper, staple/clamp, video, and physiological sensor payloads are presented. These types of self-contained surgical devices are significantly more transportable and lower in cost than current robotic surgical assistants. They could ultimately be carried and deployed by nonmedical personnel at the site of an injury to allow a remotely located surgeon to provide critical first response medical intervention irrespective of the location of the patient.      

A 3-DOF MR-Compatible Device for Magic Angle Related In Vivo Experiments

The "magic angle" effect consists of the increase in signal intensity observed at a tendon or cartilage in a magnetic resonance image, when the tissue is oriented at an angle of approximately 55deg with respect to the main magnetic field B₀. The exploitation of this phenomenon is often used to assist diagnosis of tendinous and other diseases, although practical difficulties derived from positioning target tissue at the desired orientation inside closed-bore scanners has made this exploitation hard to implement. A 3-DOF MR-compatible mechatronic system has been developed to position a variety of limbs at the magic angle inside a closed- bore scanner, actuated by a custom-developed pneumatic air motor. The system is capable of locating the desired anatomy with high accuracy, and is designed to position the target tissue at a minimal distance from the isocenter. The compatibility of the system is demonstrated, producing negligible artifacts and an insignificant reduction in signal to noise of the image. Preliminary clinical trials scanning the Achilles tendon of healthy volunteers prove the functionality of the device. An increase in signal intensity of up to 21-fold has been recorded in the tendon at the magic angle.     

An In Vitro Model of a Retinal Prosthesis

Epiretinal prostheses are being developed to bypass a degenerated photoreceptor layer and excite surviving ganglion and inner retinal cells. We used custom microfabricated multielectrode arrays with 200-mum-diameter stimulating electrodes and 10-mum-diameter recording electrodes to stimulate and record neural responses in isolated tiger salamander retina. Pharmacological agents were used to isolate direct excitation of ganglion cells from excitation of other inner retinal cells. Strength-duration data suggest that, if amplitude will be used for the coding of brightness or gray level in retinal prostheses, shorter pulses (200 mus) will allow for a smaller region in the area of the electrode to be excited over a larger dynamic range compared with longer pulses (1 ms). Both electrophysiological results and electrostatic finite-element modeling show that electrode-electrode interactions can lead to increased thresholds for sites half way between simultaneously stimulated electrodes (29.4 plusmn 6.6 nC) compared with monopolar stimulation (13.3 plusmn 1.7 nC, < 0.02). Presynaptic stimulation of the same ganglion cell with both 200- and 10- m-diameter electrodes yielded threshold charge densities of 12 plusmn 6 and 7.66 plusmn 1.30 nC/cm², respectively, while the required charge was 12.5 plusmn 6.2 and 19 plusmn 3.3 nC.     

A Tissue Framework for Simulating the Effects of Gastric Electrical Stimulation and In Vivo Validation

Gastric pacing is used to modulate normal or abnormal gastric slow-wave activity for therapeutic purposes. New protocols are required that are optimized for motility outcomes and energy efficiency. A computational tissue model was developed, incorporating smooth muscle and interstitial cell of Cajal layers, to enable predictive simulations of slow-wave entrainment efficacy under different pacing frequencies. Concurrent experimental validation was performed via high-resolution entrainment mapping in a porcine model (bipolar pacing protocol: 2 mA amplitude; 400 ms pulsewidth; 17-s period; midcorpus). Entrained gastric slow-wave activity was found to be anisotropic (circular direction: 8.51 mm${cdot}$s $^{-1}$; longitudinal: 4.58 mm${cdot}$s $^{-1}$), and the simulation velocities were specified accordingly. Simulated and experimental slow-wave activities demonstrated satisfactory agreement, showing similar propagation patterns and frequencies (3.5–3.6 cycles per minute), and comparable zones of entrainment (ZOEs; 64 cm $^2$). The area of ZOE achieved was found to depend on the phase interactions between the native and entrained activities. This model allows the predictions of phase interactions between native and entrained activities, and will be useful for determining optimal frequencies for gastric pacing, including multichannel pacing studies. The model provides a framework for the development of more sophisticated predictive gastric pacing simulations in future.      

In Vivo Evaluation of a Mechanically Oscillating Dual-Mode Applicator for Ultrasound Imaging and Thermal Ablation

Unresectable liver tumors are often treated with interstitial probes that modify tissue temperature, and efficacious treatment relies on image guidance for tissue targeting and assessment. Here, we report the in vivo evaluation of an interstitial applicator with a mechanically oscillating five-element dual-mode transducer. After thoroughly characterizing the transducer, tissue response to high-intensity ultrasound was numerically calculated to select parameters for experimentation in vivo. Using perfused porcine liver, B-mode sector images were formed before and after a 120-s therapy period, and M-mode imaging monitored the therapy axis during therapy. The time-averaged transducer surface intensity was 21 or 27 W/cm$^2$. Electroacoustic conversion efficiency was maximally 72 $pm$ 3% and impulse response length was 295 $pm$ 1.0 ns at $-$6 dB. The depth of thermal damage measured by gross histology ranged from 10 to 25 mm for 13 insertion sites. For six sites, M-mode data exhibited a reduction in gray-scale intensity that was interpreted as the temporal variation of coagulation necrosis. Contrast ratio analysis indicated that the gray-scale intensity dropped by 7.8 $pm ;$3.3 dB, and estimated the final lesion depth to an accuracy of 2.3 $pm ;$2.4 mm. This paper verified that the applicator could induce coagulation necrosis in perfused liver and demonstrated the feasibility of real-time monitoring.      

Elucidating Structure and Function In Vivo With Hybrid Fluorescence and Magnetic Resonance Imaging

While the mathematics, physics, and technology behind magnetic resonance (MR) and fluorescence image formation are distinctively different, the two modalities have significant complementary features to impart strong preclinical and clinical application synergies. Traditionally, hybrid MR and fluorescence imaging implied the use of a system where optical and MR signals can be concurrently acquired. In this case, the common geometry allows for the superposition of fluorescence images of cellular and subcellular processes onto anatomical and functional MR images. More recently, a different hybrid imaging paradigm is strongly evolving by utilizing hybrid MR-fluorescence nanoparticles. This approach offers a second paradigm of hybrid visualization where the common underlying contrast enables the coregistration of MR and fluorescence images acquired under different geometries. We review herein progress with the evolving field of multimodality MR and fluorescence imaging and discuss how these strategies offer a highly promising outlook in established and in novel preclinical and clinical applications.     

A 3-D High-Frequency Array Based 16 Channel Photoacoustic Microscopy System for In Vivo Micro-Vascular Imaging

This paper discusses the design of a novel photoacoustic microscopy imaging system with promise for studying the structure of tissue microvasculature for applications in visualizing angiogenesis. A new 16 channel analog and digital high-frequency array based photoacoustic microscopy system (PAM) was developed using an Nd:YLF pumped tunable dye laser, a 30 MHz piezo composite linear array transducer, and a custom multichannel receiver electronics system. Using offline delay and sum beamforming and beamsteering, phantom images were obtained from a 6 $mu{hbox {m}}$ carbon fiber in water at a depth of 8 mm. The measured $-6~{rm dB}$ lateral and axial spatial resolution of the system was $100pm 5~mu{hbox {m}}$ and $45pm 5~mu{hbox {m}}$, respectively. The dynamic focusing capability of the system was demonstrated by imaging a composite carbon fiber matrix through a 12.5 mm imaging depth. Next, 2-D in vivo images were formed of vessels around 100 $mu{hbox {m}}$ in diameter in the human hand. Three-dimensional in vivo images were also formed of micro-vessels 3 mm below the surface of the skin in two Sprague Dawley rats.      

High-Program/Erase-Speed SONOS With In Situ Silicon Nanocrystals

In this letter, for the first time, we have successfully fabricated silicon-oxide-nitride-oxide-silicon (SONOS) devices with embedded silicon nanocrystals (Si-NCs) in silicon nitride using in situ method. This process is simple and compatible to modern IC processes. Different Si-NCs deposition times by in situ method were investigated at first. SONOS devices with embedded Si-NCs in silicon nitride exhibit excellent characteristics in terms of larger memory windows (> 5.5 V), lower operation voltage, high P/E speed, and longer retention time (> 10⁸ s for 13% charge loss).     

A Telehealth Architecture for Networked Embedded Systems: A Case Study in In Vivo Health Monitoring

The improvement in processor performance through continuous breakthroughs in transistor technology has resulted in the proliferation of lightweight embedded systems. Advances in wireless technology and embedded systems have enabled remote healthcare and telemedicine. While medical examinations could previously extract only localized symptoms through snapshots, now continuous monitoring can discretely analyze how a patient's lifestyle affects his/her physiological conditions and if additional symptoms occur under various stimuli. We demonstrate how medical applications in particular benefit from a hierarchical networking scheme that will improve the quantity and quality of ubiquitous data collection. Our Telehealth networking infrastructure provides flexibility in terms of functionality and the type of applications that it supports. We specifically present a case study that demonstrates the effectiveness of our networked embedded infrastructure in an in vivo pressure application. Experimental results of the in vivo system demonstrate how it can wirelessly transmit pressure readings measuring from 0 to 1.5 lbf/in² with an accuracy of 0.02 lbf/in². The challenges in biocompatible packaging, transducer drift, power management, and in vivo signal transmission are also discussed. This research brings researchers a step closer to continuous, real-time systemic monitoring that will allow one to analyze the dynamic human physiology.     

A Robust Monte Carlo Model for the Extraction of Biological Absorption and Scattering In Vivo

We have a toolbox to quantify tissue optical properties that is composed of specialized fiberoptic probes for UV-visible diffuse reflectance spectroscopy and a fast, scalable inverse Monte Carlo (MC) model. In this paper, we assess the robustness of the toolbox for quantifying physiologically relevant parameters from turbid tissue-like media. In particular, we consider the effects of using different instruments, fiberoptic probes, and instrument-specific settings for a wide range of optical properties. Additionally, we test the quantitative accuracy of the inverse MC model for extracting the biologically relevant parameters of hemoglobin saturation and total hemoglobin concentration. We also test the effect of double-absorber phantoms (hemoglobin and crocin to model the absorption of hemoglobin and beta carotene, respectively, in the breast) for a range of absorption and scattering properties. We include an assessment on which reference phantom serves as the best calibration standard to enable accurate extraction of the absorption and scattering properties of the target sample. We found the best reference–target phantom combinations to be ones with similar scattering levels. The results from these phantom studies provide a set of guidelines for extracting optical parameters from clinical studies.      

In Vivo Gas Body Efficacy for Glomerular Capillary Hemorrhage Induced by Diagnostic Ultrasound in Rats

Glomerular capillary hemorrhage (GCH) in rat kidney provided a model for assessing in vivo gas body efficacy in diagnostic or therapeutic applications of ultrasound. Two diagnostic ultrasound machines were utilized: one monitored the harmonic B-mode contrast enhancement of the left kidney and the other exposed the right kidney for GCH production. Definity contrast agent was infused at 1, 2, 5, or 10 $mu$L/(kg·min) and infusion durations were 30, 60, 120, or 300 s. Exposure of the right kidney was at a peak rarefactional pressure amplitude of 2.3 MPa at 1.5 MHz. The circulating dose was estimated with a simple model of agent dilution and gas body loss. For 300 s infusion at 5 $mu$L/(kg·min), the left kidney image brightness increased to a plateau with an estimated 6.4 $pm$ 1.3 $mu$L/kg circulating dose with no GCH in histological sections. Exposure of the right kidney with a 1-s image interval reduced the estimated circulating dose to 1.3 $pm$ 0.3 $mu$ L/kg and induced 68.4% GCH. Dose and duration increases gave rapidly diminishing treatment effectiveness per gas body. The effective in vivo agent dose in rats can be reduced greatly due to high gas body destruction in the small animal, complicating predictions for similar conditions of human treatment.      

Simultaneous Molecular and Hypoxia Imaging of Brain Tumors In Vivo Using Spectroscopic Photoacoustic Tomography

Noninvasive molecular and functional imaging in vivo is promising for detecting and monitoring various physiological conditions in animals and ultimately humans. To this end, we present a novel noninvasive technology, spectroscopic photoacoustic tomography (SPAT), which offers both strong optical absorption contrast and high ultrasonic spatial resolution. Optical contrast allows spectroscopic separation of signal contributions from multiple optical absorbers (e.g., oxyhemoglobin, deoxyhemoglobin, and a molecular contrast agent), thus enabling simultaneous molecular and functional imaging. SPAT successfully imaged with high resolution the distribution of a molecular contrast agent targeting integrin overexpressed in human U87 glioblastomas in nude mouse brains. Simultaneously, SPAT also imaged the hemoglobin oxygen saturation and the total hemoglobin concentration of the vasculature, which revealed hypoxia in tumor neovasculature. Therefore, SPAT can potentially lead to better understanding of the interrelationships between hemodynamics and specific biomarkers associated with tumor progression.     

In Situ Acoustic Temperature Measurement During Variable-Frequency Microwave Curing

Variable-frequency microwave (VFM) curing can perform the same processing steps as conventional thermal processing in minutes, without compromising intrinsic material properties. With increasing demand for novel dielectrics, there is a corresponding demand for new processing techniques that lead to comparable or better properties than conventional methods. VFM processing can be a viable alternative to conventional thermal techniques. However, current limitations include a lack of reliable temperature measuring techniques. This research focuses on developing a reliable temperature measuring system using acoustic techniques to monitor low-k polymer dielectrics cured on silicon wafers in a VFM furnace. The acoustic sensor exhibits the capability to measure temperatures from 20degC to 300degC with an attainable accuracy of plusmn2 degrees.     

Comparisons Between the p--q and p--q--r Theories in Three-Phase Four-Wire Systems

This paper presents a comparative analysis between results from applications of the p-q and the p-q-r theories in shunt active power filters for three-phase four-wire systems, discussing aspects related to the influence of the system voltage in the control methods that calculate the compensating currents. It is shown that in some cases, a preprocessing of the system voltage is required if the goal is to achieve sinusoidal compensated currents. On the other hand, when the goal is to compensate zero-sequence current, the need of energy storage elements in the active filter is discussed. In this case, if zero-sequence components are present simultaneously in the system voltage and load current, they produce zero-sequence power flow, and the control methods based on both theories must contain additional calculations to allow the elimination of energy storage elements in the active filter. A control strategy based on the p-q theory is proposed to eliminate the neutral current without the need of energy storage elements, with the advantage of avoiding the extra transformation from alphabeta0 to pqr coordinates that is needed in the p-q-r theory. Simulation results are presented for the purpose of comparing the performance of both control methods.