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 degrees C). 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.     

Normative Three-Dimensional Patellofemoral and Tibiofemoral Kinematics: A Dynamic, in Vivo Study

In order to advance biomechanical modeling, knee joint implant design and clinical treatment of knee joint pathology, accurate in vivo kinematic data of the combined patellofemoral and tibiofemoral joint during volitional activity are critical. For example, one cause of the increased prevalence of anterior knee pain in the female population is hypothesized to be altered tibiofemoral kinematics, resulting in pathological patellofemoral kinematics. Thus, the objectives of this paper were to test the hypothesis that knee joint kinematics vary based on gender and to explore the correlation between the 3-D kinematics of the patellofemoral and tibiofemoral joints. In order to accomplish these goals, a large (n = 34) normative database of combined six degree of freedom patellofemoral and tibiofemoral kinematics, acquired noninvasively during volitional knee extension-flexion using fast-PC (dynamic) magnetic resonance imaging, was established. In this normative database, few correlations between tibiofemoral and patellofemoral kinematics were found. Specifically, tibial external rotation did not predict lateral patellar tilt, as has been stated in previous studies. In general, significant differences could not be found based on gender. Further investigation into these relationships in the presence of pathology is warranted.     

LED-Based Optical Device for Chronic In Vivo Cerebral Blood Volume Measurement

We demonstrate a reflectivity-based cerebral blood volume sensor comprised of surface-mount light-emitting diodes on a flexible substrate with integrated photodetectors in a form factor suitable for direct brain contact and chronic implantation. This reflectivity monitor is able to measure blood flow through the change of the surface reflectivity and, through this mechanism, detect the cerebral-blood-volume changes associated with epileptic seizures with a signal-to-noise (SNR) response of 42 dB. The device is tested in an in vivo model confirming its compatibility and sensitivity. The data taken demonstrate that placing the sensor into direct brain contact improves the SNR by more than four orders of magnitude over current noncontact technologies.     

In-Vitro and In-Vivo Trans-Scalp Evaluation of an Intracranial Pressure Implant at 2.4 GHz

Elevation of intracranial pressure is one of the most important issues in neurosurgery and neurology in clinical practice. The prevalent techniques for measuring intracranial pressure require equipments that are wired, restricted to a hospital environment, and cause patient discomfort. A novel method for measuring the intracranial pressure is described. A wireless completely implantable device, operating at an industrial-scientific-medical band of 2.4 GHz, has been developed and tested. In-vitro and in-vivo evaluations are described to demonstrate the feasibility of microwave pressure monitoring through scalp, device integrity over a long period of time, and repeatability of pressure measurements. A distinction between an epidural and sub-dural pressure monitoring techniques is also described. Histo-pathological results obtained upon a long-term device implantation favor the utilization of the sub-dural pressure monitoring method. On the other hand, in-vivo studies illustrate a maximum pressure reading error of 0.8 mm middot Hg obtained for a sub-dural device with a capacitive microelectromechanical system sensor compared to 2 mm middot Hg obtained for an epidural device with a piezoresistive sensor.     

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.     

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.     

Prototype Fabrication and Preliminary In Vitro Testing of a Shape Memory Endovascular Thrombectomy Device

An electromechanical microactuator comprised of shape memory polymer (SMP) and shape memory nickel-titanium alloy (nitinol) was developed and used in an endovascular thrombectomy device prototype. The microactuator maintains a straight rod shape until an applied current induces electro-resistive (Joule) heating, causing the microactuator to transform into a corkscrew shape. The straight-to-corkscrew transformation geometry was chosen to permit endovascular delivery through (straight form) and retrieval of (corkscrew form) a stroke-causing thrombus (blood clot) in the brain. Thermal imaging of the microactuator during actuation in air indicated that the steady-state temperature rise caused by Joule heating varied quadratically with applied current and that actuation occurred near the glass transition temperature of the SMP (86degC). To demonstrate clinical application, the device was used to retrieve a blood clot in a water-filled silicone neurovascular model. Numerical modeling of the heat transfer to the surrounding blood and associated thermal effects on the adjacent artery potentially encountered during clinical use suggested that any thermal damage would likely be confined to localized areas where the microactuator was touching the artery wall. This shape memory mechanical thrombectomy device is a promising tool for treating ischemic stroke without the need for infusion of clot-dissolving drugs.     

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 High-Throughput Maximum a Posteriori Probability Detector

This paper presents a maximum a posteriori probability (MAP) detector, based on a forward-only algorithm that can achieve high throughputs. The MAP algorithm is optimal in terms of bit error rate (BER) performance and, with Turbo processing, can approach performance close to the channel capacity limit. The implementation benefits from optimizations performed at both algorithm and circuit level. The proposed detector utilizes a deep-pipelined architecture implemented in skew-tolerant domino and experimentally measured results verify the detector can achieve throughputs greater than 750 Mb/s while consuming 2.4 W. The 16-state EEPR4 channel detector is implemented in a 0.13$ mu{hbox {m}}$ CMOS technology and has a core area of 7.1 ${hbox {mm}}^{2}$.      

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.      

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.     

Miniaturized Unconstrained on– off Pneumatic Poppet Valve—Experiment and Simulation

We present here an analysis and simulation model of an unconstrained on-off poppet valve, which includes the modeling of a piezoelectric actuator (PEA), Hertzian contact, dynamics of poppet motion, and airflow through an orifice. The flow rate generated and the input/output relationship between input frequency/flow rate and voltage/flow rate at different levels of inlet pressure were measured experimentally. Simulation models were built and verified experimentally for valves with different piezoelectric dimensions. Comparisons of simulation and experimental results showed good agreement, thus validating the proposed dynamic analysis. This model can therefore be used to understand the behavior of unconstrained on-off poppet valves. Poppet size did not have a significant effect on flow rate output. Also, the flow rate responses of different sizes of PEAs revealed that larger cross-sectional areas produced higher flow rates. Based on the experimental and simulation results, unconstrained valves were characterized as on-off valves. These findings indicate that this analytical model can be used to predict or estimate the input/output behavior of valves with different parameters.     

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.     

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.      

Finite-element analysis of hepatic cryoablation around a large blood vessel

Cryoablation is a minimally invasive ablation technique for primary and metastatic hepatic tumors. Inadequate freezing around large blood vessels due to the warm blood flow can lead to local recurrence, and thus, necessitates close application of a cryoprobe to the large blood vessels. In this study, we constructed a perfusion model with an ex vivo bovine liver and ablated the tissue around a large blood vessel with one or two cryoprobes applied to the side of the vessel. The finite-element computer model developed in our previous study was modified to include a blood vessel and its convective heat transfer to the vicinity of the blood vessel. We compared the predicted simulation results to those acquired from this ex vivo perfusion model. The results indicate that blood vessels act as a heat source and generate steep temperature profiles in the area next to the large blood vessel. After validation, the maximum allowable distance between the cryoprobe and the large blood vessel for successful cryoablation was presented. The results of this study should be considered when placing cryoprobes in the vicinity of large blood vessels.     

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 Accurate Automatic Quality-Factor Tuning Scheme for Second-Order LC Filters

This paper presents a scheme to accurately tune the quality factor of second-order LC bandpass filters. The information of the magnitude response at the center and one of the cutoff frequencies is used to tune both the amplitude and the quality factor of the filter using two independent yet interacting loops. Furthermore, the synergic interaction between the loops makes the proposed scheme stable and insensitive to the mismatch between the input amplitudes. A chip prototype was implemented in a 0.35-mum CMOS process and consumes 4.3 mA from a single 1.3-V supply. Measurement results show that at 1.97 GHz the quality factor is tunable from 60 to 220 while the amplitude is tunable between -15 and 0 dBm with worst case quality factor and amplitude tuning accuracies of 10% and 7%, respectively     

Digital Wireless—Regulation and Control Free?

Considers how different our present state of technological prowess would be if wireless systems had not been discovered and implemented, then forecasts where we are headed in the real world and what the role of government and regulators may be.