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The effects of high voltage defibrillation shocks given to six swine were studied to determine if there is a limit to the advantage gained from increasing the shock strength. An endocardial electrode was placed in the right ventricle, and a 114-cm² cutaneous patch was placed on the left lateral thorax. Monophasic (10 msec) and single capacitor biphosic (5/5 msec) shocks with leading edge voltages of 200, 400, 600, 800, and 990 volts (approximately 2.3-59 J) were tested. For monophasic shocks, the probability of successful defibrillation ranged from 0% at 200 V to 90% at 990 V. The incidence of postshock arrhythmia increased from 0% for successful shocks at 600 V to 67% for successful shocks at 990 V. For biphasic shocks, the probability of success peaked at 97% for the 600-, 800-, and 990-V shocks. The incidence of postshock arrhythmia increased from 8% at 400 V to 55% at 990 V. Although more postshock arrhythmias occurred at lower strengths for biphasic than for monophasic shocks, an efficacy criterion, quantifying the probability of defibrillation success acid the probability that a postshock arrhythmia will not occur, was always higher for biphasic shocks. The probability of success never reached 100% for either waveform while the incidence of postshock arrhythmia increased as the shock strength increased. In conclusion, for the catheter-patch electrode configuration, increasing the shock strength does not always improve the probability of success and may increase the incidence of postshock arrhythmia. [ABSTRACT FROM AUTHOR]

Real-time 3-D intracardiac echocardiography (ICE) can enable faster imaging of surfaces orthogonal to the transducer, such as the pulmonary vein (PV) antra and cardiac valve annuli. However, the requirement for a 2-D grid of individually wired elements makes a traditional matrix array challenging to implement within an intravenous catheter. Helicoid array transducers are linear array transducers twisted about their long axis, allowing imaging of different elevation slices using sub-apertures. In this work, we examined the 3-D imaging characteristics of helicoid array transducers through simulations using Field II software and experimental measurements. We report results for varying transducer parameters, such as twist rate and sub-aperture size. We also discuss design considerations for these imaging parameters as they pertain to volumetric imaging of the heart.

Objectives: Intraventricular pressure (IVP) is one of the most important measurements for evaluating cardiac function, but this measurement is not currently easily assessable in the clinic. The primary reason for this is the absence of a noninvasive technique for measuring IVP. In this study, we investigate the relationship between IVP and dynamic myocardial stiffness measured by shear wave elasticity imaging (SWEI) and assess the feasibility of measuring IVP using SWEI., Methods: In 8 isolated working rabbit hearts, IVP was recorded in the left ventricle using a pressure catheter. Simultaneously, myocardial stiffness was recorded by SWEI. Using the peak values for IVP and SWEI measured stiffness, SWEI measurements were calibrated and converted to IVP., Results: A linear relationship with zero intercept was observed between IVP and SWEI, with the average slope of 0.318 kPa/mm Hg, R 2  = 0.89. Using one point on the IVP/SWEI curve, SWEI measurements were converted to IVP. Estimated pressure using SWEI and IVP were linearly correlated with the slope of 0.95, R 2  = 0.88 (mean end diastolic pressure by pressure catheter = 12.716 mm Hg and by SWEI=14.726 mm Hg), indicating the near equivalence of the 2 measurements., Conclusion: We have shown that SWEI measurements are linearly related to IVP; therefore, pressure-based indices could potentially be derived from SWEI ultrasound elastography. The feasibility of using SWEI to estimate IVP with a single point calibration was also shown in this study., (© 2018 by the American Institute of Ultrasound in Medicine.)

Shear wave elasticity imaging (SWEI) is a novel ultrasound elastography technique for assessing tissue stiffness. In this study, we investigate the potential of SWEI for providing diastolic functional assessment. In 11 isolated rabbit hearts, pressure-volume (PV) measurements were recorded simultaneously with SWEI recordings from the left ventricle free wall before and after induction of global ischemia. PV-based end diastolic stiffness increased by 100% after ischemia (p <0.05), and SWEI stiffness showed an increase of 103% (p <0.05). The relaxation time constant (τ) before and after ischemia derived from pressure and SWEI curves showed increases of 79% and 76%, respectively (p <0.05). A linear regression between pressure-derived and SWEI-based (τ) showed a slope of 1.164 with R 2  = 0.80, indicating the near equivalence of the two assessments. SWEI can be used to derive (τ) values and myocardial end diastolic stiffness. In global conditions, these measurements are consistent with PV measurements of diastolic function., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial contractility, a significant determinant of cardiac function, is valuable for diagnosis and evaluation of treatment in cardiovascular disorders including heart failure. Shear wave elasticity imaging (SWEI) is a newly developed ultrasound-based elastographic technique that can directly assess the stiffness of cardiac tissue. The aim of this study was to verify the ability of this technique to quantify contractility changes in the myocardium., Methods: In 12 isolated rabbit hearts, SWEI measurements were made of systolic stiffness at five different coronary perfusion pressures from 0 to 92 mm Hg. The changes in coronary perfusion were used to induce acute stepwise reversible changes in cardiac contractility via the Gregg effect. The Gregg effect is the dependency of contractility on coronary perfusion. In four of the hearts, the measurements were repeated after delivery of gadolinium, which is known to block the Gregg effect., Results: Systolic stiffness measured by SWEI changed linearly with coronary perfusion pressure, with a slope of 0.27 kPa/mm Hg (mean of 95% CI, R 2  = 0.73). As expected, the change in contractility due to the Gregg effect was blocked by gadolinium, with a significant reduction of the slope to 0.08 kPa/mm Hg., Conclusions: SWEI measurements of systolic stiffness provide an index of contractility in the unloaded isolated rabbit heart. Although this study was done under ideal imaging conditions and with nonphysiologic loading conditions, it reinforces the concept that this ultrasound technique has the potential to provide a direct and noninvasive index of cardiac contractility., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

In the past decade, there has been an increased interest in characterizing cardiac tissue mechanics utilizing newly developed ultrasound-based elastography techniques. These methods excite the tissue mechanically and track the response. Two frequently used methods, acoustic radiation force impulse (ARFI) and shear-wave elasticity imaging (SWEI), have been considered qualitative and quantitative techniques providing relative and absolute measures of tissue stiffness, respectively. Depending on imaging conditions, it is desirable to identify indices of cardiac function that could be measured by ARFI and SWEI and to characterize the relationship between the measures. In this study, we have compared two indices (i.e., relaxation time constant used for diastolic dysfunction assessment and systolic/diastolic stiffness ratio) measured nearly simultaneously by M-mode ARFI and SWEI techniques. We additionally correlated ARFI-measured inverse displacements with SWEI-measured values of the shear modulus of stiffness. For the eight animals studied, the average relaxation time constant ( τ) measured by ARFI and SWEI were ([Formula: see text]) and ([Formula: see text]), respectively ([Formula: see text]). Average systolic/diastolic stiffness ratios for ARFI and SWEI measurements were 6.01±1.37 and 7.12±3.24, respectively ([Formula: see text]). Shear modulus of stiffness (SWEI) was linearly related to inverse displacement values (ARFI) with a 95% CI for the slope of 0.010-0.011 [Formula: see text] ( R(2)=0.73). In conclusion, the relaxation time constant and the systolic/diastolic stiffness ratio were calculated with good agreement between the ARFI- and SWEI-derived measurements. ARFI relative and SWEI absolute stiffness measurements were linearly related with varying slopes based on imaging conditions and subject tissue properties.

Introduction: Elastography imaging can provide radiofrequency ablation (RFA) lesion assessment due to tissue stiffening at the ablation site. An important aspect of assessment is the spatial and temporal stability of the region of stiffness increase in the peri-ablation period. The aim of this study was to use 2 ultrasound-based elastography techniques, shear wave elasticity imaging (SWEI) and acoustic radiation force impulse (ARFI) imaging, to monitor the evolution of tissue stiffness at ablation sites in the 30 minutes following lesion creation., Methods and Results: In 6 canine subjects, SWEI measurements and 2-D ARFI images were acquired at 6 ventricular endocardial RFA sites before, during, and for 30 minutes postablation. An immediate increase in tissue stiffness was detected during RFA, and the area of the postablation region of stiffness increase (RoSI) as well as the relative stiffness at the RoSI center was stable approximately 2 minutes after ablation. Of note is the observation that relative stiffness in the region adjacent to the RoSI increased slightly during the first 15 minutes, consistent with local fluid displacement or edema. The magnitude of this increase, ∼0.5-fold from baseline, was significantly less than the magnitude of the stiffness increase directly inside the RoSI, which was greater than 3-fold from baseline., Conclusions: Ultrasound-based SWEI and ARFI imaging detected an immediate increase in tissue stiffness during RFA, and the stability and magnitude of the stiffness change suggest that consistent elasticity-based lesion assessment is possible 2 minutes after and for at least 30 minutes following ablation., (© 2015 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.)

Diastolic heart failure (DHF) is a major source of cardiac related morbidity and mortality in the world today. A major contributor to, or indicator of DHF is a change in cardiac compliance. Currently, there is no accepted clinical method to evaluate the compliance of cardiac tissue in diastolic dysfunction. Shear wave elasticity imaging (SWEI) is a novel ultrasound-based elastography technique that provides a measure of tissue stiffness. Coronary perfusion pressure affects cardiac stiffness during diastole; we sought to characterize the relationship between these two parameters using the SWEI technique. In this work, we demonstrate how changes in coronary perfusion pressure are reflected in a local SWEI measurement of stiffness during diastole. Eight Langendorff perfused isolated rabbit hearts were used in this study. Coronary perfusion pressure was changed in a randomized order (0-90 mmHg range) and SWEI measurements were recorded during diastole with each change. Coronary perfusion pressure and the SWEI measurement of stiffness had a positive linear correlation with the 95% confidence interval (CI) for the slope of 0.009-0.011 m/s/mmHg ( R(2) = 0.88 ). Furthermore, shear modulus was linearly correlated to the coronary perfusion pressure with the 95% CI of this slope of 0.035-0.042 kPa/mmHg ( R(2) = 0.83). In conclusion, diastolic SWEI measurements of stiffness can be used to characterize factors affecting cardiac compliance specifically the mechanical interaction (cross-talk) between perfusion pressure in the coronary vasculature and cardiac muscle. This relationship was found to be linear over the range of pressures tested.

Background: Visual confirmation of radiofrequency ablation (RFA) lesions during clinical cardiac ablation procedures could improve procedure efficacy, safety, and efficiency. It was previously shown that acoustic radiation force impulse (ARFI) imaging can identify RFA lesions in vitro and in vivo in an animal model. This is the "first-in-human" feasibility demonstration of intracardiac ARFI imaging of RFA lesions in patients undergoing catheter ablation for atrial flutter (AFL) or atrial fibrillation (AF)., Methods and Results: Patients scheduled for right atrial (RA) ablation for AFL or left atrial (LA) ablation for drug refractory AF were eligible for imaging. Diastole-gated intracardiac ARFI images were acquired using one of two equipment configurations: (1) a Siemens ACUSON S2000™ ultrasound scanner and 8/10Fr AcuNav™ ultrasound catheter, or (2) a CARTO 3™ integrated Siemens SC2000™ and 10Fr SoundStar™ ultrasound catheter. A total of 11 patients (AFL = 3; AF = 8) were imaged. ARFI images were acquired of ablation target regions, including the RA cavotricuspid isthmus (CTI), and the LA roof, pulmonary vein ostia, posterior wall, posterior mitral valve annulus, and the ridge between the pulmonary vein and LA appendage. ARFI images revealed increased relative myocardial stiffness at ablation catheter contact sites after RFA and at anatomical mapping-tagged RFA treatment sites., Conclusions: ARFI images from a pilot group of patients undergoing catheter ablation for AFL and AF demonstrate the ability of this technique to identify intra-procedure RFA lesion formation. The results encourage further refinement of ARFI imaging clinical tools and continued investigation in larger clinical trials., (© 2014 Wiley Periodicals, Inc.)

We developed new forward-viewing matrix transducers consisting of double ring arrays of 118 total PZT elements integrated into catheters used to deploy medical interventional devices. Our goal is 3D ultrasound guidance of medical device implantation to reduce x-ray fluoroscopy exposure. The double ring arrays were fabricated on inner and outer custom polyimide flexible circuits with inter-element spacing of 0.20 mm and then wrapped around an 11 French (Fr) catheter to produce a 15 Fr catheter (outer diameter [O.D.]). We used a braided cabling technology to connect the elements to the Volumetrics Medical Imaging (VMI) real-time 3D ultrasound scanner. Transducer performance yielded an average -6 dB fractional bandwidth of 49% ± 11% centered at 4.4 MHz for 118 elements. Real-time 3D cardiac scans of the in vivo pig model yielded good image quality including en face views of the tricuspid valve and real-time 3D guidance of an endo-myocardial biopsy catheter introduced into the left ventricle., (© The Author(s) 2014.)

The most common mechanical measure of the heart integrates ventricular strain between end-diastole and end-systole in order to provide a measure of contraction. Here an approach is described for estimating a correlate to local passive mechanical properties. Passive strain is measured by estimating ventricular strain during atrial systole. During atrial systole the atria contract causing passive stretching in the ventricles from increased volume. This modification to traditional cardiac strain is here termed atrial kick induced strain (AKIS) imaging. AKIS imaging was evaluated in a canine ablation model of chronic infarct and a canine true chronic infarct model. AKIS images of ablation lesions were compared against acoustic radiation force impulse (ARFI) images and tissue blanching, and true chronic infarct AKIS images were compared against delayed enhanced-contrast magnetic resonance. AKIS images were made with 2-D and 3-D ultrasound data. In both studies, AKIS images and the comparison images show good qualitative agreement and good contrast and contrast-to-noise ratio., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

We have previously shown that intracardiac acoustic radiation force impulse (ARFI) imaging visualizes tissue stiffness changes caused by radiofrequency ablation (RFA). The objectives of this in vivo study were to (1) quantify measured ARFI-induced displacements in RFA lesion and unablated myocardium and (2) calculate the lesion contrast (C) and contrast-to-noise ratio (CNR) in two-dimensional ARFI and conventional intracardiac echo images. In eight canine subjects, an ARFI imaging-electroanatomical mapping system was used to map right atrial ablation lesion sites and guide the acquisition of ARFI images at these sites before and after ablation. Readers of the ARFI images identified lesion sites with high sensitivity (90.2%) and specificity (94.3%) and the average measured ARFI-induced displacements were higher at unablated sites (11.23 ± 1.71 µm) than at ablated sites (6.06 ± 0.94 µm). The average lesion C (0.29 ± 0.33) and CNR (1.83 ± 1.75) were significantly higher for ARFI images than for spatially registered conventional B-mode images (C = -0.03 ± 0.28, CNR = 0.74 ± 0.68).

The possibility of measuring cardiac function noninvasively has generated wide interest in elastography imaging techniques. Shear Wave Elasticity Imaging (SWEI) is an ultrasound-based elastography technique used to measure stiffness of tissues. While this technique has been studied extensively in static homogenous tissues such as liver, breast or prostate, there is still a significant need to study its capabilities to measure cardiac stiffness and function. In this research, we have studied the potential of SWEI to evaluate the coronary perfusion pressure effect on systolic and diastolic stiffness referred to as elastance and compliance of the heart. Five isolated rabbit hearts were used in this study in a Langendorff preparation. SWEI measurements of stiffness were recorded in two steps. In the first step, coronary perfusion was set to normal and then was reduced to half-normal. After 40 minutes of half-normal perfusion, it was returned to normal perfusion for the second step. SWEI velocity decreased from 6.003 m/s to 4.713 m/s in systole and from 1.948 m/s to 1.507 m/s in diastole in the first step. During the second step raising the perfusion to normal, SWEI stiffness showed an increase from 3.760 m/s to 5.468 m/s in systole and from 1.678 m/s to 2.156 m/s during diastole. Our results show that SWEI measurements of stiffness can characterize the cross talk between coronary perfusion and cardiac stiffness and also has the potential to measure compliance and elastance of the heart in systole and diastole.

Background: Arrhythmia recurrence after cardiac radiofrequency ablation (RFA) for atrial fibrillation has been linked to conduction through discontinuous lesion lines. Intraprocedural visualization and corrective ablation of lesion line discontinuities could decrease postprocedure atrial fibrillation recurrence. Intracardiac acoustic radiation force impulse (ARFI) imaging is a new imaging technique that visualizes RFA lesions by mapping the relative elasticity contrast between compliant-unablated and stiff RFA-treated myocardium., Objective: To determine whether intraprocedure ARFI images can identify RFA-treated myocardium in vivo., Methods: In 8 canines, an electroanatomical mapping-guided intracardiac echo catheter was used to acquire 2-dimensional ARFI images along right atrial ablation lines before and after RFA. ARFI images were acquired during diastole with the myocardium positioned at the ARFI focus (1.5 cm) and parallel to the intracardiac echo transducer for maximal and uniform energy delivery to the tissue. Three reviewers categorized each ARFI image as depicting no lesion, noncontiguous lesion, or contiguous lesion. For comparison, 3 separate reviewers confirmed RFA lesion presence and contiguity on the basis of functional conduction block at the imaging plane location on electroanatomical activation maps., Results: Ten percent of ARFI images were discarded because of motion artifacts. Reviewers of the ARFI images detected RFA-treated sites with high sensitivity (95.7%) and specificity (91.5%). Reviewer identification of contiguous lesions had 75.3% specificity and 47.1% sensitivity., Conclusions: Intracardiac ARFI imaging was successful in identifying endocardial RFA treatment when specific imaging conditions were maintained. Further advances in ARFI imaging technology would facilitate a wider range of imaging opportunities for clinical lesion evaluation., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Acoustic radiation force impulse (ARFI) imaging has been shown to be capable of imaging local myocardial stiffness changes throughout the cardiac cycle. Expanding on these results, the authors present experiments using cardiac ARFI imaging to visualize and quantify the propagation of mechanical stiffness during ventricular systole. In vivo ARFI images of the left ventricular free wall of two exposed canine hearts were acquired. Images were formed while the heart was externally paced by one of two electrodes positioned on the epicardial surface and either side of the imaging plane. Two-line M-mode ARFI images were acquired at a sampling frequency of 120 Hz while the heart was paced from an external stimulating electrode. Two-dimensional ARFI images were also acquired, and an average propagation velocity across the lateral field of view was calculated. Directions and speeds of myocardial stiffness propagation were measured and compared with the propagations derived from the local electrocardiogram (ECG), strain, and tissue velocity measurements estimated during systole. In all ARFI images, the direction of myocardial stiffness propagation was seen to be away from the stimulating electrode and occurred with similar velocity magnitudes in either direction. When compared with the local epicardial ECG, the mechanical stiffness waves were observed to travel in the same direction as the propagating electrical wave and with similar propagation velocities. In a comparison between ARFI, strain, and tissue velocity imaging, the three methods also yielded similar propagation velocities.

Acoustic radiation force (ARF)-based methods have been demonstrated to be a viable tool for noninvasively estimating tissue elastic properties, and shear wave velocimetry has been used to measure quantitatively the stiffening and relaxation of myocardial tissue in open-chest experiments. Dynamic stiffness metrics may prove to be indicators for certain cardiac diseases, but a clinically viable means of remotely generating and tracking transverse wave propagation in myocardium is needed. Intracardiac echocardiography (ICE) catheter-tip transducers are demonstrated here as a viable tool for making this measurement. ICE probes achieve favorable proximity to the myocardium, enabling the use of shear wave velocimetry from within the right ventricle throughout the cardiac cycle. This article describes the techniques used to overcome the challenges of using a small probe to perform ARF-driven shear-wave velocimetry and presents in vivo porcine data showing the effectiveness of this method in the interventricular septum., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

In this study, we investigated the feasibility of using 3.5-Fr intravascular ultrasound (IVUS) catheters for minimally-invasive, image-guided hyperthermia treatment of tumors in the brain. Feasibility was demonstrated by: (1) retro-fitting a commercial 3.5-Fr IVUS catheter with a 5 × 0.5 × 0.22 mm PZT-4 transducer for 9-MHz imaging and (2) testing an identical transducer for therapy potential with 3.3-MHz continuous-wave excitation. The imaging transducer was compared with a 9-Fr, 9-MHz ICE catheter when visualizing the post-mortem ovine brain and was also used to attempt vascular access to an in vivo porcine brain. A net average electrical power input of 700 mW was applied to the therapy transducer, producing a temperature rise of +13.5°C at a depth of 1.5 mm in live brain tumor tissue in the mouse model. These results suggest that it may be feasible to combine the imaging and therapeutic capabilities into a single device as a clinically-viable instrument., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Vagus nerve stimulation (VNS) is effective for treating epilepsy and depression, and has emerging indications for anxiety and heart failure. However, stimulation-evoked side effects remain a challenge for long-term compliance. We investigated the feasibility of reducing VNS side effects by using a temporally-modified stimulation pattern. In 4 anesthetized canines, we measured changes in both the heart rate and evoked laryngeal muscle activity. Compared to baseline, we found that a 5% duty cycle (measured by the number of pulses per second of stimulation) could still evoke a 21% reduction in heart rate; whereas compared to continuous stimulation (3 mA, 300 μs pulsewidth, 20 Hz) the same 5% duty cycle reduced the evoked laryngeal muscle activity by 90%. The results of this study indicate that temporally-patterned stimulation may provide an effective tool for optimizing VNS therapy.

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and depression, and it is currently under investigation for applications in Alzheimer's disease, anxiety, heart failure, and obesity. However, the mechanism(s) by which VNS has its effects are not clear, and the stimulation parameters for obtaining therapeutic outcomes appear highly variable. The purpose of this study was to quantify the excitation properties of the right cervical vagus nerve in adult dogs anesthetized with propofol and fentanyl. Input-output curves of the right cervical vagus nerve compound action potential and laryngeal muscle electromyogram were measured in response to VNS across a range of stimulation parameters: amplitudes of 0.02-50mA, pulsewidths of 10, 50, 100, 200, 300, 500, and 1,000μs, frequencies of 1-2Hz, and train lengths of 20 pulses with 3 different electrode configurations: monopolar cathode, proximal anode/distal cathode, and proximal cathode/distal anode. Electrode configuration and stimulation waveform (monophasic vs. asymmetric charge-balanced biphasic) did not affect the threshold or recruitment of the vagal nerve fibers that were activated. The rheobase currents of A- and B-fibers were 0.4mA and 0.7mA, respectively, and the chronaxie of both components was 180μs. Pulsewidth had little effect on the normalized threshold difference between activation of A- and B-fibers. The results provide insight into the complement of nerve fibers activated by VNS and guidance to clinicians for the selection of optimal stimulation parameters., (2010 Elsevier Inc. All rights reserved.)

Introduction: Lesion placement and transmurality are critical factors in the success of cardiac transcatheter radiofrequency ablation (RFA) treatments for supraventricular arrhythmias. This study investigated the capabilities of catheter transducer based acoustic radiation force impulse (ARFI) ultrasound imaging for quantifying ablation lesion dimensions., Methods and Results: RFA lesions were created in vitro in porcine ventricular myocardium and imaged with an intracardiac ultrasound catheter transducer capable of acquiring spatially registered B-mode and ARFI images. The myocardium was sliced along the imaging plane and photographed. The maximum ARFI-induced displacement images of the lesion were normalized and spatially registered with the photograph by matching the surfaces of the tissue in the B-mode and photographic images. The lesion dimensions determined by a manual segmentation of the photographed lesion based on the visible discoloration of the tissue were compared to automatic segmentations of the ARFI image using 2 different calculated thresholds. ARFI imaging accurately localized and sized the lesions within the myocardium. Differences in the maximum lateral and axial dimensions were statistically below 2 mm and 1 mm, respectively, for the 2 thresholding methods, with mean percent overlap of 68.7 +/- 5.21% and 66.3 +/- 8.4% for the 2 thresholds used., Conclusion: ARFI imaging is capable of visualizing myocardial RFA lesion dimensions to within 2 mm in vitro. Visualizing lesions during transcatheter cardiac ablation procedures could improve the success of the treatment by imaging lesion line discontinuity and potentially reducing the required number of ablation lesions and procedure time.

Thresholding is an often-used method of spike detection for implantable neural signal processors due to its computational simplicity. A means for automatically selecting the threshold is desirable, especially for high channel count data acquisition systems. Estimating the noise level and setting the threshold to a multiple of this level is a computationally simple means of automatically selecting a threshold. We present an analysis of this method as it is commonly applied to neural waveforms. Four different operators were used to estimate the noise level in neural waveforms and set thresholds for spike detection. An optimal multiplier was identified for each noise measure using a metric appropriate for a brain-machine interface application. The commonly used root-mean-square operator was found to be least advantageous for setting the threshold. Investigators using this form of automatic threshold selection or developing new unsupervised methods can benefit from the optimization framework presented here.

Shear wave elasticity imaging (SWEI) was employed to track acoustic radiation force impulse (ARFI)-induced shear waves in the mid-myocardium of the left ventricular free wall (LVFW) of a beating canine heart. Shear waves were generated and tracked with a linear ultrasound transducer that was placed directly on the exposed epicardium. Acquisition was ECG-gated and coincided with the mid-diastolic portion of the cardiac cycle. Axial displacement profiles consistent with shear wave propagation were clearly evident in all SWEI acquisitions (i.e., those including an ARFI excitation); displacement data from control cases (i.e., sequences lacking an ARFI excitation) offered no evidence of shear wave propagation and yielded a peak absolute mean displacement below 0.31 microm after motion filtering. Shear wave velocity estimates ranged from 0.82 to 2.65 m/s and were stable across multiple heartbeats for the same interrogation region, with coefficients of variation less than 19% for all matched acquisitions. Variations in velocity estimates suggest a spatial dependence of shear wave velocity through the mid-myocardium of the LVFW, with velocity estimates changing, in limited cases, through depth and lateral position.

Acoustic radiation force impulse (ARFI) imaging has been demonstrated to be capable of visualizing changes in local myocardial stiffness through a normal cardiac cycle. As a beating heart involves rapidly-moving tissue with cyclically-varying myocardial stiffness, it is desirable to form images with high frame rates and minimize susceptibility to motion artifacts. Three novel ARFI imaging methods, pre-excitation displacement estimation, parallel-transmit excitation and parallel-transmit tracking, were implemented. Along with parallel-receive, ECG-gating and multiplexed imaging, these new techniques were used to form high-quality, high-resolution epicardial ARFI images. Three-line M-mode, extended ECG-gated three-line M-mode and ECG-gated two-dimensional ARFI imaging sequences were developed to address specific challenges related to cardiac imaging. In vivo epicardial ARFI images of an ovine heart were formed using these sequences and the quality and utility of the resultant ARFI-induced displacement curves were evaluated. The ARFI-induced displacement curves demonstrate the potential for ARFI imaging to provide new and unique information into myocardial stiffness with high temporal and spatial resolution.

A fully implantable neural data acquisition system is a key component of a clinically viable brain-machine interface. This type of system must communicate with the outside world and obtain power without the use of wires that cross through the skin. We present a 96-channel fully implantable neural data acquisition system. This system performs spike detection and extraction within the body and wirelessly transmits data to an external unit. Power is supplied wirelessly through the use of inductively coupled coils. The system was implanted acutely in sheep and successfully recorded, processed and transmitted neural data. Bidirectional communication between the implanted system and an external unit was successful over a range of 2 m. The system is also shown to integrate well into a brain-machine interface. This demonstration of a high channel-count fully implanted neural data acquisition system is a critical step in the development of a clinically viable brain-machine interface.

In this study, we investigated the feasibility of an intracranial catheter transducer with dual-mode capability of real-time 3D (RT3D) imaging and ultrasound hyperthermia, for application in the visualization and treatment of tumors in the brain. Feasibility is demonstrated in two ways: first by using a 50-element linear array transducer (17 mm x 3.1 mm aperture) operating at 4.4 MHz with our Volumetrics diagnostic scanner and custom, electrical impedance-matching circuits to achieve a temperature rise over 4 degrees C in excised pork muscle, and second, by designing and constructing a 12 Fr, integrated matrix and linear-array catheter transducer prototype for combined RT3D imaging and heating capability. This dual-mode catheter incorporated 153 matrix array elements and 11 linear array elements diced on a 0.2 mm pitch, with a total aperture size of 8.4 mm x 2.3 mm. This 3.64 MHz array achieved a 3.5 degrees C in vitro temperature rise at a 2 cm focal distance in tissue-mimicking material. The dual-mode catheter prototype was compared with a Siemens 10 Fr AcuNav catheter as a gold standard in experiments assessing image quality and therapeutic potential and both probes were used in an in vivo canine brain model to image anatomical structures and color Doppler blood flow and to attempt in vivo heating.

Ultrasound image guidance of interventional devices during minimally invasive surgery provides the clinician with improved soft tissue contrast while reducing ionizing radiation exposure. One problem with ultrasound image guidance is poor visualization of the device tip during the clinical procedure. We have described previously guidance of several interventional devices using a real-time 3-D (RT3-D) ultrasound system with 3-D color Doppler combined with the ColorMark technology. We then developed an analytical model for a vibrating needle to maximize the tip vibrations and improve the reliability and sensitivity of our technique. In this paper, we use the analytical model and improved radiofrequency (RF) and color Doppler filters to detect two different vibrating devices in water tank experiments as well as in an in vivo canine experiment. We performed water tank experiments with four different 3- D transducers: a 5 MHz transesophageal (TEE) probe, a 5 MHz transthoracic (TTE) probe, a 5 MHz intracardiac catheter (ICE) transducer, and a 2.5 MHz commercial TTE probe. Each transducer was used to scan an aortic graft suspended in the water tank. An atrial septal puncture needle and an endomyocardial biopsy forceps, each vibrating at 1.3 kHz, were inserted into the vascular graft and were tracked using 3-D color Doppler. Improved RF and wall filters increased the detected color Doppler sensitivity by 14 dB. In three simultaneous planes from the in vivo 3-D scan, we identified both the septal puncture needle and the biopsy forceps within the right atrium using the 2.5 MHz probe. A new display filter was used to suppress the unwanted flash artifact associated with physiological motion.

Acoustic radiation force impulse (ARFI) imaging has been demonstrated to be capable of visualizing variations in local stiffness within soft tissue. Recent advances in ARFI beam sequencing and parallel imaging have shortened acquisition times and lessened transducer heating to a point where ARFI acquisitions can be executed at high frame rates on commercially available diagnostic scanners. In vivo ARFI images were acquired with a linear array placed on an exposed canine heart. The electrocardiogram (ECG) was also recorded. When coregistered with the ECG, ARFI displacement images of the heart reflect the expected myocardial stiffness changes during the cardiac cycle. A radio-frequency ablation was performed on the epicardial surface of the left ventricular free wall, creating a small lesion that did not vary in stiffness during a heartbeat, though continued to move with the rest of the heart. ARFI images showed a hemispherical, stiffer region at the ablation site whose displacement magnitude and temporal variation through the cardiac cycle were less than the surrounding untreated myocardium. Sequences with radiation force pulse amplitudes set to zero were acquired to measure potential cardiac motion artifacts within the ARFI images. The results show promise for real-time cardiac ARFI imaging.

A fully implantable neural data acquisition system is a key component of a clinically viable cortical brain-machine interface. We present the design and implementation of a single-chip device that serves the processing needs of such a system. Our device processes 96 channels of multi-unit neural data and performs all digital processing necessary for bidirectional wireless communication. The implementation utilizes a single programmable logic device that is responsible for performing data reduction on the 96 channels of neural data, providing a bidirectional telemetry interface to a transceiver and performing command interpretation and system supervision. The device takes as input neural data sampled at 31.25 kHz and outputs a line-encoded serial bitstream containing the information to be transmitted by the transceiver. Data can be output in one of the following four modes: (1) streaming uncompressed data from a single channel, (2) extracted spike waveforms from any subset of the 96 channels, (3) 1 ms bincounts for each channel or (4) streaming data along with extracted spikes from a single channel. The device can output up to 2000 extracted spikes per second with latencies suitable for a brain-machine interface application. This device provides all of the digital processing components required by a fully implantable system.

Spike sorting is a technologically expensive component of the signal processing chain required to interpret population spike activity acquired in a neuromotor prosthesis. No systematic analysis of the value of spike sorting has been carried out, and little is known about the effects of spike sorting error on the ability of a brain-machine interface (BMI) to decode intended motor commands. We developed a theoretical framework to examine the effects of spike processing on the information available to a BMI decoder. We computed the mutual information in neural activity in a simplified model of directional cosine tuning to compare the effects of pooling activity from up to four neurons to the effects of sorting with varying amounts of spike error. The results showed that information in a small population of cosine-tuned neurons is maximized when the responses are sorted and there is diverse tuning of units, but information was affected little when pooling units with similar preferred directions. Spike error had adverse effects on information, such that non-sorted population activity had 79-92% of the information in its sorted counterpart for reasonable amounts of detection and sorting error and for units with moderate differences in preferred direction. This quantification of information loss associated with pooling units and with spike detection and sorting error will help to guide the engineering decisions in designing a BMI spike processing system.

A transducer originally designed for transesophageal echocardiography (TEE) was adapted for real-time volumetric endoscopic imaging of the brain. The transducer consists of a 36 x 36 array with an interelement spacing of 0.18 mm. There are 504 transmitting and 252 receive channels placed in a regular pattern in the array. The operating frequency is 4.5 MHz with a -6 dB bandwidth of 30%. The transducer is fabricated on a 10-layer flexible circuit from Microconnex (Snoqualmie, WA, USA). The purpose of this study is to evaluate the clinical feasibility of real-time 3-D intracranial ultrasound with this device. The Volumetrics Medical Imaging (Durham, NC, USA) 3-D scanner was used to obtain images in a canine model. A transcalvarial acoustic window was created under general anesthesia in the animal laboratory by placing a 10-mm burr hole in the high parietal calvarium of a 50-kg canine subject. The burr-hole was placed in a left parasagittal location to avoid the sagittal sinus, and the transducer was placed against the intact dura mater for ultrasound imaging. Images of the lateral ventricles were produced, including real-time 3-D guidance of a needle puncture of one ventricle. In a second canine subject, contrast-enhanced 3-D Doppler color flow images were made of the cerebral vessels including the complete Circle of Willis. Clinical applications may include real-time 3-D guidance of cerebrospinal fluid extraction from the lateral ventricles and bedside evaluation of critically ill patients where computed tomography and magnetic resonance imaging techniques are unavailable.

Optical fiber-based mapping systems are used to record the cardiac action potential (AP) throughout the myocardium. The optical AP contains a contraction-induced motion artifact (MA), which makes it difficult to accurately measure the action potential duration (APD). MA is removed by preventing contraction with electrical-mechanical uncoupling drugs, such as 2,3-butanedione monoxime (BDM). We designed a novel fiber-based ratiometric optical channel using a blue light emitting diode, a diffraction grating, and a split photodetector that can accurately measure the cardiac AP without the need for BDM. The channel was designed based on simulations using the optical design software ZEMAX. The channel has an electrical bandwidth of 150 Hz and an root mean-square dark noise of 742 muV. The channel successfully recorded the cardiac AP from the wall of five rabbit heart preparations without the use of BDM. After 20-point median filtering, the mean signal/noise ratio was 25.3 V/V. The APD measured from the base of a rabbit heart was 134 +/- 8.4 ms, compared to 137.6 +/- 3.3 ms from simultaneous microelectrode recordings. This difference was not statistically significant (p-value = 0.3). The quantity of MA removed was also measured using the motion ratio. The reduction in MA was significant (p-value = 0.0001). This fiber-based system is the first of its kind to enable optical APD measurements in the beating heart wall without the use of BDM.

At present, there are limited methods of acquiring three-dimensional visualization of cardiac structure and function in real-time during interventional electrophysiology procedures. Images acquired for integration of computerized tomography and magnetic resonance imaging with electroanatomic mapping systems are static and are obtained earlier in time. The purpose of this study was to test the feasibility of real-time three-dimensional transesophageal echocardiography for the guidance of interventional electrophysiological studies. A matrix array transducer with 504 channels operating at 5 MHz in a 1 cm diameter steerable esophageal probe was used in conjunction with a scanner capable of real-time 3D scanning of pyramidal volumes from 65 degrees to 120 degrees at rates up to 30 volumes per second. This device has a spatial resolution of approximately 3 mm at 5 cm depth. The authors acquired real-time three-dimensional images of anatomic landmarks of value for electrophysiological procedures in five closed chest canines. Real-time, three-dimensional ultrasound imaging was also used for visualization and guidance of interventional catheter devices within the canine heart. Real-time three-dimensional images of the atria, pulmonary veins, and coronary sinus were acquired. Real-time 3-D color flow Doppler was employed to confirm patency. Multiple image planes of image volumes and rendered views were used to track catheter position and orientation. Images of left veno-atrial junctions have been confirmed by dissection. This study has demonstrated the feasiblity of using real-time three-dimensional transesophageal echocardiography for guiding interventional electrophysiology. The technology has the potential to fill a niche as an adjunct modality for cost-effective real-time interventional guidance and assessment, providing catheter and pacing lead visualization simultaneously with functional volumetric cardiac imaging.

Intracardiac echocardiography (ICE) has been demonstrated to be an effective imaging modality for the guidance of several cardiac procedures, including radiofrequency ablation (RFA). However, assessing lesion size during the ablation with conventional ultrasound has been limited, as the associated changes within the B-mode images often are subtle. Acoustic radiation force impulse (ARFI) imaging is a promising modality to monitor RFAs as it is capable of visualizing variations in local stiffnesses within the myocardium. We demonstrate ARFI imaging with an intracardiac probe that creates higher quality images of the developing lesion. We evaluated the performance of an ICE probe with ARFI imaging in monitoring RFAs. The intracardiac probe was used to create high contrast, high resolution ARFI images of a tissue-mimicking phantom containing stiffer spherical inclusions. The probe also was used to examine an excised segment of an ovine right ventricle with a RFA-created surface lesion. Although the lesion was not visible in conventional B-mode images, the ARFI images were able to show the boundaries between the lesion and the surrounding tissue. ARFI imaging with an intracardiac probe then was used to monitor cardiac ablations in vivo. RFAs were performed within the right atrium of an ovine heart, and B-mode and ARFI imaging with the intracardiac probe was used to monitor the developing lesions. Although there was little indication of a developing lesion within the B-mode images, the corresponding ARFI images displayed regions around the ablation site that displaced less.

Laparoscopic ultrasound has seen increased use as a surgical aide in general, gynecological, and urological procedures. The application of real-time, three-dimensional (RT3D) ultrasound to these laparoscopic procedures may increase information available to the surgeon and serve as an additional intraoperative guidance tool. The integration of RT3D with recent advances in robotic surgery also can increase automation and ease of use. In this study, a 1-cm diameter probe for RT3D has been used laparoscopically for in vivo imaging of a canine. The probe, which operates at 5 MHz, was used to image the spleen, liver, and gall bladder as well as to guide surgical instruments. Furthermore, the three-dimensional (3-D) measurement system of the volumetric scanner used with this probe was tested as a guidance mechanism for a robotic linear motion system in order to simulate the feasibility of RT3D/robotic surgery integration. Using images acquired with the 3-D laparoscopic ultrasound device, coordinates were acquired by the scanner and used to direct a robotically controlled needle toward desired in vitro targets as well as targets in a post-mortem canine. The rms error for these measurements was 1.34 mm using optical alignment and 0.76 mm using ultrasound alignment.

Previous studies have established the feasibility of monitoring radiofrequency (RF) ablation procedures with acoustic radiation force impulse (ARFI) imaging. However, questions remained regarding the utility of the technique in clinically realistic scenarios and at scanning depths associated with abdominal imaging in adults. We address several of these issues and detail recent progress towards the clinical relevance of the ARFI technique. Results from in vitro bovine tissues and an in vivo ovine model are presented. Additional experiments were conducted with a tissue-mimicking phantom and parallel receive tracking techniques in order to further support the clinical feasibility of the method. Thermal lesions created during RF ablation are visualized with high contrast in both in vitro and in vivo hepatic tissues, and radial lesion growth can be monitored throughout the duration of the procedure. ARFI imaging is implemented on a diagnostic ultrasonic scanner, and thus may be a convenient option to guide RF ablation procedures, particularly when electrode insertion is also performed with sonographic guidance.

Modifications were made to a commercial real-time, three-dimensional (3-D) ultrasound system for near simultaneous 3-D scanning with two matrix array transducers. As a first illustration, a transducer cable assembly was modified to incorporate two independent, 3-D intra-cardiac echo catheters, a 7 Fr (2.3 mm O.D.) side scanning catheter and a 14 Fr (4.7 mm O.D) forward viewing catheter with accessory port, each catheter using 85 channels operating at 5 MHz. For applications in treatment of atrial fibrillation, the goal is to place the sideviewing catheter within the coronary sinus to view the whole left atrium, including a pulmonary vein. Meanwhile, the forward-viewing catheter inserted within the left atrium is directed toward the ostium of a pulmonary vein for therapy using the integrated accessory port. Using preloaded, phasing data, the scanner switches between catheters automatically, at the push of a button, with a delay of about 1 second, so that the clinician can view the therapy catheter with the coronary sinus catheter and vice versa. Preliminary imaging studies in a tissue phantom and in vivo show that our system successfully guided the forward-viewing catheter toward a target while being imaged with the sideviewing catheter. The forward-viewing catheter then was activated to monitor the target while we mimicked therapy delivery. In the future, the system will switch between 3-D probes on a line-by-line basis and display both volumes simultaneously.

Aims: Contemporary ionic-based membrane models are computationally expensive and are not intended to match the properties of a given experimental preparation. The aim of this work was to use measured restitution properties of electrically remodelled atrial tissue to develop a simplified membrane model based on the Fenton-Karma (FK) equations amenable to large-scale simulation of chronic atrial fibrillation (CAF)., Methods: Two membrane models, the FK-CAF and FK-CNTRL parameter sets, were developed to match action potential duration (APD) and conduction velocity (CV) restitution properties of rapid-pacing-induced electrically remodelled sheep atria and healthy atria, respectively. The models were tested by inducing reentry in a two-dimensional anisotropic monodomain and comparing the resulting cycle lengths (CL) with measured CLs., Results: Parameters for the FK models were obtained that reproduced APD and CV restitution properties measured in the CAF and healthy sheep atria. Using the FK-CAF parameters, reentry was sustained in a 2.5 by 2.5 cm sheet with a CL = 91.0 +/- 3.0 ms. Reentry (CL = 113.2 +/- 5.2 ms) could only be sustained in the FK-CNTRL model after the tissue was first activated at a fast rate (136.5 ms)., Conclusions: The FK-CAF model is shown to approximate the restitution properties of remodelled sheep atria and can be used to simulate reentry with short CLs similar to those measured during AF episodes.

We have previously described 2D array ultrasound transducers operating up to 10 MHz for applications including real time 3D transthoracic imaging, real time volumetric intracardiac echocardiography (ICE), real time 3D intravascular ultrasound (IVUS) imaging, and real time 3D transesophageal echocardiography (TEE). We have recently built a pair of 2D array transducers for real time 3D laparoscopic ultrasonography (3D LUS). These transducers are intended to be placed down a trocar during minimally invasive surgery. The first is a forward viewing 5 MHz, 11 x 19 array with 198 operating elements. It was built on an 8 layer multilayer flex circuit. The interelement spacing is 0.20 mm yielding an aperture that is 2.2 mm x 3.8 mm. The O.D. of the completed transducer is 10.2 mm and includes a 2 mm tool port. The average measured center frequency is 4.5 MHz, and the -6 dB bandwidth ranges from 15% to 30%. The 50 omega insertion loss, including Gore MicroFlat cabling, is -81.2 dB. The second transducer is a 7 MHz, 36 x 36 array with 504 operating elements. It was built upon a 10 layer multilayer flex circuit. This transducer is in the forward viewing configuration and the interelement spacing is 0.18 mm. The total aperture size is 6.48 mm x 6.48 mm. The O.D. of the completed transducer is 11.4 mm. The average measured center frequency is 7.2 MHz, and the -6 dB bandwidth ranges from 18% to 33%. The 50 omega insertion loss is -79.5 dB, including Gore MicroFlat cable. Real-time in vivo 3D images of canine hearts have been made including an apical 4-chamber view from a substernal access with the first transducer to monitor cardiac function. In addition, we produced real time 3D rendered images of the right pulmonary veins from a right parastemal access with the second transducer, which would be valuable in the guidance of cardiac ablation catheters for treatment of atrial fibrillation.

Acoustic radiation force impulse (ARFI) imaging techniques were used to monitor radiofrequency (RF) ablation of ovine cardiac tissue in vivo. Additionally, ARFI M-mode imaging methods were used to interrogate both healthy and ablated regions of myocardial tissue. Although induced cardiac lesions were not visualized well in conventional B-mode images, ARFI images of ablation procedures allowed determination of lesion location, shape, and relative size through time. The ARFI M-mode images were capable of distinguishing differences in behavior through the cardiac cycle between healthy and damaged tissue regions. As conventional sonography is often used to guide ablation catheters, ARFI imaging, which requires no additional equipment, may be a convenient modality for monitoring lesion formation in vivo.

Transesophageal echocardiography (TEE) is an essential diagnostic tool in patients with poor transthoracic echocardiographic windows or when detailed imaging of structures distant from the chest wall is necessary. A real-time 3D TEE probe has been fabricated in our laboratory in order to increase the amount of information available during a transesophageal procedure. The 1 cm diameter esophageal probe utilizes a 2-dimensional, 5 MHz array at its tip with a 6.3 mm diameter aperture, including 504 active channels. The array has a periodic vernier geometry with an element pitch of 0.18 mm, built onto a multilayer flexible (MLF) interconnect circuit. In order to accommodate 504 channels within the device, a 1 m long Gore MicroFlat cable was utilized for wiring the MLF to the corresponding system connectors. Pulse-echo tests in a water tank have yielded a -6 dB bandwidth of 25.3%. Fully connected to the system through 3 m of cable, the probe shows an average 50 omega insertion loss of-85 dB with a standard deviation of 4 dB, as determined through pitch-catch measurements for a sampling of 10 elements. Using the completed 3D TEE probe with the Volumetrics Medical Imaging 3D scanner, real-time volumetric images of in vivo canine cardiac anatomy have been acquired, displaying atrial views, mitral valve function and interventional catheter guidance.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Most in vivo experimental research on AF is performed in a surgical setting, on animals instrumented by external devices, or using commercial implantable pacemakers. This paper describes a novel implantable cardiac telemetry system, which allows the study of AF remotely in conscious and ambulatory animals over a few month period. To validate this concept, the system was built and implanted in a sheep for 3 months. During this period, the system was used to deliver chronic rapid atrial pacing for AF induction, and to record and measure atrial electrograms and atrial effective refractory period (AERP) daily. During the course of AF induction the AERP decreased, confirming the progression of the electrical remodeling process in the atria. Episodes of paroxysmal AF were successfully induced in the animal. Burst pacing therapy was delivered with the system, however, no AF termination was observed. Result shows that this telemetry-based pacing and monitoring system can be used to study AF in a conscious animal non-invasively for an extended period of time, making this system a unique research tool.

The design, fabrication, and characterization of a 112 channel, 5 MHz, two-dimensional (2-D) array transducer constructed on a six layer flexible polyimide interconnect circuit is described. The transducer was mounted in a 7 Fr (2.33 mm outside diameter) catheter for use in real-time intracardiac volumetric imaging. Two transducers were constructed: one with a single silver epoxy matching layer and the other without a matching layer. The center frequency and -6 dB fractional bandwidth of the transducer with a matching layer were 4.9 MHz and 31%, respectively. The 50 omega pitch-catch insertion loss was 80 dB, and the typical interelement crosstalk was -30 dB. The final element yield was greater than 97% for both transducers. The transducers were used to acquire real-time, 3-D images in an in vivo sheep model. We present in vivo images of cardiac anatomy obtained from within the coronary sinus, including the left and right atria, aorta, coronary arteries, and pulmonary veins. We also present images showing the manipulation of a separate electrophysiological catheter into the coronary sinus.

We tested the feasibility of real-time, 3-D ultrasound (US) imaging in the brain. The 3-D scanner uses a matrix phased-array transducer of 512 transmit channels and 256 receive channels operating at 2.5 MHz with a 15-mm diameter footprint. The real-time system scans a 65 degrees pyramid, producing up to 30 volumetric scans per second, and features up to five image planes as well as 3-D rendering, 3-D pulsed-wave and color Doppler. In a human subject, the real-time 3-D scans produced simultaneous transcranial horizontal (axial), coronal and sagittal image planes and real-time volume-rendered images of the gross anatomy of the brain. In a transcranial sheep model, we obtained real-time 3-D color flow Doppler scans and perfusion images using bolus injection of contrast agents into the internal carotid artery.

The goal of this investigation was to examine the feasibility of guiding interventional devices using piezoelectric buzzers to create velocity sources, which were imaged and tracked with real-time 3D color flow Doppler. The interventional devices examined in this study included a pacemaker lead, Brockenbrough needle for cardiac septal puncture, cardiac guidewire and radiofrequency ablation needles for cancer therapy. Each was mechanically coupled to a piezoelectric buzzer and was imaged using a commercial real-time 3D ultrasound system with either a 2.5 MHz matrix array transducer or a 5 MHz, 22 F catheter transducer equipped with a tool port. In vitro images acquired in tissue phantoms, excised liver with a 'tumor' target and an excised sheep heart show strong vibration signals in 3D color flow Doppler, enabling real-time tracking and guidance of all the devices in three dimensions. In a sheep model, in vivo tracking of the pacing lead was performed in the superior vena cava as well as the right atrium using RT3D color flow Doppler images. The vibrating rf ablation needles were guided through the liver toward "tumor" targets in vivo with real-time 3D color flow Doppler images.

Introduction: In the hereditary long QT syndrome, arrhythmia risk changes with age despite the presence of an ion channel mutation throughout development. Age-dependent changes in the transmural dispersion of repolarization may modulate this vulnerability. We recorded cardiac action potentials in infant, periadolescent, and adult rabbit myocardium to determine if transmural heterogeneities in repolarization are developmentally determined., Methods and Results: Arterially perfused ventricular preparations were studied from 2-week (n = 7), 7-week (n = 7), and adult (n = 6) NZW rabbits. Action potentials were recorded with microelectrodes in five regions: epicardium (epi), subepicardium (subepi), midwall (mid), subendocardium (subendo), and endocardium (endo) during endocardial S1 pacing at cycle lengths of 2,000, 1,000, and 500 ms. At 2 weeks, the transmural APD90 profile was flat. With age, APD prolongation from subepi to endo created a transmural repolarization gradient. At 7 weeks, APD90 was significantly longer at subendo [204 +/- 2 ms (mean +/- SE) 2,000-ms cycle length, P < 0.05] vs both endo (193 +/- 2 ms) and epi (172 +/- 2 ms), causing a heterogeneous transmural APD90 gradient. In adults, the transmural gradient was a smooth continuum such that APD was shortest in epicardium and longest in endocardium., Conclusion: The transmural distribution of APD is developmentally determined. Tissue-specific age-dependent changes in APD can result in transmural repolarization heterogeneity. These age-related effects may modulate arrhythmia vulnerability during development.

Real time spike detection is an important requirement for developing brain machine interfaces (BMIs). We examined three classes of spike-detection algorithms to determine which is best suited for a wireless BMI with a limited transmission bandwidth and computational capabilities. The algorithms were analyzed by tabulating true and false detections when applied to a set of realistic artificial neural signals with known spike times and varying signal to noise ratios. A design-specific cost function was developed to score the relative merits of each detector; correct detections increased the score, while false detections and computational burden reduced it. Test signals both with and without overlapping action potentials were considered. We also investigated the utility of rejecting spikes that violate a minimum refractory period by occurring within a fixed time window after the preceding threshold crossing. Our results indicate that the cost-function scores for the absolute value operator were comparable to those for more elaborate nonlinear energy operator based detectors. The absolute value operator scores were enhanced when the refractory period check was used. Matched-filter-based detectors scored poorly due to their relatively large computational requirements that would be difficult to implement in a real-time system.

To be clinically viable, a brain-machine interface (BMI) requires transcutaneous telemetry. Spike-based compression algorithms can be used to reduce the amount of telemetered data, but this type of system is subject to queuing-based transmission delays. This paper examines the relationships between the ratio of output to average input bandwidth of an implanted device and transmission latency and required queue depth. The examination was performed with a computer model designed to simulate the telemetry link. The input to the model was presorted spike data taken from a macaque monkey performing a motor task. The model shows that when the output bandwidth/average input bandwidth is in unity, significant transmission latencies occur. For a 32-neuron system, transmitting 50 bytes of data per spike and with an average neuron firing rate of 8.93 spikes/s, the average maximum delay was approximately 3.2 s. It is not until the output bandwidth is four times the average input bandwidth that average maximum delays are reduced to less than 10 ms. A comparison of neuron firing rate and resulting latencies shows that high latencies result from neuron bursting. These results will impact the design of transcutaneous telemetry in a BMI.

Well-tolerated internal atrial defibrillation shocks must be below the pain threshold, which has been estimated to be less than 1 Joule. Defibrillation of the atria with low energy is made possible by delivering shocks at the low end of the defibrillation dose-response curve. We studied low-energy defibrillation in sheep to test the hypothesis that the energy that defibrillates the atria 10% of the time (ED10) is less than 1 Joule. The ED10 was estimated in seven sheep with rapid pacing induced chronic atrial fibrillation (AF). Low-energy defibrillation shocks were delivered from coronary sinus (CS) to superior vena cava (SVC) and the ED10 and ED50 (energy that defibrillates the atria 50% of the time) were then calculated using logistic regression. The mean ratio of ED10 to ED50 was 0.50, indicating that on average, the ED10 was equal to half of the ED50. ED10 shocks had energies ranging from 1.2 to 5.8 Joules. These results suggest that painless single-shock low-energy defibrillation may not be feasible.