Browsing by Author "Wolf, Patrick D"
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Item Open Access Acoustic Radiation Force Impulse Imaging of Radiofrequency Ablation Lesions for Cardiac Ablation Procedures(2013) Eyerly, Stephanie AnnThis dissertation investigates the use of intraprocedure acoustic radiation force impulse (ARFI) imaging for visualization of radiofrequency ablation (RFA) lesions during cardiac transcatheter ablation (TCA) procedures. Tens of thousands of TCA procedures are performed annually to treat atrial fibrillation (AF) and other cardiac arrhythmias. Despite the use of sophisticated electroanatomical mapping (EAM) techniques to validate the modification of the electrical substrate, post-procedure arrhythmia recurrence is common due to incomplete lesion delivery and electrical conduction through lesion line discontinuities. The clinical demand for an imaging modality that can visually confirm the presence and completeness of RFA lesion lines motivated this research.
ARFI imaging is an ultrasound-based technique that transmits radiation force impulses to locally displace tissue and uses the tissue deformation response to generate images of relative tissue stiffness. RF-induced heating causes irreversible tissue necrosis and contractile protein denaturation that increases the stiffness of the ablated region. Preliminary in vitro and in vivo feasibility studies determined RF ablated myocardium appears stiffer in ARFI images.
This thesis describes results for ARFI imaging of RFA lesions for three research milestones: 1) an in vivo experimental verification model, 2) a clinically translative animal study, and 3) a preliminary clinical feasibility trial in human patients. In all studies, 2-D ARFI images were acquired in normal sinus rhythm and during diastole to maximize the stiffness contrast between the ablated and unablated myocardium and to minimize the bulk cardiac motion during the acquisition time.
The first in vivo experiment confirmed there was a significant decrease in the measured ARFI-induced displacement at ablation sites during and after focal RFA; the displacements in the lesion border zone and the detected lesion area stabilized over the first several minutes post-ablation. The implications of these results for ARFI imaging methods and the clinical relevance of the findings are discussed.
The second and third research chapters of this thesis describe the system integration and implementation of a multi-modality intracardiac ARFI imaging-EAM system for intraprocedure lesion evaluation. EAM was used to guide the 2-D ARFI imaging plane to targeted ablation sites in the canine right atrium (RA); the presence of EAM lesions markers and conduction disturbances in the local activation time (LAT) maps were used to find the sensitivity and specificity of predicting the presence of RFA lesion with ARFI imaging. The contrast and contrast-to-noise ratio between RFA lesion and unablated myocardium were calculated for ARFI and conventional ICE images. The opportunities and potential developments for clinical translation are discussed.
The last research chapter in this thesis describes a feasibility study of intracardiac ARFI imaging of RFA lesions in clinical patients. ARFI images of clinically relevant ablation sites were acquired, and this pilot study determined ARFI-induced displacements in human myocardium decreased at targeted ablation sites after RF-delivery. The challenges and successes of this pilot study are discussed.
This work provides evidence that intraprocedure ARFI imaging is a promising technology for the visualization of RFA lesions during cardiac TCA procedures. The clinical significance of this research is discussed, as well as challenges and considerations for future iterations of this technology aiming for clinical translation.
Item Open Access An information-theoretic analysis of spike processing in a neuroprosthetic model(2007-05-03T18:53:57Z) Won, Deborah S.Neural prostheses are being developed to provide motor capabilities to patients who suffer from motor-debilitating diseases and conditions. These brain-computer interfaces (BCI) will be controlled by activity from the brain and bypass damaged parts of the spinal cord or peripheral nervous system to re-establish volitional control of motor output. Spike sorting is a technologically expensive component of the signal processing chain required to interpret population spike activity acquired in a BCI. No systematic analysis of the need for spike sorting has been carried out and little is known about the effects of spike sorting error on the ability of a BCI to decode intended motor commands. We developed a theoretical framework and a modelling environment to examine the effects of spike processing on the information available to a BCI decoder. Shannon information theory was applied to simulated neural data. Results demonstrated that reported amounts of spike sorting error reduce mutual information (MI) significantly in single-unit spike trains. These results prompted investigation into how much information is available in a cluster of pooled signals. Indirect information analysis revealed the conditions under which pooled multi-unit signals can maintain the MI that is available in the corresponding sorted signals and how the information loss grows with dissimilarity of MI among the pooled responses. To reveal the differences in non-sorted spike activity within the context of a BCI, we simulated responses of 4 neurons with the commonly observed and exploited cosine-tuning property and with varying levels of sorting error. Tolerances of angular tuning differences and spike sorting error were given for MI loss due to pooling under various conditions, such as cases of inter- and/or intra-electrode differences and combinations of various mean firing rates and tuning depths. These analyses revealed the degree to which mutual information loss due to pooling spike activity depended upon differences in tuning between pooled neurons and the amount of spike error introduced by sorting. The theoretical framework and computational tools presented in this dissertation will BCI system designers to make decisions with an understanding of the tradeoffs between a system with and without spike sorting.Item Open Access Assessment of Cardiac Function by Acoustic Radiation Force (ARF) Based Methods of Ultrasound Elastography(2017) Vejdani Jahromi, MaryamHeart Failure (HF) is a major cause of morbidity and mortality in the world. This disorder is characterized by compromised systolic and/or diastolic function of the myocardium that reduces the pumping and/or filling efficiency resulting in diminished cardiac output. Cardiovascular researchers have been attempting to develop tools for assessment of cardiac function for decades. Evaluating cardiac function helps clinicians to diagnose and to follow the progress of HF patients.
The gold standard technique for cardiac functional assessment, including systolic and diastolic function, is the pressure-volume (PV) loop measurement; however, this measurement is not typically used clinically due to the invasiveness of the technique. PV loop measurement requires the introduction of a pressure or pressure-volume catheter into the left ventricle. Cardiovascular researchers have been attempting to develop non-invasive tools for assessment of cardiac function primarily by measuring surrogates of ventricular contractility and compliance.
These measures are based on imaging and include Ejection Fraction and Doppler and ultrasound strain imaging. These measurements are indirect measures that rely on cardiac motion or volume changes. The measurements are load dependent and could be affected by the heart rhythm and valvular disorders. Despite research toward this goal, there is no clinically accepted noninvasive technique to provide a direct myocardial measurement of cardiac function.
Acoustic radiation force (ARF) based ultrasound elastography techniques were developed in early 2000s and have been used to measure the static stiffness of tissue. These techniques are being used in the clinic for diagnosis of disorders and malignancies in tissues such as liver. When applied to the heart, it was shown that dynamic changes in the stiffness of the myocardium during the cardiac cycle could be recorded using modified versions of these static techniques.
This had the potential to be a direct measure of the time-varying elastance measured during the cardiac cycle using pressure-volume measurements. The question arose as to whether these ARF based measurements of dynamic stiffness could be used for cardiac functional assessments during systole and diastole; and if so, what the relationship is between these measurements and the gold standard method. The goal of this research was to assess the ability of ARF based measurements of cardiac dynamic stiffness to provide meaningful indices of cardiac function.
In this dissertation both acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI) ultrasound elastography techniques were studied. These are qualitative and quantitative measures of stiffness, respectively. While the focus of the studies was more on SWEI due to its quantitative nature, ARFI measurements of cardiac function were also investigated and compared to SWEI.
The studies were performed in isolated rabbit hearts in Langendorff or working modes because the preparation has several significant advantages. 1) Parameters including preload, afterload, and coronary perfusion can be accurately controlled. 2) The heart’s left ventricular free wall can be easily imaged from multiple angles. 3) Confounding neurohormonal reflexes of the body can be eliminated.
SWEI measurements of stiffness were used to characterize changes in contractility induced using the Gregg effect. The Gregg effect is the active effect of coronary perfusion on cardiac contractility. It was shown that SWEI measurements of stiffness could detect the changes in contractility induced by this known effect and that the effect was blocked using a Ca channel blocker.
The relationship between ARFI and SWEI measurements was characterized and the possibility of deriving functional indices such as systolic/diastolic ratio and isovolumic relaxation time constant (τ) using either of these techniques was evaluated. It was shown that in the same imaging configuration, the measurements of ARFI and SWEI are linearly related to one another. This could be important, as the ARFI technique will likely be the first cardiac elastography measurement technique to be implemented using transthoracic ultrasound throughout the cardiac cycle.
The Garden Hose effect was used to investigate SWEI’s ability to measure cardiac compliance. SWEI was used to detect the passive effect of coronary perfusion on cardiac compliance and the relationship between perfusion pressure and stiffness was characterized. Finally, SWEI derived measurements of diastolic function were compared to the gold standard PV measurements of cardiac diastolic function including end diastolic stiffness and the relaxation time constant. It was shown that SWEI could detect the changes in cardiac stiffness after induction of global ischemia. These changes were similar to the changes in the PV measure of diastolic stiffness. Furthermore, the results indicated that SWEI could be used to derive the relaxation time constant similar to the relaxation constant derived from intra-ventricular pressure recordings.
In summary, the results of the studies presented in this thesis illustrate the assessments of systolic and diastolic function using ARFI and SWEI ultrasound based elastography. It is concluded that these measurements can be used to derive cardiac functional indices that would have the advantages of an ultrasound based technique; they would be noninvasive, less expensive and could be widely applied outside of the cath lab.
Item Open Access Contrast in intracardiac acoustic radiation force impulse images of radiofrequency ablation lesions.(Ultrason Imaging, 2014-04) Eyerly, Stephanie A; Bahnson, Tristram D; Koontz, Jason I; Bradway, David P; Dumont, Douglas M; Trahey, Gregg E; Wolf, Patrick DWe 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).Item Open Access Design and Evaluation of a Transcutaneous Energy Transfer System(2009) Bossetti, Chad AA clinically viable brain-machine interface (BMI) requires a fully-implanted wireless neural acquisition system to limit the impediments of percutaneous connections. For an implanted system with an appreciable telemetry range, and where significant
neural signal processing is performed continuously, a major obstacle for clinical application is the need for a power source. Existing battery technology and wireless power delivery systems have not addressed the need for a mid-range power supply, capable
of 1-3 W delivery, that limits both induced noise and temperature rise. These factors are crucial for the succesful operation of a fully-implanted neural acquisition system. This work seeks to fill this void, and presents both a wireless power solution suitable for a neural recording device, and a system capable of real time monitoring of tissue temperature rise.
During this research, a 2 W transcutaneous energy transfer system (TETS) was designed, built and tested. The TETS was designed specifically for a 96-channel implanted neural data acquisition system, which requires continuous power. The major design constraints were tolerance to coil misalignment, low induced noise,
and reasonable efficiency. The design of the primary circuit consists of an H-bridge switching network driving a planar spiral Litz wire primary coil. The primary also incoporates a novel circuit for detecting the presence of the secondary. The implanted secondary components include a complimentary planar spiral coil connected to a voltage doubling rectifier. The key approach to mitigating axial coil misalignments was the use of step-down switching regulators in the secondary. With this approach, link efficiency remained nearly constant at 40%, for axial coil displacements of up to 2 cm.
Noise in the recorded neural signals was minimized using two techniques. First, the 250 kHz operating frequency of the system was tuned, such that the aliased harmonics of the switching frequency lay above the bandwidth of the amplifier used for neural recording. The second approach was to limit the impact of induced displacement currents in the body by physically separating the recording front end from the power supply components. A large titanium enclosure was used to house some of the secondary electronics, and provided a low impedance return path for further
reduction of current-induced noise.
Limiting the temperature rise of internal components was also a critical design constraint. The need for real time temperature information led to the design of a six channel temperature measurement system and incorporation of the temperature data into the acquisition system data transmission scheme. This system consisted of bead thermistor temperature transducers, and an off-the-shelf microcontroller with a built-in instrumentation amplifier.
The TETS and temperature system was fully tested in an ovine model during several acute studies. Recorded temperature rise was limited to approximately 5.5° C when the system was implanted at an adequate depth in muscle. The TETS was able to successfully power the 2 W neural acquisition system during a data processing task. Received rectified voltage in the secondary ranged from 14.86 V to 20.2 V, while link efficiency remained virtually constant. Acquired neural data was examined for TETS switching noise. The measured RMS noise increased by less than 1 &mu V, averaged over several experiments. These results demonstrate the first mid-range TETS solution for powering a fully implanted neural acquisition system.
Item Open Access Electrical Interfaces to Implanted Neural Medical Devices(2016) Jochum, ThomasThe electrical interface to neural medical devices is researched from three perspectives, namely, the electronics within the device, the electrodes on the device, and the electromagnetic fields around the device.
A Brain-Machine Interface may allow paralyzed patients to control robotic limbs with neural signals sensed by fine wires inserted into the brain. The neural signals have an amplitude under one millivolt and must be amplified. A totally integrated amplifier is designed, manufactured, and characterized. The amplifier is fabricated in a standard half-micron CMOS process without capacitors or resistors. Two application issues not previously addressed are solved. First, the topology of the amplifier is shown to be less sensitive to long-term drift of transistor parameters than the standard topology. Second, a neural signal corrupted by 10 millivolts of powerline interference can be recovered. The amplifier has a gain of 58 dB, a bandwidth of 750 to 14k Hz, power consumption of 180 uW, and noise of 1.5 uV RMS. The design techniques proven in this amplifier are suitable for clinical Brain Machine Interfaces.
An implanted electroencephalogram (EEG) recorder may aid the diagnosis of infrequent seizure-like events that are currently diagnosed, without proof, as epilepsy. A proof-of-concept study quantifies the electrical characteristics of the electrodes planned for the recorder. The electrodes are implanted in an ovine model for eight weeks. Electrode impedance is less than 800 Ohm throughout the study. A frequency-domain determination of sedation performs similarly for surface versus implanted electrodes throughout the study. The time-domain correlation between an implanted electrode and a surface electrode is almost as high as between two surface electrodes (0.86 versus 0.92). EEG-certified clinicians judge that the implanted electrode quality is at least adequate and that the implanted electrodes provide the same clinical information as surface electrodes except for a noticeable amplitude difference. No significant issues are found that invalidate the concept of an implanted EEG recorder.
Transcranial stimulation may treat a multitude of neural and psychological illnesses. The stimulation may have higher repeatability and lower patient effort if an implanted device provides the stimulation. The shape of the device, 300 mm long by 1 mm in diameter, is unlike any present implanted device. Five techniques that deliver energy to the device are analyzed using computer simulations. The electrode for the techniques that employ an electric field to deliver the energy is a new design that exploits the anatomy of the scalp and skull. The electric field techniques deliver energy that is likely suitable for some stimulation protocols but not for all. The techniques that employ a magnetic field deliver more than the energy required, especially if the shape of the coil that creates the magnetic field is automatically optimized. However, the magnetic-field techniques heat the brain; the electric-field techniques do not heat the brain. This research validates the new delivery concepts and justifies future research.
Item Open Access Harmonic source wavefront aberration correction for ultrasound imaging.(2010) Dianis, Scott W.Aberration is a correctable phenomenon that degrades diagnostic quality in a significant number of ultrasound images. Previous aberration correction studies have focused on development of aberration estimation algorithms or on aberration reduction by using harmonic imaging. In the past, a major drawback of aberration estimation algorithms has been the assumptions required about the imaging target, assumptions that can limit clinical application where correction for multiple locations within a scan may be required. Harmonic imaging attempts to reduce the effect of aberration, without making assumptions about the imaging target, by using a lower-frequency transmit beam that is less prone to aberration. However, harmonic imaging does not correct for any aberration that may remain. It is hypothesized that a harmonic source wavefront correction technique is capable of creating a point-like acoustical source that allows for estimation and correction of two-dimensional aberration in a clinical setting. Harmonic source wavefront correction utilizes the reduced aberration of harmonic imaging to create a known acoustical source to satisfy the assumptions of the aberration estimation algorithms, thus improving their clinical application. Generation of a point-like acoustical source in the presence of aberration is demonstrated using both spatially correlated and spatially uncorrelated electronic aberrators varying in strength from 0.25π radians to 1.16π radians RMS focusing error. Beam properties of the 2.08 MHz fundamental, 4.16 MHz generated harmonic, and 4.17 MHz imaging beams were compared; in the presence of aberration, relative peak beam amplitude of the 4.16 MHz generated harmonic beam was up to 81% higher than the 4.17 MHz imaging beam, while -6 dB beam width indicated the 4.16 MHz generated harmonic beam was 88% narrower and more point-like than the 2.08 MHz fundamental beam. The feasibility of harmonic source wavefront correction was demonstrated by correcting for spatially uncorrelated electronic aberrators in a water tank using a point target, specular reflector, and speckle region as correction targets. Harmonic source wavefront correction was paired with a cross-correlation algorithm to estimate corrective delays and was most effective in correcting peak amplitude of the 4.17 MHz imaging beam using a point target (up to 94% improvement), followed by use of a specular reflector (up to 83% improvement), followed by use of a speckle region (up to 47% improvement). Aberration correction is sensitive to signal-to-noise ratio (SNR),and correction utilizing the 2.08 MHz fundamental, which provided higher SNR, was more effective than correction utilizing the more point-like 4.16 MHz harmonic for the experimental setup used. A harmonic SNR of 14 dB was estimated as necessary for harmonic-based correction performance to equal or surpass fundamental-based correction, regardless of fundamental SNR. Finally, performance of harmonic source wavefront correction was quantified in a clinical setting. Correction of spatially correlated electronic aberrators was performed using both ex vivo porcine kidneys and the left kidneys of 11 human volunteers as correction targets. Correction utilizing porcine kidney resulted in 10 dB greater improvement in peak beam amplitude than correction utilizing the left kidney of human volunteers. Body wall aberration present in the human volunteers was not accounted for during correction and likely caused the disparity in correction performance. An average upper limit for body wall aberration for the human subjects was estimated at 65 ns (±9 ns) RMSItem Open Access Intracardiac acoustic radiation force impulse imaging: a novel imaging method for intraprocedural evaluation of radiofrequency ablation lesions.(Heart Rhythm, 2012-11) Eyerly, Stephanie A; Bahnson, Tristram D; Koontz, Jason I; Bradway, David P; Dumont, Douglas M; Trahey, Gregg E; Wolf, Patrick DBACKGROUND: 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.Item Open Access Reduction, Telemetry, and Processing of Neural Data for a Fully Implantable Data Acquisition System(2008-11-17) Rizk, MichaelCortical brain-machine interface (BMI) systems as they currently exist within the research environment are not suitable for general clinical use. A clinical system must be fully implantable, requiring no chronic breaks in the skin. This work addresses the communication and processing needs of a fully implantable neural data acquisition system. Such a system is a key component of a clinically viable BMI. This work primarily focuses on the design, implementation, and testing of a data reduction scheme for 96 channels of neural data and a bidirectional telemetry link for sending data out of the body and providing commands and configuration information to the implanted portion of the system.
The data reduction scheme and an interface to a one megabit per second commercial transceiver were implemented in a single programmable logic device. The data reduction scheme makes use of a voltage thresholding spike detection technique. The threshold for each channel is computed automatically based on a user-defined multiplier and an estimate of the noise level. The interface to the transceiver performs all necessary serial encoding and decoding, queuing, and packet assembly and disassembly.
The data reduction portion of the system was tested using simulated neural signals. Spike detection performance was evaluated using thirty different multiplier values over a wide range of signal-to-noise ratios. Spike extraction tests showed that the system could output up to 2000 extracted spikes per second with latencies suitable for a BMI application. The circumstances under which some spikes would not be transmitted by the system were also characterized. Finally, an investigation of automatic threshold selection methods suitable for a BMI application was conducted. The results suggest that the spike detection technique used in the data reduction scheme is appropriate for this application.
The neural data acquisition system has been fully implanted in several sheep and has successfully recorded, processed, and transmitted neural data during these experiments. The system is also shown to interface well with commercial spike sorting software and with all of the necessary components of a BMI setup, demonstrating suitability for integration into systems that have already been shown to be effective in the laboratory environment.
Item Open Access Volumetric Acoustic Radiation Force Impulse Imaging Using Intracardiac Echocardiography(2020) Kim, Young-JoongIntracardiac echocardiography (ICE) based elastography methods have the potential to be useful for a number of clinical purposes including monitoring of ablation lesion formation and myocardial substrate characterization. However, 2-D field-of-view ICE catheters currently in use in the clinic have difficulties imaging face-on regions of myocardial tissue, requiring meticulous and time-consuming translational and rotational scanning of the array. This dissertation investigates the use of helicoid array transducers to perform ICE-based acoustic radiation force impulse (ARFI) imaging on multiple elevation planes at once, improving on current methods in terms of speed and ease-of-use.
The Siemens Acuson SC2000 ultrasound scanner was programmed with sequences to perform SWEI imaging on the Soundstar 8F linear array ICE catheter and to perform volumetric ARFI scans using the AcuNav V helicoid array catheter. These sequences were used respectively to characterize the stiffness contrast in ablated human atrial tissue and to characterize the performance of volumetric ARFI at detecting gaps in atrial tissue phantoms.
The first research chapter is a clinical study showing that shear wave elastography (SWE) using a traditional 2-D field-of-view ICE catheter can be used to distinguish between baseline and ablated left atrial (LA) tissue in patients undergoing radiofrequency ablation (RFA) for atrial fibrillation (AF). Shear wave velocities of baseline LA and right atrium (RA), low electrogram voltage areas of the LA, and ablated LA are reported. The second chapter investigates through simulation and experiments the volumetric B-mode imaging performance of helicoid array transducers. Experimental verification of pressure field simulations is done by the use of the Siemens Acuson AcuNav V, a 128-element helicoid array transducer. Guided by these results, a discussion of the design of helicoid array transducer imaging sequences is presented. The final chapter is about the use of the helicoid array transducer for volumetric ARFI imaging. Experiments in tissue phantoms of varying elasticities and inclusions demonstrate that it is possible to identify gaps as narrow as 1 mm when the contrast is similar to that of baseline and ablated human LA myocardium.
This work demonstrates the feasibility of using helicoid array transducers for volumetric elastography imaging of the heart and establishes a foundation for future clinical investigations using this technology.