Biomedical subjects

J Brian Fowlkes

Publications and source records attributed to J Brian Fowlkes.

At least 19 recordsLinked to original sources

PubMed2006

Pulsed cavitational ultrasound therapy for controlled tissue homogenization.

Methods were investigated to acoustically control the extent to which cavitation-mediated tissue homogenization is responsible for lesion formation in vitro. These results may guide potential therapeutic procedures that induce damage predominantly via mechanical disruption and, thereby, avoid limitations associated with thermal ablative modalities. Porcine myocardium was insonified at 750 kHz using pulse sequences consisting of high-amplitude pulses (22 MPa Pr) interleaved with variable-amplitude "sustaining" pulses (e.g., 6.9 MPa Pr), which were intended to provide sufficient acoustic input to maintain cavitation activity between primary pulses, but to increase the spatial peak temporal average intensity (I(SPTA)) only marginally. Using modest temporal-average intensities (e.g., I(SPTA) approximately 200 W/cm2), approximately 0.5 cm3 lesions were produced consisting of homogenate that could be irrigated away to reveal smooth cavities. The prevalence of homogenate in a given lesion was sensitive to both pulse-repetition frequency and sustaining pulse amplitude, suggesting the existence of optimum acoustic parameters for producing homogenized lesions largely via mechanical perturbation.

Animals↗

PubMed2006

Spatial control of gas bubbles and their effects on acoustic fields.

Because microbubbles can enhance therapy, such as by cavitation or by thermal means, treatment could be confined with localization of microbubbles. This spatial control can be achieved by the vaporization of liquid-filled droplets present throughout the medium in a process known as acoustic droplet vaporization (ADV). Bubbles in the form of an orthogonal plane or "wall" can thus be created and can scatter ultrasound to enhance the proximal acoustic field while shielding distal tissues. To investigate the possible effects of a preexistent bubble wall, tissue-mimicking polyacrylamide gels embedded with perfluorocarbon droplets were insonified under various conditions. The preliminary results presented in this paper show that a bubble wall can successfully cause proximal ADV at approximately half the transmitted pressures that are required without the use of a bubble wall, while also serving as a viable shield against ADV and potential damage in distal areas. The results seen here in a gel medium are promising and suggest further development in vivo is needed.

Acrylic Resins↗

PubMed2006

The relationship of acoustic emission and pulse-repetition frequency in the detection of gas body stability and cell death.

The effect of pulse-repetition frequency (PRF) and number of exposures on membrane damage and subsequent death of contrast agent-attached phagocytic cells was examined. Phagocytic cells of a mouse macrophage cell line were grown as monolayers on thin Mylar sheets. Optison microbubbles were attached to these cells by incubation. Focused ultrasound exposures (Pr = 2 MPa) were implemented at a frequency of 2.25 MHz with 46 cycle pulses and clinically relevant PRFs of 1 kHz, 100 Hz, 10 Hz, 1 Hz and 0.1 Hz in a degassed water bath. A 1-MHz receive transducer measured the scattered signal. The frequency spectrum was normalized to a control spectrum from linear scatterers. Photomicrographs of the cell monolayer were made before and after exposure, and a dye exclusion test (Trypan blue) was used to find the percentage of blue-stained cells indicating cell death, which was then related to acoustic emission. For 10 acoustic pulses and a high prerinse gas body concentration, there was less cell death and correspondingly lower change in the acoustic emissions at a PRF of 1 kHz than with PRFs of 100 Hz, 10 Hz, 1 Hz and 0.1 Hz (p < 0.001). The reduced effect at high PRF may be indicative of some evolution of the shelled microbubble that requires significant total exposure duration (> 10 ms, but < 100 ms).

Albumins↗

PubMed2006

Vector Doppler imaging of a spinning disc ultrasound Doppler phantom.

Vector Doppler methods are used to obtain angle independent in-plane velocity information. Velocity magnitude as well as direction are reconstructed from regular steered colour flow and from split-aperture Doppler acquisitions. Spatially resolved in-plane velocity was obtained through Doppler colour flow mode and subsequent data triangulation. A depth-invariant constant Doppler angle was achieved by using a depth expanding transmit-receive Doppler aperture. Velocities of up to 50 cm s(-1) and 360 degrees vector velocity directions were measured. This was achieved by creating a spinning solid disc phantom. Such a phantom was built to allow underwater mounting and spinning of a solid disc-shaped ultrasound phantom (maximum velocity of 50 cm s-1). Doppler triangulation was realised by steered Doppler and by a split-aperture approach. Results of both imaging methods are shown. Split-aperture results showed errors of less then 10% for velocity magnitude estimation and less then 2.5 degrees for directional information.

Humans↗

PubMed2006

Refill model of rabbit kidney vasculature.

A refill model previously developed in flow phantoms was modified to simulate the refill of cortical and medullary rabbit kidney tissues. The highly structured kidney tissues were accounted for by considering refill both within and across the scan-plane. Refill curves were acquired with ultrasound contrast from rabbit kidneys using high MI disruption pulses followed by low MI real-time imaging. The comparison of the real medullary and cortical tissues with their corresponding models resulted in an RMS error of 11% and 18%, respectively, indicating that simple assumptions about a tissue's vascular structure are predictive of refill behaviour. Tissue classification images were generated using the refill models and an exponential simplification. These images were indistinguishable and matched what is expected of a kidney, indicating that the primary distinguishing characteristic between kidney tissue types is mean transit time. However, the vascular model is useful in predicting and explaining tissue properties that affect refill behavior.

Animals↗

PubMed2006

Pulsed cavitational ultrasound: a noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney.

PURPOSE: The optimal minimally invasive treatment for small renal masses continues to evolve. Current ablative technologies rely on thermal mechanisms for tissue destruction. However, the creation of precise lesions is limited by inhomogeneous heating/cooling due to tissue variability, perfusion effects and tissue charring. We hypothesized that nonthermal mechanical effects of ultrasound (cavitation) can be used to progressively homogenize tissue in controlled fashion with predictable results. MATERIALS AND METHODS: We developed a focused annular array ultrasound system capable of delivering high intensity (greater than 20 kW/cm) short pulses (20 microseconds) of energy to a target volume. This system operates at a repetition frequency of 100 Hz, resulting in a low time averaged power output (approximately 5 W total acoustic output). Following approval from the institutional animal care committee a series of transcutaneous ablations were performed in the normal kidneys of 10 rabbits. RESULTS: Lesions created with a small number of pulses (10 or 100) produced scattered areas of damage characterized by focal hemorrhage and small areas of cellular injury in the targeted volume. Lesions created with greater numbers of pulses (1,000 or 10,000) demonstrated complete destruction of the targeted volume. Gross examination revealed that lesions contained a liquefied core with smooth walls and sharply demarcated boundaries. Histological examination demonstrated extensive areas of acellular debris surrounded by a narrow margin of cellular injury. CONCLUSIONS: This pulsed cavitational ultrasound system is capable of transcutaneous nonthermal destruction of renal tissue. Refinement of this technology for noninvasive ablation of small renal masses is currently under way.

Animals↗

PubMed2006

A new strategy to enhance cavitational tissue erosion using a high-intensity, Initiating sequence.

Our previous studies have shown that pulsed ultrasound can physically remove soft tissue through cavitation. A new strategy to enhance the cavitation-induced erosion is proposed wherein tissue erosion is initiated by a short, high-intensity sequence of pulses and sustained by lower intensity pulses. We investigated effects of the initiating sequence on erosion and cavitation sustained by lower intensity pulses. Multiple three-cycle pulses at a pulse repetition frequency of 20 kHz delivered by a 788-kHz focused transducer were used for tissue erosion. Fixing the initiating sequence at I(SPPA) of 9000 W/cm2, 16 combinations of different numbers of pulses within the initiating sequence and different sustaining pulse intensities were tested. Results showed: the initiating sequence increases the probability of erosion occurrence and the erosion rate with only slight overall increases in propagated energy; the initiating sequence containing more pulses does not increase the sustained cavitation period; and if extinguished and reinitiated, the sustained cavitation period becomes shorter after each initiation, although the waiting time between adjacent cavitation periods is random. The high-intensity, initiating sequence enhances cavitational tissue erosion and enables erosion at intensities significantly lower than what is required to initiate erosion.

Animals↗

PubMed2006

Imaging of joints with laser-based photoacoustic tomography: an animal study.

Photoacoustic tomography (PAT), a nonionizing, noninvasive, laser-based technology was adapted to joint imaging for the first time. Pulsed laser light in the near-infrared region was directed toward a joint with resultant ultrasonic signals recorded and used to reconstruct images that present the optical properties in subsurface joint tissues. The feasibility of this joint imaging system was validated on a Sprague Dawley rat tail model and verified through comparison with histology. With sufficient penetration depth, PAT realized tomographic imaging of a joint as a whole organ noninvasively. Based on the optical contrast, various intra- and extra-articular tissues, including skin, fat, muscle, blood vessels, synovium and bone, were presented successfully in images with satisfactory spatial resolution that was primarily limited by the bandwidth of detected photoacoustic signals rather than optical diffusion as occurs in traditional optical imaging. PAT, with its intrinsic advantages, may provide a unique opportunity to enable the early diagnosis of inflammatory joint disorders, e.g., rheumatoid arthritis, and to monitor therapeutic outcomes with high sensitivity and accuracy.

Acoustics↗

PubMed2006

Cost-effective assembly of a basic fiber-optic hydrophone for measurement of high-amplitude therapeutic ultrasound fields.

Design considerations, assembly details, and operating procedures of one version of a cost-effective basic fiber-optic probe hydrophone (FOPH) are described in order to convey practical information to groups interested in constructing a similar device. The use of fiber optic hydrophones can overcome some of the limitations associated with traditional polyvinylidene difluoride (PVDF) hydrophones for calibration of acoustic fields. Compared to standard PVDF hydrophones, FOPH systems generally have larger bandwidths, enhanced spatial resolution, reduced directionality, and greater immunity to electromagnetic interference, though they can be limited by significantly lower sensitivities. The FOPH system presently described employs a 100-microm multimode optical fiber as the sensing element and incorporates a 1-W laser diode module, 2 x 2 optical coupler, and general-purpose 50-MHz silicon p-i-n photodetector. Wave forms generated using the FOPH system and a reference PVDF hydrophone are compared, and intrinsic and substitution methods for calibrating the FOPH system are discussed. The voltage-to-pressure transfer factor is approximately 0.8 mV/MPa (-302 dB re 1 V/microPa), though straightforward modifications to the optical components in the FOPH system are discussed that can significantly increase this value. Recommendations are presented to guide the choice of optical components and to provide practical insight into the routine usage of the FOPH device.

Calibration↗

PubMed2006

Measurement of volumetric flow.

OBJECTIVE: The purpose of this study was to evaluate a 3-dimensional (3D) sonographic method for the measurement of volumetric flow under conditions of known flow rates and Doppler angles. METHODS: A GE/Kretz Voluson 730 system (GE Healthcare, Milwaukee, WI) and RAB2-5 probe were used to acquire 3D Doppler measurements in a custom flow phantom. Blood-mimicking fluid circulated by a computer-controlled pump provided a range of flow velocities (2-15 mL/s). A 6-axis positioning system maneuvered the ultrasound probe through a range of angles (40 degrees-70 degrees and 110 degrees -140 degrees) with respect to the tube (orthogonal to the tube being 90 degrees). Volume data sets were obtained spanning 29 degrees lateral and 20 degrees elevational angles encompassing the flow tube in a scanning time of less than 10 seconds. Power Doppler data were used to correct for partial volume effects. RESULTS: Using a single angle (110 degrees) with respect to the flow tube, measured and actual volume flow rates were within the 95% confidence interval over the full range of flow rates. At flow rates of 5 and 10 mL/s, the measured volume flow rates were all within +/-15% of actual values for the range of angles tested and also stayed within the 95% confidence interval. CONCLUSIONS: Direct comparisons of volume flow rates estimated with 3D sonography and known flow rates showed that the method has good accuracy. Subsequent comparisons under pulsatile and in vivo conditions will be needed to verify this performance for clinical applications.

Blood Flow Velocity↗

PubMed2005

Bubble splitting in bifurcating tubes: a model study of cardiovascular gas emboli transport.

The transport of long gas bubbles, suspended in liquid, through symmetric bifurcations, is investigated experimentally and theoretically as a model of cardiovascular gas bubble transport in air embolism and gas embolotherapy. The relevant dimensionless parameters in the models match the corresponding values for arteries and arterioles. The effects of roll angle (the angle the plane of the bifurcation makes with the horizontal), capillary number (a dimensionless indicator of flow), and bubble volume (or length) on the splitting of bubbles as they pass through the bifurcation are examined. Splitting is observed to be more homogenous at higher capillary numbers and lower roll angles. It is shown that, at nonzero roll angles, there is a critical value of the capillary number below which the bubbles do not split and are transported entirely into the upper branch. The value of the critical capillary number increases with roll angle and parent tube diameter. A unique bubble motion is observed at the critical capillary number and for slightly slower flows: the bubble begins to split, the meniscus in the lower branch then moves backward, and finally the entire bubble enters the upper branch. These findings suggest that, in large vessels, emboli tend to be transported upward unless flow is unusually strong but that a more homogeneous distribution of emboli occurs in smaller vessels. This corresponds to previous observations that air emboli tend to lodge in the upper regions of the lungs and suggests that relatively uniform infarction of tumors by gas embolotherapy may be possible.

Animals↗

PubMed2005

Investigation of intensity thresholds for ultrasound tissue erosion.

Our previous studies have shown that short intense pulses delivered at certain pulse repetition frequencies (PRF) can achieve localized, clean erosion in soft tissue. In this paper, the intensity thresholds for ultrasound induced erosion and the effects of pulse intensity on erosion characterized by axial erosion rate, perforation area and volume erosion rate were investigated on in vitro porcine atrial wall tissue. Ultrasound pulses with a 3-cycle pulse duration and a 20-kHz PRF were delivered by a 788-kHz single element focused transducer. I(SPPA) values of 1000 to 9000 W/cm2 were tested. Results show the following: (1) the estimated intensity threshold for generating erosion was at I(SPPA) of 3220 W/cm2; (2) the axial erosion rate increased with higher intensity at I(SPPA) < or = 5000 W/cm2, while decreased with higher intensity at I(SPPA) > or = 5000 W/cm2; and (3) the perforation area and the volume erosion rate increased with higher intensity.

Animals↗

PubMed2005

Acoustic droplet vaporization for temporal and spatial control of tissue occlusion: a kidney study.

Acoustic droplet vaporization (ADV) has been introduced with the potential application of tumor treatment via occlusion and subsequent necrosis. New Zealand White rabbits were anesthetized, and their left kidney was externalized. An imaging array and single-element transducer were positioned in a tank with direct access to the kidney's vasculature and renal artery. Filtered droplet emulsions (diameter <6 microm) were injected intra-arterially (IA) into the left heart during insonification of the renal artery, and the extent of blood flow reduction by ADV was compared to the untreated right kidney. Flow cytometry (using colored microspheres) of kidney tissue samples and reference blood from the femoral artery allowed the quantitative estimation of regional blood flow. A maximum regional blood flow reduction in the treated region of >90% and an average organ perfusion reduction of >70% was achieved using ADV. After treatment of the left kidney, the control kidney on the contralateral side showed a maximum decrease in regional blood flow of 18% relative to the pre-ADV baseline. Image-based hyper-echogenicity from ADV of IA injections was monitored for approximately 90 minutes, and cortex perfusion was reduced by >60% of its original value for more than 1 hour. This could be enough time for the onset of cell death and possible tumor treatment via ischemic necrosis. Moreover, currently used radiofrequency tissue ablation-based tumor treatment could benefit from ADV due to the decreased heat loss via vascular cooling.

Animals↗

PubMed2005

Evaluation of ultrasound tissue damage based on changes in image echogenicity in canine kidney.

Sufficiently high intensity ultrasound can create hyperechoic regions in an ultrasound image due to local bubble generation. We explore the link between the temporal extent of these hyperechoic regions and tissue damage caused by ultrasound therapy. The decay rate of increased echogenicity from the focal zone in insonated live exteriorized canine kidney was quantified and correlated to the spatial extent of tissue damage. The decay half-time, t(half), defined as the time for echogenicity enhancement to decay by a factor of 2, was observed in all cases to be greater than 41 s in spatial zones in which extensive histological damage was observed. In cases in which the measured thalf was less than 11 s, the damage was limited to minor hemorrhage, or it was not detected. These t(half) discrimination boundaries of 41 and 11 s were not statistically different for cases in which contrast agent was used to enhance therapeutic efficiency. This was true even though contrast agent infusion significantly reduced the therapy pulse duration threshold for damage production.

Animals↗

PubMed2005

Effects of contrast agent infusion rates on thresholds for tissue damage produced by single exposures of high-intensity ultrasound.

Stabilized microbubble ultrasound contrast agents (UCA) have potential to aid tissue ablation during ultrasound surgery by enhancing both cavitational and thermal damage mechanisms. Previously, we showed UCA infused at a rate of 1 microL/kg/min prior to ultrasound exposure could reduce the total energy required to produce tissue damage by up to two orders of magnitude. In this paper, we evaluate thresholds for macroscopic tissue damage with UCA infusion rates (IR) of 0.1, 0.3, 1, 3, and 10 microL/kg/min to determine IR potentially effective for ultrasound therapy. Canine kidneys were surgically externalized and insonified with single exposures of focused ultrasound. Incident exposures were 1.44 MHz tone bursts, either 250 ms in duration with intensity between 500 W/cm2 and 3200 W/cm2, or 100 micros to 1 s in duration with intensity equal to 3200 W/cm2. Probabilities of tissue damage occurrence were determined for each set of exposure conditions (intensity, duration, and IR). A threshold intensity and threshold duration, defined as the quantities for which tissue damage occurred with probability equal to 0.5, were estimated for each IR. Results show that, as IR increased from 0.1 to 10 microL/kg/min, the threshold intensity decreased by up to a factor of 3, and threshold duration decreased by up to a factor of 200. Microbubble introduction at IR up to 10 microL/kg/min thus may be effective in aiding ultrasound therapy.

Albumins↗

PubMed2005

Aberration correction by nonlinear beam mixing: generation of a pseudo point sound source.

Nonlinear beam mixing with microbubbles was explored to create a pseudo point source for aberration correction of therapeutic ultrasound. A damping coefficient for a bubble driven by a dual frequency sound field was derived by revisiting Prosperetti's linearized damping model. As a result, the overall damping term for dual frequency was obtained by linear summation of two damping terms for each frequency. The numerical simulation based on the bubble model suggests that the most efficient size range to generate a 1 MHz frequency from 4 MHz and 5 MHz sound sources is 2.6 to 3.0 microm. Furthermore, this size range constitutes the primary distribution of a specific ultrasound contrast agent. When a chamber of 0.1% of the diluted agent is sonified by 4 MHz and 5 MHz sound beams with 80 degrees incident angle between them, an approximately 100 Pa, 1 MHz difference frequency signal can be measured approximately 10 cm away. In addition, the received 1 MHz difference frequency signal shows omni-directional characteristics, even though the overlap zone of the two sound beams is on the order of the difference frequency wavelength. Therefore, the induced sound source can be considered as a pseudo point source and is expected to be useful for aberration correction for therapeutic ultrasound.

Animals↗

PubMed2005

Controlled ultrasound tissue erosion: the role of dynamic interaction between insonation and microbubble activity.

Previous studies showed that ultrasound can mechanically remove tissue in a localized, controlled manner. Moreover, enhanced acoustic backscatter is highly correlated with the erosion process. "Initiation" and "extinction" of this highly backscattering environment were studied in this paper. The relationship between initiation and erosion, variability of initiation and extinction, and effects of pulse intensity and gas saturation on time to initiation (initiation delay time) were investigated. A 788-kHz single-element transducer was used. Multiple pulses at a 3-cycle pulse duration and a 20-kHz pulse repetition frequency were applied. I(SPPA) values between 1000 and 9000 W/cm2 and gas saturation ranges of 24%-28%, 39%-49%, and 77%-81% were tested. Results show the following: (1) without initiation, erosion was never observed; (2) initiation and extinction of the highly backscattering environment were stochastic in nature and dependent on acoustic parameters; (3) initiation delay times were shorter with higher intensity and higher gas saturation (e.g., the mean initiation delay time was 66.9 s at I(SPPA) of 4000 W/cm2 and 3.6 ms at I(SPPA) of 9000 W/cm2); and (4) once initiated by high-intensity pulses, the highly backscattering environment and erosion can be sustained using a significantly lower intensity than that required to initiate the process.

Animals↗

PubMed2005

Echocardiography-based selection of quiescent heart phases: implications for cardiac imaging.

OBJECTIVE: We compared the potential effectiveness of echocardiography with electrocardiography (ECG) for the selection of phases within the cardiac cycle during which there is relatively little motion. Determination of such phases may be important for triggering other modalities such as computed tomography and magnetic resonance imaging. METHODS: In a preliminary study in 2 volunteers, simultaneous ECG and cardiac echocardiographic data were obtained and analyzed. Various phases of the echocardiographic data were cross-correlated from beat to beat. Time point pairs from different cardiac cycles with correlation of 0.8 were selected. RESULTS: Beat-to-beat correlation values peaked at around 80% of the R-R' interval near the cardiac apex and around 30% of the R-R' interval near the cardiac base for 1 subject. For the other subject, the correlation values peaked at around 75% of the R-R' interval near the cardiac apex. CONCLUSIONS: The cardiac cycle phase having maximum spatial cross-correlation for the longest period varied from subject to subject and also on the portion of the heart that was being imaged. Echocardiography may be superior to ECG in determining points in the cardiac cycle when the heart is relatively stationary and can potentially provide more optimal triggering information for cardiac computed tomography or magnetic resonance imaging.

Adult↗