Biomedical subjects

Matthew O'Donnell

Publications and source records attributed to Matthew O'Donnell.

At least 19 recordsLinked to original sources

PubMed2006

Mapping age-related elasticity changes in porcine lenses using bubble-based acoustic radiation force.

Bubble-based acoustic radiation force aims to measure highly localized tissue viscoelastic properties. In the current investigation, acoustic radiation force was applied to laser-induced bubbles to measure age-related changes in the spatial distribution of elastic properties within in vitro porcine lenses. A potential in vivo technique to map lens elasticity is crucial to understanding the onset of presbyopia and develop new treatment options. Bubble-based acoustic radiation force was investigated as a technique to measure the spatial elasticity distribution of the lens in its natural state without disrupting the lens capsule. Laser-induced optical breakdown (LIOB) generated microbubbles in a straight line across the equatorial plane of explanted porcine lenses with 1mm lateral spacing. Optical breakdown occurs when sufficiently high threshold fluence is attained at the focus of femtosecond pulsed lasers, inducing plasma formation and bubble generation. A two-element confocal ultrasonic transducer applied 6.5 ms acoustic radiation force-chirp bursts with the 1.5 MHz outer element while monitoring bubble position within the lens using pulse-echoes with the 7.44 MHz inner element. A cross-correlation method was used to measure bubble displacements and determine exponential time constants of the temporal responses. Maximum bubble displacements are inversely proportional to the local Young's modulus, while time constants are indicative of viscoelastic properties. The apparent spatial elasticity distributions in 41 porcine lenses, ranging from 4 months to 5 years in age, were measured using bubble-based acoustic radiation force. Bubble displacements decrease closer to the porcine lens center, suggesting that the nucleus is stiffer than the cortex. Bubble displacements decrease with increasing lens age, suggesting that porcine lenses become stiffer with age. Bubble-based acoustic radiation force may be well-suited as a potential in vivo technique to spatially map elastic properties of the lens and guide therapeutic procedures aimed at restoring accommodation.

Aging↗

PubMed2006

Acoustic estimation of thermal distribution in the vicinity of femtosecond laser-induced optical breakdown.

Laser-induced optical breakdown (LIOB), or photo-disruption, can generate individual microbubbles in tissues for biomedical applications. We have previously developed a co-localized high-frequency ultrasound system to detect and characterize these laser-induced microbubbles. Because ultrasound speed varies with temperature, this system can also be used to directly estimate thermal effects in the vicinity of photodisruption. In this study, individual bubbles (sizes 60-100 microm) were created at the bottom of a water tank using a 793-nm, 100-fs Ti:Sapphire laser pulsed at 250 kHz. During and after breakdown, pulse-echoes from the tank bottom in the region surrounding a bubble were recorded with a single-element 85-MHz ultrasonic transducer, and temperature-dependent pulse-echo displacements were calculated using phase-sensitive correlation tracking. These displacements were then fit to a finite-element heat transfer model to estimate the effective thermal distribution. Estimates were calculated for laser exposure times ranging from 6.25 to 312.5 ms (1600 to 78 000 laser pulses), at 1.5 and 4 J/cm2 fluences. Results suggest a minimal temperature increase (<1 degrees C) within 100 microm of a bubble created with <1600 laser pulses at 1.5 J/cm2 fluence. This implies that LIOB can be controlled to be thermally noninvasive in the bubble vicinity.

Acoustics↗

PubMed2006

Optical and acoustic detection of laser-generated microbubbles in single cells.

Acoustically monitored laser-induced optical breakdown (LIOB) has potential as an important tool to diagnose and treat living cells. Laser-induced intracellular microbubbles are readily detectable using high-frequency ultrasound, and LIOB can be controlled to operate within two distinct regimes. In the nondestructive regime, a single, short-lived bubble can be generated within a cell, without affecting its immediate viability. In the destructive regime, the induced photodisruption quickly can kill a targeted cell. To generate and monitor this range of bioeffects in real time, we have developed a system integrating an ultrafast laser source with optical and acoustic microscopy. Experiments were performed on monolayers of Chinese hamster ovary (CHO) cells. A 793 nm, 100 fs laser pulsed at 3.8 kHz was tightly focused within each cell to produce the photodisruption, and a 50 MHz ultrasonic transducer monitored the resultant bubble via continuous pulse-echo recordings. Photodisruption was also observed using bright field microscopy, and cell viability was assessed following laser exposure with a trypan blue assay. By controlling laser pulse fluence and exposure duration, either nondestructive or destructive LIOB could be produced. The intracellular position of the laser focus was also varied to demonstrate that cell viability was affected by the specific location of material breakdown.

Acoustics↗

PubMed2006

3-D ultrasound imaging using a forward-looking CMUT ring array for intravascular/intracardiac applications.

Forward-viewing ring arrays can enable new applications in intravascular and intracardiac ultrasound. This work presents compelling, full-synthetic, phased-array volumetric images from a forward-viewing capacitive micromachined ultrasonic transducer (CMUT) ring array wire bonded to a custom integrated circuit front end. The CMUT ring array has a diameter of 2 mm and 64 elements each 100 microm x 100 microm in size. In conventional mode, echo signals received from a plane reflector at 5 mm had 70% fractional bandwidth around a center frequency of 8.3 MHz. In collapse mode, 69% fractional bandwidth is measured around 19 MHz. Measured signal-to-noise ratio (SNR) of the echo averaged 16 times was 29 dB for conventional operation and 35 dB for collapse mode. B-scans were generated of a target consisting of steel wires 0.3 mm in diameter to determine resolution performance. The 6 dB axial and lateral resolutions for the B-scan of the wire target are 189 microm and 0.112 radians for 8 MHz, and 78 microm and 0.051 radians for 19 MHz. A reduced firing set suitable for real-time, intravascular applications was generated and shown to produce acceptable images. Rendered three-dimensional (3-D) images of a Palmaz-Schatz stent also are shown, demonstrating that the imaging quality is sufficient for practical applications.

Echocardiography↗

PubMed2006

Sonographic elasticity imaging of acute and chronic deep venous thrombosis in humans.

OBJECTIVE: The purpose of this study was to assess the ability of sonographic elasticity imaging to distinguish acute from chronic deep venous thrombosis (DVT). METHODS: Fifty-four patients, 26 with acute DVT and 28 with chronic DVT, were studied, and we analyzed the data in 46 patients, 23 with acute (mean age, 5.7 days) and 23 with chronic (>8 months) DVT. Scanning was performed with a 5-MHz linear array transducer during continuous freehand external deformation of each thrombus using the ultrasound scan head. The strains in the thrombi were normalized to the average strain between the skin surface and the back wall of the vein. Relative thrombus echogenicity was measured by comparing the echogenicity of the thrombus with that of the adjacent arterial lumen. Statistical analyses were performed with the Mann-Whitney U test and receiver operating characteristic analysis. RESULTS: The median normalized strain magnitude for the acute cases was 2.75, with an interquartile range of 2.4 to 3.71, whereas the median normalized strain magnitude for the chronic cases was 0.94, with interquartile range of 0.48 to 1.36. The difference was highly significant (P < 10(-7)). The area under the receiver operating characteristic curve (A(z)) was 0.97 +/- 0.02 (SE). The echogenicity difference between the populations was highly significant (P < 10(-5)), with A(z) of 0.92 +/- 0.04. The difference between the A(z) values was not significant (P > .05). CONCLUSIONS: In this population, sonographic elasticity imaging performs at least as well as thrombus echogenicity. Thrombus aging using elasticity imaging would be particularly helpful in evaluating symptoms in patients with post-thrombotic syndrome.

Acute Disease↗

PubMed2005

Correspondence of ultrasound elasticity imaging to direct mechanical measurement in aging DVT in rats.

Previous ultrasound elasticity imaging experiments supported a generally accepted concept that the hardness of deep venous thrombi increases with thrombus aging. Results also showed that this noninvasive imaging technique can accurately predict thrombus age through strain estimates, in a well-controlled animal study. In the present study, as an alternative means to characterize elastic properties of thrombi, we used a direct mechanical measurement system to estimate Young's modulus of ex vivo thrombi. Unlike conventional indentation tests, the device uses a specific compression geometry for cylindrical tissue specimens. We also proposed an approximation scheme to retrieve Young's modulus from force-displacement measurements made using the device. Finite element simulations and calibrations on tissue-mimicking phantoms validated the system. Then, using two groups of rats with surgically-induced thrombi, we further investigated the correlation between Young's modulus measured ex vivo and elasticity images reconstructed in vivo. This comparison was accomplished by converting the intrathrombus strains measured in the in vivo studies into Young's modulus estimates using a model-based approach. Good agreement between time-dependent Young's modulus estimates observed in vivo and direct measurements of Young's modulus using the mechanical device helps to confirm the ability of elasticity imaging to age deep venous thrombi for efficient treatment.

Aging↗

PubMed2005

Coded excitation for synthetic aperture ultrasound imaging.

Peak acoustic power limits the signal-to-noise ratio (SNR) of real-time ultrasound images. For most conventional scan formats, however, the average power is well below heating limits. This means the SNR can be significantly increased using coded excitation. A coded system transmits a broadband, temporally elongated excitation pulse with a finite time-bandwidth product. The received signal must be decoded to produce an imaging pulse with improved SNR resulting from the higher average power in the elongated excitation. Decoding can produce significant range side lobes, however, greatly reducing image quality. All practical coding designs, therefore, represent a trade-off between SNR gain and range side lobes. A specific coding scheme appropriate for synthetic aperture imaging is presented. A 14.5 dB SNR improvement with acceptable range side lobes is demonstrated on a forward-looking imaging system appropriate for intravascular applications.

Algorithms↗

PubMed2005

Identification of vulnerable atherosclerotic plaque using IVUS-based thermal strain imaging.

Pathology and autopsy studies have demonstrated that sudden disruption of vulnerable atherosclerotic plaque is responsible for most acute coronary syndromes. These plaques are characterized by a lipid-rich core with abundant inflammatory cells and a thin fibrous cap. Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has been proposed for high-risk arterial plaque detection, in which image contrast results from the temperature dependence of sound speed. It has the potential to distinguish a lipid-laden lesion from the arterial vascular wall due to its strong contrast between water-bearing and lipid-bearing tissue. Initial simulations indicate plaque identification is possible for a 1 degrees C temperature rise. A phantom experiment using an IVUS imaging array further supports the concept, and results agree reasonably well with prediction.

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

Bubble-based acoustic radiation force elasticity imaging.

Acoustic radiation force is applied to bubbles generated by laser-induced optical breakdown (LIOB) to study viscoelastic properties of the surrounding medium. In this investigation, femtosecond laser pulses are focused in the volume of gelatin phantoms of different concentrations to form bubbles. A two-element confocal ultrasonic transducer generates acoustic radiation force on individual bubbles while monitoring their displacement within a viscoelastic medium. Tone burst pushes of varying duration have been applied by the outer element at 1.5 MHz. The inner element receives pulse-echo recordings at 7.44 MHz before, during, and after the excitation bursts, and crosscorrelation processing is performed offline to monitor bubble position. Maximum bubble displacements are inversely related to the Young's moduli for different gel phantoms, with a maximum bubble displacement of over 200 microm in a gel phantom with a Young's modulus of 1.7 kPa. Bubble displacements scale with the applied acoustic radiation force and displacements can be normalized to correct for differences in bubble size. Exponential time constants for bubble displacement curves are independent of bubble radius and follow a decreasing trend with the Young's modulus of the surrounding medium. These results demonstrate the potential for bubble-based acoustic radiation force methods to measure tissue viscoelastic properties.

Computer Simulation↗

PubMed2005

Motion artifact reduction for IVUS-based thermal strain imaging.

Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has the potential to identify lipid pools within rupture-prone arterial plaques and serve as a valuable supplement to current IVUS systems in diagnosing acute coronary syndromes. The major challenge for in vivo application of TSI will be cardiac motion, including bulk motion and tissue deformation. Simulations based on an artery model, including a lipid-filled plaque, demonstrate that effective bulk motion compensation can be achieved within a certain motion range using spatial interpolation. We also propose a practical imaging scheme to minimize mechanical strains caused by tissue deformation based on a linear least squares fitting strategy. This scheme was tested on clinical data by artificially superimposing thermal displacements corresponding to different temperature rises. Results suggest a 1-2 degrees C temperature rise is required to detect lipids in an atherosclerotic plaque in vivo.

Arteries↗

PubMed2005

An integrated semicompliant balloon ultrasound catheter for quantitative feedback and image guidance during stent deployment.

An integrated balloon ultrasound catheter prototype was designed to image from inside the balloon for real-time guidance during stent deployment. It was fabricated using a semicompliant balloon material (polyethylene) and a 20 MHz, 64-element circumferential ultrasound array. A commercial stent, nominally 4.4 mm in diameter and 12 mm in length, was used for a phantom study and placed along the length of the integrated balloon ultrasound catheter. A rubber phantom was created with an elastic modulus of 175 kPa with a 4.36 mm diameter lumen. Real-time balloon pressure measurements were recorded using a digital pressure sensor, and real-time radio-frequency (RF) data were captured as the balloon was inflated. The slope of the area-pressure ratio (APR) was compared to a reference measure of the balloon and stent expanded in water to determine a measure for optimal stent deployment. The results clearly indicate stent deployment at 11.1 atm using this metric. The APR slope could serve as quantitative feedback parameter for guiding stent deployment to reduce arterial injury and subsequent restenosis. After the stent deployment experiment, RF data were captured as the balloon catheter was moved along the length of the stent in pullback mode to confirm successful stent deployment. Ultimately, an integrated balloon ultrasound catheter could serve as a single catheter intervention device by providing real-time intravascular ultrasound (IVUS) imaging and quantitative feedback during stent deployment.

Blood Vessel Prosthesis↗

PubMed2005

Quantitative real-time blood flow estimation with intravascular ultrasound in the presence of in-plane flow.

Previously, we showed a source of error in blood flow estimation introduced by in-plane flow using a slow-time finite-impulse response (FIR) filter-bank method measuring blood flow through the image plane of an intravascular ultrasound (IVUS) catheter array. There is a monotonic relationship between flow velocity and the normalized second moment of the slow-time spectrum when flow is orthogonal to the image plane of a side-looking catheter array. However, this relationship changes in the presence of in-plane flow, as slow-time spectra shift and spread with varying in-plane and out-of-plane components. These two effects increase the normalized spectral second moment, resulting in flow overestimates. However, by resampling the received signal with variable time delay from pulse to pulse (i.e., tilting the slow-time signals), the slow-time spectrum shifts back to direct current (DC), and the orthogonal estimation method can be used. We present a method to correct this overestimation and accurately estimate blood flow through the image plane in real time. Initially, the tilt delay needed to shift the slow-time spectrum back to DC at each point within the flow field is calculated. Knowing this tilt delay, a tilted slow-time signal is obtained for the velocity component normal to the image plane, and its spectrum is estimated using a filter-bank. That spectrum then is used to estimate the flow speed using a mapping function closely related to the monotonic relationship between the slow-time spectrum and flow speed observed for orthogonal flow. To accurately estimate flow angles, we modified the filter-bank algorithm, applying slow-time filter coefficients in a tilted arrangement and studying the slow-time spectral energy as a function of tilt. The slow-time spectral estimate is constructed with the tilted output of eight narrow, band-pass filters from a filter-bank. Independent simulations show that, for blood slowing at angles between +/-6 degrees and +/-15 degrees at a speed of 300 mm/s, flow velocity would be overestimated by as much as 38.79% and 249%, respectively, using the direct filter-bank approach. However, this error can be corrected using the modified method presented here, reducing the maximum overestimation error by a factor of 2.69 and 10.88 for those angles, respectively. Although the remaining error is not negligible, the volume flow rate, calculated by integrating the flow velocity over the entire vessel lumen, differs by only 3% or less from the true value over the angular range considered here. This represents an improvement of a factor of 40 over uncompensated estimates at maximum flow angles. Consequently, the modified real-time method can quantitatively measure flow in most IVUS applications in which the catheter's image plane is not precisely orthogonal to the flow direction.

Algorithms↗

PubMed2005

Acoustic detection of controlled laser-induced microbubble creation in gelatin.

A high-frequency (85 MHz) acoustic technique is used to identify system parameters for controlled laser-induced microbubble creation inside tissue-mimicking, gelatin phantoms. Microbubbles are generated at the focus of an ultrafast 793-nm laser source and simultaneously monitored through ultrasonic pulse-echo recordings. Displayed in wavefield form, these recordings illustrate microbubble creation, and integrated backscatter plots provide specifics about microbubble characteristics and dissolution behavior. By varying laser parameters, including pulse fluence (or pulse energy flux, J/cm2), total number of pulses delivered, and the period between pulses, the size, lifetime, and dissolution dynamics of laser-induced microbubbles may be independently controlled. Pulse fluence is the main size-controlling parameter, whereas both increases in pulse fluence and pulse number can lengthen microbubble lifetime from tens to hundreds of milliseconds. In short, a microbubble of particular lifetime does not necessarily have to be of a particular size. Microbubble behavior, furthermore, is independent of pulse periods below a fluence-dependent threshold value, but it exhibits stochastic behavior if pulse repetition is too slow. These results demonstrate that laser pulse fluence, number, and period may be varied to deposit energy in a specific temporal manner, creating and stabilizing microbubbles with particular characteristics and, therefore, potential uses in sensitive acoustic detection and manipulation schemes.

Acoustics↗

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↗

PubMed2004

Trapping cavitation bubbles with a self-focused laser beam.

We observed that laser-induced cavitation bubbles in water can be trapped in a self-focused laser beam. Both optical imaging and acoustic detection have been utilized to confirm bubble trapping. Transverse and longitudinal trapping forces were measured to be as large as 87 and 11 pN, respectively. This result is contrary to conventional wisdom, since the mechanism of trapping in conventional optical tweezers implies that a low-index particle (a bubble being the limiting case) should be antitrapped.

Equipment Design↗

PubMed2004

Staging deep venous thrombosis using ultrasound elasticity imaging: animal model.

Deep venous thrombi undergo progressive hardening with age. However, the evolution rate remains poorly characterized by both invasive and noninvasive techniques. In a previous study (Emelianov et al. 2002), we demonstrated the potential of ultrasound elasticity imaging to noninvasively detect and age thrombus using a rat-based model. Knowing that thrombi harden over time is useful, but the value of the technique relies on whether the age of a thrombus can be predicted from strain estimates, and how accurate these predictions are. The objective of the present study is to answer these two questions. In the previous study, thrombus elasticity changes were monitored only on day 3, 6 and 9 after surgically induced formation of thrombosis in rat inferior vena cavas. In this study, ultrasound elasticity imaging was performed on two independent groups of rats (16 in total) starting from day 3 through day 10 with more temporal samples through the thrombus maturation process. For each rat, thrombus hardness was quantified at each scan interval by measures of normalized strains and reconstructed relative Young's moduli. In both groups, strain magnitudes exhibit progressive decrease as clots age. The relationship between the normalized strain and the clot age was developed from the first group and evaluated by the second group. Statistical analysis showed that the age estimation accuracy is within 0.8 day. If further research can successfully transfer the animal clot-hardening model to human patients, we believe that elasticity imaging will become a key component of venous compression ultrasound for effective diagnosis and treatment of deep venous thrombosis.

Animals↗

PubMed2004

Measuring the nonlinear elastic properties of tissue-like phantoms.

A direct mechanical system simultaneously measuring external force and deformation of samples over a wide dynamic range is used to obtain force-displacement curves of tissue-like phantoms under plain strain deformation. These measurements, covering a wide deformation range, then are used to characterize the nonlinear elastic properties of the phantom materials. The model assumes incompressible media, in which several strain energy potentials are considered. Finite-element analysis is used to evaluate the performance of this material characterization procedure. The procedures developed allow calibration of nonlinear elastic phantoms for elasticity imaging experiments and finite-element simulations.

Adult↗