In the current form of multi-parametric photoacoustic microscopy (PAM), imaging hemoglobin concentration and blood flow speed requires dense sampling. Moreover, large-scale recording beyond the focal zone of ultrasonic transducer requires time-consuming mechanical scan of the optical-acoustic dual foci. Thus, the image acquisition time of multi-parametric PAM has been severely limited by the laser repetition rate and the focal diameter of the transducer.
Here, we report an ultrahigh-speed multi-parametric PAM with 1.2-MHz A-line rate for simultaneous real-time imaging of hemoglobin concentration, blood oxygenation, and blood flow in the mouse brain. Capitalizing on the pronounced stimulated Raman scattering in pure silica-core polarization-maintaining single-mode optical fibers, a dual-wavelength (532 and 558 nm) nanosecond laser with 1.2-MHz pulse repetition rate has been developed. Using a weakly focused ultrasonic transducer, we have achieved real-time acquisition of multi-parametric PAM images at a frame rate of 2.2 Hz over the 250-μm-diameter acoustic focal zone. By employing optical-mechanical hybrid scan, 25 dual-wavelength B-scans can be acquired simultaneously within one mechanical-scan trip, leading to a 25-fold improvement of imaging
speed. As a result, the imaging frame rate is improved from 0.08 Hz in the conventional multi-parametric PAM to 2.2 Hz.
The utility of this new PAM technology has been demonstrated in a mouse model of epilepsy by studying the dynamic neurovascular uncoupling during status epilepticus.
Current methods for delivery of an anti-restenosis drug to an arterial vessel wall post-percutaneous transluminal
angioplasty and stent placement are limited in terms of drug choice, dosing level, and ability to assure drug coverage
between the struts of a drug eluting stent. Intravascular ultrasound (IVUS) provides real-time, radiation-free, imaging
and assessment of atherosclerotic disease in terms of anatomical, functional and molecular information. In this
presentation, the design of a dual imaging / therapy IVUS catheter is described and results documenting gene and
drug delivery reported. Microbubbles and drug / gene (shell associated or co-injected) are dispensed from the catheter
tip. Using this approach, it becomes possible to address the need for complete vessel wall coverage and achieve
delivery in regions poorly addressed using conventional stent-based approaches. A range of in vitro, ex vivo and in
vivo results are presented. Our most recent results involve a demonstration in a pig model of coronary balloon angioplasty
that produced a 33% reduction in neointima formation versus a drug plus microbubble, but no ultrasound,
control.
Intravascular near-infrared fluorescence (NIRF) imaging offers a new approach for characterizing atherosclerotic plaque, but random catheter positioning within the vessel lumen results in variable light attenuation and can yield inaccurate measurements. We hypothesized that NIRF measurements could be corrected for variable light attenuation through blood by tracking the location of the NIRF catheter with intravascular ultrasound (IVUS). In this study, a combined NIRF-IVUS catheter was designed to acquire coregistered NIRF and IVUS data, an automated image processing algorithm was developed to measure catheter-to-vessel wall distances, and depth-dependent attenuation of the fluorescent signal was corrected by an analytical light propagation model. Performance of the catheter sensing distance correction method was evaluated in coronary artery phantoms and ex vivo arteries. The correction method produced NIRF estimates of fluorophore concentrations, in coronary artery phantoms, with an average root mean square error of 17.5%. In addition, the correction method resulted in a statistically significant improvement in correlation between spatially resolved NIRF measurements and known fluorophore spatial distributions in ex vivo arteries (from r=0.24 to 0.69, p<0.01 , n=6 ). This work demonstrates that catheter-to-vessel wall distances, measured from IVUS images, can be employed to compensate for inaccuracies caused by variable intravascular NIRF sensing distances.
Intravascular near-infrared fluorescence (NIRF) imaging is a new approach for characterizing the physiological features
of atherosclerotic plaque, but random catheter positioning within the vessel results in non-quantitative measurements due to light attenuation through variable distances through blood. We hypothesized that the construction of a combined NIRF-intravascular ultrasound (IVUS) catheter would enable tracking of the catheter position within the blood vessel and permit corrections to NIRF measurements taken at variable distances from the vessel wall. In this study, a combined NIRF-IVUS catheter was designed, co-registered NIRF and IVUS data was acquired in vessel phantoms and ex vivo arteries, depth-dependent attenuation of the fluorescent signal was corrected by an analytical light propagation model. Average root-mean-square error between NIRF estimates of fluorophore concentrations and known concentrations of fluorescent targets in coronary artery phantoms improved from 94.9% to 16.2% following NIRF corrections. We demonstrate that catheter-to-vessel wall distances derived from IVUS imaging can be employed to correct for inaccuracies caused by random NIRF catheter sensing distances.
KEYWORDS: Data modeling, In vivo imaging, Heart, 3D modeling, Image segmentation, 3D image processing, Cardiac imaging, Image processing, Transducers, Computer simulations
Active contours have been used in a wide variety of image processing applications due to their ability to effectively distinguish image boundaries with limited user input. In this paper, we consider 3D gradient vector field (GVF) active surfaces and their application in the determination of the volume of the mouse heart left ventricle. The accuracy and efficacy of a 3D active surface is strongly dependent upon the selection of several parameters, corresponding to the tension and rigidity of the active surface and the weight of the GVF. However, selection of these parameters is often subjective and iterative. We observe that the volume of the cardiac muscle is, to a good approximation, conserved through the cardiac cycle. Therefore, we propose using the degree of conservation of heart muscle volume as a metric for assessing optimality of a particular set of active surface parameters. A synthetic dataset consisting of nested ellipsoids of known volume was constructed. The outer ellipsoid contracted over time to imitate a heart cycle, and the inner ellipsoid compensated to maintain constant volume. The segmentation algorithm was also investigated in vivo using B-mode data sets obtained by scanning the hearts of three separate mice. Active surfaces were initialized using a broad range of values for each of the parameters under consideration. Conservation of volume was a useful predictor of the efficacy of the model for the range of values tested for the GVF weighting parameter, though it was less effective at predicting the efficacy of the active surface tension and rigidity parameters.
Preliminary results relating to the design, fabrication, and characterization of a 3600 (60 x 60) element, fully sampled, 5 MHz two dimensional (2D) array are presented. The viable element yield of the new array was estimated at 98.3%. Single-element pulse-echo experiments indicate that the center frequency is 4.7 MHz - 7.8% below the resonant frequency determined by Finite Element Analysis (FEA) simulation. Pulse-echo signal fractional bandwidth was measured to be 60.3% at the -6 dB level. Ringdown was longer than anticipated in experimental pulse echo voltage waveforms, which we attribute in part to a lack of matching layer and a low-loss backing material. Based on plane-wave pulse-echo experiments in a water-tank, single element signal-to-noise ratio (SNR) was calculated to be 6.0 when using a plane-wave transmit (all elements excited). Experimental angular beam patterns were more directional than predicted with the standard soft-baffle equation, but in good agreement with FEA simulations that take account of finite acoustic crosstalk.
KEYWORDS: Digital signal processing, Ultrasonography, Transducers, Prototyping, Analog electronics, LCDs, Signal processing, Phased arrays, System integration, Signal to noise ratio
Medical Ultrasound Imaging is widely used clinically because of its relatively low cost, portability, lack of
ionizing radiation, and real-time nature. However, even with these advantages ultrasound has failed to
permeate the broad array of clinical applications where its use could be of value. A prime example of this untapped potential is the routine use of ultrasound to guide intravenous access. In this particular application existing systems lack the required portability, low cost, and ease-of-use required for widespread acceptance.
Our team has been working for a number of years to develop an extremely low-cost, pocket-sized, and
intuitive ultrasound imaging system that we refer to as the "Sonic Window." We have previously described
the first generation Sonic Window prototype that was a bench-top device using a 1024 element, fully
populated array operating at a center frequency of 3.3 MHz. Through a high degree of custom front-end
integration combined with multiplexing down to a 2 channel PC based digitizer this system acquired a full
set of RF data over a course of 512 transmit events. While initial results were encouraging, this system
exhibited limitations resulting from low SNR, relatively coarse array sampling, and relatively slow data acquisition.
We have recently begun assembling a second-generation Sonic Window system. This system uses a 3600 element fully sampled array operating at 5.0 MHz with a 300 micron element pitch. This system extends the
integration of the first generation system to include front-end protection, pre-amplification, a programmable
bandpass filter, four sample and holds, and four A/D converters for all 3600 channels in a set of custom
integrated circuits with a combined area smaller than the 1.8 x 1.8 cm footprint of the transducer array. We
present initial results from this front-end and present benchmark results from a software beamformer
implemented on the Analog Devices BF-561 DSP. We discuss our immediate plans for further integration
and testing. This second prototype represents a major reduction in size and forms the foundation of a fully
functional, fully integrated, pocket sized prototype.
This work reports on the application of ultrasound elastography to prostate cancer detection using a high resolution three-dimensional (3D) ultrasound imaging system. The imaging was performed at a relatively high frequency (14 MHz), yielding very fine resolution that is optimal for prostate ultrasound imaging. The fine resolution achieved aids in locating smaller lesions than are normally detectable. Elasticity was measured with a quantitative and automatically controlled "Synthetic Digital Rectal Examination (SDRE)" wherein a smoothly increasing force was applied by injecting water, controlled by an electronic syringe pump, into a latex cover over the transrectal transducer. The lesion identified as stiffened tissue was visually enhanced by colorizing and superimposing it over the conventional B-mode image. Experimental results using a tissue-mimicking phantom demonstrated that the reconstruction accuracy of the I-Beam transducer resulted in less than 15% volumetric error. Thus, this high resolution 3D prostate elastography is possible and may provide reliable and accurate determination of the size and the location of cancers, which may result in improved specificity and sensitivity of cancer detection.
A method is described for repeatably assessing elasticity and 3D extent of suspected prostate cancers. Elasticity is measured by controlled water inflation of a sheath placed over a modified transrectal ultrasound transducer. The benefit of using fluid inflation is that it should be possible to make repeatable, accurate, measurements of elasticity that are of interest in the serial assessment of prostate cancer progression or remission. The second aspect of the work uses auxiliary tracking arrays placed at each end of the central imaging array that allow the transducer to be rotated while simultaneously collected 'tracking' information thus allowing the position of successive image planes to be located with approximately 11% volumetric accuracy in 3D space. In this way, we present a technique for quantifying volumetric extent of suspected cancer in addition to making measures of elastic anomalies.
An intact mouse model of surgically-induced myocardial infarction (MI) caused by permanent occlusion of the Left Anterior Descending (LAD) coronary artery was studied. Normal mice with no occlusion were also studied as controls. For each mouse, contrast enhanced ultrasound images of the heart were acquired in parallel cross-sections perpendicular to the sternum at millimeter increments. For accurate 3D reconstruction, ECG gating and a tri-axial adjustable micromanipulator were used for temporal and spatial registration. Ultrasound images at steady-state of blood refilling were color-coded in each slice to show relative perfusion. Myocardial perfusion defects and necrosis were also examined postmortem by staining with Phthalo blue and TTC red dyes. Good correlation (R>0.93) in perfused area size was observed between in vivo measurements and histological staining. A 3D multi-slice model and a 3D rendering of perfusion distribution were created and showed a promising match with postmortem results, lending further credence to its use as a more comprehensive and more reliable tool for in vivo assessment of myocardial perfusion than 2D tomographic analysis.
Noninvasive approaches for measuring anatomical and physiological changes resulting from myocardial ischemia / reperfusion injury in the mouse heart have significant value since the mouse provides a practical, low-cost model for modeling human heart disease. In this work, perfusion was assessed before, during and after an induced closed- chest, coronary ischemic event. Ultrasound contrast agent, similar to MP1950, in a saline suspension, was injected via cannulated carotid artery as a bolus and imaged using a Siemens Sequoia 512 scanner and a 15L8 intraoperative transducer operating in second harmonic imaging mode. Image sequences were transferred from the scanner to a PC for analysis. Regions of interest were defined in septal and anterior segments of the myocardium. During the ischemic event, when perfusion was diminished in the anterior segment, mean video intensity in the affected segment was reduced by one half. Furthermore, following reperfusion, hyperemia (enhanced blood flow) was observed in the anterior segment. Specifically, the mean video intensity in the affected segment was increased by approximately 50% over the original baseline level prior to ischemia. Following the approach of Kaul et al., [1], gamma variate curves were fitted to the time varying level of mean video intensity. This foundation suggests the possibility of quantifying myocardial blood flow in ischemic regions of a mouse heart using automated analysis of contrast image data sets. An improved approach to perfusion assessment using the destruction-reperfusion approach [2] is also presented.
KEYWORDS: Phased arrays, Ultrasonography, Digital signal processing, Data centers, Transducers, Apodization, Linear filtering, Image quality, Prototyping, Optical simulations
We describe a very low cost handheld ultrasound system that we are currently developing for routine applications such as image guided needle insertion. We provide a system overview and focus discussion on our beamforming strategy, direct sampled I/Q (DSIQ) beamforming. DSIQ beamforming is a low cost approach that relies on phase rotation of in-phase/quadrature (I/Q) data to implement focusing. The I/Q data are generated by directly sampling the received radio frequency (RF) signal, rather than through conventional baseband demodulation. We describe our efficient hardware implementation of the beamformer, which results in significant reductions in beamformer size and cost. We also present the results of experiments and simulations that compare the DSIQ beamformer to more conventional approaches, namely time delay beamforming and traditional complex demodulated I/Q beamforming. Results that show the effect of an error in the direct sampling process, as well as dependence on signal bandwidth and system f number (f#) are presented. These results indicate that the image quality and robustness of the DSIQ beamformer are adequate for routine applications.
Using a scanned laser to generate ultrasound, via the thermoelastic effect, offers an alternative approach for realizing high density, high frequency ultrasound imaging arrays. The approach bypasses the complexity and intricacy required for forming conventional piezoelectric array elements and their associated electrical connections. Thus, it is particularly well suited to 2D arrays. In this paper, the devices considered comprise a carbon black loaded PDMS polymer layer on top of a glass or PDMS substrate. PZFlex Finite Element Analysis (FEA) was used to investigate the impact of a variety of design variables including: laser spot size, substrate material and thermoelastic coupling medium. Predicted single element angular response broadly matched responses obtained by experiment. Specifically, if a low acoustic loss glass substrate is used then measurable sidelobes occur at approximately 40 degrees. However, if the glass substrate is replaced by a PDMS material, then the traveling waves that give rise to sidelobes are no longer supported and a smooth single element angular response is obtained in both experiment and FEA simulation. FEA suggests that there are other modes in addition to the Rayleigh mode observed in the experiment. It is believed that these modes are more quickly damped in the experimental case. Therefore, while FEA provides a very versatile and valuable analysis tool, the accuracy of its predictions are contingent on accurate knowledge of device geometry and relevant material properties.
An approach for acquiring 3D data using a modified transducer array was previously described. This array employs one “Imaging” array and two “Tracking” arrays placed perpendicular to the Imaging array. Any component of diagonal motion due to imperfect elevational scanning has the potential to cause dimensional error in the 3D reconstruction. In this paper, diagonal motion is determined by examining the ratio of cross-correlation values, between successive image frames, from both the Imaging array data sets and the Tracking array data sets. The elevational translation is computed using a speckle tracking method on the Tracking array data if there is more elevational motion than azimuthal motion. Similarly, the speckle tracking is performed on the Imaging array data if there is more azimuthal motion. The angle of motion and the translational component derived from one of the two orientations of arrays allows computation of the component of translation in the other direction. MATLAB simulations and experimental result illustrate that the error in speckle tracking was dependent on the angle of the diagonal motion, and that there were distinct rates of decorrelation from each array for different diagonal motions.
Conventional ultrasound Doppler velocity measurements are scaled by the cosine of the angle between the blood flow axis and ultrasound beam axis. In the approach used here, a transducer array was used to acquire a first cross-sectional Doppler data set of the vessel under examination. The transducer array was then moved to a different angle to acquire a second cross-sectional Doppler data set. Thereafter, we used the known angle between the two arrays ultrasound beams and the cosine (theta) scaled Doppler estimates to solve for the true angle between the blood flow axis and ultrasound beam axis of the first data set. Upon integrating the angle corrected velocity estimates over the entire vessel cross-section, we were able to estimate blood volume flow rate. The performance of the new approach was tested in a flow phantom that was designed to provide a constant flow in a simulated vessel. The data were collected for two sets of angles and three different flow velocities for each angle set. The unknown Doppler angle was calculated from the data and used to correct the flow velocity.
An approach for acquiring dimensionally accurate 3D ultrasound data, based on a modified 1D transducer array, is presented. Th method avoids many of the drawbacks of conventional approaches to 3D ultrasound data acquisition. Scanning is simple and easy to perform in a clinical setting. A modified 1D transducer array is employed comprising a central conventional 1D imaging array and two perpendicular tracking arrays - each integrally mounted at each end of the imaging array. As the transducer is scanned in the elevation direction of the central array, the images acquired by the tracking array remain coplanar and hence it is possible to accurately track image motion using any one of several image tracking techniques. Methods for improving the performance and ergonomics of the transducer array are presented. In particular, a crossed electrode transducer structure is proposed for minimizing the total transducer footprint (contact surface area). The versatility of the approach in terms of its suitability for scanning breast, carotid and prostate is discussed. We have acquired both phantom and in-vivo 3D ultrasound data with the prototype imaging approach. Initial studies suggest that the linear dimensional accuracy in the elevation direction (i.e., the reconstructed direction) is approximately 5%.
Medical ultrasound research is typically performed using either video image data, or summed Radio Frequency (RF) data. While such data has led to improved understanding of ultrasound image formation, and in the development of novel image formation and signal processing algorithms, it contains only a fraction of the information available in the individual beamformer channels before summation. This paper describes the development of an advanced experimental system which will simultaneously acquire RF data from 128 individual beamformer channels. We refer to such data, acquired across the transducer face, as aperture domain data. The system will be capable of continuous acquisition over a period of 1.6 seconds, the equivalent of 50 image frames. The system will also incorporate a data interface to allow future connection to custom processing units, ultimately enabling real-time processing of aperture domain data. The system will be constructed around a state of the art Agilent Technologies SONOS 5500 ultrasonic imaging system to enable real-time imaging and preserve broad signal bandwidth, high signal to noise ratio, and high dynamic range. The proposed system will facilitate research on adaptive imaging, system architecture, multidimensional blood flow estimation, broadband transducers, and a number of other areas.
Diagnostic medical ultrasound systems generally use only a portion of the available bandwidth of modern transducer arrays. A new method is presented that makes optimal use of all available bandwidth. This method achieves improved lateral resolution with no loss of frame rate. The performance of the method in the presence of tissue related phase aberration and attenuation is considered. The key elements of the additional electronic hardware required to support this technique are discussed. The extension of the method to use with 1.5D arrays and annular arrays is also discussed.
The performance of a transducer possessing several piezoelectric layers is discussed. Techniques are presented for determining excitation functions so that a pre-defined transmission characteristic is obtained in an optimal manner. The performance of a multiple layer transducer in the reception mode is considered in detail. It is evident that a high degree of transmission and reception efficiency is attainable continuously from below the fundamental thickness mode resonance to above its third harmonic. This contrasts with conventional designs which possess a null at the second harmonic. Issues regarding the stability of the technique are addressed.
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