KEYWORDS: Photoacoustic spectroscopy, Signal processing, Radar, Signal to noise ratio, Intravascular ultrasound, Modulation, Tissues, Absorption, Interference (communication), Imaging systems
Lipid composition of atherosclerotic plaques is considered to be highly related to plaque vulnerability. Therefore, a specific diagnostic or imaging modality that can sensitively evaluate plaques’ necrotic core is desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection technique that provides lipid-specific chemical information from an arterial wall with great optical contrast and long acoustic penetration depth. While, in the near-infrared window, a 1210-nm optical source is usually chosen for IVPA applications since lipids exhibit a strong absorption peak at that wavelength, the sensitivity problem arises in the conventional single-ended systems as other arterial tissues also show some degree of absorption near that spectral region, thereby generating undesirably interfering photoacoustic (PA) signals. A theory of the high-frequency frequency-domain differential photoacoustic radar (DPAR) modality is introduced as a unique detection technique for accurate and molecularly specific evaluation of vulnerable plaques. By assuming two low-power continuous-wave optical sources at ∼1210 and ∼970 nm in a differential manner, DPAR theory and the corresponding simulation/experiment studies suggest an imaging modality that is only sensitive and specific to the spectroscopically defined imaging target, cholesterol.
Intraoperative characterization of blood flow and visualization of microvasculature can have a huge impact on surgical outcomes. Knowledge about vasculature can provide diagnostic leverage, reducing operating times and improving patient recovery. Currently used Doppler-based techniques suffer from various shortcomings such as poor spatial resolution, high susceptibility to motion artifacts, and the inability to detect longitudinal flows. Our aim is to develop a fast, non-invasive approach to intraoperative microvascular imaging of slow-moving blood. In this work, we present a spatio-temporal approach to detect blood flow in vessels on the order of 0.1 mm. Specifically, a speckle-variance flow processing algorithm is used to detect small changes in B-mode pixel intensity on a micro-ultrasound (μUS) system operating in the range of 22-70 MHz. Data used in this study was acquired intraoperatively for patients undergoing neurosurgical procedures. Microcirculation was clearly visible in various anatomical structures and the spatial resolution in flow detection was much superior in comparison to Doppler-based flow detection. Moreover, using infrared optical tracking (Northern Digital Inc., Waterloo, Canada), a three-dimensional reconstruction of the microvasculature was constructed. This 3D vessel map allows for better visualization of the vasculature in the surgical cavity – allowing surgeons to plan their incisions, minimizing blood loss and potentially improving patient outcomes. To our knowledge, this is the first implementation of a three-dimensional, intraoperative microcirculation imaging technique using statistical and optical methods, alongside a non-Doppler high frequency ultrasound.
Lipid composition of atherosclerotic plaques is considered to be one of the primary indicators of plaque vulnerability. Therefore, a specific diagnostic or imaging modality that can sensitively evaluate plaques’ necrotic core is highly desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection technique that provides lipid-specific chemical information from an arterial wall with great optical contrast and long acoustic penetration depth. Within the near-infrared window, a 1210-𝑛𝑚 optical source is usually chosen for IVPA applications as lipids exhibit a strong absorption peak at that wavelength due to the second overtone of the C-H bond vibration within the lipid molecules. However, other arterial tissues also show some degree of absorption near 1210 𝑛𝑚 and thus generate undesirably interfering PA signals. In this study, a theory of the novel Frequency-Domain Differential Photoacoustic Radar (DPAR) modality is introduced as an interference-free detection technique for accurate and reliable evaluation of vulnerable plaques. By assuming two low-power continuous-wave (CW) optical sources at ~ 1210 𝑛𝑚 and ~ 970 𝑛𝑚 in a differential manner, DPAR theory and the corresponding simulation study suggest a unique imaging modality that can efficiently suppress any undesirable absorptions and system noise, while dramatically improving PA sensitivity and specificity toward cholesterol contents of atherosclerotic plaques.
Epidural anesthesia is one of the most commonly used and yet challenging techniques employed for pain management and anesthesia delivery. The major complications of this procedure are due to accidental dural puncture, with an incidence of 1-3%, which could lead to both temporary and irreversible permanent neurological complications. Needle placement under ultrasound (US) guidance has received increasing interest for improving needle placement accuracy. However, poor needle visibility in US, difficulties in displaying relevant anatomical structure such as dura mater due to attenuation and bone shadowing, and image interpretation variability among users pose significant hurdles for any US guidance system. As a result, US guidance for epidural injections has not been widely adopted for everyday use for the performance of neuraxial blocks. The difficulties in localizing the ligamentum flavum and dura with respect to the needle tip can be addressed by integrating A-mode US, provided by a single-element transducer at the needle tip, into the B-mode US guidance system. We have taken the first steps towards providing such a guidance system. Our goal is to improve the safety of this procedure with minimal changes to the clinical workflow. This work presents the design and development of a 20 MHz single-element US transducer housed at the tip of a 19 G needle hypodermic tube, which can fit inside an epidural introducer needle. In addition, the results from initial transducer characterization tests and performance evaluation of the transducer in a euthanized porcine model are provided.
Acoustic Angiography is a new approach to high-resolution contrast enhanced ultrasound imaging enabled by ultra-broadband transducer designs. The high frequency imaging technique provides signal separation from tissue which does not produce significant harmonics in the same frequency range, as well as high resolution. This approach enables imaging of microvasculature in-vivo with high resolution and signal to noise, producing images that resemble x-ray angiography. Data shows that acoustic angiography can provide important information about the presence of disease based on vascular patterns, and may enable a new paradigm in medical imaging.
Cardiovascular related diseases are ranked as the second highest cause of death in Canada. Among the most important cardiovascular diseases is atherosclerosis. Current methods of diagnosis of atherosclerosis consist of angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT). None of these methods possesses adequate sensitivity, as the ideal technique should be capable of both depth profiling, as well as functional imaging. An alternative technique is photoacoustics (PA) which can perform deep imaging and spectroscopy. The presented study explores the application of wavelength-modulated differential photoacoustic radar (WM-DPAR) for characterizing arterial vessels. The wavelength-modulated differential photoacoustic technique was shown to be able to substantially increase the dynamic range and sensitivity of hemoglobin oxygenation level detection. In this work the differential PA technique was used with a very high frequency modulation range. To perform spectroscopic PA imaging, at least two wavelengths are required. The selected wavelengths for this work are 1210 nm and 980 nm. 1210 nm corresponds to the maximum optical absorption coefficient of cholesterol and cholesteryl esters which are the main constituents of plaques. Since water, elastin and collagen also have high absorption coefficients at 1210 nm, this wavelength alone cannot provide very high sensitivity and specificity. The additional wavelength, 980 nm corresponds to high absorption coefficient of those constituents of healthy artery tissue. The simultaneous application of the abovementioned wavelengths can provide higher sensitivity and improved specificity in detecting lipids in the arterial vessels.
Accurate endoscopic detection and dysplasia in patients with Barrett’s esophagus (BE) remains a major unmet clinical need. Current diagnosis use multiple biopsies under endoscopic image guidance, where up to 99% of the tissue remains unsampled, leading to significant risk of missing dysplasia. We conducted an ex vivo clinical trial using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) with known high-grade dysplasia for the purpose of characterizing the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. EMR tissues were mounted immediately on an agar layer and covered with ultrasound gel. Digital photography guided the placement of the PAI transducer (40 MHz center frequency). The luminal side of the specimen was scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, 824, 850 and 970 nm. Acoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with H and E staining. Analysis consisted of co-registration and correlation between the intrinsic PAI features and the histological images. The initial PAI + ultrasound images from 8 BE patients have demonstrated the technical feasibility of this approach and point to the potential of PAI to reveal the microvascular pattern within EMR specimens. There are several technical factors to be considered in rigorous interpretation of the PAI characteristics, including the loss of blood from the ex vivo specimens and the limited depth penetration of the photoacoustic signal.
In 2012 approximately 800,000 spinal fusion surgeries were performed in the United States, requiring the insertion of screws into the pedicles. Their exact placement is critical and made complex due to limited visibility of the spine, continuous bleeding in the exposed regions, and variability in morphologies. The alarmingly high rate of screw misplacements (up to 20%) reported in the literature is of major concern since such misplacements can place the surrounding vital structures at risk. A potential guidance method for determining the best screw trajectory is by the use of real-time ultrasound imaging similar to that used for intravascular imaging. An endovascular transducer could be inserted into the pedicle to image the anatomy from within and identify bone boundaries. A major challenge of imaging within bone is high signal attenuation. The rapid increase of attenuation with frequency requires much lower frequencies (1-3 MHz) than those used in intravascular imaging. This study describes the custom design and fabrication of 2 MHz ultrasound probes (3.5 mm diameter/ 11 Fr) for pedicle screw guidance. Three transducer designs are explored to provide improved sensitivity and signal to noise ratio, compared to the previously tested transducer within the pedicle. Experimental measurements are compared with the results obtained using various simulation tools. The work reported in this paper represents the first stage in our ultimate goal of developing a 32- element phased array that is capable of generating a radial B-mode image.
Photoacoustic (PA) Imaging can estimate the spatial distribution of oxygen saturation (sO2) and total hemoglobin
concentration (HbT) in blood, and be co-registered with B-Mode ultrasound images of the surrounding anatomy. This
study will focus on the development of a PA imaging mode on a commercially available array based micro-ultrasound
(μUS) system that is capable of creating such images. The system will then be validated in vivo against a complementary
technique for measuring partial pressure of oxygen in blood (pO2). The pO2 estimates are converted to sO2 values based
on a standard dissociation curve found in the literature. Finally, the system will be used for assessing oxygenation in a
murine model of ischemia, both during injury and recovery.
Conventional photoacoustic imaging systems excite a photoacoustic wave by illuminating an area on the order of square
centimeters with millijoule laser pulses. Spatial resolution is then determined by the ultrasound transducer and is
typically on the order of 100 μm. We report on a system that focuses femtosecond, nanojoule pulses to a spot with a
diameter of ~ 1 μm to perform laser-scanning photoacoustics with micrometer resolution.
Near-infrared femtosecond laser pulses with a pulse energy of 2.4 nanojoules excite a train of photoacoustic waves at the
repetition rate of the pulsed laser (80 MHz). These photoacoustic waves are detected by an unfocused single-element
ultrasound transducer tuned to 80 MHz. A radiofrequency lock-in amplifier recovers the amplitude of the frequency
component of the photoacoustic signal at the pulse repetition frequency. This amplitude is an indicator of the absorption
coefficient of the sample at the laser focus and at the laser wavelength.
Initial experiments using a graphite rod as absorber reproducibly yield signals in the 0.2 - 2 microvolt range with a
signal-to-noise ratio of 18 dB, recovered from 10 mV of broadband noise.
The photoacoustic imaging system is integrated in a commercial
laser-scanning two-photon fluorescence microscope,
enabling simultaneous three-dimensional fluorescence- and photoacoustic imaging. One major application will be to
image both morphology and oxygen saturation of microvasculature in the cerebral cortex of anesthetized rodents in vivo
in the context of tumor angiogenesis.
In this paper we describe the physics of femtosecond photoacoustics and demonstrate initial results.
Non-invasive ultrasound elastography (NIVE) was recently introduced to characterize mechanical properties of superficial arteries. In this paper, the feasibility of NIVE for the purpose of studying small vessels in humans and small animals is investigated. The experiments were performed in vitro on vessel-mimicking phantoms of 1.5-mm lumen diameter and 1.5-mm wall thickness. Polyvinyl alcohol cryogel (PVA-C) was used to create double layer vessel walls. The stiffness of the interior portion of the vessels was made softer. The vessels were insonified at 32 MHz with an ultrasound biomicroscope. Radial stress was applied within the lumen of the phantom by applying incremental static pressure steps with a column of a flowing mixture of water-glycerol. The Lagrangian speckle tissue model estimator was used to assess the 2D-strain tensor, and the composite Von Mises elastograms were then computed. The two-layer vessel walls were clearly identifiable. Strain values close to 3% were measured for the interior portion, whereas strains around 1% were noted for the stiffer outside layer. In conclusion, the feasibility of NIVE for small vessel elasticity imaging was demonstrated in vitro.
One technique of elasticity imaging, elastography, uses cross- correlation between two ultrasound A-lines to obtain an axial strain image of a sample. Usually, great care is taken with respect to the assumption that the response of the sample is elastic (lossless). In this paper, we relax this assumption and extend elastography to estimate the time-varying displacement and strain status of small samples (of the order of 1 mm). Results are presented for gel phantoms and articular cartilage samples, and they are consistent with the current theories of poroelastic materials. For example, an effective Poisson's ratio of approximately 0.5 obtained at ramp completion indicates volume conservation since the ramp time was much shorter than the characteristic relaxation time of the material. Subsequent reduction in effective Poisson's ratio coincident with stress-relaxation confirms poroelastic mechanisms whereby fluid exudation dissipates internal fluid pressurization. Observed slower relaxation of strain at the center of the sample is also compatible with these types of models. Preliminary data obtained with articular cartilage also shows valuable potential of this technique to investigate tissue biomechanics.
Ceramic ultrasonic transducers with a frequency response <50MHz using lead zirconate titanate (PZT) layers in the 5-4Otm range have been difficult to achieve by bulk or thin film techniques. Advances in the production of small sized PZT ceramic powder allow the development ofthinner ceramic layers for this application. Sol gel composite thin film technology also provides a new technique for producing ceramic coatings of a thickness that successfully bridges the gap between traditional thin film and bulk techniques. So! gel composite PZT layers of 5-7Om have been coated on substrates (aluminum, platinized silicon, stainless steel, .. .) that can withstand the thermal processing of the ceramic. The thickness mode response of a thin piezoelectric layer supported by a thick substrate has been modeled from first principles using complex material constants. The LevenbergMarquart non linear regression technique has been used to extract the thickness mode elastic stiffness, dielectric constant and piezoelectric constant of the PZT, and the elastic stiffness of the substrate from the layered structure. This non-destructive technique allows for a reliable assessment of the quality of a coating prior to the fabrication of a transducer. The elastic stiffness of the substrate is not lossy enough for the required broadband response of an imaging transducer. However, aluminum can be preferentially etched, releasing the ceramic coating. Therefore it is possible to transfer the PZT film to a more suitable backing material. A processing sequence for single element PZT transducers in the frequency range of 50-200MHz has been developed. Characterization of transducers has been performed using pulse-echo techniques and by creating real time B-scan images of agar phantoms and biological tissue. Methods for patterning the PZT composite coatings are being developed with the intent to fabricate a linear array in the 40-60 MHz frequency range. Due to the very fine patterning and high concentration of cuts required for a high aspect ratio linear array, the limits of conventional etching techniques are surpassed. Laser micromachining using a frequency doubled Nd:YAG and a KrF excimer laser have the ability to pattern the array structure. In both cases, laser cuts <1Om wide have been achieved.
Two-dimensional (2-D) transducer arrays offer the potential for improving medical ultrasound imaging by producing symmetrically focused ultrasound beams which can be steered throughout a three-dimensional volume. Theoretical investigations of the beamforming properties of 2-D arrays have characterized the array parameters required to steer the beam up to 45 degree(s) off-axis. These investigations have also shown that the number of elements in a steered 2-D array can be dramatically reduced using a sparse set of elements, randomly distributed throughout the transducer aperture. The penalty paid for the use of a sparse array is the development of a `pedestal' sidelobe in the beam profile, the amplitude of which increases as the number of elements in the array decreases. The potential of 2-D arrays for medical imaging has been assessed by simulating images of spherical lesions embedded in a random scattering medium. Similar contrast characteristics over a range of cyst sizes are demonstrated for a dense 2-D array and a sparse array with 1/8th the number of elements, both operating at 5 MHz. A 32nd order sparse array was found to perform at a reduced level, producing unacceptable artifactual echoes within images of cysts. Experimental results are described which verify some of the theoretical predictions.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.