KEYWORDS: Oxygen, Photoacoustic spectroscopy, Echocardiography, In vivo imaging, Arteries, Acoustics, Lithium, Picture Archiving and Communication System, Oximetry
Mixed venous oxygen saturation (SvO2), measured from pulmonary arteries, is a gold-standard measure of the dynamic balance between the oxygen supply and demand in the body. In critical care, continuous monitoring of SvO2 plays a vital role in early detection of circulatory shock and guiding goal-oriented resuscitation. In current clinical practice, SvO2 is measured by invasive pulmonary artery catheters (PAC), which are associated with a 10% risk of severe complications. To address the unmet clinical need for a non-invasive SvO2 monitor, we are developing a new technology termed photoacoustic transesophageal echocardiography (PA-TEE). PA-TEE integrates transesophageal echocardiography with photoacoustic oximetry, and enables continuous assessment of SvO2 through an esophageal probe that can be inserted into the body in a minimally invasive manner.
We have constructed a clinically translatable PA-TEE prototype, which features a mobile OPO laser, a modified ultrasonography console and a dual-modality esophageal probe. Comprised of a rotatable acoustic array detector, a flexible optical fiber bundle and a light-integrating acoustic lens, the oximetric probe has an outer diameter smaller than 15 mm and will be tolerable for most patients. Through custom-made C++/Qt software, our device acquires and displays ultrasonic and photoacoustic images in real time to guide the deployment of the probe. SvO2 is calculated on-line and updated every second. PA-TEE has now been used to evaluate SvO2 in living swine. Our findings show that changing the fraction of oxygen in the inspired gas modulates SvO2 measured by PA-TEE. Statistic comparison between SvO2 measurements from PA-TEE in vivo the gold-standard laboratorial analysis on blood samples drawn from PACs will be presented.
It is a challenge to non-invasively visualize in vivo the neovascularization in a three-dimensional (3D) scaffold with high
spatial resolution and deep penetration depth. Here we used photoacoustic microscopy (PAM) to chronically monitor
neovascularization in an inverse opal scaffold implanted in a mouse model for up to six weeks. The neovasculature was
observed to develop gradually in the same mouse. These blood vessels not only grew on top of the implanted scaffold
but also penetrated into the scaffold. The PAM system offered a lateral resolution of ~45 μm and a penetration depth of ~3 mm into the scaffold/tissue construct. By using the 3D PAM data, we further quantified the vessel area as a function
of time.
Photoacoustic microscopy (PAM) offers label-free, optical absorption contrast. A high-speed,
high-resolution PAM system in an inverted microscope configuration with a laser pulse repetition
rate of 100,000 Hz and a stationary ultrasonic transducer was built. Four-dimensional in vivo
imaging of microcirculation in mouse skin was achieved at 18 three-dimensional volumes per
second with repeated two-dimensional raster scans of 100 by 50 points. The corresponding twodimensional
B-scan (50 A-lines) frame rate was 1800 Hz, and the one-dimensional A-scan rate
was 90,000 Hz. The lateral resolution is 0.23±0.03 μm for Au nano-wire imaging, which is 2.0
times below the diffraction limit.
KEYWORDS: Photoacoustic spectroscopy, Acoustics, Signal detection, In vivo imaging, Imaging systems, Carbon, Ultrasonography, Image processing, Signal to noise ratio, Photoacoustic microscopy
Photoacoustic tomography detecting ultrasound signals generated from photon absorption provides optical absorption
contrast in vivo for structural, functional and molecular imaging. Although photoacoustic tomography technology has
grown fast in recent years, real-time photoacoustic imaging with cellular spatial resolution are still strongly demanded.
We developed a photoacoustic microscopy which has video-rate imaging capability with cellular spatial resolution. The
system consists of a single-element focused ultrasound transducer, a fiber-based light-delivery subsystem, a voice-coil
translation stage, a motion controller, and a data acquisition subsystem. A compact cube is employed to split optical and
acoustic beams. The mass of the entire scanning photoacoustic probe is less than 40 grams, which minimizes potential
vibrations and inertial effects, therefore, makes it capable to scan fast. The imaging system is capable of acquiring 20
cross-sectional (B-scan) images per second over 9 mm, and up to 40 B-scan images per second over 1 mm. Focused
laser beams provide a lateral resolution of five microns. Confocal deployment of optical and acoustic focuses provides
higher SNR than optical scanning approach. Micron-sized carbon particles flowing in silicone tubing and in vivo blood
flows were imaged in video-rate, which demonstrated the capability to image highly dynamic biological processes in
vivo with cellular resolution. This real-time high-resolution photoacoustic imaging system provides a promising
approach for various in vivo imaging and quantitative studies.
Photoacoustic microscopy (PAM) utilizes short laser pulses to deposit energy into light
absorbers and sensitively detects the ultrasonic waves the absorbers generate in response.
PAM directly renders a three-dimensional spatial distribution of sub-surface optical absorbers.
Unlike other optical imaging technologies, PAM features label-free optical absorption contrast
and excellent imaging depths. Standard dental imaging instruments are limited to X-ray and
CCD cameras. Subsurface optical dental imaging is difficult due to the highly-scattering enamel
and dentin tissue. Thus, very few imaging methods can detect dental decay or diagnose dental
pulp, which is the innermost part of the tooth, containing the nerves, blood vessels, and other
cells. Here, we conducted a feasibility study on imaging dental decay and dental pulp with PAM.
Our results showed that PAM is sensitive to the color change associated with dental decay.
Although the relative PA signal distribution may be affected by surface contours and subsurface
reflections from deeper dental tissue, monitoring changes in the PA signals (at the same site)
over time is necessary to identify the progress of dental decay. Our results also showed that
deep-imaging, near-infrared (NIR) PAM can sensitively image blood in the dental pulp of an in
vitro tooth. In conclusion, PAM is a promising tool for imaging both dental decay and dental
pulp.
Optical-resolution photoacoustic microscopy (OR-PAM) provides superb optical absorption contrast for red blood cells
(RBCs), which makes it ideal for in vivo microvasculature imaging. In comparison, optical coherence tomography
(OCT), widely used for tissue microstructure imaging, provides high optical scattering contrast. The two contrast
mechanisms are highly complementary. In this work, we combined OR-PAM and OCT into a single, dual-modality
imaging instrument for in vivo mouse eye imaging. We demonstrated in vivo dual-modality imaging of the anterior
segment of mouse eyes with laser pulse energy within the ANSI laser safety standard.
We present a new-generation optical-resolution confocal photoacoustic microscope, consisting of a 0.25-numerical aperture optical microscope objective and a 75-MHz center-frequency spherically focused ultrasonic transducer. Experiments verified that this microscope has a transverse resolution of 2 µm, which is the highest to our knowledge among all photoacoustic imaging systems. In situ imaging of mouse ears shows the feasibility of resolving individual red blood cells in microvessels using the current system.
Both iris fluorescein angiography (IFA) and indocyanine green angiography (ICGA) provide ophthalmologists imaging
tools in studying the microvasculature structure and hemodynamics of the anterior segment of the eye in normal and
diseased status. However, a non-invasive, endogenous imaging modality is preferable for the monitoring of
hemodynamics of the iris microvasculature. We investigated the in vivo, label-free ocular anterior segment imaging
with photo-acoustic microscopy (PAM) in mouse eyes. We demonstrated the unique advantage of endogenous contrast
that is not available in both IFA and ICGA. The laser radiation was maintained within the ANSI laser safety limit. The
in vivo, label-free nature of our imaging technology has the potential for ophthalmic applications.
We previously demonstrated that multimodal microscopy combining photoacoustic microscopy and
optical coherence tomography can provide comprehensive insight into biological tissue at μm-level
resolution by exploiting both optical absorption and scattering contrasts. Recently, we have developed a
second-generation integrated photoacoustic and optical-coherence microscope, which can potentially be
adapted for clinical applications. In this new system, we can perform photoacoustic and optical-coherence
imaging simultaneously at a speed of 5,000 A-lines per second with real-time on-screen display. Also, both
modalities now work in reflection mode instead of transmission mode, allowing easy access to various
anatomical locations of interest. Imaging of skin and eye has been demonstrated in living small animals.
Advances in the brain functional imaging greatly facilitated the understanding of neurovascular coupling. For monitoring
of the microvascular response to the brain electrical stimulation in vivo we used optical-resolution photoacoustic
microscopy (OR-PAM) through the cranial openings as well as transcranially. Both types of the vascular response,
vasoconstriction and vasodilatation, were clearly observed with good spatial and temporal resolution. Obtained results
confirm one of the primary points of the neurovascular coupling theory that blood vessels could present vasoconstriction
or vasodilatation in response to electrical stimulation, depending on the balance between inhibition and excitation of the
different parts of the elements of the neurovascular coupling system.
Photoacoustic imaging for biomedical applications has seen significant growth during the past few years. Despite its
coherent nature, it possesses a unique advantage to produce images devoid of speckle artifacts. The reason responsible
for this salient feature has not been addressed so far. We found this is a direct result of its extraordinary absorption
contrast. Our discovery is explained using simulations based on a practical photoacoustic imaging system.
Photoacoustic imaging and optical coherence tomography have complementary imaging contrasts.
Photoacoustic imaging is sensitive to optical absorption, thus is able to generate detailed maps of deep
microvasculature in vivo. Optical coherence tomography exploits the optical scattering contrast, and can
provide real-time, micrometer-resolution imaging of tissue. We integrate an optical-resolution
photoacoustic microscopy and a spectral-domain optical coherence tomography into a single system. Our
preliminary experiments showed that it could be a valuable imaging tool for microcirculation studies in
vivo.
We proposed a novel time-resolved optical tomography, optical coherence computed tomography. It married the
key concepts of time-resolved diffuse optical tomography and optical coherence tomography. Both ballistic and
multiple-scattered photons were measured at multiple source-detection positions by low-coherence interferometry. It
measures the reemitted light with a temporal resolution of 56 femtoseconds, which is much better than the resolution
of conventional time-resolved detection systems. A light-tissue interaction model was established using the time-resolved
Monte Carlo method. The optical properties were then reconstructed by solving the inverse time-resolved
radiative transport problem under the first Born approximation. Our initial results showed the potential of this
technology to bridge the gap between diffuse optical tomography and optical coherence tomography.
In the postgenomic era, imaging techniques are playing an important role in visualizing gene expression in vivo. This work represents the first demonstration of photoacoustic tomography (PAT) for reporter gene imaging. Rats inoculated with 9L/lacZ gliosarcoma tumor cells are imaged with PAT before and after injection of X-gal, a colorimetric assay for the lacZ-encoded enzyme -galactosidase. Using far-red optical illumination, the genetically tagged tumors in rats are clearly visualized by PAT following the assay. The spatial resolution is quantified to be less than 400 µm, while 500-nM-level sensitivity is demonstrated. With the future development of new absorption-based reporter gene systems, it is anticipated that photoacoustic technology will provide a valuable tool for molecular imaging research.
Photoacoustic technology offers great promise for molecular imaging in vivo since it offers significant penetration, and optical contrast with ultrasonic spatial resolution. In this article we examine fundamental technical issues impacting capabilities of photoacoustic tomography for molecular imaging. First we examine how reconstructed photoacoustic tomography images are related to true absorber distributions by studying the modulation transfer function of a circular scanning tomographic system employing a modified filtered backprojection algorithm. We then study factors influencing quantitative estimation by developing a forward model of photoacoustic signal generation, and show conditions for which the system of equations can be inverted. Errors in the estimated optical fluence are shown to be a source of bias in estimates of molecular agent concentration. Finally we discuss noise propagation through the matrix inversion procedure and discuss implications for molecular imaging sensitivity and system design.
Photoacoustic tomography is emerging as a promising imaging modality for various biomedical applications. Unlike traditional ultrasound imaging that is plagued by strong speckle artifacts, no obvious speckle has so far been observed in photoacoustic images. We systematically studied the reason for this lack of speckle in photoacoustic tomography based on speckle contrast. Theoretical explanations were validated by simulation. The results here can serve as a basis for developing specific applications, such as tissue characterization, using photoacoustic methods.
In the post-genomic era, there is an increasing interest in visualizing the expression of functional genes in vivo. With the assistance of the reporter gene technique, various imaging modalities have been adopted for this purpose. In vivo gene expression imaging promises to provide biologists with a powerful tool for deepening our understanding of developmental biology, expanding our knowledge of the genetic basis of disease, and advancing the development of medicine. In this paper, we demonstrate the feasibility of imaging gene expression with photoacoustic imaging, which offers unique absorption contrast with ultrasonic resolution in vivo. We mark tumors in rats with the lacZ reporter gene. The lacZ gene encodes an enzyme β-galactosidase, which yields a dark blue product when acting on a colorimetric assay called X-gal. Photoacoustic tomography at 650nm clearly visualizes the presence of this blue product. The spectroscopic method can also potentially improve specificity. Considering how many staining methods are used in traditional biology, we believe that photoacoustic techniques will revolutionize the field of molecular imaging. The further development of reporter gene systems with high absorbing products in the NIR region is needed.
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.