Photo-mediated ultrasound therapy (PUT) is a novel antivascular therapeutic modality based on cavitation-induced bioeffects. During PUT, concurrent, synchronized laser pulses and ultrasound bursts are used to selectively and precisely remove the targeted microvessels without harming nearby tissue. In our current study, an integrated system combining PUT and spectral domain optical coherence tomography (SD-OCT) was developed, where the SD-OCT system was used to guide PUT by detecting cavitation in real time in the retina of the eye. The performance of the integrated system in treatment of choroidal microvessels was examined. The capability of detecting cavitation on a vascular-mimicking phantom was evaluated along with rabbit eyes in vivo. The findings indicate real-time OCT monitoring can improve the safety and efficiency of PUT in removing the retinal and choroidal microvasculature.
We have recently developed a novel, cavitation-based, highly selective anti-vascular technique, termed photo-mediated ultrasound therapy (PUT). In this study, the effectiveness and safety of PUT on cutaneous vascular malformation was examined through in vivo experiments in a clinically relevant chicken wattle model. The typical results showed perfusion stop of microvessel on OCT angiography and fade of the wattle color on skin imager after treatment. The safety is checked by H&E histology and immunohistochemistry evaluations include: CD31, Caspase-3, and Masson’s Trichrome (MTC) stains. The findings demonstrate that PUT can efficiently and safely remove hypervascular dermal capillaries by using laser fluence at a level which is orders of magnitude smaller than that used in conventional laser treatment of vascular lesions, thus offering a safer alternative technique for clinical management of cutaneous vascular malformations.
This study illustrates the potential of non-invasive Photoacoustic Microscopy (PAM) to monitor functional changes in a squirrel monkey brain due to peripheral mechanical stimulation. Our unique approach employs a deep Fully Convolutional Neural Network (FCNN) to significantly enhance PAM image quality, improving signal-to-noise ratio and structural similarity index. Notably, functional changes induced by peripheral mechanical stimulation were effectively observed. The study showcases the potential of PAM in neurological applications, advancing our understanding of brain hemodynamics, and the transformative effect of machine learning techniques on PAM image quality, opening new possibilities for future neuroscientific research.
Cutaneous vascular malformations (CVM), such as port wine stain (PWS), often appear in highly visible parts of patient and cause emotional and social problems. In this work, we utilized our novel anti-vascular technique, termed photo-mediated ultrasound therapy (PUT), which combines nanosecond duration laser pulses synchronized with ultrasound bursts to treat blood vessels. The feasibility of PUT in the treatment of cutaneous microvessels was evaluated in a chicken wattle model in vivo. The treatment results showed perfusion stop in microvessels up to 1.5mm deep in chicken wattle, as demonstrated by both the OCT angiography and the color change in skin images after the treatment. The treatment effect and safety such as epidermal tissue damage and inflammation were also evaluated by H&E histology.
The feasibility of using photoacoustic imaging (PAI) to measure electrically-evoked hemodynamic responses in a squirrel monkey brain in vivo was examined. A linear-array photoacoustic computed tomography (PACT) system and a high-resolution photoacoustic microscopy (PAM) system were built for imaging subcortical and cortical brain regions, respectively. The hemodynamic responses at multiple cortices, including premotor, primary motor, and primary somatosensory cortices, were monitored. The variations could be observed in all cortices and their underlying cortical and subcortical brain regions. The results from this study validated the potential of PAI technique for multiscale and multi-resolution functional brain mapping for non-human primates.
We have developed a novel anti-vascular technique, termed photo-mediated ultrasound therapy (PUT), which utilizes nanosecond duration laser pulses synchronized with ultrasound bursts to remove microvasculature through cavitation. In this work, via the experiments in a rabbit ear model in vivo, the feasibility of PUT in the treatment of cutaneous microvessels was explored. Both the short-term effects and the long-term effects up to 4 weeks post-treatment were quantitatively assessed by measuring the perfusion rates of the vessels after treatment, showing that a single PUT treatment could significantly reduce blood perfusion. With unique advantages such as low laser fluence as compared with photothermolysis and agent-free treatment as compared with PDT, PUT holds potential to be developed into a new tool for the treatment of cutaneous vascular lesions.
Photo-mediated ultrasound therapy (PUT) holds potential as a novel antivascular method. In this work, we applied PUT to precisely remove corneal neovascularization in a rabbit eye model. A stable corneal suture-induced corneal neovascularization model was established in rabbits. These rabbits were later treated by PUT or used as controls. The treatment outcomes were evaluated through red-free photography and fluorescein angiography along with histology and immunohistochemistry. The experimental results demonstrated that PUT shows promise in improving the management of eye diseases by delivering selective treatment to pathologic vessels with minimized side effects.
Photo-mediated ultrasound therapy (PUT) is a novel, non-invasive, and agent-free therapeutic technique that uses a combination of relatively low-intensity ultrasound bursts and nanosecond laser pulses to selectively and precisely remove highly optically absorptive targets. In this work, we developed an integrated ultrasound photoacoustic theranostic system (UPTS) by combining a ultrasound system (V1, Verasonics) with a pulsed laser system. The results from the ex vivo experiments in rabbit tissues demonstrated that UPTS, by working with appropriate laser wavelengths, can selectively remove tissues such as knee tendon and liver via the cavitation synergistically created by the ultrasound bursts and the laser pulses. Such a theranostic system can deliver effective PUT treatment to biological samples along with real-time monitoring by the integrated ultrasound and photoacoustic imaging.
Ocular neovascularization occurs in various eye diseases such as diabetic retinopathy, neovascular macular degeneration, and retinopathy of prematurity. Current treatment methods including conventional laser ablation therapy and anti-vascular endothelial growth factor (VEGF) injection each has drawbacks including collateral tissue damages, frequent administration, high cost, and drug toxicity. We recently developed a novel noninvasive image-guided photo-mediated ultrasound therapy (PUT) which concurrently applies nanosecond laser pulses and millisecond ultrasound bursts to precisely and safely remove pathologic microvessels in the eye. Relying on the mechanism of photoacoustic cavitation, PUT takes advantages of high optical contrast among biological tissues, and can selectively remove microvessels without causing collateral tissue damage.
To achieve personalized treatment with optimal treatment outcome, a multi-modality eye imaging system involving advanced photoacoustic microscopy (PAM) and optical coherence tomography (OCT) has been integrated with the PUT system to provide real-time feedback and online evaluation of the treatment outcome. To assess the performance of this image-guided PUT system, experiments have been conducted on rabbit eye models. During the treatment, cavitation signals were observed and monitored by OCT with good sensitivity, suggesting that OCT can be used to evaluate treatment effect in real time. The PAM was capable of mapping the 3D distributed microvessels with excellent image quality, demonstrating that PAM can help to quantitatively evaluate the treatment outcome. As indicated by the initial results from this study, imaging guidance involving both PAM and OCT could further improve the efficacy and safety of the newly invented PUT, accelerating its translation to ophthalmology clinic.
We have developed a safe, noninvasive imaging-guided localized antivascular method, namely photo-mediated ultrasound therapy (PUT), by applying synchronized laser and ultrasound pulses. Through our experimental and theoretical studies, we demonstrate that cavitation plays a key role in PUT. PUT promotes cavitation activity in blood vessels by concurrently applying ultrasound bursts and nanosecond laser pulses. The collapse of cavitation can induce damage to blood vessel endothelial cells, resulting in occlusion of microvessels. This study presents the effect of laser pulse energy, laser pulse length, ultrasound intensity, and synchronization time between laser and ultrasound. We found that, in order to produce controllable blood vessel occlusion, linear oscillation of cavitation (or non-inertial cavitation) might be the key, while strong collapse of cavitation (inertial cavitation) might induce bleeding. Under the guidance an optical coherence tomography (OCT) system, we utilized PUT to remove microvessels in the rabbit choroid. We were able to monitor cavitation activity in real-time in vivo during PUT treatment, and predict treatment outcome. Histology findings confirmed that fibrin clots were developed in the microvessels in the treated region, while no damage was found in the surrounding tissue.
Wet age-related macular degeneration (AMD) is a leading cause of vision loss in the United States. Choroidal neovascularization (CNV), the creation of new blood vessels in the choroid layer of the eye, plays a central role in the pathophysiology of wAMD. Despite advanced anti-VEGF therapy, 20% of patients become legally blind and other 30% suffer significant vision loss after 5 years. Given the significant burden imposed by wAMD on a growing aging population, there is an urgent need for developing new therapeutic techniques to remove microvessels induced by CNV. We developed a safe, noninvasive imaging-guided photo-mediated ultrasound therapy (PUT) technique as a localized antivascular method, and applied it to remove microvessels in the rabbit choroid. This technique promotes cavitation activity in blood vessels by concurrently applying ultrasound bursts and nanosecond laser pulses. The collapse of cavitation can induce damage to blood vessel endothelial cells, resulting in occlusion of microvessels. PUT takes advantages of the high native optical contrast among biological tissues, and has the unique capability to self-target microvessels without causing surrounding damages. Under the guidance of a fundus camera and an optical coherence tomography (OCT) system, our PUT system now has the capability to precisely target the treating area before the treatment procedure (through the fundus camera), and real-time intra-treatment cavitation monitor to evaluate the therapeutic effect (through the OCT system). Additionally, the safety of PUT technique is confirmed by histopathological studies.
Retinal and choroidal neovascularization play a pivotal role in the leading causes of blindness including macular degeneration and diabetic retinopathy (DR). Current therapy by focal laser photocoagulation can damage the normal surrounding cells, such as the photoreceptor inner and outer segments which are adjacent to the retinal pigment epithelium (RPE), due to the use of high laser energy and millisecond pulse duration. Therapies with pharmaceutical agents involve systemic administration of drugs, which can cause adverse effects and patients may become drug-resistant.
We have developed a noninvasive photo-mediated ultrasound therapy (PUT) technique as a localized antivascular method, and applied it to remove micro blood vessels in the retina. PUT takes advantage of the high native optical contrast among biological tissues, and has the unique capability to self-target microvessels without causing unwanted damages to the surrounding tissues. This technique promotes cavitation activity in blood vessels by synergistically applying nanosecond laser pulses and ultrasound bursts. Through the interaction between cavitation and blood vessel wall, blood clots in microvessels and vasoconstriction can be induced. As a result, microvessels can be occluded. In comparison with other techniques that involves cavitation, both laser and ultrasound energy needed in PUT is significantly lower, and hence improves the safety in therapy.
We developed a novel localized antivascular method, namely photo-mediated ultrasound therapy (PUT), by applying synchronized laser and ultrasound pulses. PUT relies on high optical contrast among biological tissues. Taking advantage of the high optical absorption of hemoglobin, PUT can selectively target microvessels without causing unwanted damages to the surrounding tissue. Moreover, PUT working at different optical wavelengths can selectively treat veins or arteries by utilizing the contrast in the optical spectra between deoxy- and oxy-hemoglobin. Through our experiments, we demonstrated that cavitation might have played a key role in PUT. The addition of a laser pulse to an existing ultrasound field can significantly improve the likelihood of inertial cavitation, which can induce microvessel damage through its mechanical effect. In comparison with conventional laser therapies, such as photothermolysis and photocoagulation, the laser energy level needed in PUT is significantly lower. When a nanosecond laser was used, our in vivo experiments showed that the needed laser fluence was in the range of 4 to 40 mJ/cm2.
Photoacoustic imaging has been recently developed for biomedical imaging. This imaging technique is based on the photoacoustic effect, which includes a process involving the absorption of photons, the subsequent thermal expansion, and propagation of photoacoustic waves. The propagation of photoacoustic waves has been modeled by using linear acoustic theories although the generated photoacoustic waves are naturally shock waves. In this work, the propagation of photoacoustic shock waves are studied by using nonlinear acoustic wave solutions based on Hugoniot’s shock relation combining Earnshaw solution with Poisson solution. The non-linear solution is compared with the existing linear solution using the propagating waveforms for spherical wave. The simulation results show a discrepancy between the two solutions.
Radiation-damaged nanodiamonds (NDs) are ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their good biocompatibility and high optical absorbance in the near-infrared (NIR) range. Acid treated NDs are oxidized to form carboxyl groups on the surface, functionalized with polyethylene glycol (PEG) and human epidermal growth factor receptor 2 (HER2) targeting ligand for breast cancer tumor imaging. Because of the specific binding of the ligand conjugated NDs to the HER2-overexpressing murine breast cancer cells (4T1.2 neu), the tumor tissues are significantly delineated from the surrounding normal tissue at wavelength of 820 nm under the PA imaging modality. Moreover, HER2 targeted NDs (HER2-PEG-NDs) result in higher accumulation in HER2 positive breast tumors as compared to non-targeted NDs after intravenous injection (i.v.). Longer retention time of HER-PEG-NDs is observed in HER2 overexpressing tumor model than that in negative tumor model (4T1.2). This demonstrates that targeting moiety conjugated NDs have great potential for the sensitive detection of cancer tumors and provide an attractive delivery strategy for anti-cancer drugs.
Most biological chromophores and molecules relax primarily through non-radiative processes; therefore, mapping of
relaxation time related to non-rediative process can be a potential indicator of tissue status. In order to map relative
nonradiative relaxation time, modulated tone-burst light is used to generate photoacoustic signals. Then nonradiative
relaxation time is indicated by the amplitude decay rate as modulation frequency increases. The results show that
although blood is an optically weak absorber at 808 nm, by using this method a significant enhancement of contrast-tonoise
ratio of a blood target compared to pulsed photoacoustic imaging at this wavelength is achieved.
Radiation-damaged nanodiamonds (DNDs) are potentially ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their low toxicity and high optical absorbance. PA imaging contrast agents have been limited to quantum dots and gold particles, since most existing carbon-based nanoparticles, including fluorescent nanodiamonds, do not have sufficient optical absorption in the near-infrared (NIR) range. A new DND by He + ion beam irradiation with very high NIR absorption was synthesized. These DNDs produced a 71-fold higher PA signal on a molar basis than similarly dimensioned gold nanorods, and 7.1 fmol of DNDs injected into rodents could be clearly imaged 3 mm below the skin surface with PA signal enhancement of 567% using an 820-nm laser wavelength.
Photoacoustic (PA) imaging was applied to detect the neuronal activity in the motor cortex of an awake, behaving monkey during forelimb movement. An adult macaque monkey was trained to perform a reach-to-grasp task while PA images were acquired through a 30-mm diameter implanted cranial chamber. Increased PA signal amplitude results from an increase in regional blood volume and is interpreted as increased neuronal activity. Additionally, depth-resolved PA signals enabled the study of functional responses in deep cortical areas. The results demonstrate the feasibility of utilizing PA imaging for studies of functional activation of cerebral cortex in awake monkeys performing behavioral tasks.
Anti-cancer drugs typically exert their pharmacological effect on tumors by inducing apoptosis, or programmed cell
death, within the cancer cells, with PCD occurring as soon as 4 hours after treatment. Detection of apoptosis in patients
could decisively report a response to treatment days or even weeks before MRI, CAT, and ultrasound indicate
morphological changes in the tumor. Here we developed a novel
near-infrared dye based imaging probe to directly detect
apoptosis with high specificity in cancer cells by utilizing a
non-invasive photoacoustic imaging technique. Nude mice
bearing head and neck tumors received cisplatin chemotherapy were imaged by PAI after tail vein injection of the
contrast agent. In vivo PAI indicated a strong apoptotic response to chemotherapy on the peripheral margins of tumors,
whereas untreated controls showed no contrast enhancement by PAI. The apoptotic status of the mouse tumor tissue was
verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. The results demonstrated the
potential of this imaging probe to guide the evaluation of chemotherapy treatment.
Functional detection in primate brains has particular advantages because of the similarity between non-human
primate brain and human brain and the potential for relevance to a wide range of conditions such as stroke and
Parkinson's disease. In this research, we used photoacoustic imaging (PAI) technique to detect functional changes
in primary motor cortex of awake rhesus monkeys. We observed strong increases in photoacoustic signal amplitude
during both passive and active forelimb movement, which indicates an increase in total hemoglobin concentration
resulting from activation of primary motor cortex. Further, with PAI approach, we were able to obtain depthresolved
functional information from primary motor cortex. The results show that PAI can reliably detect primary
motor cortex activation associated with forelimb movement in rhesus macaques with a minimal-invasive approach.
Anti-cancer drugs typically exert their pharmacological effect on tumors by inducing apoptosis, or programmed cell death, within the cancer cells. However, no tools exist in the clinic for detecting apoptosis in real time. Microscopic examination of surgical biopsies and secondary responses, such as morphological changes, are used to verify efficacy of a treatment. Here, we developed a novel near-infrared dye-based imaging probe to directly detect apoptosis with high specificity in cancer cells by utilizing a noninvasive photoacoustic imaging (PAI) technique. Nude mice bearing head and neck tumors received cisplatin chemotherapy (10 mg/kg) and were imaged by PAI after tail vein injection of the contrast agent. In vivo PAI indicated a strong apoptotic response to chemotherapy on the peripheral margins of tumors, whereas untreated controls showed no contrast enhancement by PAI. The apoptotic status of the mouse tumor tissue was verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. The results demonstrated the potential of this imaging probe to guide the evaluation of chemotherapy treatment.
Photoacoustic microscopy (PAM) was used to detect small animal brain activation in response to drug abuse. Cocaine hydrochloride in saline solution was injected into the blood stream of Sprague Dawley rats through tail veins. The rat brain functional change in response to the injection of drug was then monitored by the PAM technique. Images in the coronal view of the rat brain at the locations of 1.2 and 3.4 mm posterior to bregma were obtained. The resulted photoacoustic (PA) images showed the regional changes in the blood volume. Additionally, the regional changes in blood oxygenation were also presented. The results demonstrated that PA imaging is capable of monitoring regional hemodynamic changes induced by drug abuse.
In this study, we applied an integrated photoacoustic imaging (PAI) and high intensity focused ultrasound (HIFU)
system to noninvasively monitor the thermal damage due to HIFU ablation in vivo. A single-element, spherically focused
ultrasonic transducer, with a central frequency of 5MHz, was used to generate a HIFU area in soft tissue. Photoacoustic
signals were detected by the same ultrasonic transducer before and after HIFU treatments using different wavelengths.
The feasibility of combined contrast imaging and treatment of solid tumor in vivo by the integrated PAI and HIFU
system was also studied. Gold nanorods were used to enhance PAI during the imaging of a CT26 tumor, which was
subcutaneously inoculated on the hip of a BALB/c mouse. Subsequently, the CT26 tumor was ablated by HIFU with the
guidance of photoacoustic images. Our results suggested that the tumor was clearly visible on photoacoustic images
after the injection of gold nanorods and was ablated by HIFU. In conclusion, PAI may potentially be used for
monitoring HIFU thermal lesions with possible diagnosis and treatment of solid tumors.
Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of
cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg
per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the
injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex
of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT
system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio
(SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high
blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.
Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.
We have developed an integrated photoacoustic imaging (PAI) and high-intensity focused ultrasound (HIFU) system for solid tumor treatments. A single-element, spherically focused ultrasonic transducer, with a central frequency of 5 MHz, was used to induce HIFU lesions in soft tissue. The same ultrasonic transducer was also used as a detector during PAI to guide HIFU ablation. The use of same transducer for PAI and HIFU can reduce the requirement on acoustic windows during the imaging-guided therapy, as well as ensuring the correct alignment between the therapeutic beam and the planned treatment volume. During an experiment, targeted soft tissue was first imaged by PAI. The resulted image was used to plan the subsequent HIFU ablation. After the HIFU ablation, targeted soft tissue was imaged again by PAI to evaluate the effectiveness of treatments. Good contrast was obtained between photoacoustic images before and after HIFU ablation. In conclusion, our results demonstrated that PAI technology may potentially be integrated with HIFU ablation for image-guided therapy.
We have developed an integrated photoacoustic imaging (PAI) and high intensity focused ultrasound (HIFU) system for
solid tumor treatment. A single-element, spherically focused ultrasonic transducer, with a central frequency of 5MHz,
was used to generate a HIFU field in soft tissue. The same ultrasonic transducer was also used as a detector during
photoacoustic imaging before and after HIFU treatments. During each experiment, targeted soft tissue was first imaged
by PAI. The resulted image was used for the planning of subsequent HIFU treatment. After HIFU treatment, the sample
was imaged again by PAI to evaluate the treatment result. Good contrast was obtained between photoacoustic images
before and after HIFU treatment. It is concluded that PA imaging technology may potentially be combined with HIFU
treatment for imaging-guided therapy.
We present the application of a curved array photoacoustic tomographic imaging system that can provide rapid, high-resolution photoacoustic imaging of small animal brains. The system is optimized to produce a B-mode, 90-deg field-of-view image at sub-200-µm resolution at a frame rate of ~1 frame/second when a 10-Hz pulse repetition rate laser is employed. By rotating samples, a complete 360-deg scan can be achieved within 15 s. In previous work, two-dimensional (2-D) ex vivo mouse brain cortex imaging has been reported. We report three-dimensional (3-D) small animal brain imaging obtained with the curved array system. The results are presented as a series of 2-D cross-sectional images. Besides structural imaging, the blood oxygen saturation of the animal brain cortex is also measured in vivo. In addition, the system can measure the time-resolved relative changes in blood oxygen saturation level in the small animal brain cortex. Last, ultrasonic gel coupling, instead of the previously adopted water coupling, is conveniently used in near-real-time 2-D imaging.
We present the application of an optimized curved array photoacoustic tomographic imaging system, which can provide
rapid, high-resolution photoacoustic imaging of small animal brains. The system can produce a B-mode, 90-degree
field-of-view image at sub-200 μm resolution at a frame rate of ~1 frame/second when a 10-Hz pulse repetition rate
laser is employed. By rotating samples, a complete 360-degree scan can be achieved within 15 seconds. In previous
work, two-dimensional ex vivo mouse brain cortex imaging has been reported. In the current work, we report three-dimensional
small animal brain imaging obtained with the curved array system. The results are presented as a series of
two-dimensional cross-sectional images. Besides structural imaging, the blood oxygen saturation of the animal brain
cortex is also measured in vivo. In addition, the system can measure the time-resolved relative changes in blood oxygen
saturation level in the small animal brain cortex. Finally, ultrasonic gel coupling, instead of the previously adopted
water coupling, is conveniently used in near-real-time 2D imaging.
Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultrasound signal attenuation and distortion caused by a relatively thick skull.
Photoacoustic tomography (PAT), also referred to optoacoustic tomography, is a hybrid imaging technique that
combines an optical contrast mechanism and ultrasonic detection principles. The laser-induced photoacoustic
signals in PAT are broadband in nature, but only a bandpass approximation of the signal is recorded by use
of a conventional ultrasonic transducers due to its limited bandwidth. To circumvent this, a PAT system
has been developed that records photoacoustic signals by use of multiple ultrasonic transducers that possess
different central frequencies. In this work, we investigate a sensor fusion methodology for combining the multiple
measurements to obtain an estimate of the true photoacoustic signal that is superior to that obtainable by use
of any single transducer measurement. From the estimated photoacoustic signals, three-dimensional images of
the optical absorption distribution are reconstructed and are found to possess improved accuracy and statistical
properties as compared to the single transducer case. Preliminary computer-simulation studies are presented to
demonstrate and investigate the proposed method.
Photoacoustic tomography (PAT) is adopted to image the brain cortex of monkeys through the intact scalp and skull ex
vivo. The reconstructed PAT image shows the main structure of the blood vessels on the monkey brain cortex. For
comparison, the brain cortex is imaged without the scalp then imaged again without the scalp and skull. Ultrasound
attenuation through the skull is also measured at various angles of incidence to illuminate the effect of the incident
angle. This study demonstrates that PAT of the brain cortex is capable of surviving the ultrasound signal attenuation
and distortion caused by a considerably thick skull.
Poly(ethylene glycol)-coated Au nanocages have been evaluated as a potential near-infrared (NIR) contrast agent for
photoacoustic tomography (PAT). Previously, Au nanoshells were found to be an effective NIR contrast agent for
PAT; however, Au nanocages, with their more compact sizes (<50 nm compared to >100 nm for Au nanoshells) and
larger optical absorption cross-sections, should be better suited for in vivo applications. In this study, we tested Au
nanocages as a contrast agent for PAT. The result suggests that Au nanocages are promising contrast agents for our
applications. We also present PAT results when novel, dye-containing nanoparticles are used as contrast agents.
We image a rat cerebral cortex in situ by using a ring-based ultrasonic virtual point detector developed previously. Compared to the image generated by a finite-aperture detector, the image generated by the virtual point detector has a uniformly distributed resolution throughout the imaged area, owing to the lack of aperture effect of the ultrasonic detector. At the periphery of the image, the signal-to-noise ratio of the image obtained by the virtual point detector is also better than that of a finite-aperture detector. Furthermore, the virtual point detector can be scanned inside the brain to improve the local signal-to-noise ratio.
Exact photoacoustic tomography requires scanning over a 4&pgr; solid angle in 3D. The ultrasound detection window, however, is often limited, which makes a full scan impossible. For example, when a boundary lies closely to an object, the scanning region can cover only less than 4&pgr; in 3D. Because of incomplete information, the resolution, SNR, and fidelity of the resulting image deteriorate. Boundaries, however, can be used to our advantage; we proposed post-processing algorithms in image reconstruction to make partially scanned data complete. Here, we show the efficacy of the post-processing algorithms with both numerical and experimental results. Indeed, the algorithms can improve the resolution, SNR, and fidelity.
KEYWORDS: Sensors, Signal detection, Signal to noise ratio, Spatial resolution, Photoacoustic tomography, Photoacoustic spectroscopy, Image resolution, Acquisition tracking and pointing, Image restoration, Signal processing
We devise and explore a ring-shaped acoustic detector associated with a virtual point detector concept for photoacoustic tomography. The center of the ring transducer scans a circle around the object to be imaged and then is treated as an omni-directional virtual point detector in photoacoustic image reconstruction. The virtual point detector introduces a space-invariant point spread function in photoacoustic image reconstruction and thus improves the tangential resolution, which is due to the finite aperture. Compared with a real point detector, the virtual point detector can provide similar spatial resolution but better SNR. Compared with a real finite-aperture detector, the virtual point detector can provide similar SNR but better spatial resolution. In addition, because of its virtual feature, the virtual point detector can be placed very close to and even inside of a tissue sample to locally scan a region of interest, which yields good SNR and spatial resolution.
Recently, the field of photoacoustic tomography has experienced considerable growth. Although several commercially available pure optical imaging modalities, including confocal microscopy, two-photon microscopy, and optical coherence tomography, have been highly successful, none of these technologies can penetrate beyond ~1 mm into scattering biological tissues because all of them are based on ballistic and quasiballistic photons. Consequently, heretofore there has been a void in high-resolution optical imaging beyond this depth limit. Photoacoustic tomography has filled this void by combining high ultrasonic resolution and strong optical contrast in a single modality. However, it has been assumed in reconstruction of photoacoustic tomography until now that ultrasound propagates in a boundary-free infinite medium. We present the boundary conditions that must be considered in certain imaging configurations; the associated inverse solutions for image reconstruction are provided and validated by numerical simulation and experiment. Partial planar, cylindrical, and spherical detection configurations with a planar boundary are covered, where the boundary can be either hard or soft. Analogously to the method of images of sources, which is commonly used in forward problems, the ultrasonic detectors are imaged about the boundary to satisfy the boundary condition in the inverse problem.
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