A longitudinal study on both 3D and 2D photoacoustic and Doppler ultrasound imaging of human hand rheumatoid arthritis progression has been performed using an automatic imaging system based on GEHC VividTM E95 with L8-18i-D probe and OPOTEK tunable laser system. Bi-weekly imaging has been performed starting from baseline (before patients start medication). Both photoacoustic and Doppler ultrasound can confirm the disease development, however, photoacoustic has higher correlation coefficients (with a median of 78.9%, p = 0.039) with patients’ PGA score.
Non-invasive assessment of aggressive tumors with high spatial resolution and specificity has been challenging. This study presents an application of multispectral photoacoustic tomography (MSPT) in tumor imaging, using a specially designed hypoxia-responding agent, NOx-JS013. The developed hypoxia probe, NOx-JS013, is reduced to JS013 under hypoxic conditions common in aggressive tumors, with a shifted absorption peak. Additionally, NOx-JS013 specifically binds with NCEH1, a characteristic enzyme highly expressed in aggressive tumor cells. The results from In-vivo experiments on aggressive and non-aggressive tumors demonstrate the feasibility of the MSPT hypoxia imaging using NOx-JS013 hypoxia indicator enhanced with aggressive cancer cell targeting ability.
A longitudinal study on both 3D and 2D photoacoustic and Doppler ultrasound images of rat leg rheumatoid arthritis development has been performed using an automatic imaging system based on a GE HealthCare VividTM E95 unit with a L8-18i-D probe, an OPOTEK tunable laser system, and a Universal Robots UR3 robotic arm. Daily imaging of ankle bones was performed starting from day 0 when the lyophilized Mycobacterium butyricum was injected to induce the disease. Although both photoacoustic and Doppler ultrasound can confirm the disease development, photoacoustic imaging is more sensitive to microvasculature and enables earlier detection of inflammation than Doppler ultrasound.
KEYWORDS: Radiotherapy, Oxygen, Tumors, Photoacoustic spectroscopy, Photoacoustic imaging, Imaging spectroscopy, Tumor growth modeling, Signal generators, In vivo imaging, Chemical analysis
Presented here is an application of the new approach of chemical imaging, performing an in-vivo chemical analysis, to predict a given tumor’s response to radiation therapy. Cancer tumors’ oxygen distributions in PDX mice was imaged by photoacoustic imaging with tumor-targeted oxygen sensor nanoparticles. Following radiation therapy, we established a quantitatively significant correlation between the spatial distribution of the initial oxygen levels and the spatial distribution of the therapy’s efficacy: the higher the local oxygen, the higher the local radiation therapy efficacy. The presented cancer chemical imaging provides a non-invasive method to predict the efficacy of radiotherapy for a given tumor.
We report photoacoustic (PA) lifetime (PALT) based oxygen imaging powered by polyacrylamide (PAA) nanoparticles (NPs). The phosphorescenc indicator, oxyphor G2, was conjugated within the matrix of the NPs, giving G2-PAA NPs, followed by PEGylation for biocompatibility and F3 surface modification for tumor targeting. Two laser pulses (630 nm pumping, 920 nm probing) excite the G2-PAA NPs. By varying the delay time between the pump and the probe pulses, the exponential decay of the phosphorescence, which correlates linearly with the ambient oxygen concentration, can be measured. PALT imaging was performed, to quantitatively map the oxygen concentration in biological tissues in vivo, including both cancerous tumors and normal thigh muscles. The successful imaging experiment accomplished on animal models renders a new method for in vivo non-invasive imaging and assessment of hypoxic tumor microenvironments, which is critical for assessing cancer progression, metastasis, and treatment.
Significance: One key pathological characteristic of seronegative spondyloarthropathy (SpA) is inflammation at the insertion of tendons and ligaments into the bone (enthesitis).
Aim: We explore the potential of the emerging photoacoustic (PA) imaging in diagnosis of SpA and review its feasibility in detecting SpA-associated Achilles tendon enthesitis.
Approach: A light-emitting diode (LED)-based PA and ultrasound combined system was employed. The PA images, both along the long and the short axes of each Achilles tendon insertion region, were acquired at 850-nm wavelength, which is sensitive in depicting increased blood volume (i.e., hyperemia). To assess the hyperemia indicating enthesis inflammation, two parameters were quantified in the imaged tendons, including the average intensity and the density of the color pixels in the pseudo-color PA images. Ten SpA patients, all of which met Assessment of SpA International Society (ASAS) criteria for SpA and were found to have Achilles enthesitis by clinical exam according to a board-certified rheumatologist, were included in the study.
Results: The PA and Doppler ultrasound imaging of Achilles enthesitis resulting from these 10 SpA patients were compared to those from 10 healthy volunteers, leading to statistically significant differences (p < 0.05) in the applied t-tests.
Conclusions: This preliminary clinical study suggests that the LED-based PA imaging holds a promise for sensitive and objective assessment of SpA enthesitis in an outpatient setting of the rheumatology clinic.
Our previous research has demonstrated that photoacoustic (PA) imaging is capable of evaluating the pathological condition in human peripheral joints affected by inflammatory arthritis. In this work, we tested the performance of a PA imaging system based on the LED light source and its performance for arthritis imaging. The LED-based PA imaging system not only has less cost but also has smaller footprint and, hence, is more portable and convenient for use in rheumatology clinic. 2D B-scan PA and US images of each metacarpophalangeal (MCP) joint were acquired along the sagittal sections. Along the same sections, US Doppler images were also acquired. Images from 12 joints with clinically active arthritis (i.e., positive on Doppler US), 5 joints with subclinically active arthritis (i.e., negative on Doppler US), and 12 joints of normal volunteers were compared. The blood volume in each joint reflecting hyperemia was quantified by counting the density of the color pixels in each pseudo-color PA image. T-tests were conducted to evaluate whether PA imaging can differentiate the three groups. The results from this study suggest that LED-based PA imaging is capable of detecting hyperemia as an important biomarker of joint inflammation. In addition, PA imaging could differentiate the subclinically active arthritis group and the normal group while Doppler US could not, suggesting that PA imaging has higher sensitivity to mildly hyperemia when compared to Doppler US. The imaging technique presented may contribute to rheumatology clinic by providing a new tool for early diagnosis and treatment evaluation of joint inflammation.
Light-emitting diode (LED) light sources have recently been introduced to photoacoustic imaging (PAI). The LEDs enable a smaller footprint for PAI systems when compared to laser sources, thereby improving system portability and allowing for improved access. An LED-based PAI system has been employed to identify inflammatory arthritis in human hand joints. B-mode ultrasound (US), Doppler, and PAIs were obtained from 12 joints with clinically active arthritis, five joints with subclinically active arthritis, and 12 normal joints. The quantitative assessment of hyperemia in joints by PAI demonstrated statistically significant differences among the three conditions. The imaging results from the subclinically active arthritis joints also suggested that the LED-based PAI has a higher sensitivity to angiogenic microvascularity compared to US Doppler imaging. This initial clinical study on arthritis patients validates that PAI can be a potential imaging modality for the diagnosis of inflammatory arthritis.
Presenting highly sensitive functional information in subsurface tissue with spatial resolution comparable to ultrasound imaging, the emerging photoacoustic (PA) imaging may shed new lights to early diagnosis and treatment monitoring of human inflammatory arthritis. This paper will introduce our recent development of LED-based PA imaging and its application to human inflammatory arthritis. Facilitated by the high pulse repetition rate of the LED arrays, extensive averaging of PA signal can be performed, which boosts the signal-to-noise ratio of the LED-based PA imaging system to levels comparable to laser-based PA imaging systems. In the experiments on arthritis patients and normal volunteers, each target finger joint is scanned using the LED-based PA imaging system which is integrated with a B-scan ultrasound (US) facilitating dual imaging modalities simultaneously. 2D PA and US of a sagittal section in the joint can be acquired in a real-time fashion with a frame rate up to 30 Hz; while a series of 2D images acquired along the cross sections of the joint can be reconstructed into a 3D image for analyzing the volumetric biomarkers of joint inflammation. In this initial study on human subjects, we have confirmed the feasibility of LED-based PA imaging in detecting and characterizing arthritic joints by evaluating the hemodynamic changes associated with soft-tissue inflammation. PA imaging findings are compared to the results from Doppler US acquired using a commercial US unit. This study demonstrates that the LED-based PA imaging can be developed into a point-of-care diagnostic tool for rheumatology and radiology clinics.
Photoacoustic (PA) imaging combined with ultrasonography (US) holds promise to offer a novel and powerful tool for clinical management of inflammatory arthritis, including early detection and treatment monitoring. As a complement to US, PA imaging can assess additional hemodynamic changes in inflammatory synovium, including hyperemia and hypoxia, both important and early physiological biomarkers of synovitis reflecting the increased metabolic demand and the relatively inadequate oxygen delivery of the inflammatory synovial tissue. In this study on arthritis patients and normal volunteers, the targeted metacarpophalangeal (MCP) joints were imaged using our real-time US-PA dual-modality imaging system. The blood volume and the blood oxygenation in the segmented synovium were quantified, and the results from the arthritis patients were compared to those from the normal volunteers. This initial study on human subjects demonstrated that PA imaging, by working at the optical wavelengths that are sensitive to oxygenated and deoxygenated hemoglobin, is capable of identifying and characterizing inflammation in joints based on the detection of hemodynamic changes.
Ion selective optical nanosensors allow accurate ion measurements in biological systems, without the physical limitations and invasiveness of ion selective electrodes. Optically based nanosensors (Photonic Explorers for Bioanalysis with Biologically Localized Embedding, PEBBLEs), have been optimized for fluorescence microscopy imaging, and have been applied for imaging various biochemical analytes. In here, we report the first example of a potassium selective nanosensor optimized for photoacoustic (PA) imaging. Notably, PA imaging overcomes the severe light penetration depth problem faced by fluorescence imaging in vivo. The new potassium selective nanosensor shows excellent response in the biological range, from 0 to 200 mM, as confirmed by both UV-Vis Spectroscopy and PA Spectroscopy. Furthermore, the K+ PEBBLE showed a 2 orders of magnitude, or higher, selectivity to K+ , relative to any other biological cations, such as Li+, Na+, Ca2+, and Mg2+.
The Methylene Blue loaded Polyacrylamide Nanoparticles (MB-PAA NPs) are used for oxygen sensing and Photodynamic therapy (PDT), a promising therapeutic modality employed for various tumors, with distinct advantages of delivery of biomedical agents and protection from other bio-molecules overcoming inherent limitations of molecular dyes. Lifetime-resolved photoacoustic spectroscopy using quenched-phosphorescence method is applied with MB-PAA NPs so as to sense oxygen, while the same light source is used for PDT. The dye is excited by absorbing 650 nm wavelength light from a pump laser to reach triplet state. The probe laser at 810 nm wavelength is used to excite the first triplet state at certain delayed time to measure the dye lifetime which indicates oxygen concentration. The 9L cells (106 cells/ml) incubated with MB-PAA NP solution are used for monitoring oxygen level change during PDT in situ test. The oxygen level and PDT efficacy are confirmed with a commercial oximeter, and fluorescence microscope imaging and flow cytometry results. This technique with the MB-PAA NPs allowed us to demonstrate a potential non-invasive theragnostic operation, by monitoring oxygen depletion during PDT in situ, without the addition of secondary probes. Here, we demonstrate this theragnostic operation, in vitro, performing PDT while monitoring oxygen depletion. We also show the correlation between O2 depletion and cell death.
The ducal imaging with photoacoustic imaging (PAI) that is an emerging technology and clinical ultrasound
imaging that is an established modality is developed for the imaging of early inflammatory arthritis. PAI is sensitive
to blood volume, not limited by flow like ultrasound, holding great promise for the earliest detection of increase in
blood volume and angiogenesis - a key early finding inflammation PAI has the capability of assessing inflammation
in superficial human soft tissues, offering potential benefits in diagnosis, treatment and monitoring of inflammatory
arthritis. PAI combined with ultrasonography (US), is a real time dual-modality system developed and tested to
identify active synovitis in metacarpophalangeal (MCP) joints of 10 arthritis patients and 10 normal volunteers.
Photoacoustic images of the joints were acquired at 580-nm laser wavelength, which provided the desired balance
between the optical contrast of hemoglobin over bone cortex and the imaging depth. Confirmed by US Doppler
imaging, the results from ten patients and ten normal volunteers demonstrated satisfactory sensitivity of PAI in
assessing enhanced blood flow due to active synovitis. This preliminary study suggests that photoacoustic imaging,
by identifying early increase in blood volume, related to increased vascularity, a hallmark of joint inflammation,
could be a valuable supplement to musculoskeletal US.
With the capability of assessing high resolution optical information in soft tissues at imaging depth up to several centimeters, innovative biomedical photoacoustic imaging (PAI) offers benefits to diagnosis and treatment monitoring of inflammatory arthritis, particularly in combination with more established ultrasonography (US). In this work, a PAI and US dual-modality system facilitating both imaging functions in a real-time fashion was developed and initially tested for its clinical performance on patients with active inflammatory arthritis. Photoacoustic (PA) images of metacarpophalangeal (MCP) joints were acquired at 580-nm wavelength that provides a desired balance between optical absorption of blood and attenuation in background tissue. The results from six patients and six normal volunteers used as a control demonstrated the satisfactory sensitivity of PAI in assessing the physiological changes in the joints, specifically enhanced blood flow as a result of active synovitis. This preliminary study suggests that PAI, by revealing vascular features suggestive of joint inflammation, could be a valuable supplement to musculoskeletal US for rheumatology clinic.
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.
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.
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.
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.
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.
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.