Photoacoustic (PA) imaging is a hybrid imaging technology which combines the best of optical (contrast) and ultrasound (resolution) imaging. PA imaging uses intrinsic contrast agents in the body like blood (hemoglobin), melanin, etc. But the contrast from the intrinsic contrast agents might not be sufficient for different applications. So, external contrast agents are needed for improving the contrast of PA images. Organic dyes, inorganic dyes, and nanomaterials can be used as photoacoustic contrast agents. The major issue with using external contrast agent is that they often need FDA approval to be used for in-vivo studies. Availability of FDA approved contrast agents for PA imaging is very limited. In this work, we present the feasibility of using food and food-based dyes as photoacoustic contrast agents. We use commonly used foods like coffee, tea, chocolate and food colorants as contrast agents. We use alpinion’s E-CUBE dual mode ultrasound and photoacoustic imaging system with mobile Nd:YAG laser pumped by OPO laser to demonstrate the efficiency of the contrast agents. The contrast agents were compared with methylene blue. Out of the many different agents we tested, coffee, chocolate and few other dyes proved as efficient photoacoustic contrast agents. We performed photoacoustic spectroscopy to identify at which wavelength the dye performed best. We also tested the contrast agents for imaging sentinel lymph nodes in rats and the results are very similar to methylene blue. This will enable the transition of photoacoustic imaging to the clinics more easily.
Photoacoustic imaging holds promise in wide range of clinical and preclinical applications. Since photoacoustic imaging can be implemented in a conventional ultrasound scanner by adding light illumination, it is straight forward to realize dual-mode imaging offering complementary contrast. We recently developed an LED-based photoacoustic and ultrasound imaging system (AcousticX) with unprecedented 2D and 3D functional and structural imaging capabilities. Pulse energy offered by our LED arrays is orders of magnitude lower than conventional lasers and we perform frame averaging to keep up with the SNR, reducing the display frame rate. Even though the pulse repetition frequency of our LED arrays is 4 KHz, image frame rate we can achieve is limited by the large number of frame averages used to improve SNR. In this work, we present a deep learning-based approach to reduce the frame averaging in LED-based photoacoustic imaging without compromising the SNR. We have used convolutional neural network (U-Net) model in deep learning for improving the images with less averaging. When compared with traditional denoising methods, deep learning enables us to optimize parameters through network training. We used images from various other photoacoustic imaging systems with higher laser energy and broadband ultrasound transducers, which can generate PA images with high resolution and SNR with minimal or no averaging as training data. We validate our algorithm using LED-based photoacoustic images of phantoms utilizing Indocyanine green and methylene blue as contrast agents. In all cases, we achieved improvement in the SNR by denoising the images with lesser averaging, thereby increasing the framerate. Results demonstrate the potential of deep learning algorithms in improving temporal resolution and SNR in LED-based photoacoustic imaging.
X-ray luminescence computed tomography (XLCT) and X-ray fluorescence computed tomography (XFCT) are two emerging technologies in X-ray imaging. In these modalities, images are formed through detection of secondary emissions (light in XLCT, or secondary X-rays in XFCT) following X-ray excitations. XLCT and XFCT enable us to leverage the widely used X-ray imaging for simultaneous in vivo molecular and functional imaging. Depending on the geometry of the excitation X-ray beam (pencil-, fan-, and cone-beam or coded apertures), optimal tradeoff between imaging efficiency and spatial resolution can be achieved. The novel imaging principles of XLCT/XFCT make it possible to achieve a spatial resolution comparable to that of anatomical X-ray imaging. Here, we summarize our studies in this area in the past decade and discuss their prospects.
Deep vein thrombosis (DVT) is a disorder that occurs when a blood clot (thrombus) forms in one or more of the deep veins in your body, usually in your legs. Deep vein thrombosis can cause leg pain or swelling, but also can occur with no symptoms. If the clot moves to the vital organs like lungs, heart, brain etc., it can be very fatal and can cause death to the individual. Diagnosing it at early stages is very crucial to decide the treatment strategy. The most commonly used techniques that are used for the diagnosis includes ultrasound, x-ray, CT, etc. For definitive diagnosis contrast agents are required for better visualization of the blood clots and harmful radiations are used. For label free imaging of the blood clots, photoacoustic imaging can be used. To perform in-vivo photoacoustic imaging, high framerate imaging is needed as the velocity of the blood in the veins is between 3 cm/s to 14 cm/s. In this work, we have shown high framerate photoacoustic imaging at different framerates of 5, 10, 50, 100, 500, 1000, 2000 and 3000 fps using a pulsed laser diode of 7000 Hz frequency. We have demonstrated label free imaging of blood clots at 803 nm. Blood clot has at least 1.5 times higher SNR compared to blood and can be clearly visualized against blood as background. High framerate photoacoustic imaging can be used for label free diagnosis of deep vein thrombosis.
Contrast agents which can be used for more than one bio-imaging technique has gained a lot of attention from researchers in recent years. In this work, a microfluidic device employing a flow-focusing junction, is used for the continuous generation of monodisperse nitrogen microbubbles in methylene blue, an optically absorbing organic dye, for dual-modal photoacoustic and ultrasound imaging. Using an external phase of polyoxyethylene glycol 40 stearate (PEG 40), a non-ionic surfactant, and 50% glycerol solution at a flow rate of 1 ml/hr and gas pressure at 1.75 bar, monodisperse nitrogen microbubbles of diameter 7 microns were obtained. The external phase also contained methylene blue hydrate at a concentration of 1 gm/litre. The monodisperse microbubbles produced a strong ultrasound signal as expected. It was observed that the signal-to-noise (SNR) ratio of the photoacoustic signal for the methylene blue solution in the presence of the monodisperse microbubbles was 68.6% lower than that of methylene blue solution in the absence of microbubbles. This work is of significance because using microfluidics, we can precisely control the bubbles’ production rate and bubble size which increases ultrasound imaging efficiency. A uniform size distribution of the bubbles will have narrower resonance frequency bandwidth which will respond well to specific ultrasound frequencies.
Vesicoureteral reflux is the abnormal flow of urine from your bladder back up the tubes (ureters) that connect your kidneys to your bladder. Normally, urine flows only down from your kidneys to your bladder. Vesicoureteral reflux is usually diagnosed in infants and children. The disorder increases the risk of urinary tract infections, which, if left untreated, can lead to kidney damage. X-Ray cystography is used currently to diagnose this condition which uses ionising radiation, making it harmful for patients. In this work we demonstrate the feasibility of imaging the urinary bladder using a handheld clinical ultrasound and photoacoustic dual modal imaging system in small animals (rats). Additionally, we demonstrate imaging vesicoureteral reflux using bladder mimicking phantoms. Urinary bladder imaging is done with the help of contrast agents like black ink and gold nanoparticles which have high optical absorption at 1064 nm. Imaging up to 2 cm was demonstrated with this system. Imaging was done at a framerate of 5 frames per second.
KEYWORDS: Optical spheres, Signal to noise ratio, Transducers, Photons, Absorbance, Imaging systems, Monte Carlo methods, Lymphatic system, Ultrasonography, Tissues
Photoacoustic tomography is a hybrid imaging modality that combines optical and ultrasound imaging. It is rapidly gaining attention in the field of medical imaging. The challenge is to translate it into a clinical setup. In this work, we report the development of a handheld clinical photoacoustic imaging system. A clinical ultrasound imaging system is modified to integrate photoacoustic imaging with the ultrasound imaging. Hence, light delivery has been integrated with the ultrasound probe. The angle of light delivery is optimized in this work with respect to the depth of imaging. Optimization was performed based on Monte Carlo simulation for light transport in tissues. Based on the simulation results, the probe holders were fabricated using 3D printing. Similar results were obtained experimentally using phantoms. Phantoms were developed to mimic sentinel lymph node imaging scenario. Also, in vivo sentinel lymph node imaging was done using the same system with contrast agent methylene blue up to a depth of 1.5 cm. The results validate that one can use Monte Carlo simulation as a tool to optimize the probe holder design depending on the imaging needs. This eliminates a trial and error approach generally used for designing a probe holder.
KEYWORDS: Ultrasonography, Monte Carlo methods, Photons, Optical spheres, Imaging systems, Absorbance, Tissue optics, Signal to noise ratio, Transducers, Photoacoustic imaging
Translating photoacoustic (PA) imaging into clinical setup is a challenge. We report an integrated PA and ultrasound imaging system by combining the light delivery to the tissue with the ultrasound probe. First, Monte Carlo simulations were run to study the variation in absorbance within tissue for different angles of illumination, fiber-to-probe distance (FPD), and fiber-to-tissue distance (FTD). This is followed by simulation for different depths of the embedded sphere (object of interest). Several probe holders were designed for different light launching angles. Phantoms were developed to mimic a sentinel lymph node imaging scenario. It was observed that, for shallower imaging depths, the variation in signal-to-noise ratio (SNR) values could be as high as 100% depending on the angle of illumination at a fixed FPD and FTD. Results confirm that different light illumination angles are required for different imaging depths to get the highest SNR PA images. The results also validate that one can use Monte Carlo simulation as a tool to optimize the probe holder design depending on the imaging needs. This eliminates a trial-and-error approach generally used for designing a probe holder.
KEYWORDS: Melanoma, Photoacoustic imaging, Blood, Gold, Imaging systems, Signal to noise ratio, Near infrared, Luminescence, In vivo imaging, Absorption
Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in in vivo, noninvasive imaging of biological structures at depths but it can also be used for drug release and therapeutic applications. We explore near-infrared light-sensitive liposomes coated with gold nanostars (AuNSs) for both imaging and drug release applications using a photoacoustic imaging system. Being amphiphilic, the liposomes lipid bilayer and the aqueous core enable encapsulation of both hydrophobic and hydrophilic drugs. The AuNSs on the surface of the liposomes act as photon absorbers due to their intrinsic surface plasmon resonance. Upon excitation by laser light at specific wavelength, AuNSs facilitate rapid release of the contents encapsulated in the liposomes due to local heating and pressure wave formation (photoacoustic wave). Herein, we describe the design and optimization of the AuNSs-coated liposomes and demonstrate the release of both hydrophobic and hydrophilic model drugs (paclitaxel and calcein, respectively) through laser excitation at near-infrared wavelength. The use of AuNSs-coated liposomes as contrast agents for photoacoustic imaging is also explored with tissue phantom experiments. In comparison to blood, the AuNSs-coated liposomes have better contrast (approximately two times) at 2-cm imaging depth.
Photoacoustic tomography (PAT) is a potential hybrid imaging modality which is gaining attention in the field of medical imaging. Typically a Q-switched Nd:YAG laser is used to excite the tissue and generate photoacoustic signals. But, they are not suitable for clinical applications owing to their high cost, large size. Also, their low pulse repetition rate (PRR) of few tens of hertz prevents them from being used in real-time PAT. So, there is a growing need for an imaging system capable of real-time imaging for various clinical applications. In this work, we are using a nanosecond pulsed laser diode as an excitation source and a clinical ultrasound imaging system to obtain the photoacoustic imaging. The excitation laser is ~803 nm in wavelength with energy of ~1.4 mJ per pulse. So far, the reported frame rate for photoacoustic imaging is only a few hundred Hertz. We have demonstrated up to 7000 frames per second framerate in photoacoustic imaging (B-mode) and measured the flow rate of fast moving obje ct. Phantom experiments were performed to test the fast imaging capability and measure the flow rate of ink solution inside a tube. This fast photoacoustic imaging can be used for various clinical applications including cardiac related problems, where the blood flow rate is quite high, or other dynamic studies.
Photoacoustic tomography (PAT) is a potential hybrid imaging modality that has attracted great attention in the fields of medical imaging. In order to generate photoacoustic signal efficiently Q-switched Nd:YAG pump lasers capable of generating tens of millijoules of nanosecond laser pulses have been widely used. However, PAT systems using such lasers have limitations in clinical applications because of their high cost, large size, and cooling requirements. Furthermore, the low pulse repetition rate (PRR) of tens of hertz is not suitable for real-time PAT. So, there is a need for inexpensive, compact, simple, fast imaging system for clinical applications. Nanosecond pulsed laser diodes could meet these requirements. In this work, we present a high-speed photoacoustic tomography imaging system that uses a compact and yet relatively powerful near-infrared pulsed laser diode. The PAT system was tested on phantoms to verify its potential imaging speed. Photoacoustic reconstructed images at different scanning speeds are presented. With single ultrasound detector scanning, the system could provide PA image ~10 times faster than the Nd:YAG laser based systems.
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.