SignificanceX-ray imaging is frequently used for gastrointestinal imaging. Photoacoustic imaging (PAI) of the gastrointestinal tract is an emerging approach that has been demonstrated for preclinical imaging of small animals. A contrast agent active in both modalities could be useful for imaging applications.AimWe aimed to develop a dual-modality contrast agent comprising an admixture of barium sulfate with pigments that absorb light in the second near-infrared region (NIR-II), for preclinical imaging with both x-ray and PAI modalities.ApproachEleven different NIR-II dyes were evaluated after admixture with a 40% w/v barium sulfate mixture. The resulting NIR-II absorption in the soluble fraction and in the total mixture was characterized. Proof-of-principle imaging studies in mice were carried out.ResultsPigments that produced more uniform suspensions were assessed further for photoacoustic contrast signal at a wavelength of 1064 nm that corresponds to the output of the Nd:YAG laser used. Phantom imaging studies demonstrated that the pigment-barium sulfate mixture generated imaging contrast in both x-ray and PAI modalities. The optimal pigment selected for further study was a cyanine tetrafluoroborate salt. Ex-vivo and whole-body mouse imaging demonstrated that photoacoustic and x-ray contrast signals co-localized in the intestines for both imaging modalities.ConclusionThese data demonstrate that commercially-available NIR-II pigments can simply be admixed with barium sulfate to generate a dual-modality contrast agent appropriate for small animal gastrointestinal imaging.
Photosensitizers can be integrated with drug delivery vehicles to develop chemophototherapy agents with anti-tumor synergy between chemo- and photo- components. Long-circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) incorporates a phospholipid-like photosensitizer (2 mole %) in the bilayer of Dox-loaded stealth liposomes. Hematological effects of endotoxin-minimized LC-Dox-PoP were characterized via standardized assays. In vitro interaction with erythrocytes, platelets, and plasma coagulation cascade were generally unremarkable while complement activation was found to be similar to that of commercial Doxil. Blood partitioning suggested both the Dox and PoP components of LC-Dox-PoP were stably entrapped or incorporated in liposomes. This was further confirmed with pharmacokinetic studies in Fischer rats, which showed the PoP and Dox components of the liposomes both had nearly identical, long circulation half-lives (25-26 hours). In a large orthotopic mammary tumor model in Fischer rats, following intravenous dosing (2 mg/kg Dox), the depth of enhanced Dox delivery in response to 665 nm laser irradiation was over 1 cm. LC-Dox-PoP with laser treatment cured or potently suppressed tumor growth, with greater efficacy observed in tumors 0.8-1.2 cm compared to larger ones. The skin at the treatment site healed within approximately 30 days. Taken together, these data provide insight into nanocharacterization and photo-ablation parameters for a chemophototherapy agent.
Slit-enabled photoacoustic tomography (PAT) is a newly developed technique that improves the elevation resolution and signal to noise ratio of a linear array. The slit, placed along the transducer array focus, forms an array of virtual detectors with high receiving angle, which subsequently allows for three dimensional (3D) imaging with near-isotropic spatial resolution. Our development addressed the long-standing issue of high quality 3D imaging with a linear array and will have broad applications in preclinical and clinical imaging. This study presented the principle of slit-PAT and demonstrated its efficiency in phantom, animal, and human experiments.
This study demonstrated the performance of photoacoustic imaging at 1064 nm using phosphorus phthalocyanine (P-Pc), a contrast agent with strong absorption at 1064 nm. Due to high maximum permissible exposure of 1064 nm laser light and strong absorbance of P-Pc at 1064 nm, we demonstrated an imaging depth of 11.6 cm in chicken breast tissue. For animal imaging, we used P-Pc to target tumor and to track intestine dynamics. Thus, using a contrast medium with extreme absorption at 1064 nm readily enables high quality photoacoustic imaging at exceptional depths.
Here, we introduce a new image reconstruction algorithm that combines coherent weighting with focal-line-based three-dimensional image reconstruction. The new algorithm addresses the major limitation of a linear ultrasound transducer array, i.e., the poor elevation resolution, and does not require any modification to the imaging system or the scanning geometry. We first numerically validated our approach through simulation and then experimentally tested it in phantom and in vivo. Both simulation and experimental results proved that the method can significantly improve the elevation resolution (up to 3.4 times in our experiment) and enhance object contrast.
KEYWORDS: Imaging systems, Transducers, Photoacoustic imaging, Ultrasonography, Real time imaging, Preclinical imaging, Image processing, Tissues, In vivo imaging, Breast, Surgery
We have successfully developed a clinical real-time photoacoustic/ultrasound (PA/US) imaging system. The PA/US imaging system was adapted with a FDA approved commercial US imaging system and a portable pulsed laser system. All image processing and display tasks were performed in real-time by using a graphical processing unit of the US imaging system. We have tested performances of the system by measuring maximum penetration depth, noise equivalent sensitivity, and axial resolution of contrast agent deposited microtubes under chicken breast tissues. By adapting various US transducers (i.e., linear, convex, phased, and endocavity), adaptable capability of the system was verified. In addition, volumetric PA/US imaging was performed by applying a linear scanning along an elevational direction. We have successfully acquired volumetric PA/US images of human forearms in vivo. We believe that the developed clinical real-time PA/US imaging system can be utilized in various preclinical and clinical studies in the near future.
We have demonstrated a novel microbubbles methylene blue solution, called to “MB2” solution for a dual modality contrast. We have photoacoustically and ultrasonically imaged and quantified aqueous solutions of MB2 by varying the concentration of either microbubbles or methylene blue to investigate the dual modal imaging capability. Interestingly, as the microbubbles concentration increased with the constant methylene blue concentration, photoacoustic (PA) signal was greatly attenuated in the MB2 solution. Conversely, when methylene blue concentration increased with the fixed microbubbles concentration, no interference was observed in ultrasound (US) signals. To further confirm our findings, we switched the PA and ultrasound (US) signals using conventional ultrasound. We compared the PA and US signals of the MB2 solution before and after sonication. The PA amplitude increased 2.5 times. Conversely, the US signals were initially strong, but decreased 2.5 times following sonication. Moreover, we used a clinically modified PA/US imaging system to disrupt the microbubbles in MB2 and recover the PA signals.
Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB 2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB 2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB 2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800 -fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.
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.