Paul Kumar Upputuri

Broadband Absorbing Semiconducting Polymer Nanoparticles for Photoacoustic Imaging in Second Near-Infrared Window

Photoacoustic (PA) imaging holds great promise for preclinical research and clinical practice. However, most studies rely on the laser wavelength in the first near-infrared (NIR) window (NIR-I, 650-950 nm), while few studies have been exploited in the second NIR window (NIR-II, 1000-1700 nm), mainly due to the lack of NIR-II absorbing contrast agents. We herein report the synthesis of a broadband absorbing PA contrast agent based on semiconducting polymer nanoparticles (SPN-II) and apply it for PA imaging in NIR-II window. SPN-II can absorb in both NIR-I and NIR-II regions, providing the feasibility to directly compare PA imaging at 750 nm with that at 1064 nm. Because of the weaker background PA signals from biological tissues in NIR-II window, the signal-to-noise ratio (SNR) of SPN-II resulted PA images at 1064 nm can be 1.4-times higher than that at 750 nm when comparing at the imaging depth of 3 cm. The proof-of-concept application of NIR-II PA imaging is demonstrated in in vivo imaging of brain vasculature in living rats, which showed 1.5-times higher SNR as compared with NIR-I PA imaging. Our study not only introduces the first broadband absorbing organic contrast agent that is applicable for PA imaging in both NIR-I and NIR-II windows but also reveals the advantages of NIR-II over NIR-I in PA imaging.

Activatable Photoacoustic Nanoprobes for In Vivo Ratiometric Imaging of Peroxynitrite

Organic semiconducting nanoprobes doped with bulky borane can undergo specific activation by ONOO- even at tumor-relevant acidic pH (6.8), permitting in vivo ratiometric photoacoustic imaging of ONOO- in the tumor environment of living mice.

Performance characterization of low-cost, high-speed, portable pulsed laser diode photoacoustic tomography (PLD-PAT) system.

Photoacoustic tomography systems that uses Q-switched Nd:YAG/OPO pulsed lasers are expensive, bulky, and hence limits its use in clinical applications. The low pulse repetition rate of these lasers makes it unsuitable for real-time imaging when used with single-element ultrasound detector. In this work, we present a pulsed laser diode photoacoustic tomography (PLD-PAT) system that integrates a compact PLD inside a single-detector circular scanning geometry. We compared its performance against the traditional Nd:YAG/OPO based PAT system in terms of imaging depth, resolution, imaging time etc. The PLD provides near-infrared pulses at ~803 nm wavelength with pulse energy ~1.4 mJ/pulse at 7 kHz repetition rate. The PLD-PAT system is capable of providing 2D image in scan time as small as 3 sec with a signal-to-noise ratio ~30. High-speed and deep-tissue imaging is demonstrated on phantoms and biological samples. The PLD-PAT system is inexpensive, portable, allows high-speed PAT imaging, and its performance is as good as traditional expensive OPO based PAT system. Therefore, it holds promises for future translational biomedical imaging applications.

Recent advances toward preclinical and clinical translation of photoacoustic tomography: a review

Abstract. Photoacoustic imaging is an emerging hybrid imaging modality that can provide multicontrast, multiscale imaging of biological features ranging from organelles to organs. The three major embodiments of photoacoustic imaging are microscopy, endoscopy, and computed tomography. Photoacoustic tomography (PAT) or photoacoustic computed tomography allows deep-tissue imaging, and hence it is more suitable for whole body preclinical/clinical imaging applications. Due to fast-growing laser technology and ultrasound detector technology, PAT is evolving rapidly, leading to a quicker translation into clinical trials. We review the recent developments of PAT systems and their applications in preclinical and clinical practices.

Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine

Adequate vascularisation is key in determining the clinical outcome of stem cells and engineered tissue in regenerative medicine. Numerous imaging modalities have been developed and used for the visualization of vascularisation in tissue engineering. In this review, we briefly discuss the very recent advances aiming at high performance imaging of vasculature. We classify the vascular imaging modalities into three major groups: nonoptical methods (X-ray, magnetic resonance, ultrasound, and positron emission imaging), optical methods (optical coherence, fluorescence, multiphoton, and laser speckle imaging), and hybrid methods (photoacoustic imaging). We then summarize the strengths and challenges of these methods for preclinical and clinical applications.

Amphiphilic semiconducting polymer as multifunctional nanocarrier for fluorescence/photoacoustic imaging guided chemo-photothermal therapy

Chemo-photothermal nanotheranostics has the advantage of synergistic therapeutic effect, providing opportunities for optimized cancer therapy. However, current chemo-photothermal nanotheranostic systems generally comprise more than three components, encountering the potential issues of unstable nanostructures and unexpected conflicts in optical and biophysical properties among different components. We herein synthesize an amphiphilic semiconducting polymer (PEG-PCB) and utilize it as a multifunctional nanocarrier to simplify chemo-photothermal nanotheranostics. PEG-PCB has a semiconducting backbone that not only serves as the diagnostic component for near-infrared (NIR) fluorescence and photoacoustic (PA) imaging, but also acts as the therapeutic agent for photothermal therapy. In addition, the hydrophobic backbone of PEG-PCB provides strong hydrophobic and π-π interactions with the aromatic anticancer drug such as doxorubicin for drug encapsulation and delivery. Such a trifunctionality of PEG-PCB eventually results in a greatly simplified nanotheranostic system with only two components but multimodal imaging and therapeutic capacities, permitting effective NIR fluorescence/PA imaging guided chemo-photothermal therapy of cancer in living mice. Our study thus provides a molecular engineering approach to integrate essential properties into one polymer for multimodal nanotheranostics.

Super-resolution photoacoustic microscopy using photonic nanojets: a simulation study

Abstract. Optical resolution photoacoustic microscopy (ORPAM) is important for various biomedical applications, such as the study of cellular structures, microcirculation systems, and tumor angiogenesis. However, the lateral resolution of a conventional ORPAM is limited by optical diffraction. In this work, we report a simulation study to achieve subdiffraction-limited super-resolution in ORPAM using microspheres. Laser radiation is focused through a microsphere to generate a photonic nanojet, which provides the possibility to break the diffraction limit in ORPAM by reducing the size of the excitation volume. In our simulations using microspheres, we observed improvement in the lateral resolution up to ∼fourfold compared to conventional ORPAM. The method is simple, cost effective, and can provide far-field resolution. This approach may provide new opportunities for many biomedical imaging applications that require finer resolution.

Pulsed laser diode based optoacoustic imaging of biological tissues

Optoacoustic tomography (OAT) is a promising hybrid imaging modality for many biomedical applications. However, the use of Nd:YAG laser as excitation source makes the OAT system expensive, and non-portable. Miniaturization of OAT system is an immediate task to make it a potential tool for both preclinical and clinical studies. In this work, we present an OA system that uses a miniaturized pulsed laser diode which can provide near infrared pulses at ~803 nm. With laser fluence ~0.3 mJ cm−2 on the tissue surface, we achieved 3 cm deep imaging in chicken tissue. The high pulse repetition rate of the diode laser allowed rapid acquisition of OA cross-sectional images with good image quality. The results promise that the proposed system has potential to be used as an alternative to Nd:YAG based OAT systems for biological imaging applications.

Compact Plasmonic Blackbody for Cancer Theranosis in the Near-Infrared II Window

We have developed a class of blackbody materials, i. e., hyperbranched Au plasmonic blackbodies (AuPBs), of compact sizes (<50 nm). The AuPBs were prepared in a seedless and surfactant-free approach based on the use of mussel-inspired dopamine. Strong intraparticle plasmonic coupling among branches in close proximity leads to intense and uniform broadband absorption across 400-1350 nm. The blackbody absorption imparts the compact AuPB with a superior photothermal efficiency of >80% and closely matched photothermal activity in the first near-infrared (NIR-I) and the second near-infrared (NIR-II) spectral windows, making it a rare broadband theranostic probe for integrated photoacoustic imaging and photothermal therapy (PTT). Our comparative study, using the same probe, has demonstrated that the improved PTT outcome of NIR-II over NIR-I primarily results from its higher maximum permission exposure (MPE) rather than the deeper tissue penetration favored by longer wavelengths. The compact plasmonic broadband nanoabsorbers with tailored surface properties hold potential for a wide spectrum of light-mediated applications.

Near Infrared light-responsive liposomal contrast agent for photoacoustic imaging and drug release applications

Abstract. 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.