Multiangle Long-Axis Lateral Illumination Photoacoustic Imaging Using Linear Array Transducer.

Photoacoustic imaging (PAI) combines optical contrast with ultrasound spatial resolution and can be obtained up to a depth of a few centimeters. Hand-held PAI systems using linear array usually operate in reflection mode using a dark-field illumination scheme, where the optical fiber output is attached to both sides of the elevation plane (short-axis) of the transducer. More recently, bright-field strategies where the optical illumination is coaxial with acoustic detection have been proposed to overcome some limitations of the standard dark-field approach. In this paper, a novel multiangle long-axis lateral illumination is proposed. Monte Carlo simulations were conducted to evaluate light delivery for three different illumination schemes: bright-field, standard dark-field, and long-axis lateral illumination. Long-axis lateral illumination showed remarkable improvement in light delivery for targets with a width smaller than the transducer lateral dimension. A prototype was developed to experimentally demonstrate the feasibility of the proposed approach. In this device, the fiber bundle terminal ends are attached to both sides of the transducer's long-axis and the illumination angle of each fiber bundle can be independently controlled. The final PA image is obtained by the coherent sum of subframes acquired using different angles. The prototype was experimentally evaluated by taking images from a phantom, a mouse abdomen, forearm, and index finger of a volunteer. The system provided light delivery enhancement taking advantage of the geometry of the target, achieving sufficient signal-to-noise ratio at clinically relevant depths.

Clinically translatable quantitative molecular photoacoustic imaging with liposome-encapsulated ICG J-aggregates.

Photoacoustic (PA) imaging is a functional and molecular imaging technique capable of high sensitivity and spatiotemporal resolution at depth. Widespread use of PA imaging, however, is limited by currently available contrast agents, which either lack PA-signal-generation ability for deep imaging or their absorbance spectra overlap with hemoglobin, reducing sensitivity. Here we report on a PA contrast agent based on targeted liposomes loaded with J-aggregated indocyanine green (ICG) dye (i.e., PAtrace) that we synthesized, bioconjugated, and characterized to addresses these limitations. We then validated PAtrace in phantom, in vitro, and in vivo PA imaging environments for both spectral unmixing accuracy and targeting efficacy in a folate receptor alpha-positive ovarian cancer model. These study results show that PAtrace concurrently provides significantly improved contrast-agent quantification/sensitivity and SO2 estimation accuracy compared to monomeric ICG. PAtrace's performance attributes and composition of FDA-approved components make it a promising agent for future clinical molecular PA imaging.

Photoacoustic-based oxygen saturation assessment of murine femoral bone marrow in a preclinical model of leukemia.

A variety of hematological diseases manifest in the bone marrow (BM), broadly characterized as BM failure (BMF). BMF can be caused by acute lymphoblastic leukemia (ALL), which results in an expansion of hypoxic regions in the BM. Because of this hypoxic presentation, there is potential for improved characterization of BMF through in vivo assessment of oxygenation in the BM cavity. Photoacoustic (PA) imaging can provide local assessment of intravascular oxygen saturation (SO2), which has been shown to correlate with pimonidazole-assessed hypoxia. This study introduces an optimized PA imaging technique to assess SO2 within the femoral BM cavity through disease progression in a murine model of ALL. Results show a statistically significant difference with temporal changes in SO2 (from baseline) between control and diseased cohorts, demonstrating the potential of PA imaging for noninvasive, label-free monitoring of BMF diseases.

The effect of magnetization of natural rubber latex-coated magnetite nanoparticles on shear wave dispersion magneto-motive ultrasound.

The shear wave dispersion magneto-motive ultrasound (SDMMUS) method was recently developed to analyze the mechanical properties of a viscoelastic medium. This technique is based on the interaction of magnetic nanoparticles (MNPs) with an external magnetic field to generate a shear wave within the medium labeled with MNPs. The propagation of this wave provides information about the viscoelastic properties of the medium. In a previous work by Arsalani et al (2018), magnetite NPs were synthesized by a co-precipitation method and coated with natural rubber latex (NRL). In order to investigate the effect of NRL on the size and magnetization of MNPs, varying amounts of NRL (zero, 100 µl, and 800 µl of a stock solution of NRL) were used during the synthesis process. The results showed that MNPs prepared with 800 µl of NRL, named as MNPs-800NRL, had the smallest size and highest magnetization. In the present paper, the main objective is to investigate whether MNPs-800NRL, having the highest magnetization, is also the best option for SDMMUS experiments among others. All experiments were performed using gelatin tissue-mimicking phantoms labeled with the aforementioned MNPs. The two factors of core size and magnetization were considered, and based on the observed results, the effect of magnetization was more prominent than that of the core size on the induced displacements. MNPs coated with a thicker NRL shell, having the highest magnetization value, enhanced the sensitivity and the signal to noise ratio in SDMMUS. Various concentrations of these optimized MNPs were also examined, to investigate the lowest possible concentration for observing shear waves in the SDMMUS technique.

Improved Photoacoustic-Based Oxygen Saturation Estimation With SNR-Regularized Local Fluence Correction.

As photoacoustic (PA) imaging makes its way into the clinic, the accuracy of PA-based metrics becomes increasingly important. To address this need, a method combining finite-element-based local fluence correction (LFC) with signal-to-noise-ratio (SNR) regularization was developed and validated to accurately estimate oxygen saturation (SO2) in tissue. With data from a Vevo LAZR system, performance of our LFC approach was assessed in ex vivo blood targets (37.6%-99.6% SO2) and in vivo rat arteries. Estimation error of absolute SO2 and change in SO2 reduced from 10.1% and 6.4%, respectively, without LFC to 2.8% and 2.0%, respectively, with LFC, while the accuracy of the LFC method was correlated with the number of wavelengths acquired. This paper demonstrates the need for an SNR-regularized LFC to accurately quantify SO2 with PA imaging.

Acoustic and Elastic Properties of Glycerol in Oil-Based Gel Phantoms.

Phantoms are important tools for image quality control and medical training. Many phantom materials have been proposed for ultrasound; most of them use water as the solvent, but these materials have disadvantages such as dehydration and low temporal stability if not properly stored. To overcome these difficulties, copolymer-in-oil gel was proposed as an inert and stable material; however, speed of sound for these materials is still lower than what is described for most biological tissues. Here, we propose the glycerol dispersion in oil-based gels to modify the acoustic and elastic properties of copolymer-in-oil phantoms. We manufactured copolymer-in-oil gels using styrene-ethylene/butylene-styrene (SEBS) in concentrations 8%-15%. We used 2 types of mineral oils with different viscosities. Glycerol was added in a volume fraction 0%-30% of the total amount of liquid. The acoustic (i.e., speed of sound, attenuation and backscattering) and the mechanical (i.e., density and Young's modulus) properties of the samples were within the range of values observed for soft tissues. The acoustic parameters of the samples were dependent on oil viscosity and glycerol concentration. The speed of sound ranged 1423 m/s - 1502 m/s, while the acoustic attenuation and the ultrasonic backscattering increased by adding glycerol. The density and the Young's moduli were less affected by the presence of glycerol. We conclude that glycerol can be used to control the acoustic parameters of copolymer-in-oil gels. Additionally, it opens the possibility of incorporating other oil-insoluble substances to control further properties of the phantom.

A hybrid transducer to evaluate stomach emptying by ultrasound and susceptometric measurements: an in vivo feasibility study.

Gastric emptying reflects a diversity of important physiological functions. Alternating current biosusceptometry (ACB) is an inexpensive, radiation-free, and minimally invasive method to evaluate gastric emptying, but its response depends on the spatial distribution of the magnetized material and does not provide precise anatomical information. The hybrid transducer, which combines ACB and an ultrasound probe, is an alternative to improve susceptometry measurements, namely the spatial localization of the magnetized source. In this study, initial stomach emptying, in rats, was monitored with the aid of the hybrid transducer. Yogurt mixed with ferrite particles was injected into the rat's stomach. The hybrid transducer was placed on the rat's abdomen during experiments, and the susceptometry signal and magnetomotive ultrasound (MMUS) images were saved and postprocessed. MMUS highlighted the movement of magnetic particles due to magnetic force from ACB excitation coils, and showed the rat's stomach location. In this feasibility study, we monitored the stomach emptying of 4 rats for 20 min. The mean relative ACB signal decayed by 4.6 ± 0.1%, and the mean relative area of MMUS images decreased by 4.5 ± 0.2%, after 20 min postingestion of the magnetic meal due to stomach emptying. In a second experiment, 3-D MMUS images from axial sequences were obtained by spatially translating the hybrid transducer, providing details of the stomach wall, which may enable minimally invasive detection of abnormalities. In conclusion, the MMUS image increased ACB spatial resolution and furnished additional anatomical information.