3D-Bioprinted Phantom with Human Skin Phototypes for Biomedical Optics.

3D-bioprinted skin-mimicking phantoms with skin colors ranging across the Fitzpatrick scale are reported. These tools can help understand the impact of skin phototypes on biomedical optics. Synthetic melanin nanoparticles of different sizes (70-500 nm) and clusters are fabricated to mimic the optical behavior of melanosome. The absorption coefficient and reduced scattering coefficient of the phantoms are comparable to real human skin. Further the melanin content and distribution in the phantoms versus real human skins are validated via photoacoustic (PA) imaging. The PA signal of the phantom can be improved by: 1) increasing melanin size (3-450-fold), 2) increasing clustering (2-10.5-fold), and 3) increasing concentration (1.3-8-fold). Then, multiple biomedical optics tools (e.g., PA, fluorescence imaging, and photothermal therapy) are used to understand the impact of skin tone on these modalities. These well-defined 3D-bioprinted phantoms may have value in translating biomedical optics and reducing racial bias.

Photoacoustic imaging of posterior periodontal pocket using a commercial hockey-stick transducer.

SIGNIFICANCE: Photoacoustic imaging has shown advantages over the periodontal probing method in measuring the periodontal probing depth, but the large size of conventional photoacoustic transducers prevents imaging of the more posterior teeth. AIM: Our aim is to develop a photoacoustic imaging system to image the more posterior periodontal pocket. APPROACH: We report a clinical "hockey-stick"-style transducer integrated with fibers for periodontal photoacoustic imaging. Cuttlefish ink labeled the periodontal pocket as the photoacoustic contrast agent. RESULTS: We characterized the imaging system and then measured the pocket depth of 35 swine teeth. Three raters evaluated the performance of the hockey-stick transducer. The measurements between the Williams probing (gold standard) and the photoacoustic methods were blinded but highly correlated. We showed a bias of ∼0.3 mm for the imaging-based technique versus Williams probing. The minimum inter-reliability was over 0.60 for three different raters of varying experience, suggesting that this approach to measure the periodontal pocket is reproducible. Finally, we imaged three pre-molars of a human subject. We could access more upper and posterior teeth than conventional linear transducers. CONCLUSIONS: The unique angle shape of the hockey-stick transducer allows it to image more posterior teeth than regular linear transducers. This study demonstrated the ability of a hockey-stick transducer to measure the periodontal pocket via photoacoustic imaging.

Photoacoustic imaging phantoms for assessment of object detectability and boundary buildup artifacts.

Standardized phantoms and test methods are needed to accelerate clinical translation of emerging photoacoustic imaging (PAI) devices. Evaluating object detectability in PAI is challenging due to variations in target morphology and artifacts including boundary buildup. Here we introduce breast fat and parenchyma tissue-mimicking materials based on emulsions of silicone oil and ethylene glycol in polyacrylamide hydrogel. 3D-printed molds were used to fabricate solid target inclusions that produced more filled-in appearance than traditional PAI phantoms. Phantoms were used to assess understudied image quality characteristics (IQCs) of three PAI systems. Object detectability was characterized vs. target diameter, absorption coefficient, and depth. Boundary buildup was quantified by target core/boundary ratio, which was higher in transducers with lower center frequency. Target diameter measurement accuracy was also size-dependent and improved with increasing transducer frequency. These phantoms enable evaluation of multiple key IQCs and may support development of comprehensive standardized test methods for PAI devices.

Review of consensus test methods in medical imaging and current practices in photoacoustic image quality assessment.

SIGNIFICANCE: Photoacoustic imaging (PAI) is a powerful emerging technology with broad clinical applications, but consensus test methods are needed to standardize performance evaluation and accelerate translation. AIM: To review consensus image quality test methods for mature imaging modalities [ultrasound, magnetic resonance imaging (MRI), x-ray CT, and x-ray mammography], identify best practices in phantom design and testing procedures, and compare against current practices in PAI phantom testing. APPROACH: We reviewed scientific papers, international standards, clinical accreditation guidelines, and professional society recommendations describing medical image quality test methods. Observations are organized by image quality characteristics (IQCs), including spatial resolution, geometric accuracy, imaging depth, uniformity, sensitivity, low-contrast detectability, and artifacts. RESULTS: Consensus documents typically prescribed phantom geometry and material property requirements, as well as specific data acquisition and analysis protocols to optimize test consistency and reproducibility. While these documents considered a wide array of IQCs, reported PAI phantom testing focused heavily on in-plane resolution, depth of visualization, and sensitivity. Understudied IQCs that merit further consideration include out-of-plane resolution, geometric accuracy, uniformity, low-contrast detectability, and co-registration accuracy. CONCLUSIONS: Available medical image quality standards provide a blueprint for establishing consensus best practices for photoacoustic image quality assessment and thus hastening PAI technology advancement, translation, and clinical adoption.

Polyacrylamide hydrogel phantoms for performance evaluation of multispectral photoacoustic imaging systems.

As photoacoustic imaging (PAI) begins to mature and undergo clinical translation, there is a need for well-validated, standardized performance test methods to support device development, quality control, and regulatory evaluation. Despite recent progress, current PAI phantoms may not adequately replicate tissue light and sound transport over the full range of optical wavelengths and acoustic frequencies employed by reported PAI devices. Here we introduce polyacrylamide (PAA) hydrogel as a candidate material for fabricating stable phantoms with well-characterized optical and acoustic properties that are biologically relevant over a broad range of system design parameters. We evaluated suitability of PAA phantoms for conducting image quality assessment of three PAI systems with substantially different operating parameters including two commercial systems and a custom system. Imaging results indicated that appropriately tuned PAA phantoms are useful tools for assessing and comparing PAI system image quality. These phantoms may also facilitate future standardization of performance test methodology.

Development and Characterization of PLGA-Based Multistage Delivery System for Enhanced Payload Delivery to Targeted Vascular Endothelium.

Vascular-targeted drug delivery remains an attractive platform for therapeutic and diagnostic interventions in human diseases. This work focuses on the development of a poly-lactic-co-glycolic-acid (PLGA)-based multistage delivery system (MDS). MDS consists of two stages: a micron-sized PLGA outer shell and encapsulated drug-loaded PLGA nanoparticles. Nanoparticles with average diameters of 76, 119, and 193 nm are successfully encapsulated into 3-6 µm MDS. Sustained in vitro release of nanoparticles from MDS is observed for up to 7 days. Both MDS and nanoparticles arebiocompatible with human endothelial cells. Sialyl-Lewis-A (sLeA ) is successfully immobilized on the MDS and nanoparticle surfaces to enable specific targeting of inflamed endothelium. Functionalized MDS demonstrates a 2.7-fold improvement in endothelial binding compared to PLGA nanoparticles from human blood laminar flow. Overall, the presented results demonstrate successful development and characterization of MDS and suggest that MDS can serve as an effective drug carrier, which can enhance the margination of nanoparticles to the targeted vascular wall.

Methylene blue-filled biodegradable polymer particles as a contrast agent for optical coherence tomography.

Optical coherence tomography (OCT) images largely lack molecular information or molecular contrast. We address that issue here, reporting on the development of biodegradable micro and nano-spheres loaded with methylene blue (MB) as molecular contrast agents for OCT. MB is a constituent of FDA approved therapies and widely used as a dye in off-label clinical applications. The sequestration of MB within the polymer reduced toxicity and improved signal strength by drastically reducing the production of singlet oxygen and leuco-MB. The former leads to tissue damage and the latter to reduced image contrast. The spheres are also strongly scattering which improves molecular contrast signal localization and enhances signal strength. We demonstrate that these contrast agents may be imaged using both pump-probe OCT and photothermal OCT, using a 830 nm frequency domain OCT system and a 1.3 µm swept source OCT system. We also show that these contrast agents may be functionalized and targeted to specific receptors, e.g. the VCAM receptor known to be overexpressed in inflammation.