Significance: Microglia, a type of macrophage, were discovered a little more than a century ago by Pío del Río-Hortega. Since that time, we have gained an immense amount of knowledge on their origin and multifaceted function with the aid of labeling techniques and animal models, among other tools. Only recently have macrophage cells been imaged in living humans. Here we characterize macrophage spatial distribution and temporal dynamics in live human eyes using a label-free adaptive optics imaging approach. This investigation lays a foundation to better understand the body’s immune response not only to ocular diseases like glaucoma, but also to a vast array of neurological diseases with ocular manifestations, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.

Nanoshell-enhanced optical coherence tomography (OCT) is a novel technique with the potential for molecular imaging and improved disease detection. However, optimization of this approach will require a quantitative understanding of the influence of nanoshell parameters on detected OCT signals. In this study, OCT was performed at $1310nm$ in water and turbid tissue-simulating phantoms to which nanoshells were added. The effect of nanoshell concentration, core diameter, and shell thickness on signal enhancement was characterized. Experimental results indicated trends that were consistent with predicted optical properties—a monotonic increase in signal intensity and attenuation with increasing shell and core size. Threshold concentrations for a 2-dB OCT signal intensity gain were determined for several nanoshell geometries. For the most highly backscattering nanoshells tested—291-nm core diameter, 25-nm shell thickness—a concentration of $109$ nanoshells/mL was needed to produce this signal increase. Based on these results, we discuss various practical considerations for optimizing nanoshell-enhanced OCT. Quantitative experimental data presented here will facilitate optimization of OCT-based diagnostics and may also be relevant to other reflectance-based approaches as well.

Measuring the sensitivity of an optical coherence tomography (OCT) system determines the minimum sample reflectivity it can detect and provides a figure of merit for system optimization and comparison. The published literature lacks a detailed description of OCT sensitivity measurement procedures. Here we describe a commonly-used measurement method and introduce two new phantom-based methods, which also offer a means to directly visualize low reflectivity conditions relevant to biological tissue. We provide quantitative results for the three methods from different OCT system configurations and discuss the methods’ advantages and disadvantages.

We describe the design and performance of a multimodal and multifunctional adaptive optics (AO) system that combines scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) for simultaneous retinal imaging at 13.4 Hz. The high-speed AO-OCT channel uses a 3.4 MHz Fourier-domain mode-locked (FDML) swept source. The system achieves exquisite resolution and sensitivity for pan-macular and transretinal visualization of retinal cells and structures while providing a functional assessment of the cone photoreceptors. The ultra-high speed also enables wide-field scans for clinical usability and angiography for vascular visualization. The FDA FDML-AO system is a powerful platform for studying various retinal and neurological diseases for vision science research, retina physiology investigation, and biomarker development.

We present a novel (to our knowledge) approach for measurement of the three-dimensional point spread function (PSF) of optical coherence tomography (OCT) systems using a nanoparticle-embedded phantom (NEP), toward development of standardized test methods for biophotonic imaging. The NEP comprises highly reflective plasmonic nanoparticles, homogeneously distributed in a transparent silicone matrix. OCT image volumes were analyzed to characterize PSFs in axial and lateral directions at a variety of locations in the NEP. Results indicate submicrometer agreement with conventional approaches to measure dimensions of the PSF. The NEP offers a robust approach for validating and comparing imaging performance of OCT devices.

Photoacoustic imaging (PAI) is a rapidly emerging modality that has been proposed for numerous clinical applications including cancer detection, mammography, vascular imaging, tissue oximetry, tumor margining, and biopsy/surgical guidance, among others.^{1 – 5} This wide range of applications and the novelty of the field has resulted in a large variety in device designs. PAI device performance will generally vary with device design parameters (e.g., transducer geometry, optical source properties) as well as tissue parameters (e.g., properties and morphology). Quantitatively predicting how these parameters influence PAI device performance in vivo is challenging. Bench performance test methods can provide insight on design consequences, elucidate device working mechanisms, and help set performance expectations and limitations. Tissue-mimicking phantoms provide an invaluable approach for objective, quantitative evaluation of fundamental image quality characteristics (IQCs) as well as more technology-specific aspects of PAI system performance such as oximetry measurement accuracy, spectral recovery, or chromophore concentration accuracy.^{6 – 11}