Syeda Tabassum

Three-dimensional printed optical phantoms with customized absorption and scattering properties.

Three-dimensional (3D) printing offers the promise of fabricating optical phantoms with arbitrary geometry, but commercially available thermoplastics provide only a small range of physiologically relevant absorption (µa) and reduced scattering (µs`) values. Here we demonstrate customizable acrylonitrile butadiene styrene (ABS) filaments for dual extrusion 3D printing of tissue mimicking optical phantoms. µa and µs` values were adjusted by incorporating nigrosin and titanium dioxide (TiO2) in the filament extrusion process. A wide range of physiologically relevant optical properties was demonstrated with an average repeatability within 11.5% for µa and 7.71% for µs`. Additionally, a mouse-simulating phantom, which mimicked both the geometry and optical properties of a hairless mouse with an implanted xenograft tumor, was printed using dual extrusion methods. 3D printed tumor optical properties matched the live tumor with less than 3% error at a wavelength of 659 nm. 3D printing with user defined optical properties may provide a viable method for durable optically diffusive phantoms for instrument characterization and calibration.

Angle correction for small animal tumor imaging with spatial frequency domain imaging (SFDI)

Spatial frequency domain imaging (SFDI) is a widefield imaging technique that allows for the quantitative extraction of tissue optical properties. SFDI is currently being explored for small animal tumor imaging, but severe imaging artifacts occur for highly curved surfaces (e.g. the tumor edge). We propose a modified Lambertian angle correction, adapted from the Minnaert correction method for satellite imagery, to account for tissue surface angles up to 75°. The method was tested in a hemisphere phantom study as well as a small animal tumor model. The proposed method reduced µa and µs` extraction errors by an average of 64% and 16% respectively compared to performing no angle correction, and provided more physiologically agreeable optical property and chromophore values on tumors.

Feasibility of spatial frequency domain imaging (SFDI) for optically characterizing a preclinical oncology model

Determination of chemotherapy efficacy early during treatment would provide more opportunities for physicians to alter and adapt treatment plans. Diffuse optical technologies may be ideally suited to track early biological events following chemotherapy administration due to low cost and high information content. We evaluated the use of spatial frequency domain imaging (SFDI) to characterize a small animal tumor model in order to move towards the goal of endogenous optical monitoring of cancer therapy in a controlled preclinical setting. The effects of key measurement parameters including the choice of imaging spatial frequency and the repeatability of measurements were evaluated. The precision of SFDI optical property extractions over repeat mouse measurements was determined to be within 3.52% for move and replace experiments. Baseline optical properties and chromophore values as well as intratumor heterogeneity were evaluated over 25 tumors. Additionally, tumor growth and chemotherapy response were monitored over a 45 day longitudinal study in a small number of mice to demonstrate the ability of SFDI to track treatment effects. Optical scattering and oxygen saturation increased as much as 70% and 25% respectively in treated tumors, suggesting SFDI may be useful for preclinical tracking of cancer therapies.

Long-term longitudinal monitoring of chemotherapy response using Spatial Frequency Domain Imaging using an improved two-layer Monte Carlo based inverse model (Conference Presentation)

Spatial Frequency Domain Imaging (SFDI) is a Diffuse Optical Imaging (DOI) technique that is well suited for preclinical functional imaging. Recently, we have shown that SFDI can successfully be used for longitudinal monitoring of a prostate subcutaneous tumor xenograft, where we have applied a look-up-table (LUT) based approach to extract tissue absorption (μa) and scattering properties (μs’). This LUT assumes a semi-infinite homogeneous medium and simulates reflectance (Rd) in spatial domain, and scales Rd for all μa and μs’ of interest from a single Monte Carlo simulation. However, converting Rd to spatial frequency domain (SFD) and scaling for μs’ may introduces unacceptable errors. Most importantly, the homogeneous model fails to mimic the actual physiology of a subcutaneous tumor, which can be described as a two-layer medium with a thin skin layer above the tumor layer. To overcome these limitations, we have developed a Monte Carlo based two-layer LUT with a wide range of tumor (bottom) layer optical properties, and fixed skin (top) properties. The two-layer LUT will be validated by two-layer silicone phantoms and tested for sensitivity to inaccurate layer assumptions. Additionally, the homogeneous and two-layer LUTs will be used on a large mouse tumor database (n=54 mice monitored over 3 months) to identify how the two-layer LUT can improve accuracy of SFDI by more accurately reflecting in vivo physiology, and reducing discretization and scaling errors. Improved SFDI findings in small animals, in the long run, will help establish clinical DOI tools for early detection of chemotherapy efficacy during treatment.

Customized three-dimensional printed optical phantoms with user defined absorption and scattering

The use of reliable tissue-simulating phantoms spans multiple applications in spectroscopic imaging including device calibration and testing of new imaging procedures. Three-dimensional (3D) printing allows for the possibility of optical phantoms with arbitrary geometries and spatially varying optical properties. We recently demonstrated the ability to 3D print tissue-simulating phantoms with customized absorption (μa) and reduced scattering (μs`) by incorporating nigrosin, an absorbing dye, and titanium dioxide (TiO2), a scattering agent, to acrylonitrile butadiene styrene (ABS) during filament extrusion. A physiologically relevant range of μa and μs` was demonstrated with high repeatability. We expand our prior work here by evaluating the effect of two important 3D-printing parameters, percent infill and layer height, on both μa and μs`. 2 cm3 cubes were printed with percent infill ranging from 10% to 100% and layer height ranging from 0.15 to 0.40 mm. The range in μa and μs` was 27.3% and 19.5% respectively for different percent infills at 471 nm. For varying layer height, the range in μa and μs` was 27.8% and 15.4% respectively at 471 nm. These results indicate that percent infill and layer height substantially alter optical properties and should be carefully controlled during phantom fabrication. Through the use of inexpensive hobby-level printers, the fabrication of optical phantoms may advance the complexity and availability of fully customizable phantoms over multiple spatial scales. This technique exhibits a wider range of adaptability than other common methods of fabricating optical phantoms and may lead to improved instrument characterization and calibration.

Longitudinal Monitoring of Therapy Response in a Preclinical Model using Spatial Frequency Domain Imaging

We present here a proof-of-concept longitudinal study of cytotoxic and antiangiogenic therapy response in a preclinical model using Spatial Frequency Domain Imaging. Significant changes in optical scattering and hemoglobin were observed in tumors.

Preclinical and Clinical Chemotherapy Response Monitoring with Diffuse Optical Technologies

We will present initial data demonstrating that Spatial Frequency-Domain Imaging (SFDI) can be used to inform clinical translation by tracking chemotherapy-induced changes of both endogenous and exogenous optical markers of chemotherapy response in preclinical models.