For early detection and targeted therapy, receptor expression profiling is instrumental to classifying breast cancer into
sub-groups. In particular, human epidermal growth factor receptor 2 (HER2) expression has been shown to have both
prognostic and predictive values. Recently, an increasingly more complex view of HER2 in breast cancer has emerged
from genome sequencing that highlights the role of inter- and intra-tumor heterogeneity in therapy resistance. Studies on
such heterogeneity demand high-content, high-resolution functional and molecular imaging in vivo, which cannot be
achieved using any single imaging tool. Clearly, there is a critical need to develop a multimodality approach for breast
cancer imaging. Since 2006, grating-based x-ray imaging has been developed for much-improved x-ray images. In 2014,
the demonstration of fluorescence molecular tomography (FMT) guided by x-ray grating-based micro-CT was reported
with encouraging results and major drawbacks. In this paper, we propose to integrate grating-based x-ray tomography
(GXT) and high-dimensional optical tomography (HOT) into the first-of-its-kind truly-fused GXT-HOT (pronounced as
“Get Hot”) system for imaging of breast tumor heterogeneity, HER2 expression and dimerization, and therapeutic
response. The primary innovation lies in developing a brand-new high-content, high-throughput x-ray optical imager
based on several contemporary techniques to have MRI-type soft tissue contrast, PET-like sensitivity and specificity, and
micro-CT-equivalent resolution. This system consists of two orthogonal x-ray Talbot-Lau interferometric imaging chains
and a hyperspectral time-resolved single-pixel optical imager. Both the system design and pilot results will be reported in
this paper, along with relevant issues under further investigation.
Single-pixel imaging based on compressive sensing theory has been a highlighted technique in the biomedical imaging field for many years. This interest has been driven by the possibility of performing microscopic or macroscopic imaging based on low-cost detector arrays, increased SNR (signal-to-noise ratio) in the acquired data sets and the ability to perform high quality image reconstruction with compressed data sets by exploiting signal sparsity. In this work, we present our recent work in implementing this technique to perform time domain fluorescence-labeled investigations in preclinical settings. More precisely, we report on our time-resolved hyperspectral single-pixel camera for fast, wide-field mapping of molecular labels and lifetime-based quantification. The hyperspectral single-pixel camera implements a DMD (Digital micro-mirror device) to generate optical masks for modulating the illumination field before it is delivered onto the sample and focuses the emission light signals into a multi-anode hyperspectral time-resolved PMT (Photomultiplier tube) to acquire spatial, temporal and spectral information enriched 4-D data sets. Fluorescence dyes with lifetime and spectral contrast are embedded in well plates and thin tissues. L-1 norm based regularization or the least square method, is applied to solve the underdetermined inverse problem during image reconstruction. These experimental results prove the possibility of fast, wide-field mapping of fluorescent labels with lifetime and spectral contrast in thin media.
Proc. SPIE. 8937, Multimodal Biomedical Imaging IX
KEYWORDS: Imaging systems, Scattering, Luminescence, Data acquisition, Monte Carlo methods, Digital micromirror devices, Digital Light Processing, Absorption, Diffuse optical tomography, Structured light
Time-resolved Diffuse Optical Tomography (DOT) has experienced rapid progress in recent years. It is a powerful
functional imaging technique that allows acquiring abundant quantitative optical information from turbid media.
However, the application of time domain DOT systems is hampered by the tradeoff between gathering dense data sets
and practical acquisition times. Recently, wide-field structured illumination patterns have been applied in time-resolved
DOT platforms to drastically accelerate the data acquisition process. In this work, we present a novel structured light
based imaging strategy for DOT that can generate time domain datasets enriched by hyperspectral information with short
data acquisition times. We employ two digital light processors to generate wide-field imaging pattern both in the
illumination and detection channels to capture tomographic data sets over large areas. The hyperspectral data sets are
acquired using a time-resolved spectrophotometer built around a multi-anode photomultiplier tube (PMT) that can detect
photons in 16 wavelength channels simultaneously based on time-correlated single photon counting (TCSPC) technique.
The characteristics of the system are tested in the spatial, temporal and spectral dimensions. The performance of the
imaging system is validated through preliminary 3D reconstruction of absorption heterogeneity distribution within a
murine model phantom. The application of digital light modulators in illumination and detection combined with timeresolved
PMT spectrophotometer enables our system to acquire dense time domain data sets both in the spatial, temporal
and spectral dimensions at an unprecedented speed. The phantom validation shows that proposed strategy is a promising
technique for fast, high resolution, quantitative three dimensional volumetric imaging.