Quan Zhang

Bio: Quan Zhang is an academic researcher from Harvard University. The author has contributed to research in topics: Diffuse optical imaging & Iterative reconstruction. The author has an hindex of 22, co-authored 50 publications receiving 3345 citations. Previous affiliations of Quan Zhang include University of Pennsylvania & Shriners Hospitals for Children.

Imaging the body with diffuse optical tomography

Abstract: Diffuse optical tomography (DOT) is an ongoing medical imaging modality in which tissue is illuminated by near-infrared light from an array of sources, the multiply-scattered light which emerges is observed with an array of detectors, and then a model of the propagation physics is used to infer the localized optical properties of the illuminated tissue. The three primary absorbers at these wavelengths, water and both oxygenated and deoxygenated hemoglobin, all have relatively weak absorption. This fortuitous fact provides a spectral window through which we can attempt to localize absorption (primarily by the two forms of hemoglobin) and scattering in the tissue. The most important current applications of DOT are detecting tumors in the breast and imaging the brain. We introduce the basic idea of DOT and review the history of optical methods in medicine as relevant to the development of DOT. We then detail the concept of DOT, including a review of the tissue's optical properties, modes of operation for DOT, and the challenges which the development of DOT must overcome. The basics of modelling the DOT forward problem and some critical issues among the numerous implementations that have been investigated for the DOT inverse problem, with an emphasis on signal processing. We summarize with some specific results as examples of the current state of DOT research.

Fluorescence optical diffusion tomography

Abstract: A nonlinear, Bayesian optimization scheme is presented for reconstructing fluorescent yield and lifetime, the absorption coefficient, and the diffusion coefficient in turbid media, such as biological tissue. The method utilizes measurements at both the excitation and the emission wavelengths to reconstruct all unknown parameters. The effectiveness of the reconstruction algorithm is demonstrated by simulation and by application to experimental data from a tissue phantom containing the fluorescent agent Indocyanine Green.

Tomographic optical breast imaging guided by three-dimensional mammography

Abstract: We introduce a modified Tikhonov regularization method to include three-dimensional x-ray mammography as a prior in the diffuse optical tomography reconstruction. With simulations we show that the optical image reconstruction resolution and contrast are improved by implementing this x-ray-guided spatial constraint. We suggest an approach to find the optimal regularization parameters. The presented preliminary clinical result indicates the utility of the method.

Coregistered tomographic x-ray and optical breast imaging: initial results.

Abstract: We describe what is, to the best of our knowledge, the first pilot study of coregistered tomographic x-ray and optical breast imaging The purpose of this pilot study is to develop both hardware and data processing algorithms for a multimodality imaging method that provides information that neither x-ray nor diffuse optical tomography (DOT) can provide alone We present in detail the instrumentation and algorithms developed for this multimodality imaging We also present results from our initial pilot clinical tests These results demonstrate that strictly coregistered x-ray and optical images enable a detailed comparison of the two images This comparison will ultimately lead to a better understanding of the relationship between the functional contrast afforded by optical imaging and the structural contrast provided by x-ray imaging

Depth sensitivity and source-detector separations for near infrared spectroscopy based on the Colin27 brain template.

Abstract: Understanding the spatial and depth sensitivity of non-invasive near-infrared spectroscopy (NIRS) measurements to brain tissue-i.e., near-infrared neuromonitoring (NIN) - is essential for designing experiments as well as interpreting research findings. However, a thorough characterization of such sensitivity in realistic head models has remained unavailable. In this study, we conducted 3,555 Monte Carlo (MC) simulations to densely cover the scalp of a well-characterized, adult male template brain (Colin27). We sought to evaluate: (i) the spatial sensitivity profile of NIRS to brain tissue as a function of source-detector separation, (ii) the NIRS sensitivity to brain tissue as a function of depth in this realistic and complex head model, and (iii) the effect of NIRS instrument sensitivity on detecting brain activation. We found that increasing the source-detector (SD) separation from 20 to 65 mm provides monotonic increases in sensitivity to brain tissue. For every 10 mm increase in SD separation (up to ~45 mm), sensitivity to gray matter increased an additional 4%. Our analyses also demonstrate that sensitivity in depth (S) decreases exponentially, with a "rule-of-thumb" formula S=0.75*0.85(depth). Thus, while the depth sensitivity of NIRS is not strictly limited, NIN signals in adult humans are strongly biased towards the outermost 10-15 mm of intracranial space. These general results, along with the detailed quantitation of sensitivity estimates around the head, can provide detailed guidance for interpreting the likely sources of NIRS signals, as well as help NIRS investigators design and plan better NIRS experiments, head probes and instruments.

Shedding light onto live molecular targets

Abstract: Optical sensing of specific molecular targets and pathways deep inside living mice has become possible as a result of a number of advances. These include design of biocompatible near-infrared fluorochromes, development of targeted and activatable 'smart' imaging probes, engineered photoproteins and advances in photon migration theory and reconstruction. Together, these advances will provide new tools making it possible to understand more fully the functioning of protein networks, diagnose disease earlier and speed along drug discovery.

Going deeper than microscopy: the optical imaging frontier in biology

Abstract: Optical microscopy has been a fundamental tool of biological discovery for more than three centuries, but its in vivo tissue imaging ability has been restricted by light scattering to superficial investigations, even when confocal or multiphoton methods are used. Recent advances in optical and optoacoustic (photoacoustic) imaging now allow imaging at depths and resolutions unprecedented for optical methods. These abilities are increasingly important to understand the dynamic interactions of cellular processes at different systems levels, a major challenge of postgenome biology. This Review discusses promising photonic methods that have the ability to visualize cellular and subcellular components in tissues across different penetration scales. The methods are classified into microscopic, mesoscopic and macroscopic approaches, according to the tissue depth at which they operate. Key characteristics associated with different imaging implementations are described and the potential of these technologies in biological applications is discussed.

Looking and listening to light: the evolution of whole-body photonic imaging.

Abstract: Optical imaging of live animals has grown into an important tool in biomedical research as advances in photonic technology and reporter strategies have led to widespread exploration of biological processes in vivo. Although much attention has been paid to microscopy, macroscopic imaging has allowed small-animal imaging with larger fields of view (from several millimeters to several centimeters depending on implementation). Photographic methods have been the mainstay for fluorescence and bioluminescence macroscopy in whole animals, but emphasis is shifting to photonic methods that use tomographic principles to noninvasively image optical contrast at depths of several millimeters to centimeters with high sensitivity and sub-millimeter to millimeter resolution. Recent theoretical and instrumentation advances allow the use of large data sets and multiple projections and offer practical systems for quantitative, three-dimensional whole-body images. For photonic imaging to fully realize its potential, however, further progress will be needed in refining optical inversion methods and data acquisition techniques.