Our aim is to develop of a new type of imaging """"""""macroscope"""""""" that performs ultra-deep (several millimeters) fluorescence imaging in thick tissue while providing out-of-focus background rejection. Our proposed method for out-of-focus blur rejection is based on a novel technique called Dynamic Speckle Illumination (DSI) microscopy that was recently invented in our lab. Our goal is to build a portable DSI macroscope and establish its potential for in-vivo molecular-imaging applications such as cancer research and diagnosis, as well as small animal imaging and surgery. DSI microscopy consists of a simple modification to a standard widefield fluorescence microscope. Sample illumination is performed with random laser speckle patterns rather than with a lamp. The main advantage of DSI microscopy is that it provides depth discrimination and out-of-focus blur reduction in thick tissues without the use of a complicated scanning mechanism. We have developed the full theory of DSI microscopy and already demonstrated sub-micron-resolution imaging with confocal-like background rejection of GFP-labeled neurons, down to about 100?m in mice brain. We propose to develop a new instrument that performs much deeper imaging but with lower resolution. Our targeted depth is several millimeters, down to perhaps a centimeter. To attain this goal we propose to significantly re-design of our DSI microscope to incorporate a long working-distance telecentric objective, near-infrared laser illumination, and a more sensitive CCD camera. We also plan to combine DSI with structured illumination contrast and multipsectral imaging (for the latter, we will work with Cambridge Research & Instrumentation). The defining advantage of our DSI macroscope compared to conventional commercially available macroscopes will be that DSI provides out-of-focus background rejection, enabling significantly better localization and visualization of labeled structures within thick tissue. Initial testing of our DSI prototype will be performed on tissue phantoms provided by a radiology lab. Widefield fluorescence macroscopy with out-of-focus blur rejection. Public health: We propose to develop a simple and inexpensive device that performs ultra-deep fluorescence imaging with out-of-focus blur rejection, for small animal cancer-model imaging. Our goal is to build a new tool for cancer research that can eventually be implemented in the clinic. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB007338-01
Application #
7241369
Study Section
Microscopic Imaging Study Section (MI)
Program Officer
Zhang, Yantian
Project Start
2007-09-01
Project End
2009-07-31
Budget Start
2007-09-01
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$268,750
Indirect Cost
Name
Boston University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
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Santos, Silvia; Chu, Kengyeh K; Lim, Daryl et al. (2009) Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle. J Biomed Opt 14:030502
Lim, Daryl; Chu, Kengyeh K; Mertz, Jerome (2008) Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy. Opt Lett 33:1819-21
Bozinovic, Nenad; Ventalon, Cathie; Ford, Tim et al. (2008) Fluorescence endomicroscopy with structured illumination. Opt Express 16:8016-25