The goal of this proposal is to construct, optimize, and test a bench top x-ray fluorescence computed tomography (XFCT) system based on a promising new geometry we have recently developed and validated using synchrotron radiation. The novel geometry involves pencil-beam x-ray illumination of the sample coupled with slit collimation of a position- and energy-sensitive fluorescence x-ray detector. This allows for direct acquisition of the distribution of elements along the illuminated line without solving an ill-posed inverse problem. While the technology has the potential to be used in vivo, our aim in this proposal is to perform very high quality ex-vivo imaging of trace metals in biological samples. Many endogenous metals and metal ions, such as iron, copper, and zinc, play critical roles in signal transduction and reaction catalysis, while others, such as mercury, cadmium, and lead, are quite toxic even in trace quantities. In the post-genomic era, the new disciplines of metallogenomics, metalloproteomics, and metallomics are emerging for the systematic study of endogenous metals. These disciplines would benefit greatly from the spatially resolved maps of trace-element distribution and speciation provided by the methods being explored in the proposal. We seek to construct a system that can image sub-centimeter specimens (such as mouse organs) at 100 micron spatial resolution, with reasonable imaging times (~ 1-4 hours) and at radiation doses below damage threshold.
The specific aims of the proposal are:
Aim 1 : The system design will be optimized for sensitivity using analytic and Monte Carlo-based tools Aim 2: A benchtop XFCT system will be fabricated Aim 3: Calibration procedures and image formation algorithms will be developed Aim 4: The system will be tested on phantoms and samples of biological interest

Public Health Relevance

The overall goal of this proposal is to develop a lab-based, bench top x-ray fluorescence tomography system for imaging trace metals in biological specimens using novel acquisition geometry we have recently validated using synchrotron radiation. Many endogenous metals play critical roles in the healthy operation of cells and their deregulation may be implicated in a number of diseases including Alzheimer's and Parkinson's diseases. The techniques developed in this proposal will advance our understanding of these processes by allowing for 3D mapping of metals at high resolution in tissue samples.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Sastre, Antonio
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University of Chicago
Schools of Medicine
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Wu, Yicong; Kumar, Abhishek; Smith, Corey et al. (2017) Reflective imaging improves spatiotemporal resolution and collection efficiency in light sheet microscopy. Nat Commun 8:1452
Rigie, David S; Sanchez, Adrian A; La Rivière, Patrick J (2017) Assessment of vectorial total variation penalties on realistic dual-energy CT data. Phys Med Biol 62:3284-3298
Quigley, Bryan P; Smith, Corey D; Cheng, Shih-Hsun et al. (2017) Sensitivity evaluation and selective plane imaging geometry for x-ray-induced luminescence imaging. Med Phys 44:5367-5377
Day, Kasey J; La Rivière, Patrick J; Chandler, Talon et al. (2017) Improved deconvolution of very weak confocal signals. F1000Res 6:787
Rigie, D S; La Rivière, P J (2016) Optimizing spectral CT parameters for material classification tasks. Phys Med Biol 61:4599-622
Wu, Yicong; Chandris, Panagiotis; Winter, Peter W et al. (2016) Simultaneous multiview capture and fusion improves spatial resolution in wide-field and light-sheet microscopy. Optica 3:897-910
Mehta, Shalin B; McQuilken, Molly; La Riviere, Patrick J et al. (2016) Dissection of molecular assembly dynamics by tracking orientation and position of single molecules in live cells. Proc Natl Acad Sci U S A 113:E6352-E6361
Modgil, Dimple; Rigie, David S; Wang, Yuxin et al. (2015) Material identification in x-ray microscopy and micro CT using multi-layer, multi-color scintillation detectors. Phys Med Biol 60:8025-45
Groll, A; George, J; Vargas, P et al. (2015) Element Mapping in Organic Samples Utilizing a Benchtop X-Ray Fluorescence Emission Tomography (XFET) System. IEEE Trans Nucl Sci 62:2310-2317
Rigie, David S; La Rivière, Patrick J (2015) Joint reconstruction of multi-channel, spectral CT data via constrained total nuclear variation minimization. Phys Med Biol 60:1741-62

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