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Scientific Opportunities: Life Sciences

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Biological and Medical Imaging

Overview
The high brightness of NSLS-II will make it possible to tightly focus the beam to create very intense nanoprobes for high-resolution cellular imaging and sensitive trace element mapping in biological specimens. The brightness will also provide highly collimated beams of high intensity and large transverse dimensions for novel forms of medical imaging and tomography. NSLS-II will also provide the broadest range of wavelengths to users in a single facility, extending from hard X-rays to the far-infrared and enabling a wide array of analytical techniques, including: X-ray microscopy (hard and soft; scanning and full-field), diffraction imaging, X-ray tomography, X-ray microprobe, diffraction-enhanced imaging (DEI), and infrared imaging. These diverse imaging tools will span the resolution scale from nanometers to millimeters, allowing non-destructive analysis of biological subjects ranging from sub-cellular structures to humans.

Synchrotron facilities worldwide, including the NSLS, demonstrate the value of using a synchrotron for biological and medical imaging. Information that could once be obtained only on pure, spatially homogeneous samples is now obtained from heterogeneous natural and complex biological samples on length scales of tens of nanometers. NSLS-II will extend this to less than 10 nm, enabling studies of nanoscale phases and compositional variations and providing deeper insight into nature (see figure).

With NSLS-II, the spatial resolution of X-ray microprobes and DEI will be reduced to below 1 m. This spatial resolution will enable the imaging of plant and animal tissues on the sub-cellular level, and importantly, in their natural state.

Imaging Molecular Machines
Biological cells are composed of complex macromolecular assemblies that work together in functional networks. These machines execute important metabolic functions, mediate information flow within and among cells, and build cellular structures. Imaging of whole cells, and the macromolecular assemblies within cells, is critical for understanding these interactions.

For example, one problem in cellular biology is the way the mammalian cell packages its genetic material under different conditions, such as how the organization of genetic material is different in the sperm cell than other cells. The ability to image hidden abnormalities in the composition of sperm nuclei is important in order to understand how the morphology of the sperm cell affects male fertility. Recently, X-ray microscopy was introduced for the evaluation of a single sperm (see figure). Sperm have a size in the 1-2 micron range, and the structures of interest are typically 30 nm. The high brightness of NSLS-II will improve the resolution of sperm imaging to 10 nm. NSLS-II will also enable higher resolution for imaging whole cells, which promises to be a remarkably fertile line of research.

Fundamental Basis of Disease
Biological tissues are composed of individual cells and a complex extracellular matrix that holds cells together to make a tissue. Many diseases involve alterations in the chemistry of the cells and extracellular matrix. For example, cancerous tumors, scar tissue, and atherosclerotic (blood vessel) and neuritic (brain) plaques all form through some combination of irregular cell growth, and breakdown and remodeling of the extracellular matrix around them. Imaging of whole tissues, encompassing the interactions between cells and the extracellular matrix, is critical for understanding these disease processes.

Current limitations for X-ray imaging of neuritic plaques, for example, include spatial resolution and beamtime availability. Although many neuritic plaques are large (50-200 microns in diameter), others are much smaller and more diffuse. The higher brightness and coherence of NSLS-II, including increased insertion device capacity, will enable X-ray analysis at below 1 micron resolution, even down to 70-100 nm resolution. NSLS-II will also allow lengthy in-vivo studies to track disease progression and the evolution of pathology during the treatment of neurodegenerative diseases.

Early Disease Detection
Challenges remain in clinical diagnostic and screening imaging, despite recent advancements in mammography, MRI, CT, PET, and SPECT. The rate of false negative in mammography is still about 10%; cartilage is difficult to visualize by radiological means; and the contrast of chest X-ray is too low to detect early stages of emphysema and edema. Since early intervention of these diseases is typically life-saving, development of new radiography methods for diagnosis and screening is of great interest.

Diffraction enhanced imaging (DEI), a technique developed at the NSLS, is advantageous for mammography because it provides increased sensitivity to soft-tissue contrast. The figure shows images of breast tissue with invasive lobular carcinoma that extends to the edge. It illustrates the improved visualization of spiculations representing tumor extension by DEI, compared to standard radiographs. DEI breast images are currently limited to a spatial resolution of about fifty microns and it is important to visualize smaller calcifications and small spiculations. NSLS-II will provide a major advance by extending this to below one micron, and will enable study of the cancer biology and morphological features of animal models of breast cancer and other cancers that are typically too small to be reliably detected by the current DEI resolution.

 

Last Modified: May 2, 2014
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