Radiolabeled cells have been imaged for decades in the field of autoradiography. Recent advances in detector and
microelectronics technologies have enabled the new field of "digital autoradiography" which remains limited to ex vivo
specimens of thin tissue slices. The 3D field-of-view (FOV) of single cell imaging can be extended to millimeters if the
low energy (10-30 keV) photon emissions of radionuclides are used for single-photon nuclear imaging. This new
microscope uses a coded aperture foil made of highly attenuating elements such as gold or platinum to form the image as
a kind of "lens". The detectors used for single-photon emission microscopy are typically silicon detectors with a pixel
pitch less than 60 μm. The goal of this work is to image radiolabeled mesenchymal stem cells in vivo in an animal
model of tendon repair processes. Single-photon nuclear imaging is an attractive modality for translational medicine
since the labeled cells can be imaged simultaneously with the reparative processes by using the dual-isotope imaging
technique. The details our microscope's two-layer gold aperture and the operation of the energy-dispersive, pixellated
silicon detector are presented along with the first demonstration of energy discrimination with a 57Co source. Cell
labeling techniques have been augmented by genetic engineering with the sodium-iodide symporter, a type of reporter
gene imaging method that enables in vivo uptake of free 99mTc or an iodine isotope at a time point days or weeks after
the insertion of the genetically modified stem cells into the animal model. This microscopy work in animal research
may expand to the imaging of reporter-enabled stem cells simultaneously with the expected biological repair process in
human clinical trials of stem cell therapies.
The need to understand the behavior of individual stem cells at the various stages of their differentiation and to assess
the resulting reparative action in pre-clinical model systems, which typically involves laboratory animals, provides the
motivation for imaging of stem cells in vivo at high resolution. Our initial focus is to image cells and cellular events at
single cell resolution in vivo in shallow tissues (few mm of intervening tissue) in laboratory mice and rates. In order to
accomplish this goal we are building a SPECT-based microscope. We based our design on earlier theoretical work with
near-field coded apertures and have adjusted the components of the system to meet the real-world demands of instrument
construction and of animal imaging. Our instrumental design possesses a reasonable trade-off between field-of-view,
sensitivity, and contrast performance (photon penetration). A layered gold aperture containing 100 pinholes and
intended for use in coded aperture imaging application has been designed and constructed. A silicon detector connected
to a TimePix readout from the CERN collaborative group was selected for use in our prototype microscope because of
its ultra-high spatial and energy resolution capabilities. The combination of the source, aperture, and detector has been
modeled and the coded aperture reconstruction of simulated sources is presented in this work.
The kidney is composed of many structurally and functionally different tissues. These functionally distinct tissues
exhibit different magnetic resonance signal characteristics in typical MR Urography. This work exploits the tissue
functional differences to construct a physiological feature space for renal segmentation, which has the more distinct
meaning for directly functional evaluation, and lower requirements for storage and computation. In this preliminary
research, a segmentation method was developed and investigated to demonstrate its feasibility on images obtained using
a typical MR Urograpy protocol.
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