A Novel SPECT Microscope:Design and Simulation



What we do?

We are building a SPECT microscope for the purpose of imaging cells and cellular events at single cell resolution in vivo in shallow tissues (few mm intervening tissue) in laboratory mice.  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 animal imaging.  A layered coded aperture was designed to meet the optimum trade-off between field-of-view, sensitivity, and contrast performance (photon penetration).   An ultra-high resolution silicon detector from the CERN collaborative group, TimePix,  was selected for use in this prototype microscope.  The combination of the source, aperture, and detector has been modeled and the coded aperture reconstruction of the simulated sources is presented in this work.  Understanding of the behavior of individual stem cells at the stages of their differentiation and reparative action in laboratory animals lays a foundation for imaging of stem cells and their effects in future human treatments

Nuclear Microscopy

Coded Apertures

Low energiesAn overview of coded aperture imaging is given by Skinner2, and a low-energy, near-field application with 55Fe was reported by Accorsi3, achieving 20 µm resolution.  A modified uniformly redundant array (MURA) was designed by Dr. Accorsi for our use in this project

Detector

A 300 µm-thick silicon detector attached to the “TimePix”4 readout was selected due to its pixel pitch and energy resolving capability (Figure 2).  TimePix is a version of the MediPix2 ASIC, made available for this project by the Medipix2 Collaboration under the direction of Dr. Michael Campbell (CERN) and Dr. Michael Fiederle (University of Freiburg). 
Higher sensitivity can be achieved by using multiple Si/TimePix detectors (for expanded area) and by replacing the silicon with CdTe after feasibility is shown.  Figure 3 shows pixellated images of counts (two left figures) from 55Fe and 57Co.  At middle right of Figure 3 the two spectra are clearly separated, with an ROC analysis showing the separation of the two peaks at the far right.

Microscope Design

Coded Aperture Fabrication

Use of layered gold foils (right) to emulate the desired conical hole shapes

Photograph of one of the coded aperture holes, showing 30 m hole in 60 m Au foil and 145 m hole in 90 m Au foil

 

Simulation

At right is shown the resulting reconstruction of two point sources of cell-size through the 100-hole (4x25) MURA coded aperture of Figure 1.  Note the residual artifacts of the coded aperture pattern from the reconstruction processes.
In the projection, each ray omitted from the object is geometrically traced, through the mask and projected to the detector plane. A constant PSF (Point Spread Function) is assumed over the detector. A 2D Gaussian kernel is convolved to the projection data to simulate the intrinsic PSF blurring. The geometric resolution is determined by the pinhole size and magnification.
The projected images are reconstructed in the frequency domain using the Fourier transform. The reconstruction decodes the patterned projected image into a reconstructed image by the delta decoding method8.

Publication

- Rex A. Moats, Yang Tang, James W. Hugg, et.al , Basic design and simulation of a SPECT microscope for in vivo stem cell imaging, SPIE medical imaging conference, 7961, 79614B (2011);

- DJ Wagenaar, RA Moats,Yang Tang, et al., High-performance imaging of stem cells using single-photon emissions, SPIE Medical Applications of Radiation Detectors , San Diego,CA (2011);