Abstract While improvements in SPECT imaging techniques constitute a significant advance in biomedical science
and cancer diagnosis, their limited spatial resolution has hindered their application to small animal research and early tumour
detection. Using recent breakthroughs established by the high-energy astrophysics community, focusing X-ray optics provides a
method to overcome the paradigm of low resolution and presents the possibility of imaging small objects with sub-millimetre
resolution. This thesis aims to tackle the constraints associated with the current SPECT imaging designs by exploiting the notion of
focusing high energy photons through Laue lens diffraction and developing a means of performing gamma rays imaging that would
not rely on parallel or pinhole collimators. The gradual development of the novel system is discussed, starting from the single,
modular, and multi-Laue lens-based SPECT. A customized 3D reconstruction algorithm was developed to reconstruct an accurate
3D radioactivity distribution from focused projections. A plug-in implementing the Laue diffraction concept was developed and
used to model gamma rays focusing in the GEANT4 toolkit. The plug-in will be incorporated into GEANT4 upon final approval
from its developers. The single lens-based, modular lens-based and multi lens-based SPECT models detected one hit per 42 source
photons (sensitivity of 790 ⁄), three hits per 42 source photons (sensitivity of 2,373 ⁄), and one hit per 20 source
photons (sensitivity of 1,670 ⁄), respectively. Based on the generated 3D reconstructed images, the achievable spatial
resolution was found to be 0.1 full width at half maximum (FWHM). The proposed design’s performance parameters were
compared against the existing SIEMENS parallel LEHR and multi-pinhole (5-MWB-1.0) Inveon SPECT. The achievable spatial
resolution is decoupled from the sensitivity of the system, which is in stark contrast with the existing collimators that suffer from
the resolution-sensitivity trade-off and are limited to a resolution of 2 . The proposed system allows discrimination between
adjacent volumes as small as 0.113 , which is substantially smaller than what can be imaged by any existing SPECT or PET
system. The proposed design could lay the foundation for a new SPECT imaging technology akin to a combination of tomosynthesis
and lightfield imaging