There are several important physical and instrumentation factors that affect the measured data and subsequently the SPECT images. As described earlier, gamma-ray photons that emit from an internal source may experience photoelectric absorption within the patient without contributing to the acquired data, Compton scattering with change in direction and loss of energy, or no interaction before exiting the patient’s body. The exiting photons will be further selected by the geometric response of the collimator–detector. The photoelectric and Compton interactions and the characteristics of the collimator–detector have significant effects on both the quality and quantitative accuracy of SPECT image.

Photon attenuation is defined as the effect due to photoelectric and Compton interactions resulting in a reduced number of photons that would have been detected without them. The degree of attenuation is determined by the linear attenuation coefficient, which is a function of photon energy and the amount and types of materials contained in the attenuating medium. For example, the attenuation coefficient for the 140-keV photon emitted from the commonly used Tc-99m in water or soft tissue is 0.15 cm⁻¹. This gives rise to a half-valued-layer, the thickness of material that attenuates half the incident photons, or 4.5 cm H₂O for the 140-keV photon. Attenuation is the most important factor that affects the quantitative accuracy of SPECT images.

Attenuation effect is complicated by the fact that within the patient the attenuation coefficient can be quite different in various organs. The effect is most prominent in the thorax, where the attenuation coefficients range from as low as 0.05 cm⁻¹ in the lung to as high as 0.18 cm⁻¹ in the compact bone for the 140-keV photons. In x-ray CT, the attenuation coefficient distribution is the target for image reconstruction. In SPECT, however, the wide range of attenuation coefficient values and the variations of attenuation coefficient distributions among patients are major difficulties in obtaining quantitative accurate SPECT images. Therefore, compensation for attenuation is important to ensure good image quality and quantitatively high accuracy in SPECT.

Photons that have been scattered before reaching the radiation detector provide misplaced spatial information about the origin of the radioactive source. The results are inaccurate quantitative information and poor contrast in the SPECT images. For radiation detectors with perfect energy discrimination, scattered photons can be completely rejected. In a typical scintillation camera system, however, the energy resolution is in the order of 10% at 140 keV. With this energy resolution, the ratio of scattered to scattered total photons detected by a typical scintillation detector is about 20–30% in brain and about 30–40% in cardiac and body SPECT studies for 140-keV photons. Furthermore, the effect of scatter depends on the distribution of the radiopharmaceutical, the proximity of the source organ to the target organ, and the energy window used in addition to the photon energy and the energy resolution of the scintillation detector. The compensation of scatter is another important aspect of SPECT to ensure good image quality and quantitative accuracy.

The advances in SPECT can be attributed to simultaneous development of new radiopharmaceuticals, instrumentation, reconstruction methods, and clinical applications. Most radiopharmaceuticals that are developed for conventional nuclear medicine can readily be used in SPECT, and review of these developments is beyond the scope of this chapter. Recent advances include new agents that are labeled with iodine and technetium for blood perfusion for brain and cardiac studies. Also, the use of receptor agents and labeled antibiotics is being investigated. These developments have resulted in radiopharmaceuticals with improved uptake distribution, biokinetics properties, and potentially new clinical applications. The following subsections will concentrate on the development of instrumentation and image reconstruction methods that have made substantial impact on SPECT.