The nuclear medicine imaging techniques SPECT and PET are sensitive tools in mapping various physiological and biochemical processes in vivo. This work was devoted to investigations of methodological and physical properties of the SPECT technique as well as developing methods for validation and correction. Brain imaging was the major focus in this work, but the results are applicable to other examination areas. In the first part regional cerebral blood flow (rCBF) as measured by PET - the golden standard - and by SPECT was compared using a computerised brain atlas. Overall the differences were surprisingly small but revealed an apparent reduced grey-to-white matter ratio for SPECT, mainly due to the lack of scatter correction in SPECT, a lower spatial resolution and a non-linear extraction of the SPECT radiopharmaceutical. Furthermore, the reproducibility of resting state rCBF with SPECT was investigated, imperative information whenever scans are being repeated, as in activation studies, or when comparing an individual scan to a database of scans from healthy individuals. The results indicate that normalised flow data show high intra- and inter-individual reproducibility, expressed as standard deviations, ±1.3% and ±2.9%, respectively. The major error was addressed to the methodology, i.e. the scanning procedure and the atlas adaptation.

At that stage of the study, using a clinical protocol, without scatter correction and proper attenuation correction there was no possibility to extract quantitative information from the SPECT images. Therefore, in the subsequent work, a phantom concept (the stack phantom) was designed aiming at experimental validation of the SPECT methodology, including effects of photon interactions. Extracting information where the primary (unscattered) photons are separated from the ones undergoing scattering or attenuation before detection, was, until now, only possible using Monte Carlo simulations. The basis of the novel phantom concept is to sample various 3D-activity distributions from a set of 2D samples. The 2D samples are ordinary paper sheets where the cross sectional radioactivity distribution is printed out using radioactive ink. Mounting the samples together with a certain equidistant axial spacing, using either tissue equivalent material or some low-density material, give possibilities to mimick the very same activity distribution clinically (with degrading photon interactions) as well as almost "pure" primary photon images. The phantom concept is very flexible, any activity distribution may be constructed, pathological patterns can easily be introduced and varied. Moreover, correction methods and software evaluation tools may be assessed and validated with the phantom. However, the phantom has not only applicability in research areas - recurrent quality assurance programs can as well make use of dedicated stack phantoms.

In the last phase of this work a scatter correction algorithm was developed, making use of the stack phantom. The correction was developed using a multi-spectral acquisition system. This allowed for spectral acquisitions in each pixel in the projection images. After correcting for the scatter contribution in the upper half of the photo-peak using the shape of the scatter distribution from the Klein-Nishina cross section the resulting estimate of primary photons was mirrored (folded) over to estimate the primary photons in the lower half of the photo-peak. The scatter correction works in each spectrum and hence corrects for the scatter contribution locally. The correction method was validated both with Monte Carlo simulations and the stack-phantom, both indicating accurate results.