Quantification of dopaminergic neurotransmission SPECT studies with 123 l-labelled radioligands

Abstract

Dopaminergic neurotransmission SPECT studies with 123I-labelled radioligands can help in the diagnosis of neurological and psychiatric disorders such as Parkinson¿s disease and schizophrenia. Nowadays, interpretation of SPECT images is based mainly on visual assessment by experienced observers. However, a quantitative evaluation of the images is recommended in current clinical guidelines. Quantitative information can help diagnose the disease at the early pre-clinical stages, follow its progression and assess the effects of treatment strategies.

SPECT images are affected by a number of effects that are inherent in the image formation: attenuation and scattering of photons, system response and partial volume effect. These effects degrade the contrast and resolution of the images and, as a consequence, the real activity distribution of the radiotracer is distorted. Whilst the photon emission of 123I is dominated by a low-energy line of 159 keV, it also emits several high-energy lines. When 123I-labelled radioligands are used, a non-negligible fraction of high-energy photons undergoes backscattering in the detector and the gantry and reaches the detector within the energy window.

In this work, a complete methodology for the compensation of all the degrading effects involved in dopaminergic neurotransmission SPECT imaging with 123I is presented. The proposed method uses Monte Carlo simulation to estimate the scattered photons detected in the projections. For this purpose, the SimSET Monte Carlo code was modified so as to adapt it to the more complex simulation of high-energy photons emitted by 123I. Once validated, the modified SimSET code was used to simulate 123I SPECT studies of an anthropomorphic striatal phantom using different imaging systems. The projections obtained showed that scatter is strongly dependent on the imaging system and comprises at least 40% of the detected photons. Applying the new methodology demonstrated that absolute quantification can be achieved when the method includes accurate compensations for all the degrading effects. When the method did not include correction for all degradations, calculated values depended on the imaging system, although a linear relationship was found between calculated and true values. It was also found that partial volume effect and scatter corrections play a major role in the recovery of nominal values.

Despite the advantages of absolute quantification, the computational and methodological requirements needed severely limit the possibility of application in clinical routine. Thus, for the time being, absolute quantification is limited to academic studies and research trials. In a clinical context, reliable, simple and rapid methods are needed, thus, semi-quantitative methods are used. Diagnosis also requires the establishment of robust reference values for healthy controls. These values are usually derived from a large data pool obtained in multicentre clinical trials. The comparison between the semi-quantitative values obtained from a patient and the reference is only feasible if the quantitative values have been previously standardised, i.e. they are independent of the gamma camera, acquisition protocol, reconstruction parameters and quantification procedure applied. Thus, standardisation requires that the calculated values are compensated somehow for all the image-degrading phenomena.

In this thesis dissertation, a methodology for the standardisation of the quantitative values extracted from dopaminergic neurotransmission SPECT studies with 123I is evaluated using Monte Carlo simulation. This methodology is based on the linear relationship found between calculated and true values for a group of studies corresponding to different subjects with non-negligible anatomical and tracer uptake differences. Reconstruction and quantification methods were found to have a high impact on the linearity of the relationship and on the accuracy of the standardised results.