Quantitative multi-pinhole small-animal SPECT: uniform versus non-uniform Chang attenuation correction.

Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. We propose a Chang-based non-uniform attenuation correction (NUA-CT) for small-animal SPECT/CT with focusing pinhole collimation, and compare the quantitative accuracy with uniform Chang correction based on (i) body outlines extracted from x-ray CT (UA-CT) and (ii) on hand drawn body contours on the images obtained with three integrated optical cameras (UA-BC). Measurements in phantoms and rats containing known activities of isotopes were conducted for evaluation. In (125)I, (201)Tl, (99m)Tc and (111)In phantom experiments, average relative errors comparing to the gold standards measured in a dose calibrator were reduced to 5.5%, 6.8%, 4.9% and 2.8%, respectively, with NUA-CT. In animal studies, these errors were 2.1%, 3.3%, 2.0% and 2.0%, respectively. Differences in accuracy on average between results of NUA-CT, UA-CT and UA-BC were less than 2.3% in phantom studies and 3.1% in animal studies except for (125)I (3.6% and 5.1%, respectively). All methods tested provide reasonable attenuation correction and result in high quantitative accuracy. NUA-CT shows superior accuracy except for (125)I, where other factors may have more impact on the quantitative accuracy than the selected attenuation correction.

An efficient simulator for pinhole imaging of PET isotopes.

Today, small-animal multi-pinhole single photon emission computed tomography (SPECT) can reach sub-half-millimeter image resolution. Recently we have shown that dedicated multi-pinhole collimators can also image PET tracers at sub-mm level. Simulations play a vital role in the design and optimization of such collimators. Here we propose and validate an efficient simulator that models the whole imaging chain from emitted positron to detector signal. This analytical simulator for pinhole positron emission computed tomography (ASPECT) combines analytical models for pinhole and detector response with Monte Carlo (MC)-generated kernels for positron range. Accuracy of ASPECT was validated by means of a MC simulator (MCS) that uses a kernel-based step for detector response with an angle-dependent detector kernel based on experiments. Digital phantom simulations with ASPECT and MCS converge to almost identical images. However, ASPECT converges to an equal image noise level three to four orders of magnitude faster than MCS. We conclude that ASPECT could serve as a practical tool in collimator design and iterative image reconstruction for novel multi-pinhole PET.

Movies of dopamine transporter occupancy with ultra-high resolution focusing pinhole SPECT.

A pivotal question in neuropharmacology is how the function of neurotransmitter systems relates to psychiatric diseases. In experimental neuropharmacology, we have dreamt about a looking glass that would allow us to see neurotransmitter systems in action, and about animals that would faithfully serve us as models for human psychiatric disease. Analysis of animal models has been limited by the availability of methods to study in vivo neurotransmitter dynamics. Now, a single photon emission computed tomography system called U-SPECT can localize dopamine transporters in sub-compartments of the mouse brain during a range of points in time. Applied to the midbrain dopamine system of different models of disease, this will aid the understanding of dynamic processes of this neurotransmitter that underlie brain functions and human brain pathology.

Optimizing multi-pinhole SPECT geometries using an analytical model.

State-of-the-art multi-pinhole SPECT devices allow for sub-mm resolution imaging of radio-molecule distributions in small laboratory animals. The optimization of multi-pinhole and detector geometries using simulations based on ray-tracing or Monte Carlo algorithms is time-consuming, particularly because many system parameters need to be varied. As an efficient alternative we develop a continuous analytical model of a pinhole SPECT system with a stationary detector set-up, which we apply to focused imaging of a mouse. The model assumes that the multi-pinhole collimator and the detector both have the shape of a spherical layer, and uses analytical expressions for effective pinhole diameters, sensitivity and spatial resolution. For fixed fields-of-view, a pinhole-diameter adapting feedback loop allows for the comparison of the system resolution of different systems at equal system sensitivity, and vice versa. The model predicts that (i) for optimal resolution or sensitivity the collimator layer with pinholes should be placed as closely as possible around the animal given a fixed detector layer, (ii) with high-resolution detectors a resolution improvement up to 31% can be achieved compared to optimized systems, (iii) high-resolution detectors can be placed close to the collimator without significant resolution losses, (iv) interestingly, systems with a physical pinhole diameter of 0 mm can have an excellent resolution when high-resolution detectors are used.