ECAT High Resolution Research Tomograph Research Articles

PET imaging of freely moving interacting rats

Awake rat brain positron emission tomography (PET) has previously been developed to avoid the influence of anesthesia on the rat brain response. In the present work, we further the awake rat brain scanning methodology to establish simultaneous scanning of two interacting rats in a high resolution, large field of view PET scanner. Awake rat imaging methodology based on point source tracking was adapted to be used in a dedicated human brain scanner, the ECAT high resolution research tomograph (HRRT). Rats could freely run on a horizontal platform of 19.4 × 23 cm placed inside the HRRT. The developed methodology was validated using a motion resolution phantom experiment, 3 awake single rat [18F]FDG scans as well as an [18F]FDG scan of 2 interacting rats. The precision of the point source based motion tracking was 0.359 mm (standard deviation). Minor loss of spatial resolution was observed in the motion corrected reconstructions (MC) of the resolution phantom compared to the motion-free reconstructions (MF). The full-width-at-half-maximum of the phantom rods were increased by on average 0.37 mm in the MC compared to the MF. During the awake scans, extensive motion was observed with rats moving throughout the platform area. The average rat head motion speed was 1.69 cm/s. Brain regions such as hippocampus, cortex and cerebellum could be recovered in the motion corrected reconstructions. Relative regional brain uptake of MC and MF was strongly correlated (Pearson's r ranging from 0.82 to 0.95, p < 0.0001). Awake rat brain PET imaging of interacting rats was successfully implemented on the HRRT scanner. The present method allows a large range of motion throughout a large field of view as well as to image two rats simultaneously opening the way to novel rat brain PET study designs.

Evaluation of analytical reconstruction with a new gap-filling method in comparison to iterative reconstruction in [ $$_{ }^{11}\mathrm C$$ 11 C ]-raclopride PET studies

The aim of the study was (1) to evaluate the reconstruction strategies with dynamic [¹¹C]-raclopride human positron emission tomography (PET) studies acquired from ECAT high-resolution research tomograph (HRRT) scanner and (2) to justify for the selected gap-filling method for analytical reconstruction with simulated phantom data. A new transradial bicubic interpolation method has been implemented to enable faster analytical 3D-reprojection (3DRP) reconstructions for the ECAT HRRT PET scanner data. The transradial bicubic interpolation method was compared to the other gap-filling methods visually and quantitatively using the numerical Shepp-Logan phantom. The performance of the analytical 3DRP reconstruction method with this new gap-filling method was evaluated in comparison with the iterative statistical methods: ordinary Poisson ordered subsets expectation maximization (OPOSEM) and resolution modeled OPOSEM methods. The image reconstruction strategies were evaluated using human data at different count statistics and consequently at different noise levels. In the assessments, 14 [¹¹C]-raclopride dynamic PET studies (test-retest studies of 7 healthy subjects) acquired from the HRRT PET scanner were used. Besides the visual comparisons of the methods, we performed regional quantitative evaluations over the cerebellum, caudate and putamen structures. We compared the regional time-activity curves (TACs), areas under the TACs and binding potential (BPND) values. The results showed that the new gap-filling method preserves the linearity of the 3DRP method. Results with the 3DRP after gap-filling method exhibited hardly any dependency on the count statistics (noise levels) in the sinograms while we observed changes in the quantitative results with the EM-based methods for different noise contamination in the data. With this study, we showed that 3DRP with transradial bicubic gap-filling method is feasible for the reconstruction of high-resolution PET data with missing sinogram bins. The calculated intraclass correlation coefficient (ICC) values were similar for all tested methods and validated the test-retest study. The gap-filling and 3DRP method can be used for quantitative PET studies in which high temporal information is crucial and can serve as a reference method for comparison studies of the other reconstruction methods.

Scanning rats on the high resolution research tomograph (HRRT): A comparison study with a dedicated micro‐PET

The Siemens ECAT high resolution research tomograph (HRRT) is a dedicated human brain PET camera with a 6% absolute sensitivity and a (2.3 mm)(3) spatial resolution, improving to (1.8 mm)(3) when point spread function (PSF) modeling algorithms are used. These values are very close to those of dedicated small animal PET cameras such as the Siemens microPET FOCUS 120 (F120). The larger axial and transaxial field of view of the HRRT compared to the F120 allows, in principle, for simultaneous imaging of several rodents thus potentially reducing scanning costs and time. This study investigates the feasibility of using the HRRT for quantitative small animal brain studies. We compare, in terms of magnitude, reproducibility, and asymmetry, the nondisplaceable tissue input binding potentials (BP(ND)) in the striata obtained from [(11)C]methylphenidate scans of the same rats imaged on both the F120 and the HRRT. The animal studies are complemented by a phantom study aimed at investigating noise properties relevant to the size of typical regions of interest used in rat brain image analysis. (i) The BP(ND) values obtained from HRRT data are lower than those obtained on the F120 by 38% when PSF modeling is not used, while they are 7% higher with PSF modeling. (ii) The within animal reproducibility on the HRRT is 18% without PSF modeling, worse than the 6% reproducibility on the F120, and is even further degraded to a value of 27% with the use of PSF modeling. (iii) The asymmetry between the left and right striatum in healthy rats worsens from 4.7% in the F120 images to 7.8% in the HRRT images reconstructed without PSF modeling, and is even worse with a value of 14.8% when PSF modeling is used. (iv) Overshooting artifacts and clumpiness in the noise structure of the HRRT images reconstructed with PSF modeling are clearly visible. The spatial resolution achieved on the HRRT without the use of resolution recovery techniques is not sufficient to allow for reliable quantitative small animal brain imaging. While PSF modeling in the reconstruction of the HRRT images in principle improves the resolution close to the level of the F120, it also introduces small scale nonuniformity artifacts and overshooting artifacts which preclude reliable quantitative small animal brain imaging on the HRRT.

Quantification of serotonin transporter availability with [11C]MADAM — A comparison between the ECAT HRRT and HR systems

The High Resolution Research Tomograph (HRRT) is the PET system providing the highest resolution for imaging of the human brain. In this study, the improved quantitative performance of the HRRT was evaluated in comparison with a previously developed lower resolution PET system, the ECAT HR. The radioligand [(11)C]MADAM was chosen for the purpose since it provides a signal for serotonin transporter (5-HTT) binding in cortical and sub-cortical brain regions of different sizes and expressing different 5-HTT densities. A secondary objective was to assess the effect of partial volume effect (PVE) correction on the cross-comparability between the two systems. Six male control subjects (ages 20-35 yr) were examined twice using the HRRT and the HR system, respectively. Regions of interest (ROIs) included cortical regions (frontal cortex, temporal cortex, insula, anterior cingulate cortex, and hippocampus), sub-cortical regions (caudate, putamen, thalamus, dorsal brainstem and ventral midbrain) and cerebellum. The ROIs were manually delineated on T1-weighted MRI-images and subsequently applied to both HRRT and HR images. Regional binding potential (BP(ND)) values were calculated with the simplified reference tissue model (SRTM) using cerebellum as the reference region. The percent difference in BP(ND) between the systems was calculated for each ROI. In addition, both HRRT and HR data were corrected for PVE using established MRI-based methods described by Meltzer and Müller-Gärtner. The effect of PVE correction (PVEc) on the agreement between the systems was assessed via percent difference calculation and linear regression analysis. Quantification with SRTM showed that regional BP(ND) values for [(11)C]MADAM were on average 23% higher for the HRRT than those obtained by the HR system. More specifically, BP(ND) measured with HRRT was 31.1±48.1% higher in neocortical/limbic regions and 14.6±20.9% higher in sub-cortical regions. The effect of PVEc varied between regions. After correction according to Müller-Gärtner, the agreement between systems was best in the neocortical/limbic regions (3.7±22.5%). With the exception of the caudate, in which the agreement was improved by approximately 17% using the Meltzer method, the effect of PVEc in sub-cortical regions was less pronounced. Linear regression analysis showed improved correlation between the two systems after PVEc, particularly in the neocortical/limbic regions. As expected, BP(ND) values measured with the HRRT were higher than those measured with the HR due to higher resolution and recovery. The difference in BP(ND) between the two systems was approximately 30% in the neocortical/limbic regions. PVEc improved the agreement between the systems in particular for the neocortical/limbic regions. In these regions, the best agreement was found after applying Müller-Gärtner's PVEc. The demonstrated agreement provides an opportunity for combining data between the two systems in clinical studies aimed at evaluating receptor/transporter availability in cortical brain regions.

Gap-filling methods for 3D PlanTIS data

The range of positron emitters and their labeled compounds have led to high-resolution PET scanners becoming widely used, not only in clinical and pre-clinical studies but also in plant studies. A high-resolution PET scanner, plant tomographic imaging system (PlanTIS), was designed to study metabolic and physiological functions of plants noninvasively. The gantry of the PlanTIS scanner has detector-free regions. Even when the gantry of the PlanTIS is rotated during the scan, these regions result in missing sinogram bins in the acquired data. Missing data need to be estimated prior to the analytical image reconstructions in order to avoid artifacts in the final reconstructed images. In this study, we propose three gap-filling methods for estimation of the unique gaps existing in the 3D PlanTIS sinogram data. The 3D sinogram data were gap-filled either by linear interpolation in the transaxial planes or by the bicubic interpolation method (proposed for the ECAT high-resolution research tomograph) in the transradial planes or by the inpainting method in the transangular planes. Each gap-filling method independently compensates for slices in one of three orthogonal sinogram planes (transaxial, transradial and transangular planes). A 3D numerical Shepp–Logan phantom and the NEMA image quality phantom were used to evaluate the methods. The gap-filled sinograms were reconstructed using the analytical 3D reprojection (3DRP) method. The NEMA phantom sinograms were also reconstructed by the iterative reconstruction method, ordered subsets maximum a posteriori one step late (OSMAPOSL), to compare the results of gap filling followed by 3DRP with the results of OSMAPOSL reconstruction without gap filling. The three methods were evaluated quantitatively (by mean square error and coefficients of variation) over the selected regions of the 3D numerical Shepp–Logan phantom at eight different Poisson noise levels. Moreover, the NEMA phantom scan data were used in visual assessments of the methods. We observed that all methods improved the reconstructed images both quantitatively and visually. Therefore, the proposed gap-filling methods followed by the analytical 3DRP are alternative for the reconstructions of not only the 3D PlanTIS data, but also other PET scanner data of the ClearPET family.

Performance evaluation of the ECAT HRRT: an LSO-LYSO double layer high resolution, high sensitivity scanner

The ECAT high resolution research tomograph (HRRT) is a dedicated brain and small animal PET scanner, with design features that enable high image spatial resolution combined with high sensitivity. The HRRT is the first commercially available scanner that utilizes a double layer of LSO/LYSO crystals to achieve photon detection with depth-of-interaction information. In this study, the performance of the commercial LSO/LYSO HRRT was characterized, using the NEMA protocol as a guideline. Besides measurement of spatial resolution, energy resolution, sensitivity, scatter fraction, count rate performance, correction for attenuation and scatter, hot spot recovery and image quality, a clinical evaluation was performed by means of a HR+/HRRT human brain comparison study. Point source resolution varied across the field of view from approximately 2.3 to 3.2 mm (FWHM) in the transaxial direction and from 2.5 to 3.4 mm in the axial direction. Absolute line-source sensitivity ranged from 2.5 to 3.3% and the NEMA-2001 scatter fraction equalled 45%. Maximum NECR was 45 kcps and 148 kcps according to the NEMA-2001 and 1994 protocols, respectively. Attenuation and scatter correction led to a volume uniformity of 6.3% and a system uniformity of 3.1%. Reconstructed values deviated up to 15 and 8% in regions with high and low densities, respectively, which can possibly be assigned to inaccuracies in scatter estimation. Hot spot recovery ranged from 60 to 94% for spheres with diameters of 1 to 2.2 cm. A high quantitative agreement was met between HR+ and HRRT clinical data. In conclusion, the ECAT HRRT has excellent resolution and sensitivity properties, which is a crucial advantage in many research studies.

The ECAT HRRT: an example of NEMA scatter estimation issues for LSO-based PET systems

The ECAT high-resolution research tomograph (HRRT) is a three-dimensional (3-D)-only dedicated brain positron emission tomograph with LSO and GSO scintillators. In this paper, the system has been looked at as an example of issues that need to be addressed when evaluating LSO-based system following the recent NEMA NU 2-2001 protocols. The LSO scintillators contain the isotope /sup 176/Lu which is radioactive and creates a small amount of single counts and, depending on the low level discriminator threshold for validated singles, also true coincidence events from a cascade of gamma rays following the beta decay of /sup 176/Lu into /sup 176/Hf. The presence of intrinsic random and true coincidence events has an effect on the scatter fraction determination if using the guidelines according to NU 2-2001. We show here that these guidelines have to be changed in order to obtain accurate determination of the scatter fraction. In this paper, we have determined the scatter fraction for different low level discriminator settings. Since the scatter fraction determinations also comprise full count rate studies for the NEMA phantom, we have in addition extracted the sensitivity information for singles, true + scatter, and for the NEC data.

The ECAT HRRT: NEMA NEC evaluation of the HRRT system, the new high-resolution research tomograph

The ECAT HRRT (high-resolution research tomograph) is a three-dimensional(3-D)-only dedicated brain positron emission tomograph (PET) with LSO and GSO scintillators. The system is based on eight panels of detectors. The HRRT's imaging performance has previously been tested with phantoms and FDG scans performed in animal and human brains that showed significantly improved spatial resolution, below 2.5 mm for animal studies and below 3 mm for brain studies. The NEC count rate performance has been evaluated based on the NU 2-2001 protocol. The results show a peak NEC approximately 30% higher than the performance of the ECAT HR+, this in spite of a more shallow detector for the HRRT, only 15 mm relative to the 30 mm for the HR+. However, peak NEC as derived from the 70-cm line source phantom is not optimized for the performance of dedicated brain scanner. NEC data derived with a 20-cm diameter, 20-cm long phantoms show a peak NEC more than 60% higher than for the HR+. The reasons for the high performance are due to several factors, the large axial coverage, the short timing window of 6 ns, and the low detector dead time, all factors that imply the use of fast LSO and GSO scintillators.