Optimization of the reconstruction parameters in [123I]FP-CIT SPECT.

The aim of this work was to obtain a set of parameters to be applied in [123I]FP-CIT SPECT reconstruction in order to minimize the error between standardized and true values of the specific uptake ratio (SUR) in dopaminergic neurotransmission SPECT studies. To this end, Monte Carlo simulation was used to generate a database of 1380 projection data-sets from 23 subjects, including normal cases and a variety of pathologies. Studies were reconstructed using filtered back projection (FBP) with attenuation correction and ordered subset expectation maximization (OSEM) with correction for different degradations (attenuation, scatter and PSF). Reconstruction parameters to be optimized were the cut-off frequency of a 2D Butterworth pre-filter in FBP, and the number of iterations and the full width at Half maximum of a 3D Gaussian post-filter in OSEM. Reconstructed images were quantified using regions of interest (ROIs) derived from Magnetic Resonance scans and from the Automated Anatomical Labeling map. Results were standardized by applying a simple linear regression line obtained from the entire patient dataset. Our findings show that we can obtain a set of optimal parameters for each reconstruction strategy. The accuracy of the standardized SUR increases when the reconstruction method includes more corrections. The use of generic ROIs instead of subject-specific ROIs adds significant inaccuracies. Thus, after reconstruction with OSEM and correction for all degradations, subject-specific ROIs led to errors between standardized and true SUR values in the range [-0.5, +0.5] in 87% and 92% of the cases for caudate and putamen, respectively. These percentages dropped to 75% and 88% when the generic ROIs were used.

Integration of advanced 3D SPECT modeling into the open-source STIR framework.

PURPOSE: The Software for Tomographic Image Reconstruction (STIR, http://stir.sourceforge.net) package is an open source object-oriented library implemented in C++. Although its modular design is suitable for reconstructing data from several modalities, it currently only supports Positron Emission Tomography (PET) data. In this work, the authors present results for Single Photon Emission Computed Tomography (SPECT) imaging. METHODS: This was achieved by the complete integration of a 3D SPECT system matrix modeling library into STIR. RESULTS: The authors demonstrate the flexibility of the combined software by reconstructing simulated and acquired projections from three different scanners with different iterative algorithms of STIR. CONCLUSIONS: The extension of the open source STIR project with advanced SPECT modeling will enable the research community to study the performance of several algorithms on SPECT data, and potentially implement new algorithms by expanding the existing framework.

Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study.

BACKGROUND: Serial dopamine transporter (DAT) imaging in patients with Parkinson's disease (PD) and other synucleinopathies shows progressive nigrostriatal dopaminergic dysfunction. Because idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) can precede the classic symptoms of PD and other synucleinopathies, we postulated that serial DAT imaging in patients with IRBD could be used to detect decline in striatal tracer uptake, indicating progressive nigrostriatal cell degeneration. METHODS: In a prospective study, 20 patients with IRBD (mean age 70·55 years [SD 6·02]) underwent serial DAT imaging with (123)I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ((123)I-FP-CIT) SPECT at baseline and again after 1·5 years and 3 years; 20 age-matched and sex-matched control participants (69·50 years [6·77]) underwent imaging at baseline and 3 years. The striatum to occipital cortex uptake ratios were calculated for the putamen and caudate nucleus in each hemisphere. In patients, the ratio was judged to be reduced when it was less than two SD of the mean ratio in controls at the same timepoint. Differences in (123)I-FP-CIT uptake between patients and controls in each striatal region and rates of decline were assessed by use of multivariate ANOVA (MANOVA). FINDINGS: Compared with controls, patients had significantly reduced mean (123)I-FP-CIT binding in all four striatal regions at baseline and after 3 years. Striatal (123)I-FP-CIT uptake was reduced compared with that in controls in ten patients at baseline and in 13 patients after 3 years. In patients, the mean reduction in (123)I-FP-CIT uptake from baseline to 3 years was 19·36% (95% CI 15·14 to 23·59) in the left putamen, 15·57% (10·87 to 20·28) in the right putamen, 10·81% (6·49 to 15·18) in the left caudate nucleus, and 7·14% (2·74 to 11·56) in the right caudate nucleus. After adjustment for the baseline (123)I-FP-CIT uptake ratios, the decline in (123)I-FP-CIT binding at baseline to 3 years was significantly greater in patients than in controls in the left putamen (9·78% difference between groups, 95% CI 3·22 to 16·32), right putamen (5·43%, 1·99 to 12·86), and left caudate nucleus (8·07%, 1·44 to 14·70), but not in the right caudate nucleus (4·16%, -3·00 to 11·34). At the 3-year assessment, three patients were diagnosed with PD. These patients had the lowest (123)I-FP-CIT uptake at baseline and a mean reduction in (123)I-FP-CIT uptake at 3 years of 32·81% in the left putamen, 30·40% in the right putamen, 26·51% in the left caudate nucleus, and 23·75% in the right caudate nucleus. INTERPRETATION: In patients with IRBD, serial (123)I-FP-CIT SPECT shows decline in striatal tracer uptake that reflects progressive nigrostriatal dopaminergic dysfunction. Serial (123)I-FP-CIT SPECT can be used to monitor the progression of nigrostriatal deficits in patients with IRBD, and could be useful in studies of potential disease-modifying compounds in these patients. FUNDING: Fondo de Investigaciones Sanitarias of Spain.

A 4-year dopamine transporter (DAT) imaging study in neuroleptic-naive first episode schizophrenia patients.

Alterations in the dopaminergic system have long been implicated in schizophrenia. A key component in dopaminergic neurotransmission is the striatal dopamine transporter (DAT). To date, there have been no longitudinal studies evaluating the course of DAT in schizophrenia. A 4-year follow-up study was therefore conducted in which single photon emission computed tomography was used to measure DAT binding in 14 patients and 7 controls. We compared the difference over time in [(123)I] FP-CIT striatal/occipital uptake ratios (SOUR) between patients and controls and the relationship between this difference and both symptomatology and functional outcome at follow-up. We also calculated the relationship between baseline SOUR, symptoms and functional outcome at follow-up. There were no statistically significant differences between patients' SOUR changes over time and those of controls. A significant negative correlation was observed between patients' SOUR changes over time and negative symptomatology at follow-up. A significant negative correlation was also found between baseline SOUR in patients and negative symptomatology, and there was a significant association between lower SOUR at baseline and poor outcome. Although the study found no overall differences in DAT binding during follow-up between schizophrenia patients and controls, it demonstrated that differences in DAT binding relate to patients' characteristics at follow-up.

Assessment of SPM in perfusion brain SPECT studies. A numerical simulation study using bootstrap resampling methods.

Statistical parametric mapping (SPM) has become the technique of choice to statistically evaluate positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and single photon emission computed tomography (SPECT) functional brain studies. Nevertheless, only a few methodological studies have been carried out to assess the performance of SPM in SPECT. The aim of this paper was to study the performance of SPM in detecting changes in regional cerebral blood flow (rCBF) in hypo- and hyperperfused areas in brain SPECT studies. The paper seeks to determine the relationship between the group size and the rCBF changes, and the influence of the correction for degradations. The assessment was carried out using simulated brain SPECT studies. Projections were obtained with Monte Carlo techniques, and a fan-beam collimator was considered in the simulation process. Reconstruction was performed by using the ordered subsets expectation maximization (OSEM) algorithm with and without compensation for attenuation, scattering, and spatial variant collimator response. Significance probability maps were obtained with SPM2 by using a one-tailed two-sample t-test. A bootstrap resampling approach was used to determine the sample size for SPM to detect the between-group differences. Our findings show that the correction for degradations results in a diminution of the sample size, which is more significant for small regions and low-activation factors. Differences in sample size were found between hypo- and hyperperfusion. These differences were larger for small regions and low-activation factors, and when no corrections were included in the reconstruction algorithm.

Quantification of dopaminergic neurotransmission SPECT studies with 123I-labelled radioligands. A comparison between different imaging systems and data acquisition protocols using Monte Carlo simulation.

PURPOSE: (123)I-labelled radioligands are commonly used for single-photon emission computed tomography (SPECT) imaging of the dopaminergic system to study the dopamine transporter binding. The aim of this work was to compare the quantitative capabilities of two different SPECT systems through Monte Carlo (MC) simulation. METHODS: The SimSET MC code was employed to generate simulated projections of a numerical phantom for two gamma cameras equipped with a parallel and a fan-beam collimator, respectively. A fully 3D iterative reconstruction algorithm was used to compensate for attenuation, the spatially variant point spread function (PSF) and scatter. A post-reconstruction partial volume effect (PVE) compensation was also developed. RESULTS: For both systems, the correction for all degradations and PVE compensation resulted in recovery factors of the theoretical specific uptake ratio (SUR) close to 100%. For a SUR value of 4, the recovered SUR for the parallel imaging system was 33% for a reconstruction without corrections (OSEM), 45% for a reconstruction with attenuation correction (OSEM-A), 56% for a 3D reconstruction with attenuation and PSF corrections (OSEM-AP), 68% for OSEM-AP with scatter correction (OSEM-APS) and 97% for OSEM-APS plus PVE compensation (OSEM-APSV). For the fan-beam imaging system, the recovered SUR was 41% without corrections, 55% for OSEM-A, 65% for OSEM-AP, 75% for OSEM-APS and 102% for OSEM-APSV. CONCLUSION: Our findings indicate that the correction for degradations increases the quantification accuracy, with PVE compensation playing a major role in the SUR quantification. The proposed methodology allows us to reach similar SUR values for different SPECT systems, thereby allowing a reliable standardisation in multicentric studies.

Test-retest variability and reliability of 123I-IBZM SPECT measurement of striatal dopamine D2 receptor availability in healthy volunteers and influence of iterative reconstruction algorithms.

OBJECTIVE: 123I-IBZM single photon emission computed tomography (SPECT) is a widely used method to measure D(2) receptor availability. However, test-retest variability and reliability have not been reported yet. This study aimed to further characterize 123I-IBZM SPECT in healthy volunteers (HVs), by assessing (1) pseudoequilibrium interval after bolus injection; (2) normal specific uptake ratio (SUR) values using filtered-backprojection (FBP); and the iterative reconstruction algorithm ordered-subsets expectation maximization (OSEM); (3) test-retest variability and reliability (intraclass correlation coefficient); and (4) influence of OSEM on test-retest variability and reliability. METHODS: Ten HVs (Group A) were scanned twice 48 h apart for test-retest variability and reliability measurements, and n = 4 of them were sequentially scanned over time. Eighteen HVs (Group B) were scanned once at pseudoequilibrium. For reconstruction FBP was used. Test-retest scans were reconstructed in addition using OSEM. SPECT-MRI coregistration was used for region of interest drawing. RESULTS: Pseudoequilibrium was achieved at 90 min postinjection (p.i.) and maintained until the end of the SPECT session (n = 4), and mean SUR at this time point was 0.96 +/- 0.14 (Groups A + B, n = 28). Mean SUR at test was 0.96 +/- 0.19 and at retest 0.94 +/- 0.19 (Group A, n = 10). Using FBP, test-retest variability was (12.7 +/- 9.6)% and reliability was 0.74. Using OSEM with 18 equivalent iterations, test-retest variability and reliability were improved to (6.5 +/- 5.2)% and 0.84, respectively. CONCLUSIONS: 123I-IBZM SPECT imaging using the bolus injection and a single scan at 90 min p.i. is a reproducible method showing acceptable test-retest variability and reliability. Test-retest variability and reliability can be substantially improved using OSEM with 12-36 equivalent iterations.

Absolute quantification in dopaminergic neurotransmission SPECT using a Monte Carlo-based scatter correction and fully 3-dimensional reconstruction.

UNLABELLED: Dopamine transporter (DAT) ligands have been developed for in vivo imaging of the dopaminergic system in SPECT. Although the visual analysis of SPECT images is, in general, suitable for clinical assessment, the accurate quantification of the striatal uptake might increase the sensitivity of the technique and help in the early diagnosis, follow-up, and eventual treatment response of Parkinson's disease (PD). This work is focused on assessment of the quantification of specific uptake of (99m)Tc-DAT ligands when compensation for all degrading phenomena is performed. METHODS: The SimSET Monte Carlo (MC) code was used to generate a set of SPECT projections of a numeric striatal phantom with different specific uptake ratios (SURs). An absolute quantification method (AQM), which performs a MC-based scatter compensation and a fully 3-dimensional (3D) reconstruction, was implemented. The scatter estimate was included in the reconstruction algorithm. RESULTS: The use of attenuation, point-spread-function (PSF), and scatter corrections resulted in an improvement in the value of the SUR of 37% on average with respect to the reconstruction without corrections. The magnitude of each improvement corresponded to 7% for the attenuation correction, 12% for the PSF correction using a 2-dimensional reconstruction algorithm and a further 11% for the PSF correction using a 3D reconstruction algorithm, and 7% for the scatter correction. CONCLUSION: Our findings indicate that the PSF correction plays a major role in the quantification of striatal uptake in comparison with the attenuation correction and the scatter correction. The implemented method also provides an absolute quantification procedure based on MC methods that do not depend on empiric approximations. The relative quantification results using the proposed AQM accounted for 96%-97% of the nominal SUR, whereas the limit achieved using only primary photons attained 98%-99%. The volumetric activity values obtained using the AQM converged toward the nominal values.

Iterative reconstruction with correction of the spatially variant fan-beam collimator response in neurotransmission SPET imaging.

The dopamine transporter (DAT) has been shown to be a sensitive indicator of nigrostriatal dopamine function. Although visual inspection is often sufficient to assess DAT imaging, quantification could improve the diagnostic accuracy of single-photon emission tomography (SPET) studies of the dopaminergic system. The aim of this study was to assess the accuracy of quantification of the striatal/background uptake ratio when correction for attenuation, scatter and spatially variant fan-beam collimator response is performed in technetium-99m and iodine-123 SPET imaging. A numerical striatal phantom was implemented, and simulated projections of low-energy photons were obtained by using the SimSET Monte Carlo code. High-energy contamination in 123I studies was modelled from experimental measurements with 99mTc and 123I. The ordered subsets expectation maximisation (OSEM) algorithm was employed in reconstruction. Mean improvements of 8% and 16% were obtained in the calculated striatal/background uptake ratio in the putamen and the caudate, respectively, when the spatially variant point spread function was included in the transition matrix. Ideal scatter correction resulted in improvements in the putamen and caudate of 9% for 99mTc agents and 19% for 123I agents. Improvements averaged 31% in the putamen and 43% in the caudate when correction for attenuation, scatter and spatially variant collimator response was included in the reconstruction.