Validation of semi-quantitative methods for DAT SPECT: influence of anatomical variability and partial volume effect.

The aim of this work was to evaluate the influence of anatomical variability between subjects and of the partial volume effect (PVE) on the standardized Specific Uptake Ratio (SUR) in [(123)I]FP-bib SPECT studies. To this end, magnetic resonance (MR) images of 23 subjects with differences in the striatal volume of up to 44% were segmented and used to generate a database of 138 Monte Carlo simulated SPECT studies. Data included normal uptakes and pathological cases. Studies were reconstructed by filtered back projection (FBP) and the ordered-subset expectation-maximization algorithm. Quantification was carried out by applying a reference method based on regions of interest (ROIs) derived from the MR images and ROIs derived from the Automated Anatomical Labelling map. Our results showed that, regardless of anatomical variability, the relationship between calculated and true SUR values for caudate and putamen could be described by a multiple linear model which took into account the spill-over phenomenon caused by PVE (R² ≥ 0.963 for caudate and ≥0.980 for putamen) and also by a simple linear model (R(2) ≥ 0.952 for caudate and ≥0.973 for putamen). Calculated values were standardized by inverting both linear systems. Differences between standardized and true values showed that, although the multiple linear model was the best approach in terms of variability (X² ≥ 11.79 for caudate and ≤7.36 for putamen), standardization based on a simple linear model was also suitable (X² ≥ 12.44 for caudate and ≤12.57 for putamen).

Quantification of rat brain SPECT with (123)I-ioflupane: evaluation of different reconstruction methods and image degradation compensations using Monte Carlo simulation.

SPECT studies with (123)I-ioflupane facilitate the diagnosis of Parkinson's disease (PD). The effect on quantification of image degradations has been extensively evaluated in human studies but their impact on studies of experimental PD models is still unclear. The aim of this work was to assess the effect of compensating for the degrading phenomena on the quantification of small animal SPECT studies using (123)I-ioflupane. This assessment enabled us to evaluate the feasibility of quantitatively detecting small pathological changes using different reconstruction methods and levels of compensation for the image degrading phenomena. Monte Carlo simulated studies of a rat phantom were reconstructed and quantified. Compensations for point spread function (PSF), scattering, attenuation and partial volume effect were progressively included in the quantification protocol. A linear relationship was found between calculated and simulated specific uptake ratio (SUR) in all cases. In order to significantly distinguish disease stages, noise-reduction during the reconstruction process was the most relevant factor, followed by PSF compensation. The smallest detectable SUR interval was determined by biological variability rather than by image degradations or coregistration errors. The quantification methods that gave the best results allowed us to distinguish PD stages with SUR values that are as close as 0.5 using groups of six rats to represent each stage.

Decreased striatal dopamine transporter uptake in the non-fluent/agrammatic variant of primary progressive aphasia.

BACKGROUND AND PURPOSE: Patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) may develop atypical parkinsonian syndromes. However, there is no current biomarker to assess which patients are at high risk of developing parkinsonism. 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT)-SPECT detects striatal dopamine dysfunction in vivo. The objective of the present study was to study whether non-fluent/agrammatic patients without parkinsonism at baseline present decreased striatal 123I-FP-CIT uptake. METHODS: Visual and semi-quantitative assessments of the striatal 123I-FP-CIT uptake ratio were carried out in 15 patients with nfvPPA, eight patients with the logopenic variant of PPA (lvPPA) and 18 controls. To rule out progranulin mutations or underlying Alzheimer's disease (AD), serum progranulin levels and cerebrospinal fluid (CSF) biomarkers of AD (Aß42 , total-tau, phosphorylated-tau181 ) were determined. A second 123I-FP-CIT-SPECT analysis in the biomarker-enriched groups was also carried out. RESULTS: Patients with nfvPPA presented reduced striatal 123I-FP-CIT binding, especially in the left hemisphere (P = 0.002), compared with controls. All lvPPA patients had normal striatal 123I-FP-CIT uptake. 123I-FP-CIT striatal binding in nfvPPA patients with normal progranulin and CSF biomarker levels (nfvPPA/bio-) was also significantly reduced (P < 0.05) compared with lvPPA patients with positive AD biomarkers. Sixty-four per cent (9/14) of nfvPPA patients and 80% of nfvPPA/bio- patients (8/10) showed a diminished individual left striatal 123I-FP-CIT uptake ratio. On follow-up, seven nfvPPA/bio- patients developed parkinsonism (median 1.9 years; range 1.2-2.9), six of them with baseline reduced 123I-FP-CIT uptake. CONCLUSIONS: Reduced striatal tracer uptake in nfvPPA patients prior to clinical parkinsonism can be detected by 123I-FP-CIT-SPECT, especially in those with nfvPPA/bio-, suggesting subclinical nigrostriatal degeneration. Decreased striatal 123I-FP-CIT binding might identify PPA patients at increased risk of developing atypical parkinsonian syndromes, probably related to tau-pathology.

Impact of scatter correction on D2 receptor occupancy measurements using 123I-IBZM SPECT: comparison to 11C-Raclopride PET.

Reported values of D(2) receptor occupancy (RO) achieved by antipsychotic drugs tend to be lower when measured with (123)I-IBZM SPECT than with (11)C-Raclopride PET. Image degrading factors such as attenuation, distance-dependent collimator response and scatter could account for this difference. While attenuation correction is routinely applied to SPECT images, the other degradations are not usually accounted for. The aim of this work was to assess the impact of scatter correction on D(2) RO quantification with (123)I-IBZM SPECT, and to compare the results of both corrected and un-corrected SPECT values with (11)C-Raclopride PET measurements. Phantom experiments as well as within-subject human data from a previous study were used for this purpose. SPECT images were reconstructed using filtered back-projection including attenuation correction (FBP(A)), ordered subsets expectation maximization including attenuation and point spread function corrections (OSEM(A+PSF)) and ordered subsets expectation maximization including attenuation, point spread function and scatter corrections (OSEM(A+PSF+SCT)). PET images were reconstructed using the FBP algorithm and corrected for attenuation, scatter, random coincidences and dead time. Quantification of receptor availability was performed using the tissue ratio at pseudoequilibrium for SPECT, and the simplified reference tissue model (SRTM) for PET. Analysis was performed using both occipital cortex (occ) and cerebellum (cer) as reference regions for both modalities. When images were reconstructed using FBP(A), SPECT D(2) RO values were significantly lower as compared with PET leading to a D(2) RO difference of -20% (CI(95%): -13, -27%) (occ) and -23% (CI(95%): -14, -31%) (cer). When images were reconstructed using OSEM(A+PSF), SPECT D(2) RO values were also lower as compared with PET leading to a D(2) RO difference of -21% (CI(95%): -14, -27%) (occ) and -24% (CI(95%): -18, -30%) (cer). When images were reconstructed using OSEM(A+PSF+SCT), the D(2) RO bias was reduced to -6% (CI(95%): 0, -13%) (occ) and -11% (CI(95%): -4, -18%) (cer). These data suggest that the scatter correction plays a major role in explaining the differences between D(2) RO measurements using (123)I-IBZM SPECT and (11)C-Raclopride PET.

Neurotransmission SPECT and MR registration combining mutual and gradient information.

PURPOSE: Image registration is important in functional image analysis. In neurotransmission single photon emission tomography (nSPECT), specific uptake sites can be accurately localized by superimposing the SPECT study onto a high-resolution structural image such as a magnetic resonance (MR) of the subject. Mutual-information (MI)-based algorithms are usually employed for this purpose. Nevertheless, nSPECT/MR registration using MI is often limited by the low count rates present in nSPECT. Several works have proposed extensions of the MI measures to include gradient information (GI) from the images but their performance has not been evaluated in SPECT studies. METHODS: In this work, the accuracy of the MI including gradient information (MIG) was compared with the standard MI using data from healthy volunteers and data simulating a specific uptake reduction using three different radioligands: 123I-IBZM, 123I-ADAM, 123I-R91150. RESULTS: The results showed that MIG-based registration yielded better accuracy than MI. The MIG-based similarity measures were less sensitive to sparse sampling and diminished computational time without a substantial decrease in registration accuracy. CONCLUSIONS: Accuracy of nSPECT/MR registration is improved when gradient information is included in the MI-based algorithm, which makes MIG-based registration potentially useful for clinical applications.

Effect of anatomical variability, reconstruction algorithms and scattered photons on the SPM output of brain PET studies.

Statistical parametric mapping (SPM) has become the standard technique to statistically evaluate differences between functional images. The aim of this paper was to assess the effect of anatomical variability of skull, the reconstruction algorithm and the scattering of photons in the brain on the output of an SPM analysis of brain PET studies. To this end, Monte Carlo simulation was used to generate suitable PET sinograms and bootstrap techniques were employed to increase the reliability of the conclusions. Activity distribution maps were obtained by segmenting thirty nine T1-weighted magnetic resonance images. Foci were placed on the posterior cingulate cortex (PCC) and the superior temporal cortex (STC) and activation factors ranging between -25% and +25% were simulated. Preprocessing of the reconstructed images and statistical analysis were performed using SPM2. Our findings show that intersubject anatomical differences can cause the minimum sample size to increase between 10 and 42% for posterior cingulate Cortex and between 40 and 80% for superior temporal cortex. Ideal scatter correction (ISC) allowed us to diminish the sample size up to 18% and fully 3D reconstruction reduced the minimum sample size between 8 and 33%. Detection sensitivity was higher for hypo-activation than for hyper-activation situations and higher for superior temporal cortex than for posterior cingulate cortex.

Study of the point spread function (PSF) for 123I SPECT imaging using Monte Carlo simulation.

The iterative reconstruction algorithms employed in brain single-photon emission computed tomography (SPECT) allow some quantitative parameters of the image to be improved. These algorithms require accurate modelling of the so-called point spread function (PSF). Nowadays, most in vivo neurotransmitter SPECT studies employ pharmaceuticals radiolabelled with 123I. In addition to an intense line at 159 keV, the decay scheme of this radioisotope includes some higher energy gammas which may have a non-negligible contribution to the PSF. The aim of this work is to study this contribution for two low-energy high-resolution collimator configurations, namely, the parallel and the fan beam. The transport of radiation through the material system is simulated with the Monte Carlo code PENELOPE. We have developed a main program that deals with the intricacies associated with tracking photon trajectories through the geometry of the collimator and detection systems. The simulated PSFs are partly validated with a set of experimental measurements that use the 511 keV annihilation photons emitted by a 18F source. Sensitivity and spatial resolution have been studied, showing that a significant fraction of the detection events in the energy window centred at 159 keV (up to approximately 49% for the parallel collimator) are originated by higher energy gamma rays, which contribute to the spatial profile of the PSF mostly outside the 'geometrical' region dominated by the low-energy photons. Therefore, these high-energy counts are to be considered as noise, a fact that should be taken into account when modelling PSFs for reconstruction algorithms. We also show that the fan beam collimator gives higher signal-to-noise ratios than the parallel collimator for all the source positions analysed.

Dynamic model of the left ventricle for use in simulation of myocardial perfusion SPECT and gated SPECT.

Simulation is a useful tool in cardiac SPECT to assess quantification algorithms. However, simple equation-based models are limited in their ability to simulate realistic heart motion and perfusion. We present a numerical dynamic model of the left ventricle, which allows us to simulate normal and anomalous cardiac cycles, as well as perfusion defects. Bicubic splines were fitted to a number of control points to represent endocardial and epicardial surfaces of the left ventricle. A transformation from each point on the surface to a template of activity was made to represent the myocardial perfusion. Geometry-based and patient-based simulations were performed to illustrate this model. Geometry-based simulations modeled (1) a normal patient, (2) a well-perfused patient with abnormal regional function, (3) an ischaemic patient with abnormal regional function, and (4) a patient study including tracer kinetics. Patient-based simulation consisted of a left ventricle including a realistic shape and motion obtained from a magnetic resonance study. We conclude that this model has the potential to study the influence of several physical parameters and the left ventricle contraction in myocardial perfusion SPECT and gated-SPECT studies.

Characterisation of fan-beam collimators.

Fan-beam collimators offer a good balance between resolution and noise. The collimator response may be included in iterative reconstruction algorithms in order to improve single-photon emission tomography (SPET) resolution. To this end, accurate determination of the focal region and characterisation of the collimator response as a function of the source co-ordinates must be performed. In this paper, a method to characterise fanbeam collimators is evaluated. First, we calculated the real focal region and the accuracy of the collimator convergence. Then, we confirmed the hypothesis that Gaussian distributions adequately fit the collimator responses, although no individualised treatment was performed for the tails of detector response which are associated with scattering and septal penetration. Finally, analytical functions were used to model the resolution and sensitivity. The parameter values in these functions were obtained from experimental measures by non-linear regression fitting. Our findings show differences of 1.43% between nominal and real focal length and standard deviations of 2.5 mm in the x-direction and 7.1 mm in the y-direction for the focal convergence. The correlation coefficients between experimental and predicted values were 0.994 for resolution and 0.991 for sensitivity. As a consequence, the proposed method can be used to characterise the collimator response.

Separation, identification and quantitative determination of free amino acids from plant extracts.

This research presents the results obtained from the separation, identification and quantitative determination of free amino acids from Gingko biloba and Hedera helix leaf extracts, using three modern techniques: thin layer chromatography (TLC), high performance liquid chromatography (HPLC), and gas chromatography-mass spectrometry. The presence of the determined amino acids explains the utilisation of G. biloba and H. helix leaf extracts in cosmetic and pharmaceutical products.