[Show abstract][Hide abstract] ABSTRACT: Background:
The APOE effect on Alzheimer Disease (AD) risk is stronger in women than in men but its mechanisms have not been established. We assessed the APOE-by-sex interaction on core CSF biomarkers, brain metabolism and structure in healthy elderly control individuals (HC).
Cross-sectional study. HC from the Alzheimer's Disease Neuroimaging Initiative with available CSF (n = 274) and/or 3T-MRI (n = 168) and/or a FDG-PET analyses (n = 328) were selected. CSF amyloid-β1-42 (Aβ1-42), total-tau (t-tau) and phospho-tau (p-tau181p) levels were measured by Luminex assays. We analyzed the APOE-by-sex interaction on the CSF biomarkers in an analysis of covariance (ANCOVA). FDG uptake was analyzed by SPM8 and cortical thickness (CTh) was measured by FreeSurfer. FDG and CTh difference maps were derived from interaction and group analyses.
APOE4 carriers had lower CSF Aβ1-42 and higher CSF p-tau181p values than non-carriers, but there was no APOE-by-sex interaction on CSF biomarkers. The APOE-by-sex interaction on brain metabolism and brain structure was significant. Sex stratification showed that female APOE4 carriers presented widespread brain hypometabolism and cortical thinning compared to female non-carriers whereas male APOE4 carriers showed only a small cluster of hypometabolism and regions of cortical thickening compared to male non-carriers.
The impact of APOE4 on brain metabolism and structure is modified by sex. Female APOE4 carriers show greater hypometabolism and atrophy than male carriers. This APOE-by-sex interaction should be considered in clinical trials in preclinical AD where APOE4 status is a selection criterion.
[Show abstract][Hide abstract] ABSTRACT: 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 ([Formula: see text] 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 ([Formula: see text] ≥ 11.79 for caudate and ≤7.36 for putamen), standardization based on a simple linear model was also suitable ([Formula: see text] ≥ 12.44 for caudate and ≤12.57 for putamen).
No preview · Article · Jul 2015 · Physics in Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Single photon emission computed tomography
(SPECT) has become an important noninvasive imaging technique in small-animal research. Due to the high resolution required in small-animal SPECT
systems, the spatially variant system response needs to be included in the reconstruction algorithm. Accurate modeling of the system response should result in a major improvement in the quality of reconstructed images. The aim of this study was to quantitatively assess the impact that an accurate modeling of spatially variant collimator/detector response has on image-quality parameters, using a low magnification SPECT
system equipped with a pinhole collimator and a small gamma camera.
[Show abstract][Hide abstract] ABSTRACT: In this work a comparison between experimental and simulated data using GATE and PeneloPET Monte Carlo simulation packages is presented. All simulated setups, as well as the experimental measurements, followed exactly the guidelines of the NEMA NU 4-2008 standards using the microPET R4 scanner. The comparison was focused on spatial resolution, sensitivity, scatter fraction and counting rates performance. Both GATE and PeneloPET showed reasonable agreement for the spatial resolution when compared to experimental measurements, although they lead to slight underestimations for the points close to the edge. High accuracy was obtained between experiments and simulations of the system's sensitivity and scatter fraction for an energy window of 350-650 keV, as well as for the counting rate simulations. The latter was the most complicated test to perform since each code demands different specifications for the characterization of the system's dead time. Although simulated and experimental results were in excellent agreement for both simulation codes, PeneloPET demanded more information about the behavior of the real data acquisition system. To our knowledge, this constitutes the first validation of these Monte Carlo codes for the full NEMA NU 4-2008 standards for small animal PET imaging systems.
No preview · Article · Dec 2014 · Physics in Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: It is well-known that in pinhole SPECT (single-photon-emission computed
tomography), iterative reconstruction methods including accurate estimations
of the system response matrix can lead to submillimeter spatial resolution.
There are two different methods for obtaining the system response matrix:
those that model the system analytically using an approach including an
experimental characterization of the detector response, and those that make
use of Monte Carlo simulations. Methods based on analytical approaches
are faster and handle the statistical noise better than those based on Monte
Carlo simulations, but they require tedious experimental measurements of
the detector response. One suggested approach for avoiding an experimental
characterization, circumventing the problem of statistical noise introduced
by Monte Carlo simulations, is to perform an analytical computation of the
system response matrix combined with a Monte Carlo characterization of the detector response. Our findings showed that this approach can achieve high
spatial resolution similar to that obtained when the system response matrix
computation includes an experimental characterization. Furthermore, we have
shown that using simulated detector responses has the advantage of yielding
a precise estimate of the shift between the point of entry of the photon beam
into the detector and the point of interaction inside the detector. Considering
this, it was possible to slightly improve the spatial resolution in the edge of
the field of view.
Full-text · Article · Nov 2014 · Physics in Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: Middle cerebral artery occlusion (MCAO) in rodents causes brain infarctions of variable sizes that depend on multiple factors, particularly in models of ischemia/reperfusion. This is a major problem for infarct volume comparisons between different experimental groups since unavoidable variability can induce biases in the results and imposes the use of large number of subjects. MRI can help to minimize these difficulties by ensuring that the severity of ischemia is comparable between groups. Furthermore, several studies showed that infarct volumes can be predicted with MRI data obtained soon after ischemia onset. However, such predictive studies require multiparametric MRI acquisitions that cannot be routinely performed, and data processing using complex algorithms that are often not available. The aim here was to provide a simplified method for infarct volume prediction using apparent diffusion coefficient (ADC) data in a model of transient MCAO in rats. ADC images were obtained before, during MCAO and after 60 min of reperfusion. Probability histograms were generated using ADC data obtained either during MCAO, after reperfusion, or both combined. The results were compared to real infarct volumes, i.e.T2 maps obtained at day 7. Assessment of the performance of the estimations showed better results combining ADC data obtained during occlusion and at reperfusion. Therefore, ADC data alone can provide sufficient information for a reasonable prediction of infarct volume if the MRI information is obtained both during the occlusion and soon after reperfusion. This approach can be used to check whether drug administration after MRI acquisition can change infarct volume prediction.
[Show abstract][Hide abstract] ABSTRACT: SPECT studies with 123I-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 123I-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.
Full-text · Article · Jul 2014 · Physics in Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To assess the performance of two approaches to the system response matrix (SRM) calculation in pinhole single photon emission computed tomography (SPECT) reconstruction.
Evaluation was performed using experimental data from a low magnification pinhole SPECT system that consisted of a rotating flat detector with a monolithic scintillator crystal. The SRM was computed following two approaches, which were based on Monte Carlo simulations (MC-SRM) and analytical techniques in combination with an experimental characterization (AE-SRM). The spatial response of the system, obtained by using the two approaches, was compared with experimental data. The effect of the MC-SRM and AE-SRM approaches on the reconstructed image was assessed in terms of image contrast, signal-to-noise ratio, image quality, and spatial resolution. To this end, acquisitions were carried out using a hot cylinder phantom (consisting of five fillable rods with diameters of 5, 4, 3, 2, and 1 mm and a uniform cylindrical chamber) and a custom-made Derenzo phantom, with center-to-center distances between adjacent rods of 1.5, 2.0, and 3.0 mm.
Good agreement was found for the spatial response of the system between measured data and results derived from MC-SRM and AE-SRM. Only minor differences for point sources at distances smaller than the radius of rotation and large incidence angles were found. Assessment of the effect on the reconstructed image showed a similar contrast for both approaches, with values higher than 0.9 for rod diameters greater than 1 mm and higher than 0.8 for rod diameter of 1 mm. The comparison in terms of image quality showed that all rods in the different sections of a custom-made Derenzo phantom could be distinguished. The spatial resolution (FWHM) was 0.7 mm at iteration 100 using both approaches. The SNR was lower for reconstructed images using MC-SRM than for those reconstructed using AE-SRM, indicating that AE-SRM deals better with the projection noise than MC-SRM.
The authors' findings show that both approaches provide good solutions to the problem of calculating the SRM in pinhole SPECT reconstruction. The AE-SRM was faster to create and handle the projection noise better than MC-SRM. Nevertheless, the AE-SRM required a tedious experimental characterization of the intrinsic detector response. Creation of the MC-SRM required longer computation time and handled the projection noise worse than the AE-SRM.Nevertheless, the MC-SRM inherently incorporates extensive modeling of the system and therefore experimental characterization was not required.
[Show abstract][Hide abstract] ABSTRACT: Quantification of neurotransmission Single-Photon Emission Computed Tomography (SPECT) studies of the dopaminergic system can be used to track, stage and facilitate early diagnosis of the disease. The aim of this study was to implement QuantiDOPA, a semi-automatic quantification software of application in clinical routine to reconstruct and quantify neurotransmission SPECT studies using radioligands which bind the dopamine transporter (DAT). To this end, a workflow oriented framework for the biomedical imaging (GIMIAS) was employed. QuantiDOPA allows the user to perform a semiautomatic quantification of striatal uptake by following three stages: reconstruction, normalization and quantification. QuantiDOPA is a useful tool for semi-automatic quantification inDAT SPECT imaging and it has revealed simple and flexible.
No preview · Article · Jan 2014 · IFMBE proceedings
[Show abstract][Hide abstract] ABSTRACT: 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.
This was achieved by the complete integration of a 3D SPECT system matrix modeling library into STIR.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Very recent clinical research has investigated whether obstructive sleep apnea (OSA) may modulate bone homeostasis but the few data available are conflicting. Here we report novel data obtained in a mouse study specifically designed to determine whether chronic intermittent hypoxia realistically mimicking OSA modifies bone mineral density (BMD). Normal male and female mice and orchidectomized mice (N=10 each group) were subjected to a pattern of high-frequency intermittent hypoxia (20 s at 5% and 40 s at 21%, 60 cycles/h) for 6h/day. Identical groups breathing room air (normoxia) were the controls. After 32 days of intermittent hypoxia/normoxia the trabecular bone mineral density (BMD) in the peripheral femora were measured by micro-CT scanning. When compared with normoxia (two-way ANOVA), intermittent hypoxia did not significantly modify BMD in the three animal groups tested. Data in this study suggest that the type of intermittent hypoxia characterizing OSA, applied as a single challenge, preserves bone homeostasis.
No preview · Article · Aug 2013 · Respiratory Physiology & Neurobiology
[Show abstract][Hide abstract] ABSTRACT: A 3D SPECT system matrix modelling library has recently been incorporated into STIR - a software package for tomographic image reconstruction. The SPECT modelling accounts for the effects of attenuation and spatially variant resolution by incorporating them into the system matrix. Attenuation calculation can be done either along a single line (simple model), or along multiple lines for the various detector pixels covered by the PSF (full model). Due to practical reasons, a simple central-line approximation is often used for the attenuation modelling in SPECT. Our aim was to evaluate the effect of this approximation in the reconstructed images using STIR. A rotating SPECT system was modelled, equipped with different collimators. We generated noise-free projection data using the full model and reconstructed images using both models. We used a phantom consisting of an ellipse containing 4 spherical inserts with the same activity concentration but different attenuation coefficients. Images were reconstructed using the OS-MAP algorithm, 12 subsets and up to 100 iterations. With the simple model, the four spheres were all different in terms of intensity as well as distribution. When using the full attenuation model, all spheres appeared quite similar, independent of the attenuation. Our results show that the simple attenuation model can lead to artifacts and inaccurate quantification, while the full model adds significant accuracy and stability to the reconstructed images.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this work was to evaluate the performance of the microPET R4 system for rodents according to the NU 4-2008 standards of the National Electrical Manufacturers Association (NEMA) for small-animal positron emission tomography (PET) systems and to compare it against its previous evaluation according the adapted clinical NEMA NU 2-2001. The performance parameters evaluated here were spatial resolution, sensitivity, scatter fraction, counting rates for rat- and mouse-sized phantoms, and image quality. Spatial resolution and sensitivity were measured with a 22Na point source, while scatter fraction and count rate performance were determined using a mouse and rat phantoms with an 18F line source. The image quality of the system was assessed using the NEMA image quality phantom. Assessment of attenuation correction was performed using γ-ray transmission and computed tomography (CT)-based attenuation correction methods. At the center of the field of view, a spatial resolution of 2.12 mm at full width at half maximum (FWHM) (radial), 2.66 mm FWHM (tangential), and 2.23 mm FWHM (axial) was measured. The absolute sensitivity was found to be 1.9% at the center of the scanner. Scatter fraction for mouse-sized phantoms was 8.5 %, and the peak count rate was 311 kcps at 153.5 MBq. The rat scatter fraction was 22%, and the peak count rate was 117 kcps at 123.24 MBq. Image uniformity showed better results with 2-D filtered back projection (FBP), while an overestimation of the recovery coefficients was observed when using 2-D and 3-D OSEM MAP reconstruction algorithm. All measurements were made for an energy window of 350-650 keV and a coincidence window of 6 ns. Histogramming and reconstruction parameters were used according to the manufacturer's recommendations. The microPET R4 scanner was fully characterized according to the NEMA NU 4-2008 standards. Our results diverge considerably from those previously reported with an adapted version- of the NEMA NU 2-2001 clinical standards. These discrepancies can be attributed to the modifications in NEMA methodology, thereby highlighting the relevance of specific small-animal standards for the performance evaluation of PET systems.
Full-text · Article · Oct 2012 · IEEE Transactions on Nuclear Science
[Show abstract][Hide abstract] ABSTRACT: Introduction: The key characteristics of positron emission tomography (PET) are its quantitative capability and its sensitivity, which allow the in vivo imaging of biochemical interactions with small amounts of tracer concentrations. Therefore, accurate quantification is important. However, it can be sensitive to several physical factors. The aim of this investigation is the assessment of the effect of physical effects, such as: scatter coincidences, partial volume, positron range and non-colinearity on the quantification of FDOPA uptake using PET. Methods: The SimSET Monte Carlo package was employed to simulate acquisitions of the PET/CT Siemens Biograph scanner. The study was performed with a numerical brain model obtained from the CT scan of a commercial striatal phantom. Theoretical pharmacokinetic values were simulated. The simulations were carried out with and without scatter, positron range and non-colinearity effects. The OSEM algorithm from STIR library was used to reconstruct the PET data. Different correction strategies were employed in order to evaluate the effects caused by the different type of degradation on results obtained with Patlak analysis. Results: The FDOPA uptake of Patlak plot increased from 70.4% of the theoretical value to 80.4%, if scatter was perfectly corrected, and it increased to 99% of the theoretical value when the partial volume correction was employed, as well. No significant improvement was found for positron range and non-colinearity effects when the partial volume correction was employed. Conclusions: The results show that the compensation for scatter and partial volume degradations increases accuracy in the uptake calculation.
No preview · Article · Sep 2012 · Iranian Journal of Nuclear Medicine
[Show abstract][Hide abstract] ABSTRACT: Subtraction of Ictal SPECT Co-registered to MRI (SISCOM) is an imaging technique used to localize the epileptogenic focus in patients with intractable partial epilepsy. The aim of this study was to determine the accuracy of registration algorithms involved in SISCOM analysis using FocusDET, a new user-friendly application. To this end, Monte Carlo simulation was employed to generate realistic SPECT studies. Simulated sinograms were reconstructed by using the Filtered BackProjection (FBP) algorithm and an Ordered Subsets Expectation Maximization (OSEM) reconstruction method that included compensation for all degradations. Registration errors in SPECT-SPECT and SPECT-MRI registration were evaluated by comparing the theoretical and actual transforms. Patient studies with well-localized epilepsy were also included in the registration assessment. Global registration errors including SPECT-SPECT and SPECT-MRI registration errors were less than 1.2 mm on average, exceeding the voxel size (3.32 mm) of SPECT studies in no case. Although images reconstructed using OSEM led to lower registration errors than images reconstructed with FBP, differences after using OSEM or FBP in reconstruction were less than 0.2 mm on average. This indicates that correction for degradations does not play a major role in the SISCOM process, thereby facilitating the application of the methodology in centers where OSEM is not implemented with correction of all degradations. These findings together with those obtained by clinicians from patients via MRI, interictal and ictal SPECT and video-EEG, show that FocusDET is a robust application for performing SISCOM analysis in clinical practice.
[Show abstract][Hide abstract] ABSTRACT: 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.
In a prospective study, 20 patients with IRBD (mean age 70·55 years [SD 6·02]) underwent serial DAT imaging with (123)I-2β-carbomethoxy-3β-(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).
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.
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.
Fondo de Investigaciones Sanitarias of Spain.
No preview · Article · Sep 2011 · The Lancet Neurology
[Show abstract][Hide abstract] ABSTRACT: Auditory verbal hallucinations (AVHs) are a core symptom of schizophrenia. Previous reports on neural activity patterns associated with AVHs are inconsistent, arguably owing to the lack of an adequate control group (i.e., patients with similar characteristics but without AVHs) and neglect of the potential confounding effects of medication.
The current study was conducted in a homogeneous group of patients with schizophrenia to assess whether the presence or absence of AVHs was associated with differential regional cerebral glucose metabolic patterns. We investigated differences between patients with commenting AVHs and patients without AVHs among a group of dextral antipsychotic-naive inpatients with acute first-episode schizophrenia examined with [(18)F]fluoro-deoxyglucose positron emission tomography (FDG-PET) at rest. Univariate and multivariate approaches were used to establish between-group differences.
We included 9 patients with AVHs and 7 patients without AVHs in this study. Patients experiencing AVHs during FDG uptake had significantly higher metabolic rates in the left superior and middle temporal cortices, bilateral superior medial frontal cortex and left caudate nucleus (cluster level p < 0.005, family wise error-corrected, and bootstrap ratio > 3.3, respectively). Additionally, the multivariate method identified hippocampal-parahippocampal, cerebellar and parietal relative hypoactivity during AVHs in both hemispheres (bootstrap ratio < -3.3).
The FDG-PET imaging technique does not provide information regarding the temporal course of neural activity. The limited sample size may have increased the risk of false-negative findings.
Our results indicate that AVHs in patients with schizophrenia may be mediated by an alteration of neural pathways responsible for normal language function. Our findings also point to the potential role of the dominant caudate nucleus and the parahippocampal gyri in the pathophysiology of AVHs. We discuss the relevance of phenomenology-based grouping in the study of AVHs.