Analytical, experimental, and Monte Carlo system response matrix for pinhole SPECT reconstruction

PURPOSE: To assess the performance of two approaches to the system response matrix (SRM) calculation in pinhole single photon emission computed tomography (SPECT) reconstruction. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

Impact of Region-of-Interest Delineation Methods, Reconstruction Algorithms, and Intra- and Inter-Operator Variability on Internal Dosimetry Estimates Using PET

Purpose: Human dosimetry studies play a central role in radioligand development for positron emission tomography (PET). Drawing regions of interest (ROIs) on the PET images is used to measure the dose in each organ. In the study aspects related to ROI delineation methods were evaluated for two radioligands of different biodistribution (intestinal vs urinary). Procedures: PET images were simulated from a human voxel-based phantom. Several ROI delineation methods were tested: antero-posterior projections (AP), 3D sub-samples of the organs (S), and a 3D volume covering the whole-organ (W). Inter- and intra-operator variability ROI drawing was evaluated by using human data. Results: The effective dose estimates using S and W methods were comparable to the true values. AP methods overestimated (49 %) the dose for the radioligand with intestinal biodistribution. Moreover, the AP method showed the highest inter-operator variability: 11 ± 1 %. Conclusions: The sub-sampled organ method showed the best balance between quantitative accuracy and inter- and intra-operator variability

Improved image quality in pinhole SPECT by accurate modeling of the point spread function in low magnification systems

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

Regional patterns of 18F-florbetaben uptake in presenilin 1 mutation carriers

Individuals with autosomal dominant Alzheimer's disease (ADAD) present amyloid deposits before symptoms onset. We aimed to investigate efficacy and safety of 18F-florbetaben (FBB) for assessing amyloid deposition in ADAD. We acquired FBB positron emission tomography and magnetic resonance imaging of 25 individuals from PSEN1 families (NCT02362880). We studied individual uptake patterns, group differences, and correlation with estimated years to symptoms onset, as well as adverse events. We found that asymptomatic carriers (N = 14) showed increased FBB uptake across the cerebral cortex and in the caudate. FBB accumulation appeared more than 15 years before onset in the precuneus and bankssts, among other regions, overlapping regions showing increased cortical thickness in the same subjects. FBB uptake correlated with estimated years to symptoms onset in several areas, especially the rostral anterior cingulate. Symptomatic carriers (N = 7) had an elevated FBB uptake plateau. No adverse events were reported. Overall, we found progressive FBB uptake in ADAD starting 2 decades before symptoms. The rostral anterior cingulate is a candidate area to track Aβ deposition in addition to the precuneus

Epileptogenic zone localization with (18)FDG PET using a new dynamic parametric analysis

Introduction: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM). Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good post-operative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p < 0.05 and cluster size k = 50 and at uncorrected p < 0.001 and k = 100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p-value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to post-surgical follow-up. Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p < 0.05) than that obtained with the SPM threshold p < 0.001/k = 100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p < 0.05/k = 50. Concordance was substantial for PET-analysis (κ = 0.643) and visual interpretation (κ = 0.622), being fair for SPM (κ = 0.242). Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization

APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls

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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Procesado de secuencias dinámicas en medicina nuclear

[spa] El uso de los ordenadores en Medicina Nuclear ha permitido la cuantificación de exploraciones, sobre todo las dinámicas. Debido a la gran cantidad de información presente en estos estudios es preciso efectuar una compresión de estos datos, de forma que hagan más fácil su interpretación. Una de las formas de reducción consiste en la obtención de imágenes paramétricas. El objetivo de este trabajo se centra en analizar la utilidad de estas imágenes paramétricas para la cuantificación de estudios dinámicos en tres aplicaciones. La primera aplicación es en los estudios de perfusión miocárdica que se utilizan para evaluar la irrigación del miocardio cuando se sospecha la existencia de enfermedad coronaria. En estos estudios se registran imágenes de esfuerzo y de redistribución, e interesa cuantificar la diferencia entre ambas. Nuestro objetivo fue cuantificar las diferencias entre las imágenes de esfuerzo y reposo por medio de una imagen paramétrica de “washout”, para lo cual es necesario eliminar la actividad extracardíaca y superponer ambas imágenes. Para comprobar la eficacia de diferentes métodos utilizables, se diseñó un modelo simulado por computador que incluía miocardio, fondo y posibles artefactos, a los que se les añadió un ruido. Se simularon imágenes de esfuerzo y reposo con cambios controlados en su distribución. Para efectuar la estimación del fondo se probaron diversos métodos de interpolación. Las pruebas realizadas demuestran que el método de Watson modificado es el que tiene el mejor comportamiento. Para alinear las imágenes de esfuerzo y redistribución de forma automática, probamos diversos algoritmos basados en la correlación. La correlación bidimensional restringida a la zona de mayor captación del miocardio, utilizando pixels alternos, se muestra como un método capaz de alinear las imágenes de esfuerzo y redistribución con suficiente precisión. Una vez efectuado el alineamiento de las imágenes se calculé la imagen paramétrica de “washout”. La cuantificación por medio de los valores medios en los diversos sectores estudiados, da resultados acordes con los teóricos. El método se aplicó sobre casos reales, obteniendo resultados concordantes con la patología. De esta parte se concluye que el método formado por la sustracción de fondo, la alineación de las imágenes y la construcción de la imagen paramétrica de “washout” es factible para la cuantificación de estudios planares de perfusión miocárdica. La segunda aplicación es sobre la ventriculografía isotópica en equilibrio, que es una exploración que permite estudiar el contenido de las cavidades ventriculares a lo largo del ciclo cardiaco, permitiendo estudiar el funcionalismo ventricular. Ha sido muy difundida la utilización de imágenes paramétricas de amplitud y fase del primer armónico del desarrollo de Fourier, que proporcionan información sobre la contractilidad y el sincronismo cardiaco. En este trabajo proponemos la utilización de dos armónicos para obtener nuevas imágenes paramétricas que reflejen las distintas fases del ciclo cardiaco. Estas corresponden a los parámetros: amplitud, tiempo de telesistole, fracción de eyección, máximas velocidades de vaciado y llenado y tiempos en los que se producen, además de una cuantificación utilizando el valor medio y desviación estándar de los valores de los parámetros en cada ventrículo. Los objetivos planteados fueron implementar el método compararlo con el estándar de un armónico. Se ha aplicado el método a un grupo formado por 13 voluntarios sanos, 10 hombres y 3 mujeres, lo que nos ha permitido estimar el rango de normalidad de los distintos parámetros en cada ventrículo. Los valores medios y desviaciones estándar de estos parámetros son distintos en los dos ventrículos. También se ha encontrando que los valores de tiempo de telesistole obtenidos con uno y dos arménicos son significativamente distintos siendo más altos y más dispersos, los obtenidos con un armónico. Las imágenes paramétricas calculadas mediante dos armónicos son más uniformes, existiendo diferencias significativas con los valores obtenidos mediante un armónico. El método también fue aplicado en varios sujetos con patología. En conjunto, puede concluirse que el método propuesto utilizando dos armónicos obtiene unos parámetros capaces de discriminar diversas patologías, siendo de utilidad para el estudio del funcionalismo cardíaco. La última aplicación es en los estudios de motilidad ciliar los cuales sirven para estudiar el comportamiento de los cilios de las mucosas que recubren las vías respiratorias. Su misión es transportar las partículas que se hayan depositado sobre ellos, hacia el exterior, a través de la boca. La velocidad con que estos cilios transportan estas partículas es importante ya que se ha observado que los enfermos con afección de las vías respiratorias presentan una disminución de esta capacidad protectora. Se ha desarrollado un método que permite cuantificar la velocidad de transporte en cualquier parte de la trayectoria. El método puede aplicarse los dos epitelios ciliadas que se encuentran en el organismo humano, corno son la mucosa nasal y la bronquial. Un conjunto de 14 sujetos normales voluntarios fue estudiado por esta técnica. El promedio de la velocidad media, en este grupo fue de S.3±1.4 mm/min. También se estudió un grupo de 16 laringectomizados, obteniendo un valor de 3.6±1.2 mm/min. La diferencia significativa hallada (p<0,005) demuestra que, en las personas laringectomizadas, se produce una alteración en la función de transporte probablemente l por atrofia de la mucosa nasal. El método implementado permite cuantificar con precisión la velocidad de transporte incluso en las diferentes partes del trayecto, pudiendo detectar zonas con motilidad ciliar anómalas por lo que puede ser de utilidad en el diagnóstico.[eng] The aim of this work is to analyze the usefulness of the parametric images in the quantification of dynamic studies. To this purpose, they have been applied in three different situations. First, in myocardial perfusion this thesis studies to quantify the difference between the stress and redistribution images. In this case, a parametric image of washout was used. Methods of background substraction to eliminate non-cardiac activity and of superimposition of both stress and redistribution images were studied and their efficacy checked by means of a computer-simulated model. The results of the quantification method were in agreement with the theoretical ones. It was also applied to real images and the results were in agreement with the patient's pathology. The second application is on equilibrium radionuclide angiocardiography, in which the utilization of two harmonics is proposed in order to calculate parametric images of amplitude, time to end-systole, ejection fraction, peak ejection and peak tilling rates, and time-to-peak ejection and time-to-peak filling rates. The quantification of these images was made by using the mean and standard deviation of the values of these functional parameters for each ventricle. The method has been applied to the studies of 13 healthy volunteers, which has allowed us to determine the range of normal values for each parameter. It was also applied to subjects with cardiac pathology. The last application is studies of ciliary motility. A method has been developed which allows to quantity the velocity of transportation in any part of the trajectory of a drop of radiopharmaceutical placed on the nasal cilia. This technique was applied to 14 normal subjects and to 16 laringectomized patients. It was found that the velocity was lesser in the pathological group (3.6±1.2 mm/min) than in normals (5.3±1.4 mm/min), being the difference statistically significant (p<0,005). This demonstrates that in laringectomized patients an alteration of the transportation function occurs, probably for atrophy of nasal mucosa

Tècniques de reconstrucció d'imatges en SPECT

L'espectacular avenç en la tecnologia mèdica que s'ha produït en els darrers anys, i l'augment de potencia de càlcul dels ordinadors, han generalitzat la utilització de tècniques cada vegada més sofisticades en l'àmbit del diagnòstic per la imatge. En l'actualitat disposem de tècniques d'obtenció d'imatges biomèdiques que, en aportar informació complementària morfològica i funcional, estan augmentant la capacitat de diagnòstic mitjançant tècniques no invasives. Com a exemple cal destacar la tomografia per ordinador de raigs X (SO) -impròpiament coneguda com a TC o tomografia computeritzada-, l'ecografia, la ressonància magnetita nuclear (RMN) i la tomografia d'emissió de fotons, en les dues vessants, emissió de fotó únic (SPECT, single photon emission computed tomography) o emissió de dos fotons d'aniquilació (PET, positron emission tomography). Així, les radiografies convencionals d'atenuació de raigs X, o les gammagrafies planars obtingudes per emissió de radiació γ d'un traçador, s'han vist complementades amb imatges transversals del cos humà, obtingudes a partir de projeccions bidimensionals

Improved image quality in pinhole SPECT by accurate modeling of the point spread function in low magnification systems

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