The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.

Background: The feasibility of beta cell mass (BCM) imaging and quantification with positron emission tomography (PET) in the pancreas is controversial. In an effort to shed some light on this topic, we have used a xenograft model of rat insulinoma (RIN) in mice, mimicking an intramuscular islet transplantation situation. Methods: A total of 105 RIN cells were subcutaneously implanted in nude mice (N.=8). Tumor size and glycaemia levels were determined daily. Rat C-peptide was measured to demonstrate rat insulin production. PET imaging with 11C-(+)-¿-dihydrotetrabenazine (11C-DTBZ) was done at 3 and 4 weeks and compared with 18F-FDG and 18F-DOPA studies in the same mice. Ex-vivo autoradiography with 11C-DTBZ was carried out in frozen sections of tumors. VMAT2 expression was measured by Western-blot and immunohistochemistry in tumors and RIN cells. Results: Functional rat insulin production in mice was demonstrated by substantial decrease in glycaemia (<50 mg/dL by week 4) and rat C-peptide levels (7.2±2.6 ng/mL) similar to those measured in control rats. PET studies showed that tumor imaging with 11C-DTBZ at four (N.=8) and five (N.=5) weeks was negative; only bigger tumors could be seen with 18F-DOPA. In explanted tumors 11C-DTBZ autoradiography was negative, albeit VMAT2 expression measured by Western-blot and immunohistochemistry was lower than in cultured RIN cells. Conclusions: Although insulinomas are fully functional it does not seem feasible to use 11C-DTBZ for in-vivo measuring of BCM. This might either be due to inherent technical limitations of PET, decrease in VMAT2 expression in the tumors due to unknown reasons, or other biological limiting facts.

The aim of this study was to assess the physical performance of a new PET/CT system, the Discovery IQ with 5-ring detector blocks. Methods: Performance was measured using the National Electrical Manufacturers Association NU2-2012 methodology. Image quality was extended by accounting for different acquisition parameters (lesion-to-background ratios [8:1, 4:1, and 2:1] and acquisition times) and reconstruction algorithms (VUE-point HD [VPHD], VPHD with point-spread-function modeling [VPHD-S], and Q.Clear). Tomographic reconstruction was also assessed using a Jaszczak phantom. Additionally, 30 patient lesions were analyzed to account for differences in lesion volume and SUV quantification between reconstruction algorithms. Results: Spatial resolution ranged from 4.2 mm at 1 cm to 8.5 mm at 20 cm. Sensitivity measured at the center and at 10 cm was 22.8 and 20.4 kps/kBq, respectively. The noise-equivalent counting rate peak was 124 kcps at 9.1 kBq/cm(3). The scatter fraction was 36.2%. The accuracy of correction for count losses and randoms was 3.9%. In the image quality test, contrast recovery for VPHD, VPHD-S, and Q.Clear ranged from 18%, 18%, and 13%, respectively (hot contrast; 10-mm sphere diameter; ratio, 2:1), to 68%, 67%, and 81%, respectively (cold contrast; 37-mm sphere diameter; ratio, 8:1). Background variability ranged from 3.4%, 3.0%, and 2.1%, respectively (ratio, 2: 1), to 5.5%, 4.8%, and 3.7%, respectively (ratio, 8: 1). On Q.Clear reconstruction, the decrease in the penalty term (b) increased the contrast recovery coefficients and background variability. With the Jaszczak phantom, image quality increased overall when a reconstruction algorithm modeling the point-spread function was used, and use of Q.Clear increased the signal-to-noise ratio. Lesions nalyzed using VPHD-S and Q.Clear had an SUVmean of 6.5 +/- 3 and 7 6 3, respectively (P<0.01), and an SUVmax of 11 +/- 4.8 and 12 +/- 4, respectively (P<0.01). No significant difference in mean lesion volume was found between algorithms. Conclusion: Among the various Discovery bismuth germanium oxide-based PET/CT scanners, the IQ with 5-ring detector blocks has the highest overall performance, with improved sensitivity and counting rate performance. Q.Clear reconstruction improves the PET image quality, with higher recovery coefficients and lower background variability.

Background. Osteosarcoma paediatric patients are usually treated with intra-arterial chemotherapy (QTia) which is administered directly to the tumour. This procedure exposes patients to ionizing radiation. Paediatric patients are especially sensitive to this exposure. Methods. The total amount of ionizing radiation received from QTia administration was quantified in a group of 16 osteosarcoma paediatric patients from the Clinica Universidad de Navarra. Results. The median of the total radiation received per patient was 33.4 Gy.cm(2) (IQR: 43.33 Gy.cm(2)), and the median number of procedures performed per subject was 10 (IQR: 6.5). Conclusions. The study highlights the importance of quantifying the radiation received by a group of children and adolescents affected by osteosarcoma during treatment with QTia. Long-term side effects of this radiation should be considered in paediatric patients. Currently, there are no previous studies that provide data of the amount of ionizing radiation received through this procedure.

It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions

Optimization of reconstruction algorithm and parameters has been performed to take particular advantage of the last generation PET scanner, recommending specific settings for different brain PET radiotracers.

Background: [F-18]-tetrafluoroborate is a PET radiotracer taken up by the sodium/iodide symporter (NIS). Albeit the in vivo behavior in rodents is similar to the (99)mTc-pertechnetate, no studies exist in primates or in humans. The aims of this study were to evaluate the biodistribution of [F-18]-tetrafluoroborate in non-human primates with PET and to estimate the absorbed dose in organs. Methods: Whole-body PET imaging was done in a Siemens ECAT HR+ scanner in two male Macaca fascicularis monkeys. After an i.v. injection of 24.93 +/- 0.05 MBq/kg of [F-18]-tetrafluoroborate, prepared by isotopic exchange of sodium tetrafluoroborate with [F-18]-fluoride under acidic conditions, eight sequential images from the head to the thigh (five beds) were collected for a total duration of 132 min. The whole-body emission scan was reconstructed applying attenuation and scatter corrections. After image reconstruction, three-dimensional volumes of interest (VOIs) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and the organ residence times were calculated by integration of the time-activity curves. Human absorbed doses were estimated using the OLINDA/EXM software and the standard human model. Results: [F-18]-tetrafluoroborate was able to discriminate clearly the thyroid gland with an excellent signal-to-noise ratio. Most of the radiotracers (residence time) are localised in the orga

The improved multichannel dosimetric method is able to remove many of the common disturbances usually present in radiochromic films and improves the gamma analysis results compared with the other three methods.

Qualitative and quantitative 90Y PET imaging improved with the introduction of TOF in a PET/CT scanner, thereby allowing the visualization of microsphere deposition in lesions not visible in non-TOF images. This technique accurately quantifies the total activity delivered to the liver during radioembolization with (90)Y-microspheres and allows dose estimation.

La imagen preclínica engloba distintas técnicas de imagen molecular que utilizan radiaciones ionizantes, destacando la tomografía por emisión de fotón único (SPECT), la tomografía de emisión de positrones (PET) y la imagen autorradiográfica. Cada una de ellas utiliza distintas sondas que permiten obtener imágenes de una gran variedad de procesos metabólicos. En ocasiones se emplean junto a equipos de rayos X que permiten obtener imágenes anatómicas. En consecuencia, la investigación en las instalaciones de imagen molecular preclínica deberá realizarse en un contexto en el que se aplique la protección radiológica. De entre los riesgos radiológicos del personal que opera este tipo de instalaciones destaca la irradiación de las manos producida tanto por la administración de los radiotrazadores a los animales como por la manipulación de los mismos, siendo importante el entrenamiento y el uso de los blindajes. El diseño de la instalación radiactiva estará determinado por la actividad que en ella se realice. En particular dependerá tanto de las distintas técnicas de imagen molecular preclínica que se desarrollen como de la relación funcional que la instalación tenga con el resto del centro en el que se encuentre, en particular con el animalario y la unidad de radiofarmacia.

Objetivo Diseñar una técnica novedosa de adquisición ex-vivo para establecer un marco común de validación de diferentes técnicas de segmentación para imágenes PET oncológicas. Evaluar sobre estas imágenes el funcionamiento de varios algoritmos de segmentación automática. Material y métodos En 15 pacientes oncológicos se realizaron estudios PET ex-vivo de las piezas quirúrgicas extraídas durante la cirugía, previa inyección de 18F-FDG, adquiriéndose imágenes en 2 tomógrafos: un PET/CT clínico y un tomógrafo PET de alta resolución. Se determinó el volumen tumoral real en cada paciente, generándose una imagen de referencia para la segmentación de cada tumor. Las imágenes se segmentaron con 12 algoritmos automáticos y con un método estándar para PET (umbral relativo del 42%) y se evaluaron los resultados mediante parámetros cuantitativos. Resultados La segmentación de imágenes PET de piezas quirúrgicas ha demostrado que para imágenes PET de alta resolución 8 de las 12 técnicas de segmentación evaluadas superan al método estándar del 42%. Sin embargo, ninguno de los algoritmos superó al método estándar en las imágenes procedentes del PET/CT clínico. Debido al gran interés de este conjunto de imágenes PET, todos los estudios se han publicado a través de Internet con el fin de servir de marco común de validación y comparación de diferentes técnicas de segmentación. Conclusiones Se ha propuesto una técnica novedosa para validar técnicas de segmentación para imágenes PET oncológicas, adquiriéndose estudios ex-vivo de piezas quirúrgicas. Se ha demostrado la utilidad de este conjunto de imágenes PET mediante la evaluación de varios algoritmos automáticos.

Objectives: To investigate quantitative methods of tumor proliferation using 3'-[F-18]fluoro-3'-deoxythymidine ([F-18]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [F-18]FLT-PET uptake with the Ki67 index. Material and methods: Thirty patients with newly diagnosed, untreated BC underwent a [F-18]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [F-18]FLT (385 +/- 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. Results: [F-18]FLT uptake parameters decreased significantly (p < 0.001) after treatment: SUV50 = 3.09 +/- 1.21 vs 2.22 +/- 0.96; SUV40 = 3.00 +/- 1.18 vs 2.14 +/- 0.95, Ki_LV(10-3) = 52[22-116] vs 38[13-80] and Ki_DA(10-3) = 49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson = 0.35

To introduce, evaluate and validate a voxel-based analysis method of F-18-FDG PET imaging for determining the probability of Alzheimer's disease (AD) in a particular individual. The subject groups for model derivation comprised 80 healthy subjects (HS), 36 patients with mild cognitive impairment (MCI) who converted to AD dementia within 18 months, 85 non-converter MCI patients who did not convert within 24 months, and 67 AD dementia patients with baseline FDG PET scan were recruited from the AD Neuroimaging Initiative (ADNI) database. Additionally, baseline FDG PET scans from 20 HS, 27 MCI and 21 AD dementia patients from our institutional cohort were included for model validation. The analysis technique was designed on the basis of the AD-related hypometabolic convergence index adapted for our laboratory-specific context (AD-PET index), and combined in a multivariable model with age and gender for AD dementia detection (AD score). A logistic regression analysis of different cortical PET indexes and clinical variables was applied to search for relevant predictive factors to include in the multivariable model for the prediction of MCI conversion to AD dementia (AD-Conv score). The resultant scores were stratified into sixtiles for probabilistic diagnosis. The area under the receiver operating characteristic curve (AUC) for the AD score detecting AD dementia in the ADNI database was 0.879, and the observed probability of AD dementia in the six defined groups ranged from 8 % to 100 % in a monotonic trend. For predicting MCI conversion to AD dementia, only the posterior cingulate index, Mini-Mental State Examination (MMSE) score and apolipoprotein E4 genotype (ApoE4) exhibited significant independent effects in the univariable and multivariable models. When only the latter two clinical variables were included in the model, the AUC was 0.742 (95 % CI 0.646 - 0.838), but this increased to 0.804 (95 % CI 0.714 - 0.894, bootstrap p = 0.027) with the addition of the posterior cingulate index (AD-Conv score). Baseline clinical diagnosis of MCI showed 29.7 % of converters after 18 months. The observed probability of conversion in relation to baseline AD-Conv score was 75 % in the high probability group (sixtile 6), 34 % in the medium probability group (merged sixtiles 4 and 5), 20 % in the low probability group (sixtile 3) and 7.5 % in the very low probability group (merged sixtiles 1 and 2). In the validation population, the AD score reached an AUC of 0.948 (95 % CI 0.625 - 0.969) and the AD-Conv score reached 0.968 (95 % CI 0.908 - 1.000), with AD patients and MCI converters included in the highest probability categories. Posterior cingulate hypometabolism, when combined in a multivariable model with age and gender as well as MMSE score and ApoE4 data, improved the determination of the likelihood of patients with MCI converting to AD dementia compared with clinical variables alone. The probabilistic model described here provides a new tool that may aid in the clinical diagnosis of AD and MCI conversion.

Objective: To characterize the performance of the Biograph mCT PET/CT TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. Material and methods: The PET/CT scanner combines a 64-slice CT and PET scanner that incorporates in the reconstruction the TOF and PSF information. PET operating characteristics were evaluated according to the standard NEMA NU 2-2007, expanding some tests. In addition, different reconstruction algorithms were included, and the intrinsic radiation and tomographic uniformity were also evaluated. Results: The spatial resolution (FWHM) at 1 and 10 cm was 4.4 and 5.3 mm, improving to 2.6 and 2.5 mm when PSF is introduced. Sensitivity was 10.9 and 10.2 Kcps/MBq at 0 and 10 cm from the axis. Scatter fraction was less than 34% at low concentrations and the noise equivalent count rate (NECR) was maximal at 27.8 kBq/mL with 182 Kcps, the intrinsic radiation produced a rate of 4.42 true coincidences per second. Coefficient of variation of the volume and system uniformity were 4.7 and 0.8% respectively. The image quality test showed better results when PSF and TOF were included together. PSF improved the hot spheres contrast and background variability, while TOF improved the cold spheres contrast. Conclusions: The Biograph mCT TrueV scanner has good performance characteristics. The image quality improves when the information from the PSF and the TOF is incorporated in the reconstruction.

Background: Accuracy in the quantification of the SUV is a critical point in PET because proper quantification of tumor uptake is essential for therapy monitoring and prognosis evaluation. Recent advances such as time-of-flight (TOF) and point-spread-function (PSF) reconstructions have dramatically improved detectability. However, first experiences with these techniques have shown a consistent tendency to measure markedly high SUV values, bewildering nuclear medicine physicians and referring clinicians. Purpose: We investigated different reconstruction and quantification procedures to determine the optimum protocol for an accurate SUV quantification in last generation PET scanners. Methods: Both phantom and patient images were evaluated. A complete set of experiments was performed using a body phantom containing 6 spheres with different background levels and contrasts. Whole-body FDG PET/CT of 20 patients with breast and lung cancer was evaluated. One hundred five foci were identified by 2 experienced nuclear medicine physicians. Each acquisition was reconstructed both with classical and advanced (TOF, PSF) reconstruction techniques. Each sphere and each in vivo lesion was quantified with different parameters as follows: SUVmax, SUVmean, and SUV50 (mean within a 50% isocontour). Results: This study has confirmed that quantification with SUVmax produces important overestimation of metabolism in new generation PET scanners. This is a relevant result because, currently, SUVmax is the standard parameter for quantification. SUV50 has been shown as the best alternative, especially when applied to images reconstructed with PSF + TOF. Conclusions: SUV50 provides accurate quantification and should replace SUVmax in PET tomographs incorporating advanced reconstruction techniques. PSF + TOF reconstruction is the optimum for both detection and accurate quantification.

Neuronal loss in Alzheimer's disease, a better correlate of cognitive impairment than amyloid deposition, is currently gauged by the degree of regional atrophy. However, functional markers, such as GABA(A) receptor density, a marker of neuronal integrity, could be more sensitive. In post-mortem hippocampus, GABA(A) messenger RNA expression is reduced even in mild cognitive impairment. We measured whole-brain GABA(A) binding potential in vivo using [(11)C]-flumazenil positron emission tomography and compared GABA(A) binding with metabolic and volumetric measurements. For this purpose, we studied 12 subjects, six patients with early Alzheimer's disease and six healthy controls, with [(11)C]-flumazenil and [(18)F]-fluorodeoxyglucose positron emission tomography, as well as with high-resolution magnetic resonance imaging. Data were evaluated with both voxel-based parametric methods and volume of interest methods. We found that in early Alzheimer's disease, with voxel-based analysis, [(11)C]-flumazenil binding was decreased in infero-medial temporal cortex, retrosplenial cortex and posterior perisylvian regions. Inter-group differences reached corrected significance when using an arterial input function. Metabolism measured with positron emission tomography and volumetric measurements obtained with magnetic resonance imaging showed changes in regions affected in early Alzheimer's disease, but, unlike with [(11)C]-flumazenil binding and probably due to sample size, the voxel-based findings failed to reach corrected significance in any region of the brain. With volume of interest analysis, hippocampi and posterior cingulate gyrus showed decreased [(11)C]-flumazenil binding. In addition, [(11)C]-flumazenil hippocampal binding correlated with memory performance. Remarkably, [(11)C]-flumazenil binding was decreased precisely in the regions showing the greatest degree of neuronal loss in post-mortem studies of early Alzheimer's disease. From these data, we conclude that [(11)C]-flumazenil binding could be a useful marker of neuronal loss in early Alzheimer's disease

PURPOSE: The aim of the study was to evaluate the volumetric integration patterns of standard MRI and (11)C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade. METHODS: We studied 23 patients with suspected or previously treated glioma who underwent preoperative (11)C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by (11)C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately. RESULTS: Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high (11)C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p¿<¿0.001, ¿¿=¿0.72). GBM was associated with pattern vMRI-in-vPET (9/10), low-grade with pattern vPET-in-vMRI (7/8) and anaplastic with pattern vMRI-diff-vPET (3/5). CONCLUSION: The metabolically active tumour volume observed in (11)C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in (11)C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas.

Tumor volume delineation over positron emission tomography (PET) images is of great interest for proper diagnosis and therapy planning. However, standard segmentation techniques (manual or semi-automated) are operator dependent and time consuming while fully automated procedures are cumbersome or require complex mathematical development. The aim of this study was to segment PET images in a fully automated way by implementing a set of 12 automated thresholding algorithms, classical in the fields of optical character recognition, tissue engineering or non-destructive testing images in high-tech structures. Automated thresholding algorithms select a specific threshold for each image without any a priori spatial information of the segmented object or any special calibration of the tomograph, as opposed to usual thresholding methods for PET. Spherical (18)F-filled objects of different volumes were acquired on clinical PET/CT and on a small animal PET scanner, with three different signal-to-background ratios. Images were segmented with 12 automatic thresholding algorithms and results were compared with the standard segmentation reference, a threshold at 42% of the maximum uptake. Ridler and Ramesh thresholding algorithms based on clustering and histogram-shape information, respectively, provided better results that the classical 42%-based threshold (p < 0.05). We have herein demonstrated that fully automated thresholding algorithms can provide better results than classical PET segmentation tools

This study focuses on the occupational doses of technologists working at an Animal Research Unit using PET radiotracers and on the environmental dose rates produced by the animals (mice, rats and monkeys). In particular, whole body and extremity monitoring is reported and related with the workload. The study shows that doses not only depend on the amount of activity injected but also on the type of animals and radiotracers managed. The extremities, with a great variability of the doses received, are the limiting organs as far as regulatory dose limits for workers are concerned. Mean H¿(10) rates in contact and at 20 cm from the animals, when they are handled by the technologist, range from around 1 mSv/h to 20 ¿Sv/h, respectively.

This study demonstrates that any difference detected with SPM analysis of MOSAIC PET images of rat brain is detected also by the gold standard autoradiographic technique, confirming that this methodology provides reliable results, although partial volume effects might make it difficult to detect slight differences in small regions.

Compared with standard (18)F-FDG PET studies, quantitative dual-time-point (18)F-FDG PET can improve sensitivity for the identification and volume delineation of high-grade brain tumors.

The anatomy of metabolic abnormalities in vascular disease with dementia suggests that, at least in some cases, dementia with vascular disease may be independent of AD. The metabolic abnormality involves the thalamus, caudate, and frontal lobe, a pattern concordant with the neuropsychological findings of impaired executive function characteristic of vascular dementia.

Neuroimaging using both functional and structural examinations like positron emission tomography (PET), single photon emission tomography (SPECT), computed tomography (CT) and magnetic nuclear imaging (MRI) provide supportive information of great importance for the diagnosis and treatment of patients with central nervous system disorders. Therefore, they have become commonplace in clinical practice and basic biomedical research. In recent years we have seen the development of multimodality equipment that enables PET or SPECT to be combined with a CT structural image. Moreover, experimental equipment combining PET and MRI has now been developed. Additionally, methodological features that provide a higher image quality, and analysis tools for objective quantification and interpretation have been refined. This article reviews the technical aspects of those imaging methods, highlighting the most significant and recent advances in the development of neuroimaging.