Churg-Strauss syndrome cardiac involvement evaluated by cardiac magnetic resonance imaging and positron-emission tomography: a prospective study on 20 patients.

OBJECTIVE: Churg-Strauss syndrome (CSS) cardiac involvement is associated with a poor prognosis. Recently cardiac MRI (CMRI) has emerged as a promising technique to detect early CSS cardiac involvement. However, CMRI-detected myocardial delayed enhancement (MDE) could correspond to fibrosis or inflammation. Fluoro-2-deoxyglucose PET (FDG-PET) was previously used in other systemic diseases to distinguish between them. To determine whether the CMRI-MDE detected in CSS patients reflected fibrosis or myocardial inflammation, patients in CSS remission underwent FDG-PET. METHODS: Twenty consecutive CSS patients in remission (BVAS = 0) were recruited. Fourteen patients [eight men, six women; mean (S.D.) age 49 (9) years; mean disease duration 3.5 (2.9) years] with CMRI-detected MDE, and six patients [four men, two women; mean (S.D.) age 44 (15) years; mean disease duration 3.5 (5.3) years] with normal CMRI underwent FDG-PET. Segments with MDE on CMRI were analysed on FDG-PET images, with myocardial FDG hypofixation defining fibrosis and hyperfixation corresponding inflammation. RESULTS: Among the 14 patients with MDE on CMRI, FDG-PET showed 10 had hypofixation, 2 had hyperfixation and 2 had normal scans. CSS duration at the time of CMRI was shorter for patients with myocardial inflammation than in those with fibrosis. The six patients with normal CMRI had normal FDG-PET images. CONCLUSION: For CSS patients in remission, CMRI detected subclinical active myocardial lesions and could be recommended to assess cardiac involvement. However, because CMRI-detected MDE can reflect fibrosis or inflammation, FDG-PET might help to distinguish between the two.

Minimally invasive input function for 2-18F-fluoro-A-85380 brain PET studies.

PURPOSE: Quantitative neuroreceptor positron emission tomography (PET) studies often require arterial cannulation to measure input function. While population-based input function (PBIF) would be a less invasive alternative, it has only rarely been used in conjunction with neuroreceptor PET tracers. The aims of this study were (1) to validate the use of PBIF for 2-(18)F-fluoro-A-85380, a tracer for nicotinic receptors; (2) to compare the accuracy of measures obtained via PBIF to those obtained via blood-scaled image-derived input function (IDIF) from carotid arteries; and (3) to explore the possibility of using venous instead of arterial samples for both PBIF and IDIF. METHODS: Ten healthy volunteers underwent a dynamic 2-(18)F-fluoro-A-85380 brain PET scan with arterial and, in seven subjects, concurrent venous serial blood sampling. PBIF was obtained by averaging the normalized metabolite-corrected arterial input function and subsequently scaling each curve with individual blood samples. IDIF was obtained from the carotid arteries using a blood-scaling method. Estimated Logan distribution volume (V(T)) values were compared to the reference values obtained from arterial cannulation. RESULTS: For all subjects, PBIF curves scaled with arterial samples were similar in shape and magnitude to the reference arterial input function. The Logan V(T) ratio was 1.00 ± 0.05; all subjects had an estimation error <10%. IDIF gave slightly less accurate results (V(T) ratio 1.03 ± 0.07; eight of ten subjects had an error <10%). PBIF scaled with venous samples yielded inaccurate results (V(T) ratio 1.13 ± 0.13; only three of seven subjects had an error <10%). Due to arteriovenous differences at early time points, IDIF could not be calculated using venous samples. CONCLUSION: PBIF scaled with arterial samples accurately estimates Logan V(T) for 2-(18)F-fluoro-A-85380. Results obtained with PBIF were slightly better than those obtained with IDIF. Due to arteriovenous concentration differences, venous samples cannot be substituted for arterial samples.

Comparison of 3 methods of automated internal carotid segmentation in human brain PET studies: application to the estimation of arterial input function.

UNLABELLED: Quantitative brain (18)F-FDG PET studies often require the plasma time-activity curve (input function) for estimation of the cerebral metabolic rate of glucose (CMRglc). The gold standard for input function measurement is arterial blood sampling, which is invasive and time-consuming. Alternatively, input function can be estimated from dynamic images. This estimation often implies the use of manually placed regions of interest (ROIs) over cerebral vasculature, which is an operator-dependent and time-consuming task. The aim of our study was to compare 3 algorithms of image segmentation (local means analysis [LMA], soft-decision similar component analysis [SCA], and k-means) to automatically segment internal carotid arteries from dynamic (18)F-FDG brain studies. METHODS: The accuracy of automatic carotid segmentation algorithms was first tested using numeric phantoms of the human brain, by quantitatively assessing the overlap between the segmented carotids and the reference regions in the phantom. Then, the algorithm that yielded the best results was applied to data from 4 healthy volunteers, who underwent an (18)F-FDG dynamic 3-dimensional PET brain study. Concordance between manual and automatic ROIs, both uncorrected and after partial-volume effect and spillover correction, was first assessed. Linear regression was then used to compare manual versus automatic CMRglc values obtained using Patlak analysis. CMRglc values obtained by arterial sampling were used as a reference. RESULTS: In phantom studies, LMA was shown to be superior to the other segmentation algorithms. By visual inspection, volunteers' internal carotids segmented by LMA were anatomically relevant. No significant difference was found between ROI values obtained by manual and automatic segmentation, either uncorrected or corrected for partial-volume effect. Linear regression demonstrated excellent agreement between the manual and automatic image-derived CMRglc values (P < 0.0001), and both correlated well with the reference values obtained by plasma samples. CONCLUSION: The LMA segmentation algorithm allows accurate automatic delineation of internal carotids from dynamic PET brain studies. After correction for partial-volume effect, the main application would be the estimation of an image-derived input function.

Comparison of two commercial whole body PET systems based on LSO and BGO crystals respectively for brain imaging.

The prevalence of neurodegenerative diseases is growing in western countries and PET imaging is increasingly frequently used for clinical and research purposes. However, few PET cameras are dedicated to cerebral imaging. The Biograph 6 (Biograph6) (Siemens Medical Solutions) is a PET/CT dedicated to high throughput whole body studies. Its performance for cerebral imaging has not yet been assessed. The aims of this study were to compare the quantification and detectability of the Biograph for cerebral imaging with those of a well-validated PET camera, the ECAT EXACT HR+ (HR+) (Siemens Medical Solutions). A phantom measuring 19 cm long and 20 cm in diameter was filled with a 18F-fluorodeoxyglucose (18F-FDG) solution. Two 5.7 and 20 ml spheres filled with water (cold-spots), three 0.25 ml spheres (sphere-to-background: 3, 6, and 12), one 1.14 ml sphere (sphere-to-background: 3), and one 11.27 ml sphere (sphere-to-background: 2) filled with a radioactive solution were inserted into the phantom. The activity concentration was chosen so that the count rates for the phantom measurements matched those of typical brain studies on both cameras. Images were reconstructed using FORE and OSEM algorithms. The reconstruction parameters were adjusted to obtain a similar signal-to-noise ratio in images acquired with the two cameras. The contrast recovery (CR) coefficients were similar on the two scanners for the 5.7 and 20 ml spheres (cold spheres) and the 1.14 and 11.27 ml spheres (hot spheres). For the 0.25 ml spheres, the CR values were 35% higher for the sphere-to-background ratio of 12 and 39% higher for the sphere-to-background ratio of 6 on the Biograph6 for the 3 min scan. The variability of measurements was lower on the Biograph6 than on the HR+. The detectability for the smallest spheres on the Biograph6 was close to that on the HR+. The Biograph has similar performances as the HR+ reference tomograph for the detection and quantification of small hot spots and cold spots.

Impact of image-space resolution modeling for studies with the high-resolution research tomograph.

UNLABELLED: Brain PET in small structures is challenged by low resolution inducing bias in the activity measurements. Improved spatial resolution may be obtained by using dedicated tomographs and more comprehensive modeling of the acquisition system during reconstruction. In this study, we assess the impact of resolution modeling (RM) during reconstruction on image quality and on the estimates of biologic parameters in a clinical study performed on a high-resolution research tomograph. METHODS: An accelerated list-mode ordinary Poisson ordered-subset expectation maximization (OP-OSEM) algorithm, including sinogram-based corrections and an experimental stationary model of resolution, has been designed. Experimental phantom studies are used to assess contrast and noise characteristics of the reconstructed images. The binding potential of a selective tracer of the dopamine transporter is also assessed in anatomic volumes of interest in a 5-patient study. RESULTS: In the phantom experiment, a slower convergence and a higher contrast recovery are observed for RM-OP-OSEM than for OP-OSEM for the same level of statistical noise. RM-OP-OSEM yields contrast recovery levels that could not be reached without RM as well as better visual recovery of the smallest spheres and better delineation of the structures in the reconstructed images. Statistical noise has lower variance at the voxel level with RM than without at matched resolution. In a uniform activity region, RM induces higher positive and lower negative correlations with neighboring voxels, leading to lower spatial variance. Clinical images reconstructed with RM demonstrate better delineation of cortical and subcortical structures in both time-averaged and parametric images. The binding potential in the striatum is also increased, a result similar to the one observed in the phantom study. CONCLUSION: In high-resolution PET, RM during reconstruction improves quantitative accuracy by reducing the partial-volume effects.

Estimation of the beta+ dose to the embryo resulting from 18F-FDG administration during early pregnancy.

UNLABELLED: Although 18F-FDG examinations are widely used, data are lacking on the dose to human embryo tissues in cases of exposure in early pregnancy. Although the photon component can easily be estimated from available data on the pharmacokinetics of 18F-FDG in female organs and from phantom measurements (considering the uterus as the target organ), the intensity of embryo tissue uptake, which is essential for deriving the beta+ dose, is not known. We report the case of a patient who underwent 18F-FDG PET/CT for tumor surveillance and who was later found to have been pregnant at the time of the examination (embryo age, 8 wk). METHODS: The patient received 320 MBq of (18)F-FDG. Imaging started with an unenhanced CT scan 1 h after the injection, followed by PET acquisition. PET images were used to compute the total number of beta+ emissions in embryo tissues per unit of injected activity, from standardized uptake value (SUV) measurements corrected for partial-volume effects. A Monte Carlo track structure code was then used to derive the beta+ self-dose and the beta+ cross-dose from amniotic fluid. The photon and CT doses were added to obtain the final dose received by the embryo. RESULTS: The mean SUV in embryo tissues was 2.7, after correction for the partial-volume effect. The mean corrected SUV of amniotic fluid was 1.1. Monte Carlo simulation showed that the beta+ dose to the embryo (self-dose plus cross-dose from amniotic fluid) was 1.8E-2 mGy per MBq of injected 18F-FDG. Based on MIRD data for the photon dose to the uterus, the estimated photon dose to the embryo was 1.5E-2 mGy/MBq. Thus, the specific 18F-FDG dose to the embryo was 3.3E-2 mGy/MBq (10.6 mGy in this patient). The CT scan added a further 8.3 mGy. CONCLUSION: The dose to the embryo is 3.3E-2 mGy/MBq of 18F-FDG. The beta+ dose contributes 55% of the total dose. This value is higher than previous estimates in late nonhuman-primate pregnancies.

Segmentation of rodent whole-body dynamic PET images: an unsupervised method based on voxel dynamics.

Positron emission tomography (PET) is a useful tool for pharmacokinetics studies in rodents during the preclinical phase of drug and tracer development. However, rodent organs are small as compared to the scanner's intrinsic resolution and are affected by physiological movements. We present a new method for the segmentation of rodent whole-body PET images that takes these two difficulties into account by estimating the pharmacokinetics far from organ borders. The segmentation method proved efficient on whole-body numerical rat phantom simulations, including 3-14 organs, together with physiological movements (heart beating, breathing, and bladder filling). The method was resistant to spillover and physiological movements, while other methods failed to obtain a correct segmentation. The radioactivity concentrations calculated with this method also showed an excellent correlation with the manual delineation of organs in a large set of preclinical images. In addition, it was faster, detected more organs, and extracted organs' mean time activity curves with a better confidence on the measure than manual delineation.

Assessment of 11C-PE2I binding to the neuronal dopamine transporter in humans with the high-spatial-resolution PET scanner HRRT.

UNLABELLED: The high-resolution research tomograph (HRRT), dedicated to brain imaging, may offer new perspectives for identifying small brain nuclei that remain neglected by the spatial resolution of conventional scanners. However, the use of HRRT for neuroimaging applications still needs to be fully assessed. The present study aimed at evaluating the HRRT for measurement of the dopamine transporter (DAT) binding to validate its quantification and explore the gain induced by the increased spatial resolution in comparison with conventional PET scanners. METHODS: Fifteen and 11 healthy subjects were examined using the selective DAT radioligand (11)C-PE2I with HRRT and HR+ scanners, respectively. Quantification of the DAT binding was assessed by the calculation of binding potential (BP) values using the simplified reference tissue model in anatomic regions of interest (ROIs) defined on the dorsal striatum and in a standardized ROI defined on the midbrain. RESULTS: Quantification of (11)C-PE2I binding to the DAT measured in the midbrain and striatum with both scanners at the same spatial resolution (smoothed HRRT images) exhibited similar BP values and intersubject variability, thus validating the quantification of DAT binding on the HRRT. For age-paired comparison, BP values of subjects examined with HRRT were significantly higher than those of the subjects examined with HR+. The increase ranged from 29% in the caudate and 35% in the putamen to 92% in the midbrain. The decline in DAT binding with age in the striatum was in good agreement between both scanners and literature, whereas no significant decrease in DAT binding with age was observed in the midbrain with either HRRT or HR+. CONCLUSION: HRRT allows quantitative measurements of neurotransmission processes in small brain nuclei and allows recovering higher values as compared with coarser spatial resolution PET scanners. High-spatial-resolution PET appears promising for a more accurate detection of neurobiologic modifications and also for the exploration of subtle modifications in small and complex brain structures largely affected by the partial-volume effect.

11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation.

UNLABELLED: The induction of neuroinflammatory processes, characterized by upregulation of the peripheral benzodiazepine receptor (PBR) expressed by microglial cells, is well correlated with neurodegenerative diseases and with acute neuronal loss. The continually increasing incidence of neurodegenerative diseases in developed countries has become a major health problem, for which the development of diagnostic and follow-up tools is required. Here we investigated a new PBR ligand suitable for PET to monitor neuroinflammatory processes as an indirect hallmark of neurodegeneration. METHODS: We compared PK11195, the reference compound for PBR binding sites, with the new ligand DPA-713 (N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide), using a small-animal dedicated PET camera in a model of neuroinflammation in rats. Seven days after intrastriatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), a PET scan was performed using (11)C-PK11195 or (11)C-DPA-713. Immunohistochemistry for neuronal (NeuN), astrocyte (glial fibrillary acidic protein), and microglial (CD11) specific markers as well as (3)H-PK11195 autoradiographic studies were then correlated with the imaging data. RESULTS: Seven days after a unilateral injection of AMPA in the striatum, (11)C-DPA-713 exhibits a better contrast between healthy and damaged brain parenchyma than (11)C-PK11195 (2.5-fold +/- 0.14 increase vs. 1.6-fold +/- 0.05 increase, respectively). (11)C-DPA-713 and (11)C-PK11195 exhibit similar brain uptake in the ipsilateral side, whereas, in the contralateral side, (11)C-DPA-713 uptake was significantly lower than (11)C-PK11195. Modeling of the data using the simplified reference tissue model shows that the binding potential was significantly higher for (11)C-DPA-713 than for (11)C-PK11195. CONCLUSION: (11)C-DPA-713 displays a higher signal-to-noise ratio than (11)C-PK11195 because of a lower level of unspecific binding that is likely related to the lower lipophilicity of (11)C-DPA-713. Although further studies in humans are required, (11)C-DPA-713 represents a suitable alternative to (11)C-PK11195 for PET of PBR as a tracer of neuroinflammatory processes induced by neuronal stress.

Joint estimation of dynamic PET images and temporal basis functions using fully 4D ML-EM.

A fully 4D joint-estimation approach to reconstruction of temporal sequences of 3D positron emission tomography (PET) images is proposed. The method estimates both a set of temporal basis functions and the corresponding coefficient for each basis function at each spatial location within the image. The joint estimation is performed through a fully 4D version of the maximum likelihood expectation maximization (ML-EM) algorithm in conjunction with two different models of the mean of the Poisson measured data. The first model regards the coefficients of the temporal basis functions as the unknown parameters to be estimated and the second model regards the temporal basis functions themselves as the unknown parameters. The fully 4D methodology is compared to the conventional frame-by-frame independent reconstruction approach (3D ML-EM) for varying levels of both spatial and temporal post-reconstruction smoothing. It is found that using a set of temporally extensive basis functions (estimated from the data by 4D ML-EM) significantly reduces the spatial noise when compared to the independent method for a given level of image resolution. In addition to spatial image quality advantages, for smaller regions of interest (where statistical quality is often limited) the reconstructed time-activity curves show a lower level of bias and a lower level of noise compared to the independent reconstruction approach. Finally, the method is demonstrated on clinical 4D PET data.

Optimization of brain PET imaging for a multicentre trial: the French CATI experience.

BACKGROUND: CATI is a French initiative launched in 2010 to handle the neuroimaging of a large cohort of subjects recruited for an Alzheimer's research program called MEMENTO. This paper presents our test protocol and results obtained for the 22 PET centres (overall 13 different scanners) involved in the MEMENTO cohort. We determined acquisition parameters using phantom experiments prior to patient studies, with the aim of optimizing PET quantitative values to the highest possible per site, while reducing, if possible, variability across centres. METHODS: Jaszczak's and 3D-Hoffman's phantom measurements were used to assess image spatial resolution (ISR), recovery coefficients (RC) in hot and cold spheres, and signal-to-noise ratio (SNR). For each centre, the optimal reconstruction parameters were chosen as those maximizing ISR and RC without a noticeable decrease in SNR. Point-spread-function (PSF) modelling reconstructions were discarded. The three figures of merit extracted from the images reconstructed with optimized parameters and routine schemes were compared, as were volumes of interest ratios extracted from Hoffman acquisitions. The net effect of the 3D-OSEM reconstruction parameter optimization was investigated on a subset of 18 scanners without PSF modelling reconstruction. RESULTS: Compared to the routine parameters of the 22 PET centres, average RC in the two smallest hot and cold spheres and average ISR remained stable or were improved with the optimized reconstruction, at the expense of slight SNR degradation, while the dispersion of values was reduced. For the subset of scanners without PSF modelling, the mean RC of the smallest hot sphere obtained with the optimized reconstruction was significantly higher than with routine reconstruction. The putamen and caudate-to-white matter ratios measured on 3D-Hoffman acquisitions of all centres were also significantly improved by the optimization, while the variance was reduced. CONCLUSIONS: This study provides guidelines for optimizing quantitative results for multicentric PET neuroimaging trials.

CATI: A Large Distributed Infrastructure for the Neuroimaging of Cohorts.

This paper provides an overview of CATI, a platform dedicated to multicenter neuroimaging. Initiated by the French Alzheimer's plan (2008-2012), CATI is a research project called on to provide service to other projects like an industrial partner. Its core mission is to support the neuroimaging of large populations, providing concrete solutions to the increasing complexity involved in such projects by bringing together a service infrastructure, the know-how of its expert academic teams and a large-scale, harmonized network of imaging facilities. CATI aims to make data sharing across studies easier and promotes sharing as much as possible. In the last 4 years, CATI has assisted the clinical community by taking charge of 35 projects so far and has emerged as a recognized actor at the national and international levels.

Evaluating image reconstruction methods for tumor detection in 3-dimensional whole-body PET oncology imaging.

UNLABELLED: We compare 3 image reconstruction algorithms for use in 3-dimensional (3D) whole-body PET oncology imaging. We have previously shown that combining Fourier rebinning (FORE) with 2-dimensional (2D) statistical image reconstruction via the ordered-subsets expectation-maximization (OSEM) and attenuation-weighted OSEM (AWOSEM) algorithms demonstrates improvements in image signal-to-noise ratios compared with the commonly used analytic 3D reprojection (3DRP) or FORE+FBP (2D filtered backprojection) reconstruction methods. To assess the impact of these reconstruction methods on detecting and localizing small lesions, we performed a human observer study comparing the different reconstruction methods. The observer study used the same volumetric visualization software tool that is used in clinical practice, instead of a planar viewing mode as is generally used with the standard receiver operating characteristic (ROC) methodology. This change in the human evaluation strategy disallowed the use of a ROC analysis, so instead we compared the fraction of actual targets found and reported (fraction-found) and also investigated the use of an alternative free-response operating characteristic (AFROC) analysis. METHODS: We used a non-Monte Carlo technique to generate 50 statistically accurate realizations of 3D whole-body PET data based on an extended mathematic cardiac torso (MCAT) phantom and with noise levels typical of clinical scans performed on a PET scanner. To each realization, we added 7 randomly located 1-cm-diameter lesions (targets) whose contrasts were varied to sample the range of detectability. These targets were inserted in 3 organs of interest: lungs, liver, and soft tissues. The images were reconstructed with 3 reconstruction strategies (FORE+OSEM, FORE+AWOSEM, and FORE+FBP). Five human observers reported (localized and rated) 7 targets within each volume image. An observer's performance accuracy with each algorithm was measured, as a function of the lesion contrast and organ type, by the fraction of those targets reported and by the area below the AFROC curve. This AFROC curve plots the fraction of reported targets at each rating threshold against the fraction of cases with (> or =1) similarly rated false reports. RESULTS: Images reconstructed with FORE+AWOSEM yielded the best overall target detection as compared with FORE+FBP and FORE+OSEM, although these differences in detectability were region specific. The FORE+FBP and FORE+AWOSEM algorithms had similar performances for liver targets. The FORE+OSEM algorithm performed significantly worse at target detection, especially in the liver. We speculate that this is the result of using an incorrect statistical model for OSEM and that the incorporation of attenuation weighting in AWOSEM largely compensates for this model inaccuracy. These results were consistent for both the fraction of actual targets found and the AFROC analysis. CONCLUSION: We demonstrated the efficacy of performing observer detection studies using the same visualization tools as those used in clinical PET oncology imaging. These studies demonstrated that the FORE+AWOSEM algorithm led to the best overall detection and localization performance for 1-cm-diameter targets compared with the FORE+OSEM and FORE+FBP algorithms.

Optimization of injected dose based on noise equivalent count rates for 2- and 3-dimensional whole-body PET.

UNLABELLED: The noise equivalent count (NEC) rate index is used to derive guidelines on the optimal injected dose to the patient for 2-dimensional (2D) and 3-dimensional (3D) whole-body PET acquisitions. METHODS: We performed 2D and 3D whole-body acquisitions of an anthropomorphic phantom modeling the conditions for (18)F-FDG PET of the torso and measured the NEC rates for different activity levels for several organs of interest. The correlations between count rates measured from the phantom and those from a series of whole-body patient scans were then analyzed. This analysis allowed validation of our approach and estimation of the injected dose that maximizes NEC rate as a function of patient morphology for both acquisition modes. RESULTS: Variations of the phantom and patient prompt and random coincidence rates as a function of single-photon rates correlated well. On the basis of these correlations, we demonstrated that the patient NEC rate can be predicted for a given single-photon rate. Finally, we determined that patient single-photon rates correlated with the mean dose per weight at acquisition start when normalized by the body mass index. This correlation allows modifying the injected dose as a function of patient body mass index to reach the peak NEC rate in 3D mode. Conversely, we found that the peak NEC rates were never reached in 2D mode within an acceptable range of injected dose. CONCLUSION: The injected dose was adapted to patient morphology for 2D and 3D whole-body acquisitions using the NEC rate as a figure of merit of the statistical quality of the sinogram data. This study is a first step toward a more comprehensive comparison of the image quality obtained using both acquisition modes.

In vivo quantification and parametric images of the cardiac beta-adrenergic receptor density.

UNLABELLED: Previous studies showed that the in vivo concentration of beta-adrenergic receptor sites can be estimated by PET using (-)-4-((S)-3-tert-butylamino-2-hydroxypropoxy)-1,3-dihydrobenzoimidazol-2-one (CGP 12177), a hydrophilic ligand. A graphic method was previously proposed and used by several groups. However, this approach was not completely validated. The purpose of this study was to improve and confirm the validity of this approach through a better knowledge of the associated ligand-receptor model, estimated for the first time using the multiinjection approach. METHODS: The concentration of beta-adrenergic receptor sites was estimated for mini pigs using 2 methods. The first was the usual multiinjection approach, which permits estimation of all model parameters, including receptor concentration. However, this approach needs a complex protocol, including blood sampling, thereby making it difficult to use for studies on patients. The second method was the CGP 12177 graphic method. This approach permits the estimation of only receptor concentration but has the advantage of not requiring blood sampling. Another advantage is the ability to generate parametric images easily. RESULTS: Using the multiinjection approach, we obtained for the first time a complete model describing interactions between CGP 12177 and beta-adrenergic receptors. Knowledge of all parameters of this model permitted good validation of the assumptions included in the graphic method. The concentration of beta-adrenergic receptor sites in mini pigs was estimated at 15.2 +/- 3.4 pmol/mL. CONCLUSION: The graphic method has been improved by taking into account various phenomena, such as protein binding and the nonlinearity between plasma concentration and injected dose. This method is now usable for patient studies and offers the ability to estimate the beta-adrenergic receptor concentration from a single PET experiment without blood sampling. Parametric imaging will enable screening of the receptor site location and observation of potential anomalies in patients.

Co-registration of glucose metabolism with positron emission tomography and vascularity with fluorescent diffuse optical tomography in mouse tumors.

BACKGROUND: Bimodal molecular imaging with fluorescence diffuse optical tomography (fDOT) and positron emission tomography (PET) has the capacity to provide multiple molecular information of mouse tumors. The objective of the present study is to co-register fDOT and PET molecular images of tumors in mice automatically. METHODS: The coordinates of bimodal fiducial markers (FM) in regions of detection were automatically detected in planar optical images (x, y positions) in laser pattern optical surface images (z position) and in 3-D PET images. A transformation matrix was calculated from the coordinates of the FM in fDOT and in PET and applied in order to co-register images of mice bearing neuroendocrine tumors. RESULTS: The method yielded accurate non-supervised co-registration of fDOT and PET images. The mean fiducial registration error was smaller than the respective voxel sizes for both modalities, allowing comparison of the distribution of contrast agents from both modalities in mice. Combined imaging depicting tumor metabolism with PET-[18 F]2-deoxy-2-fluoro-d-glucose and blood pool with fDOT demonstrated partial overlap of the two signals. CONCLUSIONS: This automatic method for co-registration of fDOT with PET and other modalities is efficient, simple and rapid, opening up multiplexing capacities for experimental in vivo molecular imaging.

Absorbed 18F-FDG dose to the fetus during early pregnancy.

UNLABELLED: We describe a rare case of a woman who underwent (18)F-FDG PET/CT during early pregnancy (fetus age, 10 wk). The fetal absorbed dose was calculated by taking into account the (18)F-FDG fetal self-dose, photon dose coming from the maternal tissues, and CT dose received by both mother and fetus. METHODS: The patient (weight, 71 kg) had received 296 MBq of (18)F-FDG. Imaging started at 1 h, with unenhanced CT acquisition, followed by PET acquisition. From the standardized uptake value measured in fetal tissues, we calculated the total number of disintegrations per unit of injected activity. Monte Carlo analysis was then used to derive the fetal (18)F-FDG self-dose, including positrons and self-absorbed photons. Photon dose from maternal tissues and CT dose were added to obtain the final dose. RESULTS: The maximum standardized uptake value in fetal tissues was 4.5. Monte Carlo simulation showed that the fetal self-dose was 3.0 x 10(-2) mGy/MBq (2.7 x 10(-2) mGy/MBq from positrons and 0.3 x 10(-2) mGy/MBq from photons). The estimated photon dose to the fetus from maternal tissues was 1.04 x 10(-2) mGy/MBq. Accordingly, the specific (18)F-FDG dose to the fetus was about 4.0 x 10(-2) mGy/MBq (11.8 mGy in this patient). The CT scan added a further 10 mGy. CONCLUSION: The dose to the fetus during early pregnancy can be as high as 4.0 x 10(-2) mGy/MBq of (18)F-FDG. Current dosimetric standards in early pregnancy may need to be revised.

In vivo quantification of 18f-fdg uptake in human placenta during early pregnancy.

18F-FDG is the most widely used PET radiopharmaceutical. Nevertheless, no data for 18F-FDG uptake in the human placenta have been reported. We recently reported on embryo dosimetry in a woman who underwent an 18F-FDG PET/CT scan during early pregnancy. In the present work we attempt an in vivo quantification of the 18F-FDG uptake by the placenta. The 27-y-old woman received 320 MBq of 18F-FDG for a follow-up study for Hodgkin's lymphoma and was later discovered to be pregnant (embryo age = 8 wk). Imaging started 1 h after injection. The maximum placental tissue uptake (SUVmax) was 2.5. This value was conservatively attributed to the entire placental volume, i.e., 45 mL, a value representative of the average dimensions of a normal placenta at 8 wk. On the basis of these measurements, placenta 18F-FDG uptake in our patient was 0.19% of the injected activity. A Monte Carlo simulation was used to derive the photon dose to the embryo from the placenta (0.022 x 10(-2) mGy per MBq of injected 18F-FDG) and from the surrounding amniotic fluid (0.017 x 10(-2) mGy MBq(-1)). This increases our previously calculated dose (3.3 x 10(-2) mGy MBq(-1)) by only a small fraction (1.18%), which does not justify modifying the previous estimate given the overall uncertainties.

Comparison of eight methods for the estimation of the image-derived input function in dynamic [(18)F]-FDG PET human brain studies.

The aim of this study was to compare eight methods for the estimation of the image-derived input function (IDIF) in [(18)F]-FDG positron emission tomography (PET) dynamic brain studies. The methods were tested on two digital phantoms and on four healthy volunteers. Image-derived input functions obtained with each method were compared with the reference input functions, that is, the activity in the carotid labels of the phantoms and arterial blood samples for the volunteers, in terms of visual inspection, areas under the curve, cerebral metabolic rates of glucose (CMRglc), and individual rate constants. Blood-sample-free methods provided less reliable results as compared with those obtained using the methods that require the use of blood samples. For some of the blood-sample-free methods, CMRglc estimations considerably improved when the IDIF was calibrated with a single blood sample. Only one of the methods tested in this study, and only in phantom studies, allowed a reliable calculation of the individual rate constants. For the estimation of CMRglc values using an IDIF in [(18)F]-FDG PET brain studies, a reliable absolute blood-sample-free procedure is not available yet.

Spatiotemporal decomposition in object-space along reconstruction in emission tomography.

Emission tomography has provided a new insight in brain mechanisms past years. Although reconstructions are nowadays mostly static, trend is going toward dynamic acquisitions and reconstructions. This opens a new range of investigations, for instance for drugs discovery. Indeed new drugs are studied through the dynamic ability of tissues to catch them. However, it is required to know radiotracer concentration of blood that irrigates tissues in order to draw conclusions on potentials of these drugs. This concentration is called 'input function' and this paper presents a new method for measuring it in a non-invasive way. Our new method relies on simultaneous estimations of vessels kinetics and vessels spatial distribution. These estimations are performed during the reconstruction process and take into account the statistical nature of measured signals. Indeed, this method is based on the maximisation of the likelihood of counts in detectors. It takes advantages of a non-negative matrix factorisation which separate spatial and temporal components. Results are very promising, since it estimates arterial input function accurately although object emits just a limited amount of photons, especially within the first minutes.