Gravitational Experimental Platform for Animal Models, a New Platform at ESA's Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models.

Using rotors to expose animals to different levels of hypergravity is an efficient means of understanding how altered gravity affects physiological functions, interactions between physiological systems and animal development. Furthermore, rotors can be used to prepare space experiments, e.g., conducting hypergravity experiments to demonstrate the feasibility of a study before its implementation and to complement inflight experiments by comparing the effects of micro- and hypergravity. In this paper, we present a new platform called the Gravitational Experimental Platform for Animal Models (GEPAM), which has been part of European Space Agency (ESA)'s portfolio of ground-based facilities since 2020, to study the effects of altered gravity on aquatic animal models (amphibian embryos/tadpoles) and mice. This platform comprises rotors for hypergravity exposure (three aquatic rotors and one rodent rotor) and models to simulate microgravity (cages for mouse hindlimb unloading and a random positioning machine (RPM)). Four species of amphibians can be used at present. All murine strains can be used and are maintained in a specific pathogen-free area. This platform is surrounded by numerous facilities for sample preparation and analysis using state-of-the-art techniques. Finally, we illustrate how GEPAM can contribute to the understanding of molecular and cellular mechanisms and the identification of countermeasures.

A 1-week extension of a ketogenic diet provides a further decrease in myocardial 18F-FDG uptake and a high detectability of myocarditis with FDG-PET.

BACKGROUND: Short periods of fasting and/or low-carbohydrate diet have been proven beneficial for decreasing the myocardial uptake of 18F-fluorodeoxyglucose (18F-FDG) and enhancing the detection of inflammatory heart diseases by 18F-FDG positron emission tomography (PET). This study aimed at determining whether this benefit is increased when a low-carbohydrate ketogenic diet is prolonged up to 7 days. METHODS: Wistar rats underwent serial 18F-FDG-PET imaging after an 18-hour fasting period and after 2, 4 and 7 days of a ketogenic diet (3% carbohydrate) and they were compared to rats submitted to the same protocol but with normal diet (44% carbohydrate). The 18F-FDG-PET/ketogenic protocol was also applied in rats with immune myocarditis (injection of porcine cardiac myosin). RESULTS: The 7-day ketogenic diet was associated with (1) a sustained increase in circulating ketone bodies at an equivalent level to that reached after 18-hour fasting, (2) a gradual decrease in 18F-FDG uptake within normal myocardium reaching a lower level compared to fasting at the 7th day (myocardium-to-blood ratios: 1.68 ± 1.02 vs 3.25 ± 1.40, P < .05) and (3) a high 18F-FDG-PET detectability of myocarditis areas. CONCLUSION: One-week extension of a ketogenic diet provides a further decrease in the 18F-FDG uptake of normal myocardium and a high detectability of inflammatory areas.

Physiological Whole-Brain Distribution of [18F]FDOPA Uptake Index in Relation to Age and Gender: Results from a Voxel-Based Semi-quantitative Analysis.

PURPOSE: 6-[18F]fluoro-L-DOPA ([18F]FDOPA), a positron emission tomography (PET) amino-acid tracer of brain decarboxylase activity, is used to assess the brain dopaminergic system. Using a voxel-based semi-quantitative analysis, this study aimed to determine whether a current brain uptake index of [18F]FDOPA, expressed relative to the occipital background level, varies according to age and gender. PROCEDURES: One hundred and seventy-seven subjects were retrospectively included. A whole-brain statistical parametric mapping analysis of the [18F]FDOPA uptake index in parametric PET images was performed at a voxel threshold of p < 0.05 (corrected) and p < 0.005 (uncorrected, k cluster > 125). RESULTS: Striatal uptake indices were influenced by age, negatively for the caudate nucleus and positively for the putamen, as well as by gender, with a lower left putaminal uptake index in women. Extra-striatal uptake indices were influenced by age, negatively for the frontal cortex and brainstem and positively for the occipital cortex and cerebellum, as well as by gender (diffuse increase in women). CONCLUSIONS: The uptake index of [18F]FDOPA exhibited significant physiological variations according to age and gender and should therefore be considered for PET interpretation.

PET imaging of 68Ga-NODAGA-RGD, as compared with 18F-fluorodeoxyglucose, in experimental rodent models of engrafted glioblastoma.

BACKGROUND: Tracers triggering αvß3 integrins, such as certain RGD-containing peptides, were found promising in previous pilot studies characterizing high-grade gliomas. However, only limited comparisons have been performed with current PET tracers. This study aimed at comparing the biodistribution of 18F-fluorodeoxyglucose (18F-FDG) with that of 68Ga-NODAGA-RGD, an easily synthesized monomeric RGD compound with rapid kinetics, in two different rodent models of engrafted human glioblastoma. METHODS: Nude rodents bearing human U87-MG glioblastoma tumor xenografts in the flank (34 tumors in mice) or in the brain (5 tumors in rats) were analyzed. Kinetics of 68Ga-NODAGA-RGD and of 18F-FDG were compared with PET imaging in the same animals, along with additional autohistoradiographic analyses and blocking tests for 68Ga-NODAGA-RGD. RESULTS: Both tracers showed a primary renal route of clearance, although with faster clearance for 68Ga-NODAGA-RGD resulting in higher activities in the kidneys and bladder. The tumor activity from 68Ga-NODAGA-RGD, likely corresponding to true integrin binding (i.e., suppressed by co-injection of a saturating excess of unlabeled RGD), was found relatively high, but only at the 2nd hour following injection, corresponding on average to 53% of total tumor activity. Tumor uptake of 68Ga-NODAGA-RGD decreased progressively with time, contrary to that of 18F-FDG, although 68Ga-NODAGA-RGD exhibited 3.4 and 3.7-fold higher tumor-to-normal brain ratios on average compared to 18F-FDG in mice and rat models, respectively. Finally, ex-vivo analyses revealed that the tumor areas with high 68Ga-NODAGA-RGD uptake also exhibited the highest rates of cell proliferation and αv integrin expression, irrespective of cell density. CONCLUSIONS: 68Ga-NODAGA-RGD has a high potential for PET imaging of glioblastomas, especially for areas with high integrin expression and cell proliferation, although PET recording needs to be delayed until the 2nd hour following injection in order to provide sufficiently high integrin specificity.

Routine evaluation of left ventricular function using CZT-SPECT, with low injected activities and limited recording times.

PURPOSE: Gamma-cameras, with Cadmium-Zinc-Telluride (CZT) detectors, allow to perform myocardial perfusion imaging (MPI) with limited injected activities and recorded times. This study aimed at determining whether the routine assessment of left ventricular (LV) function with such limited counts protocols compares well with reference values from cardiac MRI. METHODS: The study included patients who have undergone cardiac MRI and an MPI routinely planned on a CZT camera with a low-dose protocol (120 MBq of Sestamibi for stress and 360 MBq at rest for 75 kg body weight), while targeting the recording of only 500 myocardial kcounts in order to limit the recording times (<10 minutes for stress, <4 minutes for rest). SPECT images were reconstructed with a method maintaining rather high spatial (8 mm) and temporal (16 frames/cycle) resolutions. RESULTS: Seventy-six patients were included, and mean effective dose was 3.5 ± 1.7 mSv for the total MPI protocol. Correlations between CZT-SPECT and MRI were good to excellent for ejection fraction (r 2 = 0.77), end-diastolic (r 2 = 0.88) and end-systolic (r 2 = 0.93) volumes, and the analysis of segmental contractility correlated well between the two techniques (kappa score = 0.72 ± 0.02). CONCLUSION: LV function, assessed on a CZT camera with low injected activities and limited recording times, correlates well with the reference assessment from cardiac MRI.

Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction.

BACKGROUND: The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs). This study sought to address (i) the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii) the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI) in rats. METHODS: rat BMSCs were harvested and cultured in normoxic (21% O2, n=27) or hypoxic conditions (5% O2, n=27) until Passage 4 (P4). Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6) or hypoxia (n=6) were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization. RESULTS: Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility. CONCLUSION: Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting angiogenesis.

Synthesis and preliminary in vivo evaluation of new [18F]fluoro-inositols as Positron Emission Tomography radiotracers.

This study describes the synthesis and radiosynthesis of eight new [18F]fluoro-inositol-based radiotracers in myo- and scyllo-inositol configuration. These radiotracers are equipped with a propyl linker bearing fluorine-18. This fluorinated arm is either on a hydroxyl group, i.e. O-alkylated inositols, or on the cyclohexyl backbone, i.e. C-branched derivatives. To modulate lipophilicity, inositols were synthesized in acetylated or hydroxylated form. Automated radiosynthesis was performed on the AllInOne module and the radiotracers were produced in good radiochemical yields (15-31.5% dc). Preliminary in vivo preclinical evaluation of these eight [18F]fluoro-inositols as Positron Emission Tomography (PET) imaging agents in a breast tumour-bearing mouse model was performed and compared with [18F]-2-fluoro-2-deoxy-d-glucose ([18F]FDG). Amongst the different inositols, [18F]myo-2 showed the highest tumour uptake 2.34±0.39%ID/g, revealing the potential of this tracer for monitoring breast cancer.

Quantitative SPM Analysis Involving an Adaptive Template May Be Easily Applied to [18F]FDG PET Images of the Rat Brain.

PURPOSE: The Statistical Parametric Mapping (SPM) software is frequently used for the quantitative analysis of patients' brain images obtained from 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG PET). However, its adaptation to small animals is difficult, particularly for the initial step of spatial normalization which requires a specific brain anatomical template. This study was aimed at determining whether SPM analysis can be applied to rat, and more specifically to the lithium-pilocarpine model of epilepsy, by using an adaptive template. This template developed for PET clinical imaging is constructed from a block matching algorithm. PROCEDURES: SPM analysis of brain [18F]FDG PET images from Sprague-Dawley rats was used with the block matching (BM) adaptive template for the detection of brain abnormalities (1) artificially inserted within the initially normal brain images of 10 rats (50 % decrease in signal intensity within 40 spheres of 0.5 to 1.0 mm in diameter) and (2) occurring at 4 h (n = 16), 48 h (n = 15), and 8 days (n = 13) after lithium-pilocarpine treatment. RESULTS: Concordant positive clusters were documented for all inserted abnormalities, whereas no aberrant clusters were documented in remote brain areas. Positive clusters were also detected on sites known to be involved in the epileptogenesis process of the lithium-pilocarpine model (piriform and entorhinal cortex, hippocampus), with the expected time-specific changes involving an early hypermetabolism followed by a severe hypometabolism and a subsequent partial recovery. CONCLUSION: A quantitative SPM analysis of brain [18F]FDG PET images may be applied to the monitoring of rat brain function when using an adaptive BM template.

Temporal epilepsy lesions may be detected by the voxel-based quantitative analysis of brain FDG-PET images using an original block-matching normalization software.

INTRODUCTION: Statistical parametric mapping (SPM) provides useful voxel-by-voxel analyses of brain images from (18)F-fluorodesoxyglucose positron emission tomography (FDG-PET) after an initial step of spatial normalization through an anatomical template model. In the setting of the preoperative workup of patients with temporal epilepsy, this study aimed at assessing a block-matching (BM) normalization method, where most transformations are computed through small blocks, a principle that minimizes artefacts and overcomes additional image-filtering. METHODS: Brain FDG-PET images from 31 patients with well-characterised temporal lobe epilepsy and among whom 22 had common mesial temporal lobe epilepsy were retrospectively analysed using both BM and conventional SPM normalization methods and with PET images from age-adjusted controls. Different threshold p values corrected for cluster volume were considered (0.01, 0.005, and 0.001). RESULTS: The use of BM provided equivalent values to those of SPM with regard to the overall volumes of temporal and extra-temporal hypometabolism, as well as similar sensitivity for detecting the involved temporal lobe, reaching 87 and 94 % for SPM and BM, respectively, at a threshold p value of 0.01. However, the ability to more accurately localize brain lesions within the mesial portion of the temporal lobe was a little higher with BM than with SPM with respective sensitivities reaching 78 % for BM and 45 % for SPM (p < 0.05). CONCLUSIONS: BM normalization compares well with conventional SPM for the voxel-based quantitative analysis of the FDG-PET images from temporal epilepsy patients. Further studies in different population are needed to determine whether BM is truly an accurate alternative to SPM in this setting.

Development of 6-[(18) F]fluoro-carbohydrate-based prosthetic groups and their conjugation to peptides via click chemistry.

This work describes the development of new 6-[(18) F]fluoro-carbohydrate-based prosthetic groups equipped with an azido arm that are able to participate in copper(I)-catalyzed cycloadditions for (18) F labeling of biomolecules under mild conditions. The radiolabeling in high radiochemical yields (up to 68 ± 6%) of these different prosthetic groups is presented. The flexibility of the azido arm introduced on the carbohydrate moieties allows efficient click reactions with different alkyne functionalized peptides such as gluthation or Arg-Gly-Asp derivatives in order to prepare glycopeptides. The radiosyntheses of (18) F-labeled glycopeptides proceed in high radiochemical yields (up to 76%) in an automated process with excellent radiochemical purity. The addition of a sugar moiety on peptides should enhance the bioavailability, pharmacokinetic, and in vivo clearance properties of these glycopeptides, compared with the unlabeled native peptide, and these properties are highly favorable for positron emission tomography imaging. A high uptake of (18) F-ß-gluco-c(RGDfC) is shown by positron emission tomography imaging in a subcutaneous abscess model in the rat, revealing the potential of this tracer to monitor integrin expression as a part of inflammation and/or angiogenesis processes.

Age-related changes in FDG brain uptake are more accurately assessed when applying an adaptive template to the SPM method of voxel-based quantitative analysis.

INTRODUCTION: The impact of age is crucial and must be taken into account when applying a voxel-based quantitative analysis on brain images from [¹8F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET). This study aimed to determine whether age-related changes in brain FDG-PET images are more accurately assessed when the conventional statistical parametric mapping (SPM) normalization method is used with an adaptive template, obtained from analysed PET images using a Block-Matching (BM) algorithm to fit with the characteristics of these images. METHODS: Age-related changes in FDG-PET images were computed with linear models in 84 neurologically healthy subjects (35 women, 19 to 82-year-old), and compared between results provided by the SPM normalization algorithm applied on its dedicated conventional template or on the adaptive BM template. A threshold P value of 0.05 was used together with a family-wise error correction. RESULTS: The age-related changes in FDG-PET images were much more apparent when computed with the adaptive template than with the conventional template as evidenced by: (1) stronger correlation coefficients with age for the overall frontal and temporal uptake values (respective R² values of 0.20 and 0.07) and (2) larger extents of involved areas (13 and 5% of whole brain template volume, respectively), leading to reveal several age-dependent areas (especially in dorsolateral prefrontal, inferior temporal/fusiform and primary somatosensory cortices). CONCLUSION: Age-related changes in brain FDG uptake may be more accurately determined when applying the SPM method of voxel-based quantitative analysis on a template that best fits the characteristics of the analysed TEP images.

Stress-first protocol for myocardial perfusion SPECT imaging with semiconductor cameras: high diagnostic performances with significant reduction in patient radiation doses.

PURPOSE: Effective doses of 14 mSv or higher are currently being attained in patients having stress and rest myocardial perfusion imaging (MPI) single photon emission computed tomography (SPECT) performed on the same day with conventional protocols. This study aimed to assess the actual reduction in effective doses as well as diagnostic performances for MPI routinely planned with: (1) high-sensitivity cadmium zinc telluride (CZT) cameras, (2) very low injected activities and (3) a stress-first protocol where the normality of stress images may lead to avoiding rest imaging. METHODS: During a 1-year period, 2,845 patients had MPI on a CZT camera, a single-day stress-first protocol and low injected activities (120 MBq of (99m)Tc-sestamibi at stress for 75 kg body weight and threefold higher at rest). The ability to detect > 50% coronary stenosis was assessed in a subgroup of 149 patients who also had coronary angiography, while the normalcy rate was assessed in a subgroup of 128 patients with a low pretest likelihood of coronary artery disease (<10%). RESULTS: Overall, 33% of patients had abnormal MPI of which 34% were women and 34% were obese. The mean effective doses and the percentage of exams involving only stress images were: (1) 3.53 ± 2.10 mSv and 37% in the overall population, (2) 4.83 ± 1.56 mSv and 5% in the subgroup with angiography and (3) 1.96 ± 1.52 mSv and 71 % in the low-probability subgroup. Sensitivity and global accuracy for identifying the 106 patients with coronary stenosis were 88 and 80%, respectively, while the normalcy rate was 97 %. CONCLUSION: When planned with a low-dose stress-first protocol on a CZT camera, MPI provides high diagnostic performances and a dramatic reduction in patient radiation doses. This reduction is even greater in low-risk subgroups with high rates of normal stress images, thus allowing the mean radiation dose to be balanced against cardiac risk in targeted populations.

Assessment of a Monte-Carlo simulation of SPECT recordings from a new-generation heart-centric semiconductor camera: from point sources to human images.

Geant4 application for tomographic emission (GATE), a Monte-Carlo simulation platform, has previously been used for optimizing tomoscintigraphic images recorded with scintillation Anger cameras but not with the new-generation heart-centric cadmium-zinc-telluride (CZT) cameras. Using the GATE platform, this study aimed at simulating the SPECT recordings from one of these new CZT cameras and to assess this simulation by direct comparison between simulated and actual recorded data, ranging from point sources to human images. Geometry and movement of detectors, as well as their respective energy responses, were modeled for the CZT 'D.SPECT' camera in the GATE platform. Both simulated and actual recorded data were obtained from: (1) point and linear sources of (99m)Tc for compared assessments of detection sensitivity and spatial resolution, (2) a cardiac insert filled with a (99m)Tc solution for compared assessments of contrast-to-noise ratio and sharpness of myocardial borders and (3) in a patient with myocardial infarction using segmented cardiac magnetic resonance imaging images. Most of the data from the simulated images exhibited high concordance with the results of actual images with relative differences of only: (1) 0.5% for detection sensitivity, (2) 6.7% for spatial resolution, (3) 2.6% for contrast-to-noise ratio and 5.0% for sharpness index on the cardiac insert placed in a diffusing environment. There was also good concordance between actual and simulated gated-SPECT patient images for the delineation of the myocardial infarction area, although the quality of the simulated images was clearly superior with increases around 50% for both contrast-to-noise ratio and sharpness index. SPECT recordings from a new heart-centric CZT camera can be simulated with the GATE software with high concordance relative to the actual physical properties of this camera. These simulations may be conducted up to the stage of human SPECT-images even if further refinement is needed in this setting.

Complementarity of visual and voxel-based FDG-PET analysis to detect MCI-like hypometabolic pattern in elderly patients with hypertension and isolated memory complaints.

BACKGROUND: 18F-FDG PET can be used to aid in the diagnosis of Alzheimer's disease (AD) and clarify the diagnosis and prognosis of patients with mild cognitive impairment (MCI). PURPOSE: To compare the results of a quantitative analysis of FDG-PET brain images to a standard visual analysis (SVA) with regards to the detection of MCI-like hypometabolic pattern in elderly patients with hypertension and subjective, isolated memory complaints. MATERIAL AND METHODS: FDG-PET brain was performed in 71 patients (mean age, 76.4 ± 5.1 years; women, 53.5%). Images were analyzed for the presence of an MCI-like hypometabolic pattern using an SVA by 2 physicians and a voxel-based statistical procedure (statistical parametric mapping [SPM]) that compared each patient's images to normal reference samples from 19 elderly individuals obtained using the same PET camera. The reliability of these analyses was evaluated according to neuropsychological assessment results, including the Grober & Buschke Free and Cued Selective Reminding Test, and a combined analysis by a neuropsychologist. RESULTS: An MCI-like hypometabolic pattern was documented in 5 patients (7%) by SVA and 7 patients (10%) by SPM analysis; however, only 2 of these patients were selected by both methods. The group characteristics of the 7 patients identified by the quantitative method were consistent with the MCI pattern, which included a higher rate of abnormal GB-FCSRT in Free Recall (57% vs. 9%, p < 0.05) or in Total Recall (29% vs. 8%, p < 0.05) when compared with other patients. In contrast, the group identified by SVA did not exhibit these characteristics. CONCLUSION: A combined visual and quantitative analysis improves the diagnostic accuracy to detect an MCI-like hypometabolic pattern in elderly patients with hypertension and subjective, isolated memory complaints.

Assessment of the early stage of cardiac remodeling of spontaneously hypertensive heart failure rats using the quantitative 3-dimensional analysis provided by acipimox-enhanced FDG-PET.

Spontaneously hypertensive heart failure rats (SHHF) appear to constitute an original model for analyzing the evolution of the metabolic syndrome towards heart failure. This study aimed to characterize early cardiac dysfunction and remodeling in SHHF rats: (1) as compared with spontaneously hypertensive rats (SHR) and with a control group of Kyoto rats (WKY), and (2) by using the 3-dimensional quantitative analysis provided by acipimox-enhanced positron emission tomography (PET) with (18)F-fluorodesoxyglucose (FDG). Left ventricular (LV) ejection fraction (EF) and volume were quantified by automatic software on the FDG-PET images recorded in SHR (n = 20), SHHF (n = 18) and WKY-rats (n = 19) at ages 3 or 10 months old. Arterial blood pressure was determined by cardiac catheterization and cardiac fibrosis was quantified after sacrifice. Blood pressure was similarly elevated in SHR and SHHF rats (respective systolic blood pressures at 10-months: 199 ± 39 vs. 205 ± 2 mmHg), but SHHF rats had higher body mass than SHR rats (at 10-months, 630 ± 36 vs. 413 ± 27 g, p < 0.05) and higher blood levels of cholesterol and of triglycerides. At 3 months, cardiac parameters did not show significant differences between groups but at 10-months, SHHF and SHR rats exhibited an enhancement in myocardial mass and fibrosis associated with a clear decline in LV-EF (SHHF: 46 ± 6 %; SHR: 47 ± 5 %) as compared with WKY (56 ± 6 %, p < 0.01 for both comparisons). Cardiac remodeling of SHHF rats was clearly observable by FDG-PET from the age of 10-months, but in a similar way to that observed for SHR rats, suggesting a predominant role of hypertension.

Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera.

PURPOSE: Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. METHODS: Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with (201)Tl (84 patients) or (99m)Tc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for (201)Tl (78 patients) or (99m)Tc-sestamibi (80 patients) exercise CZT SPECT. RESULTS: The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for (201)Tl than for (99m)Tc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26% error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for (99m)Tc-sestamibi and 30.5 and 13.1ppm for (201)Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for (99m)Tc-sestamibi and 39 and 91 MBq for (201)Tl, respectively. CONCLUSION: Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for (99m)Tc-sestamibi and in non-obese subjects.

Cardioprotective effects of adenosine within the border and remote areas of myocardial infarction.

BACKGROUND: Adenosine may have beneficial effects on left ventricular function after myocardial infarction (MI), but the magnitude of this effect on remote and MI areas is controversial. We assessed the long-term effects of adenosine after MI using electrocardiogram-triggered 18 F-fluorodeoxyglucose positron emission tomography. METHODS: Wistar rats were subjected to coronary ligation and randomized into three groups treated daily for 2 months by NaCl (control; n = 7), 2-chloroadenosine (CADO; n = 8) or CADO with 8-sulfophenyltheophilline, an antagonist of adenosine receptors (8-SPT; n = 8). RESULTS: After 2 months, control rats exhibited left ventricular remodelling, with increased end-diastolic volume and decreased ejection fraction. Left ventricular remodelling was not significantly inhibited by CADO. Segmental contractility, as assessed by the change in myocardial thickening after 2 months, was improved in CADO rats compared to control rats (+1.6% ± 0.8% vs. -2.3% ± 0.8%, p < 0.001). This improvement was significant in border (+5.6% ± 0.8% vs. +1.5% ± 0.8%, p < 0.001) and remote (-4.0% ± 1.0% vs. -10.4% ± 1.3%, p < 0.001) segments, but absent in MI segments. Histological analyses revealed that CADO reduced fibrosis, cardiomyocyte hypertrophy and apoptosis. Protective effects of CADO were blunted by 8-SPT. CONCLUSION: Long-term administration of adenosine protects the left ventricle from contractile dysfunction following MI.

Sustained therapeutic perfusion outside transplanted sites in chronic myocardial infarction after stem cell transplantation.

This study aimed at comparing long-term variations in the perfusion of chronic myocardial infarction (MI) areas after local injections of autologous bone marrow stem cells (BMSCs). 14 coronary ligated rats with transmural chronic MI (4 months) were used: a control group (n = 7) versus a treated group (n = 7) in which (111)In labeled-BMSCs were directly engrafted on MI areas. By using (111)In/(99m)Tc SPECT and Sestamibi gated-SPECT,. left ventricle perfusion and function were monitored in all animals by serial (99m)Tc-Sestamibi pinhole gated-SPECT over a period of 6 months. Post-therapeutic myocardial perfusion improved as early as 48 h following injection in the 2 groups. This benefice was sustained during the 6-month follow-up in the non-engrafted MI-areas from treated rats (at 6-months: +10 ± 5 %), whereas the engrafted ones, as well as the MI areas from control rats, exhibited progressive deterioration over time (at 6-months: -9 ± 10 % and -5 ± 3 %, respectively). Perfusion enhancement of the chronic MI areas treated by BMSCs transplantation is: (1) marked in the following days, presumably because of an unspecific inflammatory reaction, and (2) sustained over the long term but only outside the sites of cell engraftment, suggesting a distant paracrine effect of transplanted cells.

Comparison between stress myocardial perfusion SPECT recorded with cadmium-zinc-telluride and Anger cameras in various study protocols.

PURPOSE: The results of stress myocardial perfusion SPECT could be enhanced by new cadmium-zinc-telluride (CZT) cameras, although differences compared to the results with conventional Anger cameras remain poorly known for most study protocols. This study was aimed at comparing the results of CZT and Anger SPECT according to various study protocols while taking into account the influence of obesity. METHODS: The study population, which was from three different institutions equipped with identical CZT cameras, comprised 276 patients referred for study using protocols involving (201)Tl (n = 120) or (99m)Tc-sestamibi injected at low dose at stress ((99m)Tc-Low; stress/rest 1-day protocol; n = 110) or at high dose at stress ((99m)Tc-High; rest/stress 1-day or 2-day protocol; n = 46). Each Anger SPECT scan was followed by a high-speed CZT SPECT scan (2 to 4 min). RESULTS: Agreement rates between CZT and Anger SPECT were good irrespective of the study protocol (for abnormal SPECT, (201)Tl 92 %, (99m)Tc-Low 86 %, (99m)Tc-High 98 %), although quality scores were much higher for CZT SPECT with all study protocols. Overall correlations were high for the extent of myocardial infarction (r = 0.80) and a little lower for ischaemic areas (r = 0.72), the latter being larger on Anger SPECT (p < 0.001). This larger extent was mainly observed in 50 obese patients who were in the (201)Tl or (99m)Tc-Low group and in whom stress myocardial counts were particularly low with Anger SPECT (228 ± 101 kcounts) and dramatically enhanced with CZT SPECT (+279 ± 251 %). CONCLUSION: Concordance between the results of CZT and Anger SPECT is good regardless of study protocol and especially when excluding obese patients who have low-count Anger SPECT and for whom myocardial counts are dramatically enhanced on CZT SPECT.

Compared performance of high-sensitivity cameras dedicated to myocardial perfusion SPECT: a comprehensive analysis of phantom and human images.

UNLABELLED: Differences in the performance of cadmium-zinc-telluride (CZT) cameras or collimation systems that have recently been commercialized for myocardial SPECT remain unclear. In the present study, the performance of 3 of these systems was compared by a comprehensive analysis of phantom and human SPECT images. METHODS: We evaluated the Discovery NM 530c and DSPECT CZT cameras, as well as the Symbia Anger camera equipped with an astigmatic (IQ x SPECT) or parallel-hole (conventional SPECT) collimator. Physical performance was compared on reconstructed SPECT images from a phantom and from comparable groups of healthy subjects. RESULTS: Classifications were as follows, in order of performance. For count sensitivity on cardiac phantom images (counts x s(-1) x MBq(-1)), DSPECT had a sensitivity of 850; Discovery NM 530c, 460; IQ x SPECT, 390; and conventional SPECT, 130. This classification was similar to that of myocardial counts normalized to injected activities from human images (respective mean values, in counts x s(-1) x MBq(-1): 11.4 ± 2.6, 5.6 ± 1.4, 2.7 ± 0.7, and 0.6 ± 0.1). For central spatial resolution: Discovery NM 530c was 6.7 mm; DSPECT, 8.6 mm; IQ x SPECT, 15.0 mm; and conventional SPECT, 15.3 mm, also in accordance with the analysis of the sharpness of myocardial contours on human images (in cm(-1): 1.02 ± 0.17, 0.92 ± 0.11, 0.64 ± 0.12, and 0.65 ± 0.06, respectively). For contrast-to-noise ratio on the phantom: Discovery NM 530c had a ratio of 4.6; DSPECT, 4.1; IQ x SPECT, 3.9; and conventional SPECT, 3.5, similar to ratios documented on human images (5.2 ± 1.0, 4.5 ± 0.5, 3.9 ± 0.6, and 3.4 ± 0.3, respectively). CONCLUSION: The performance of CZT cameras is dramatically higher than that of Anger cameras, even for human SPECT images. However, CZT cameras differ in that spatial resolution and contrast-to-noise ratio are better with the Discovery NM 530c, whereas count sensitivity is markedly higher with the DSPECT.