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SLC5A8 is a sodium-coupled monocarboxylate and ketone transporter expressed in various epithelial cells. A putative role of SLC5A8 in neuroenergetics has been also hypothesized. To clarify this issue, we studied the cerebral phenotype of SLC5A8-deficient mice during aging. Elderly SLC5A8-deficient mice presented diffuse leukoencephalopathy characterized by intramyelinic oedema without demyelination suggesting chronic energetic crisis. Hypo-metabolism in the white matter of elderly SLC5A8-deficient mice was found using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission CT (SPECT). Since the SLC5A8 protein could not be detected in the mouse brain, it was hypothesized that the leukoencephalopathy of aging SLC5A8-deficient mice was caused by the absence of slc5a8 expression in a peripheral organ, i.e. the kidney, where SLC5A8 is strongly expressed. A hyper-excretion of the ketone β-hydroxybutyrate (BHB) in the urine of SLC5A8-deficient mice was observed and showed that SLC5A8-deficient mice suffered a cerebral BHB insufficiency. Elderly SLC5A8-deficient mice also presented altered glucose metabolism. We propose that the continuous renal loss of BHB leads to a chronic energetic deficiency in the brain of elderly SLC5A8-deficient mice who are unable to counterbalance their glucose deficit. This study highlights the importance of alternative energetic substrates in neuroenergetics especially under conditions of restricted glucose availability.

Background: Tc-99m pertechnetate is a well-known anion, used for clinical imaging of thyroid function. This gamma emitter is transported by the sodium iodide symporter but is not incorporated into thyroglobulin. Scintigraphy using Tc-99m pertechnetate or 123 iodide represents a powerful tool for the study of sodium iodide symporter activity in different organs of living animal models. However, in many studies that have been performed in mice, the thyroid could not be distinguished from the salivary glands. In this work, we have evaluated the use of a clinically dedicated single-photon emission computed tomography (SPECT) camera for thyroid imaging and assessed what improvements are necessary for the development of this technique. Methods: SPECT of the mouse neck region, with pinhole collimation and geometric calibration, was used for the individual measurement of Tc-99m pertechnetate uptake in the thyroid and the salivary glands. Uptake in the stomach was studied by planar whole-body imaging. Uptake kinetics and biodistribution studies were performed by sequential imaging. Results: This work has shown that thyroid imaging in living mice can be performed with a SPECT camera originally built for clinical use. Our experiments indicate that Tc-99m pertechnetate uptake is faster in the thyroid than in the salivary glands and the stomach. The decrease in Tc-99m pertechnetate uptake after injection of iodide or perchlorate as competitive inhibitors was also studied. The resulting rate decreases were faster in the thyroid than in the salivary glands or the stomach. Conclusions: We have shown that a clinically dedicated SPECT camera can be used for thyroid imaging. In our experiments, SPECT imaging allowed the analysis of Tc-99m pertechnetate accumulation in individual organs and revealed differences in uptake kinetics.

International audience; In the present study, we evaluated, in mice, the efficacy of the tetrafunctional block copolymer 704 as a nonviral gene delivery vector to the lungs. SPECT/CT molecular imaging of gene expression, biochemical assays, and immunohistochemistry were used. Our dataset shows that the formulation 704 resulted in higher levels of reporter gene expression than the GL67A formulation currently being used in a clinical trial in cystic fibrosis patients. The inflammatory response associated with this gene transfer was lower than that induced by the GL67A formulation, and the 704 formulation was amenable to repeated administrations. The cell types transfected by the 704 formulation were type I and type II pneumocytes, and transgene expression could not be detected in macrophages. These results emphasize the relevance of the 704 formulation as a nonviral gene delivery vector for lung gene therapy. Further studies will be required to validate this vector in larger animals, in which the lungs are more similar to human lungs.

Assessment of myocardial viability is an important clinical issue for patient management during the acute and chronic stages of myocardial infarction. BMIPP (15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid) is a free fatty acid analogue which is trapped in the myocardium, thus permitting for metabolic imaging with single photon emission computerized tomography (SPECT). Less BMIPP than flow tracers that may be observed in the areas of infarction, may reflect the metabolic shift from fatty acid to glucose utilization in ischaemic myocardium. In this sense, the combined imaging of BMIPP and a flow tracer with SPECT may provide similar and important information as fluoro-18 deoxyglucose (FDG) and positron emission tomography (PET) regarding the assessment of myocardial viability. The purpose of this article is to review the clinical impact of BMIPP in patients with acute and with chronic left ventricular dysfunction for the identification of jeopardized but viable myocardium and the prediction of the functional outcome.

International audience; Respiratory motion may blur the tomographic reconstruction of PET or SPECT images, which subsequently impairs quantitative measurements, e.g. in the upper abdomen area. Respiratory phase-based gated reconstruction addresses this problem for CT images, but deteriorates the signal-to-noise ratio and other intensity-based quality measures for ET images. This article describes an image-based motion detection method for dynamic images, which works for both 4D-CT and 4D-SPECT images. This method allowed us to identify the motionless phases from the image-based motion signal. Interestingly, we found that the peak of motion according to the pressure signal, recorded during the acquisition and considered as a reference, is temporally shifted compared to the motion-phases identified by the proposed method. Moreover, these observations permit to reconstruct a breath hold like 3D SPECT image improving the quality of the 3D reconstruction compared to both 4D reconstruction and standard 3D reconstruction.

Respiratory motion can blur the tomographic reconstruction of positron emission tomography or single-photon emission computed tomography (SPECT) images, which subsequently impair quantitative measurements, e.g. in the upper abdomen area. Respiratory signal phase-based gated reconstruction addresses this problem, but deteriorates the signal-to-noise ratio (SNR) and other intensity-based quality measures. This paper proposes a 3D reconstruction method dedicated to micro-SPECT imaging of mice. From a 4D acquisition, the phase images exhibiting motion are identified and the associated list-mode data are discarded, which enables the reconstruction of a 3D image without respiratory artefacts. The proposed method allows a motion-free reconstruction exhibiting both satisfactory count statistics and accuracy of measures. With respect to standard 3D reconstruction (non-gated 3D reconstruction) without breathing motion correction, an increase of 14.6% of the mean standardized uptake value has been observed, while, with respect to a gated 4D reconstruction, up to 60% less noise and an increase of up to 124% of the SNR have been demonstrated.

The utilisation of the Na/I symporter (NIS) and associated radiotracers as a reporter system for imaging gene expression is now reaching the clinical setting in cancer gene therapy applications. However, a formal assessment of the methodology in terms of normalisation of the data still remains to be performed, particularly in the context of the assessment of activities in individual subjects in longitudinal studies. In this context, we administered to mice a recombinant, replication-incompetent adenovirus encoding rat NIS, or a human colorectal carcinoma cell line (HT29) encoding mouse NIS. We used (99m)Tc pertechnetate as a radiotracer for SPECT/CT imaging to determine the pattern of ectopic NIS expression in longitudinal kinetic studies. Some animals of the cohort were culled and NIS expression was measured by quantitative RT-PCR and immunohistochemistry. The radioactive content of some liver biopsies was also measured ex vivo. Our results show that in longitudinal studies involving datasets taken from individual mice, the presentation of non-normalised data (activity expressed as %ID/g or %ID/cc) leads to 'noisy', and sometimes incoherent, results. This variability is due to the fact that the blood pertechnetate concentration can vary up to three-fold from day to day. Normalisation of these data with blood activities corrects for these inconsistencies. We advocate that, blood pertechnetate activity should be determined and used to normalise the activity measured in the organ/region of interest that expresses NIS ectopically. Considering that NIS imaging has already reached the clinical setting in the context of cancer gene therapy, this normalisation may be essential in order to obtain accurate and predictive information in future longitudinal clinical studies in biotherapy.

Introduction: Progress with gene-based therapies has been hampered by difficulties in monitoring the biodistribution and kinetics of vector-mediated gene expression. Recent developments in non-invasive imaging have allowed researchers and clinicians to assess the location, magnitude and persistence of gene expression in animals and humans. Such advances should eventually lead to improvement in the efficacy and safety of current clinical protocols for future treatments. Areas covered: The molecular imaging techniques for monitoring gene therapy in the living subject, with a specific highlight on the key reporter gene approaches that have been developed and validated in preclinical models using the latest imaging modalities. The applications of molecular imaging to biotherapy, with a particular emphasis on monitoring of gene and vector biodistribution and on image-guided radiotherapy. Expert opinion: Among the reporter gene/probe combinations that have been described so far, one stands out, in our view, as the most versatile and easy to implement: the Na/I symporter. This strategy, exploiting more than 50 years of experience in the treatment of differentiated thyroid carcinomas, has been validated in different types of experimental cancers and with different types of oncolytic viruses and is likely to become a key tool in the implementation of human gene therapy.

Serotonergic drugs may lead to valvular heart disease in humans and more recently also in rats. Although clinical data suggest that dose dependency and reversibility after drug cessation might occur, proof of this is lacking. For that purpose, a total of 106 rats were prospectively enrolled: 22 control animals and 7 groups of 12 rats that received daily subcutaneous serotonin injections (5, 10, 20, 30, 40, 50 and 60 mg/kg respectively) for 12 weeks. At 12 weeks, half of the animals of each group were killed for histological analysis, whereas the remaining rats were further followed (without serotonin injections) for an additional 8 weeks. After 12 weeks of serotonin treatment, aortic and mitral regurgitation (AR, MR) were more frequently observed in the high dose groups (> 30 mg/kg) compared to controls. Moreover, aortic and mitral valves were also thicker in the high dose groups compared to controls. After 8 weeks free of serotonin injections, AR and MR were no longer significantly higher than controls. Moreover, aortic and mitral valve thickness had normalized, returning to control levels. In conclusion, this study provides evidence for a dose-dependent valvular toxicity of serotonergic drugs, which appears to be reversible after drug withdrawal.

The aim of this study was the comparison of the tumour uptake and the long-term retention of [I-123]-2-I-L-phenylalanine and [I-123]-2-I-D-phenylalanine with those of [I-123]-2-I-L-tyrosine and [I-123]-2-I-D-tyrosine in RIM rhabdomyosarcoma tumour-bearing rats. The biodistribution of the radioactivity as a function of time in RIM tumour-bearing rats was measured by planar gamma camera imaging (dynamic and static). If dissection was applied, the activity in the tumours and tissues of interest was measured by gamma counting.[I-123]-2-iodo-L-phenylalanine, [I-123]-2-iodo-D-phenylalaine, [I-123] -2-I-L-tyrosine showed a considerable turnout uptake reaching a maximum between 10 and 30 min. At 30 min p.i. the differential uptake ratio values of this uptake were, respectively, 2.1, 2.3, 2.5 and 1.7. The activity in the tumour was shown to be related to a tumour cell uptake and not to an increased blood pool activity. All the tracers showed a clearance from the blood to the bladder without renal retention. At longer times both L- and D-[I-123]-2-I-tyrosine were cleared for a large part from the tumours and the body. [I-123]-2-I-L-Phe and [I-123]-2-I-D-Phe showed a considerable and equal retention in the tumours: as compared with 0.5 h, 91% at 24 h and 80% at 48 h. This was related to the longer retention of activity in the blood pool noticed for these compounds (81% at 24 h and 65% at 48 h). The tumour-to-background ratio increased with 25% at those longer times. At short times all the tracers were taken up to a considerable extent in the tumours. In the RIM-bearing Wag/Rij rat model only [I-123]-2-1-L-phenylalanine and [I-123]-2-I-D-phenylalanine showed an especially high retention at long times without any significant difference between the enantiomers.

AIM: Stem cell homing to injured tissue is necessary for local tissue repair. But homing of stem cells in chronic ischemic heart disease (CIHD) is poorly understood. This study investigated homing of peripheral blood stem cells (PBSC) expressing the CD133 antigen. After intracoronary injection. The cells were (111)In labeled for in vivo visualization. METHODS: PBSC were mobilized with granulocyte-colony stimulating factor and collected by apheresis on d-1. On d0, CD133+ cells were enriched up to a median purity of 89% (range: 79-97%) with an immunomagnetic separation device (CliniMACS, Miltenyi). A fraction of the cells was radiolabeled with [(111)In]oxine in 0.1 M TRIS at pH 7.4 for 45-60 min. Cell viability after labeling was assessed using trypan-blue. The cells were injected at a radioactive concentration of 0.9 MBq/10(6) cells into the target open coronary vessel through a balloon catheter. During balloon inflation [(99m)Tc]sestamibi was injected intravenously to identify the myocardium and the target vascular territory. Eight patients (mean age: 53 years; range: 50-72 years) with stable CIHD and reduced left ventricular function (NYHA class I-II) after acute myocardial infarction (>12 months) were studied. After a first cohort of 3 patients received an injectate of 5-10x10(6) cells, our final protocol was applied in 5 patients in whom an average of 34.4x10(6) (range: 18.6-49.4) CD133+ cells was injected. Whole body and single photon emission computed tomography (SPECT) scans were acquired at different time points after injection (energy windows set at 140, 171 and 245 keV). Residual activity in the heart was assessed by drawing a region of interest around the heart on the anterior whole body views. RESULTS: Mean labeling efficiency of [111In]oxine labeling was 51.2% and cell viability after labeling averaged 88%. In the 5 patients receiving the higher amount of labeled cells, a clear (111)In-signal was observed in the heart region up to 3 days after administration. Fused [(99m)Tc]sestamibi/(111)In SPECT images demonstrated that the regional distribution of the transplanted cells within the target zone, as delineated by the flow tracer, remained unchanged over time. A biodistribution study in 2 patients showed a residual activity in the heart, liver and spleen of 6.9-8%, 23.1-26.8%, 3.1-3.7%, respectively, after 1-2 h and 2.3-3.2% 23.8-28.3%, 3.5-3.8%, respectively, after 12 h (decay corrected and expressed as a percentage of total body initial activity). No adverse events were observed during the procedure and up to 3 months follow-up. CONCLUSIONS: Radiolabeling with [(111)In]oxine is a suitable method for follow-up of cell distribution during the first days after transplantation. A significant amount of CD133+ PBSC home to the heart after intracoronary injection in patients with CIHD. The results of this study are useful for the design of trials that evaluate the tissue repair potential of CD133+ PBSC in the setting of CIHD.

PURPOSE: 123I-2-iodo-tyrosine (123I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. METHODS: For the biodistribution study, six male volunteers received 60-95 MBq 123I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of 123I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. RESULTS: 123I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, 123I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39-3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). CONCLUSION: 123I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients.

Recent experimental and clinical studies have shown that autologous cell based therapy using skeletal myoblasts or bone marrow-derived stem cells might have beneficial effects in chronic ischemic heart disease. The underlying concept is based on the repopulation of necrotic tissue by either readily contractile myoblasts or by bone marrow-derived stem cells. However, there is a need to resolve a number of issues for determining the better way to perform these treatments and, moreover, for assessing the real beneficial functional effect of each of these cell therapies. In this mini-review, we will discuss (i) the issues of the selection of chronic infarct animal to truly determine the impact of cell therapy on cardiac function recovery, and (ii) the evaluation of the bio-availability and the bio-distribution of transplanted cells. Some new investigational methodologies based on clinical end-points are also proposed.

Background: Despite encouraging preliminar y results of cell-based therapies in patients with ischemic hear t disease there is still a need to develop animal models where abnormalities of myocardial perfusion and left ventricular function can be quantified precisely and followed on a long term basis. Pinhole gated SPECT allows rapid, reproducible and repeatable measurements of myocardial perfusion and function in rats. Aim: To evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on myocardial perfusion and function in a rat model of chronic infarction. Methods: 111Indium-oxine labeled autologous BMSCs were injected within the infarct area in 11 male Wistar rats 3 months after the surgical ligature of the left anterior descending coronar y ar ter y. One animal died during the transplantation. The distribution of the implanted cells was determined by dual isotope (111InThe distribution of the implanted cells was determined by dual isotope (111In and 99mTc-sestamibi) pinhole SPECT performed 2 days later. Myocardial perfusion and left ventricular function were calculated by 99mTc-sestamibi pinhole gated SPECT obtained before, and 1 and 3 months after cell transplantation. Polar maps of myocardial perfusion were generated. Perfusion abnormalities with values below 2 SD of a normal database were defined as infarct areas. Left ventricular volumes and ejection fraction were quantified from the gated data using an automatic program (Univ. of Michigan). Results: Transplanted cells were clearly visualized within the infarct area in all animals. Perfusion defect size ranged from 3 to 47% of the left ventricular surface before transplantation. Perfusion normalized in 1 animal, improved in 3 and was unchanged or deteriorated in the remaining 7 animals. No significant changes in left ventricular volumes and ejection fraction were observed except in the animal in whom perfusion was normalized. Conclusion: Pinhole (gated) SPECT is useful to assess the intra-myocardial distribution of transplanted cells and to monitor the effects of cell-based therapies in rats.

Positron emission tomography (PET) using fluorodeoxyglucose (FDG) plays an important role in the management of oncologic diseases. Interpretation of the FDG-PET data requires a profound knowledge of the normal variety of FDG biodistribution and of the different pitfalls that may mimic addit

3-(123)I-Iodo-L-alpha-methyltyrosine (3-IMT) is an amino acid analog used for tumor imaging. Specific accumulation is mediated mainly by the system L amino acid transport system. System L activity is known to increase when cells are loaded with amino acids. The aim of our study was to measure the effects of amino acid preload on (123)I-3-IMT tumor uptake and image contrast in a rat tumor model using in vivo dynamic imaging. METHODS: Rhabdomyosarcoma (R1M) tumor-bearing rats underwent 2 dynamic (123)I-3-IMT studies on separate days: 1 baseline study and 1 after intraperitoneal injection (0.25 mmol/kg) of a single amino acid (arginine, proline, glutamate, asparagine, tryptophan, or phenylalanine) administered 30 min before intravenous injection of 18.5 MBq (123)I-3-IMT. A (99m)Tc-labeled human serum albumin study was performed on each rat for the calculation of the blood-pool activity inside the tumor. Time-activity curves were generated for tumor, contralateral background region, kidney, heart, and total body.Tumor uptake was corrected for blood-pool and background activity. Image contrast was calculated as the ratio between tumor and background activity. The rate (K(1)) of tracer entering the tumor was obtained using Patlak analysis. A displacement study was performed on a separate group of rats, in which a high dose of phenylalanine was administered 40 min after (123)I-3-IMT injection. RESULTS: (123)I-3-IMT accumulation in tumor reached a plateau 10 min after injection. Tumor uptake on the baseline scans correlated well with tumor size (r = 0.92). After preloading, tumor uptake and contrast increased in all conditions: arginine, +26% and +26%; proline, +15% and +13%; glutamate, +14% and +9%; asparagine, +19% and +15%; tryptophan, +36% and 11%; phenylalanine, +22% and + 13%. K(1) values also increased. Administration of an afterload with phenylalanine induced a significant displacement of (123)I-3-IMT tumor accumulation. CONCLUSION: Prior amino acid administration increases (123)I-3-IMT tumor accumulation and image contrast. This effect can be explained by the increased antiporter activity of the amino acid transport system L in preloaded conditions. Our results indicate that the fasted state might not be the optimal metabolic condition to study tumor accumulation of L-transported tracers such as (123)I-3-IMT. Amino acid administration before (123)I-3-IMT injection could improve tumor uptake and image contrast.

But de la presentation La representation mentale de l’anatomie du rocher en trois dimensions est difficile mais s’avere indispensable avant toute chirurgie otologique. Par ailleurs le scanner conventionnel ne permet pas d’identifier precisement la microanatomie du labyrinthe cochleaire et ses rapports avec l’os du promontoire, ce qui est particulierement interessant en implantologie cochleaire. Les coupes histologiques fournissent des informations de tres haute resolution mais peuvent conduire a des distorsions geometriques de l’anatomie pendant la preparation. En revanche, le micro-scanner preserve la forme, la structure et la composition des tissus mous avec un protocole d’acquisition simple, mais necessite de petits volumes d’acquisition. L’objectif de ce travail est d’ameliorer la comprehension du scanner de l’os temporal humain en s’aidant de la segmentation semi-automatique d’un micro-scanner. Materiel et methodes Des images scanner et micro-scanner de 5 paires d’os temporaux fraichement preleves ont ete acquises. Les micro-scanners ont ete segmentes de maniere semi-automatique en utilisant un algorithme de segmentation base sur des points remarquables. Les structures d’interet incluent les couches corticales et trabeculaires de l’ensemble de l’os temporal, le labyrinthe cochleaire avec la rampe tympanique et vestibulaire, les osselets et leurs ligaments, la membrane tympanique, les muscles de l’oreille moyenne et leurs tendons, l’artere carotide interne, l’arborisation osseuse du nerf vestibulaire, le nerf facial et la corde du tympan. Il a ensuite ete realise un recalage rigide entre les images focalisees du micro-scanner sur celles du scanner plus globales dans le but de fusionner les 2 images. Resultats Les structures segmentees en haute resolution sont fusionnees et visualisees sur les images scanner correspondantes. La transparence des structures anatomiques peut etre commandee individuellement. Cette experience ameliore considerablement la reconnaissance visuelle et la representation spatiale des structures partiellement visibles sur un scanner classique (par exemple la corde du tympan ou les rampes intra cochleaire). Conclusion Des reconstructions 3D anatomiques geometriquement precises de l’os temporal fournissent d’abord un outil d’enseignement novateur de l’anatomie et de la chirurgie de l’oreille. Cet outil peut egalement constituer un atout dans la planification d’une implantation cochleaire en constituant un moyen simple mais precis de visualisation de l’anatomie en 3D du labyrinthe. La comprehension des relations spatiales entre les structures anatomiques ainsi que la visualisation des approches chirurgicales en est grandement facilitee.

Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In this context, the discovery that the low-energy electron emitter, 99mTc, can induce stunning on primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated in vivo, this observation suggests that a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid physiology. The aims of this study were to determine whether 99mTc pertechnetate (99mTcO4−) is capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of 99mTcO4− required to induce this stunning, and to analyze the biological events associated/concomitant with this effect. Our results show that 99mTcO4−–mediated thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the absorbed dose in the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduced level of functional Na/I symporter (NIS) protein, with no significant cell death. It is reversible within a few days. At the cellular and molecular levels, a decrease in NIS mRNA, the generation of double-strand DNA breaks, and the activation of the p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore, induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of at least 20 Gy, a level unlikely to be encountered in clinical practice. Nevertheless this report presents an unexpected effect of low-energy electrons on a normal tissue in vivo, and provides a unique experimental setup to understand the fine molecular mechanisms involved in their biological effects.

To characterize the myocardium after thrombolytic therapy for infarction single photon emission computed tomographic (SPECT) studies with 123I-(ortho-iodophenyl)-pentadecanoic acid (oPPA) and 99Tcm-methoxyisobutyl isonitrile (MIBI) were obtained at rest in nine patients within a fortnight after the acute event. A decreased oPPA activity compared to MIBI was observed in 15/45 segments (7/9 patients). The segments with discordant oPPA/MIBI activities showed less severe wall motion abnormalities than the segments with concordant decreased oPPA and MIBI activities (P = 0.004). A significant association was found between discordant oPPA/MIBI activities and the early evolution of wall motion following thrombolysis: discordant oPPA/MIBI activities were present in nine of the 11 segments (82%) with improved wall motion, while the wall motion of the seven segments with similar decreased oPPA and MIBI activities was unchanged or had deteriorated (P = 0.018). It is concluded that metabolic abnormalities often persist longer than perfusion and wall motion abnormalities soon after thrombolysis, and that 123I-oPPA in combination with 99Tcm-MIBI is useful to demonstrate myocardial areas which have been salvaged by thrombolysis.

info:eu-repo/semantics/published

A patient with diffuse hepatic arteriovenous microfistulae suffered from secondary high-output right ventricular failure, pulmonary hypertension, and ascites, all of which could be managed by selective embolization of the hepatic artery. The vascular lesion of the liver seems to be essential, although hemorrhagic hereditary telangiectasia ,perhaps aggravated by administration of oral contraceptives, may be considered contributory factors in this case., info:eu-repo/semantics/published

Sodium acetoacetate (AcAc) was infused at a constant rate for 60 min in 2 groups of normal dogs. In the first group, the resulting hyperketonemia provoked a decrease of 19 mg/100 ml in blood glucose and an overall 40% drop in plasma free fatty acids (FFA) and blood glycerol; a sharp, but transient rise in peripheral and portal venous immunoreactive insulin (IRI) levels was observed. In the second group, a 5% glucose solution was given with the AcAc; normoglycemia was thus maintained and IRI levels remained high throughout the experiment. This indicates that glucose exerts a permissive effect on the insulinotropic action of ketone bodies in vivo.

Background. The 13C urea breath test (13C-UBT) is the most convenient method for diagnosing Helicobacter pylori infection noninvasively. Nondispersive isotope-selective infrared spectrometry (NDIRS) is an inexpensive and easy alternative to mass spectrometry. The objective of this study was to evaluate: (1) the reproducibility of the 13C-UBT as performed by using the NDIRS method; (2) the repeatability of bags analysis and the impact of delayed analysis; and (3) the need for fasting status for the 13C-UBT. Methods. The 13C-UBT was performed with 75 mg urea labeled with 13C, with breath samples collected at times 0 and 30 minutes. Results are expressed as delta over baseline (0/00). Fifty-three patients underwent two successive 13C-UBTs with an interval of 48 to 72 hours. The 106 collected bags were randomly reanalyzed immediately or 72 hours later. In 26 volunteer subjects, the 13C-UBT was performed both in a fasting condition and after a nonstandardized meal. The reproducibility was assessed by the method of Bland and Altman. Results. The mean of difference between two successive tests was 0.14 0/00 (standard deviation, 0.90), and the coefficient of repeatability was 1.80 (confidence interval, 95%). The difference between two successive analyses was always less than 2.2% of the initial value. The coefficient of variation between two successive tests for the influence of a meal was 11.24. Conclusion. The 13C-UBT as performed by using NDIRS is reproducible, analyses can be delayed up to 72 hours, and the test must be performed in fasting conditions.

Recent experimental and clinical studies have shown that autologous cell based therapy using skeletal myoblasts or bone marrow-derived stem cells might have beneficial effects in chronic ischemic heart disease. The underlying concept is based on the repopulation of necrotic tissue by either readily contractile myoblasts or by bone marrow-derived stem cells. However, there is a need to resolve a number of issues for determining the better way to perform these treatments and, moreover, for assessing the real beneficial functional effect of each of these cell therapies. In this mini-review, we will discuss (i) the issues of the selection of chronic infarct animal to truly determine the impact of cell therapy on cardiac function recovery, and (ii) the evaluation of the bio-availability and the bio-distribution of transplanted cells. Some new investigational methodologies based on clinical end-points are also proposed.

Aging is associated with morphologic and functional alterations of the rat's left ventricle. However, the time-course of valvular function and morphology in normal aging rats has not yet been studied. For this purpose, 30 male Wistar rats (318 ± 5 g , 10 weeks old) underwent serial echocardiograms for 58 weeks under sodium pentobarbital 50 mg/kg IP anesthetization followed by necropsy. Histopathology was also performed in two additional groups of 10 rats at 10 and 30 weeks of age. Regurgitations were considered as any retrograde flow on 2-D or M-mode color Doppler echocardiography. Tricuspid regurgitation was already found at 10 weeks of age and became more frequent with age. Pulmonary, mitral and aortic regurgitation was seldom observed at 10 weeks but became more frequent after 30 weeks. For the mitral and aortic valve, this was also associated with an increase in valvular thickness because of nodular or segmental myxoid leaflet changes. The severity of valvular regurgitations did not increase with age. In conclusion, aging leads to morphologic and functional valvular changes in normal rats. This is important when investigating models of valvular heart disease in small animals. (E-mail: steven_droogmans@yahoo.com )

Aim: Limited data are available about the use of Doppler myocardial imaging (DMI) in small animals. We intend to provide reference values for velocity, strain and strain rate in a large group of healthy rats and studied the reproducibility and repeatability of these parameters. Methods and results: A total of 33 mate Wistar rats (503 +/- 41 g) underwent baseline transthoracic echocardiography with DMI of the anterior and inferior wall in a short-axis view using a 13 MHz linear probe. Adequate tissue Doppler measurements could be obtained in 30 rats. On average 10 +/- 4 consecutive cycles were studied in post-processing using dedicated software (SPEQLE). Mean radial peak systolic velocity, strain and strain rate were respectively -0.8 +/- 0.3 cm/s, 38 +/- 8% and 9.1 +/- 2.0/s in the anterior watt and 3.1 +/- 0.6 cm/s, 49 +/- 10% and 13.7 +/- 3.7/s in the inferior wall. The reproducibility and repeatability of the DMI measurements assessed in 10 rats was good. Conclusion: DMI is feasible and reproducible in healthy rats. Establishing reference values opens new perspectives towards the use of strain and strain rate imaging in small rodents in the assessment of myocardial diseases. (C) 2006 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.