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Biomedical subjects

J J Vaquero

Publications and source records attributed to J J Vaquero.

At least 19 recordsLinked to original sources
PubMed2007

Effects of MDMA on blood glucose levels and brain glucose metabolism.

PURPOSE: This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. METHODS: Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. RESULTS: Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. CONCLUSION: These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis.

Adrenergic Uptake Inhibitors↗
PubMed2006

FIRST: Fast Iterative Reconstruction Software for (PET) tomography.

Small animal PET scanners require high spatial resolution and good sensitivity. To reconstruct high-resolution images in 3D-PET, iterative methods, such as OSEM, are superior to analytical reconstruction algorithms, although their high computational cost is still a serious drawback. The higher performance of modern computers could make iterative image reconstruction fast enough to be viable, provided we are able to deal with the large number of probability coefficients for the system response matrix in high-resolution PET scanners, which is a difficult task that prevents the algorithms from reaching peak computing performance. Considering all possible axial and in-plane symmetries, as well as certain quasi-symmetries, we have been able to reduce the memory requirements to store the system response matrix (SRM) well below 1 GB, which allows us to keep the whole response matrix of the system inside RAM of ordinary industry-standard computers, so that the reconstruction algorithm can achieve near peak performance. The elements of the SRM are stored as cubic spline profiles and matched to voxel size during reconstruction. In this way, the advantages of 'on-the-fly' calculation and of fully stored SRM are combined. The on-the-fly part of the calculation (matching the profile functions to voxel size) of the SRM accounts for 10-30% of the reconstruction time, depending on the number of voxels chosen. We tested our approach with real data from a commercial small animal PET scanner. The results (image quality and reconstruction time) show that the proposed technique is a feasible solution.

Algorithms↗
PubMed2004

Experiment assessment of mass effects in the rat: implications for small animal PET imaging.

In vivo imaging using positron emission tomography (PET) is important in the development of new radiopharmaceuticals in rodent animal models for use as biochemical probes, diagnostic agents, or in drug development. We have shown mathematically that, if small animal imaging studies in rodents are to have the same "quality" as human PET studies, the same number of coincidence events must be detected from a typical rodent imaging "voxel" as from the human imaging voxel. To achieve this using the same specific activity preparation, we show that roughly the same total amount of radiopharmaceutical must be given to a rodent as to a human subject. At high specific activities, the mass associated with human doses, when administered to a rodent, may not decrease the uptake of radioactivity at non saturable sites or sites where an enzyme has a high capacity for a substrate. However, in the case of binding sites of low density such as receptors, the increased mass injected could saturate the receptor and lead to physiologic effects and non-linear kinetics. Because of the importance of the mass injected for small animal PET imaging, we experimentally compared high and low mass preparations using ex vivo biodistribution and phosphorimaging of three compounds: 2-fluoro-2-deoxyglucose (FDG), 6-fluoro-L-metatyrosine (FMT) and one receptor-directed compound, the serotonin 5HT1A receptor ligand, trans-4-fluoro-N-[2-[4-(2-methoxylphenyl) piperazino]ethyl]-N-(2-pyridyl) cyclohexane- carboxamide (FCWAY). Changes in the mass injected per rat did not affect the distribution of FDG, FMT, and FCWAY in the range of 0.6-1.9 nmol per rat. Changes in the target to nontarget ratio were observed for injected masses of FCWAY in the range of approximately 5-50 nmol per rat. If the specific activity of such compounds and/or the sensitivity of small animal scanners are not increased relative to human studies, small animal PET imaging will not correctly portray the "true" tracer distribution. These difficulties will only be exacerbated in animals smaller than the rat, e.g., mice.

Algorithms↗
PubMed2002

Monitoring the correction of glycogen storage disease type 1a in a mouse model using [(18)F]FDG and a dedicated animal scanner.

Monitoring gene therapy of glycogen storage disease type 1a in a mouse model was achieved using [(18)F]FDG and a dedicated animal scanner. The G6Pase knockout (KO) mice were compared to the same mice after infusion with a recombinant adenovirus containing the murine G6Pase gene (Ad-mG6Pase). Serial images of the same mouse before and after therapy were obtained and compared with wild-type (WT) mice of the same strain to determine the uptake and retention of [(18)F]FDG in the liver. Image data were acquired from heart, blood pool and liver for twenty minutes after injection of [(18)F]FDG. The retention of [(18)F]FDG was lower for the WT mice compared to the KO mice. The mice treated with adenovirus-mediated gene therapy had retention similar to that found in age-matched WT mice. These studies show that FDG can be used to monitor the G6Pase concentration in liver of WT mice as compared to G6Pase KO mice. In these mice, gene therapy returned the liver function to that found in age matched WT controls as measured by the FDG kinetics in the liver compared to that found in age matched wild type controls.

Animals↗
PubMed2002

A novel approach using transcomplementing adenoviral vectors for gene therapy of adrenocortical cancer.

Current therapies for adrenocortical carcinomas do not improve the life expectancy of patients. In this study, we tested whether a gene-transfer therapy based upon a suicide gene/prodrug system would be effective in an animal model of the disease. We employed E4- and E1A/B-depleted, herpes simplex virus-thymidine kinase-expressing adenoviral mutants that transcomplement each other within tumor cells, hereby improving transgene delivery and efficacy by viral replication in situ. Transcomplementation of vectors increased the fraction of transduced of tumor cells. This increase was accompanied by greater tumor volume reduction compared to non-transcomplementing approaches. Survival time improved with non-replicating vectors plus GCV compared to controls. However, transcomplementation/replication of vectors led to a further significant increment in anti-tumor activity and survival time (p < 0.02). In treated animals, we observed a high number of apoptotic nuclei both adjacent to and distant from injection sites and sites of viral oncolysis. Ultrastructural analyses exhibited nuclear inclusion bodies characteristic of virus production in situ, and provided further evidence that this therapy induced apoptotic cell death within tumor cells. We conclude that the efficacy of suicide gene therapy is significantly amplified by viral replication and, in combination with GCV, significantly reduces tumor burden and increases survival time.

Adenoviridae↗
PubMed2001

1,4- and 1,3-dipolar reactivity of alpha-alkoxycarbonylcycloimmonium N-aminides with dipolarophiles: synthesis of new imidazo[2,1-f][1,2,4]triazinium inner salts.

2-Alkoxycarbonylazolium N-aminides are interesting species, as they have the potential to act as efficient 1,4-dipole equivalents when they react with heterocumulenes, such as iso(thio)cyanates and carbodiimides. These reactions give heterobetaines containing the imidazo[2,1-f][1,2,4]triazinium system, in a formal [4 + 2] cyclocondensation process. These N-aminides, however, can also behave as 1,3-dipoles when they react with isocyanates to afford a cycloadduct that, depending on the position of alkoxycarbonyl group, can undergo a reversion process or a ring expansion to the more stable heterobetaine system.

Journal Article↗
PubMed2001

Potential use of the undersampling technique in the acquisition of nuclear magnetic resonance signals.

This communication reviews the use of undersampling techniques to acquire NMR signals. Undersampling transforms bandpass free induction decay (FID) signals, centered at high frequencies, into lowpass signals or bandpass signals centered at much lower frequencies. Consequently, the analog electronic stages that perform the demodulation can be eliminated, gaining in stability and reducing the phase distortion while maintaining an equivalent or better signal to noise ratio when an adequate sampling rate is chosen. The technique has been tested on a BRUKER BIOSPEC BMT 47/40, and the results show that undersampling could be used to process NMR and MRI signals, extending the range of applications of the 'digital radio' techniques to NMR and MRI apparatus.

Magnetic Resonance Imaging↗
PubMed1999

Probe efficiency improvement with remote and transmission line tuning and matching.

In certain nuclear magnetic resonance (NMR) applications in which accessibility to the gantry is limited, performing optimal tuning and matching represents a major problem. Here, we discuss a method of tuning NMR probe circuits and matching their impedances which uses cables with different impedance values. This simple but efficient method may be advantageous compared with much more difficult perfect tuning and matching.

Magnetic Resonance Spectroscopy↗
PubMed1998

MRI visualization of small structures using improved surface coils.

In this paper we present the spatial resolution enhancement and noise reduction level achieved with an optimized inductively coupled surface coil specifically designed for our experiments. The technique of designing and implementing customized coils for magnetic resonance imaging of very small structures is described. We have designed a low cost prototype of an inductively coupled circular surface coil, tuned for 1H magnetic resonance imaging at 200 MHz. The coil is mounted on a customized teflon support. The inductive coupling used in this coil improves the signal-to-noise ratio by reducing various loss mechanisms (specially the dielectric losses). Test images have been acquired to determine the evolution of induced articular lesions in a rabbit animal model, as well as brain tumors in rats. The images show high spatial resolution, excellent B1 field homogeneity and no "hot spots". Comparing these images with those acquired with conventional coils, one finds better spatial resolution and signal-to-noise ratio, as well as larger field of view with less intense illumination artifact. The methodology can be used in any application that requires high quality imaging of small structures.

Animals↗
PubMed1998

Performance characteristics of a compact position-sensitive LSO detector module.

We assembled a compact detector module comprised of an array of small, individual crystals of lutetium oxyorthosilicate:Ce (LSO) coupled directly to a miniature, metal-can, position-sensitive photomultiplier tube (PSPMT). We exposed this module to sources of 511-keV annihilation radiation and beams of 30- and 140-keV photons and measured spatial linearity; spatial variations in module gain, energy resolution, and event positioning; coincidence timing; the accuracy and sensitivity of identifying the crystal-of-first-interaction at 511 keV; and the effects of intercrystal scatter and LSO background radioactivity. The results suggest that this scintillator/phototube combination should be highly effective in the coincidence mode and can be used, with some limitations, to image relatively low-energy single photon emitters. Photons that are completely absorbed on their first interaction at 511 keV are positioned by the module at the center of a crystal. Intercrystal scatter events, even those that lead to total absorption of the incident photon, are placed by the module in a regular "connect-the-dot" pattern that joins crystal centers. As a result, the accuracy of event positioning can be made to exceed 90%, though at significantly reduced sensitivity, by retaining only events that occur within small regions-of-interest around each crystal center and rejecting events that occur outside these regions in the connect-the-dot pattern.

Animals↗
PubMed1997

Applying watershed algorithms to the segmentation of clustered nuclei.

Cluster division is a critical issue in fluorescence microscopy-based analytical cytology when preparation protocols do not provide appropriate separation of objects. Overlooking clustered nuclei and analyzing only isolated nuclei may dramatically increase analysis time or affect the statistical validation of the results. Automatic segmentation of clustered nuclei requires the implementation of specific image segmentation tools. Most algorithms are inspired by one of the two following strategies: 1) cluster division by the detection of internuclei gradients; or 2) division by definition of domains of influence (geometrical approach). Both strategies lead to completely different implementations, and usually algorithms based on a single view strategy fail to correctly segment most clustered nuclei, or perform well just for a specific type of sample. An algorithm based on morphological watersheds has been implemented and tested on the segmentation of microscopic nuclei clusters. This algorithm provides a tool that can be used for the implementation of both gradient- and domain-based algorithms, and, more importantly, for the implementation of mixed (gradient- and shape-based) algorithms. Using this algorithm, almost 90% of the test clusters were correctly segmented in peripheral blood and bone marrow preparations. The algorithm was valid for both types of samples, using the appropriate markers and transformations.

Algorithms↗
PubMed1997

Evaluation of autofocus functions in molecular cytogenetic analysis.

This work describes a systematic evaluation of several autofocus functions used for analytical fluorescent image cytometry studies of counterstained nuclei. Focusing is the first step in the automatic fluorescence in situ hybridization analysis of cells. Thirteen functions have been evaluated using qualitative and quantitative procedures. For the last of these procedures a figure-of-merit (FOM) is defined and proposed. This new FOM takes into account five important features of the focusing function. Our results show that functions based on correlation measures have the best performance for this type of image.

Algorithms↗
PubMed1996

Dynamic circular buffering: a technique for equilibrium gated blood pool imaging.

We have devised a software technique called "dynamic circular buffering" (DCB) with which we create a gated blood pool image sequence of the heart in real time using the best features of LIST and FRAME mode methods of acquisition/processing. The routine is based on the concept of independent "agents" acting on the timing and position data continuously written into the DCB. This approach allows efficient asynchronous operation on PC-type machines and enhanced capability on systems capable of true multiprocessing and multithreading.

Gated Blood-Pool Imaging↗