Biomedical subjects

Patrick Dupont

Publications and source records attributed to Patrick Dupont.

23 records · Page 2Linked to original sources

PubMed2003

Synthesis of 18F-fluoroalkyl-beta-D-glucosides and their evaluation as tracers for sodium-dependent glucose transporters.

UNLABELLED: Three omega-(18)F-fluoro-n-alkyl-beta-D-glucosides (alkyl = ethyl (5a)), n-butyl (5b), and n-octyl (5c)) were synthesized and evaluated as potential substrates for the sodium/D-glucose cotransporter SGLT1. METHODS: The ligands were prepared by (18)F-fluoride displacement of the corresponding tetraacetyl-protected tosylate alkylglucoside precursors in CH(3)CN, followed by hydrolysis of the protective acetate esters with NaOMe/MeOH. Transport of the nonradioactive analogs 5a, 5b, and 5c by the human sodium-D-glucose cotransporter hSGLT1 was characterized in vitro in oocytes of Xenopus laevis that expressed hSGLT1. The biodistribution of the tracers was determined in mice and the presence of metabolites in the blood was investigated. Compound 5a was also evaluated in mice pretreated with phlorizin. The intrarenal distribution of 5a in mice kidney was visualized using autoradiography. RESULTS: The radiochemical yield of 5a, 5b, and 5c was in the range of 8%-15% (end of bombardment) with a total synthesis time of 90 min. The in vitro evaluation after expression of the hSGLT1 showed that 2'-fluoroethyl-beta-D-glucoside (5a) was transported with similar Michaelis-Menten K(m) and V(max) (maximum velocity) values as compared with methyl-alpha-D-glucopyranoside (alpha MDG). The more lipophilic compounds 5b and 5c were not transported but inhibited transport of alpha MDG. In vivo tissue distribution in mice revealed that 5a, 5b, and 5c were cleared mainly by the renal pathway and that 5a showed a significantly higher accumulation in the kidneys and a slower renal excretion as compared with 5b and 5c. Compound 5a was retained mainly in the renal outer medulla containing S3 segments of proximal tubules and the accumulation could be blocked by phlorizin pretreatment. Compound 5c passed the blood-brain barrier to some extent. CONCLUSION: The data indicate that 2'-(18)F-fluoroethyl-beta-D-glucoside (5a) is a specific tracer of Na(+)-dependent glucose transport that may be used to visualize this transport activity in the S3 segments of renal proximal tubules.

Animals↗

PubMed2002

The quantitative nature of a visual task differentiates between ventral and dorsal stream.

The aim of the present positron emission tomography (PET) study was to investigate how visual processing in dorsal and ventral streams depends on the quantitative nature of the task. In the same-different task, participants identified the presence of an orientation difference between two gratings, presented centrally in succession. In the quantification task, participants estimated the magnitude of the difference and compared it to a fixed standard. Detection of dimming of the fixation point was used as a control task. Visual input, motor responses, and performance were equated across tasks. Subtracting same-different from quantification yielded significant activation in the left superior parietal lobule and left ventral premotor cortex, consistent with results obtained in number-processing tasks. The reverse subtraction yielded activation in the right inferior temporal gyrus, in agreement with earlier results. These results demonstrate that a single attribute can be processed either in the ventral or dorsal stream, depending on the cognitive operations required by the tasks.

Adult↗

PubMed2002

Human brain regions involved in visual categorization.

Categorization of dot patterns is a frequently used paradigm in the behavioral study of natural categorization. To determine the human brain regions involved in categorization, we used Positron Emission Tomography to compare regional Cerebral Blood Flow patterns in two tasks employing patterns that consisted of nine dots. In the categorization task, subjects categorized novel exemplars of two categories, generated by distorting two prototypes, and other random dot patterns. In the control task, subjects judged the position of similarly distorted patterns. Each task was presented at two matched levels of difficulty. Fixation of the fixation target served as baseline condition. The categorization task differentially activated the orbitofrontal cortex and two dorsolateral prefrontal regions. These three prefrontal regions were equally weakly active in the position discrimination task and the baseline condition. The intraparietal sulcus was activated in both tasks, albeit significantly less in the position discrimination than in the categorization task. A similar activation pattern was present in the neostriatum. Task difficulty had no effect. These functional imaging results show that the dot-pattern categorization task strongly engages prefrontal and parietal cortical areas. The activation of prefrontal cortex during visual categorization in humans agrees with the recent finding of category-related responses in macaque prefrontal neurons.

Adult↗

PubMed2002

Reducing loss of image quality because of the attenuation artifact in uncorrected PET whole-body images.

UNLABELLED: In whole-body PET, it is not unusual to shorten the study time by omitting the transmission scan and to ignore attenuation during reconstruction. If a transmission scan is available, many centers reconstruct the images with, but also without, attenuation correction. Although ignoring attenuation leads to an artifact in the reconstructed images, these images still provide valuable diagnostic information in oncologic applications. Several authors have reported that the attenuation artifact may actually increase the tumor-to-background ratio. In this study, we analyzed the causes of the artifact and proposed a new algorithm to reduce the adverse effects on visual image quality. METHODS: We analyzed the causes of the attenuation artifact mathematically and numerically, and we examined its effect on tumor-to-background ratio and on signal-to-noise ratio. In addition, we showed that the attenuation artifact may lead to loss of image detail in conventional maximum-likelihood expectation maximization (MLEM) reconstruction. A new maximum-likelihood algorithm allowing negative reconstruction values (NEG-ML) was derived to reduce this loss. RESULTS: The attenuation artifact consists of 2 components. The first component is the well-known scaling effect: The apparent activity is reduced because attenuation decreases the fraction of detected photons. The second component is a relatively smooth negative contribution that is added to attenuated regions surrounded by activity. The second component tends to increase the tumor-to-background ratio. However, a simulation experiment shows that this increase in signal may be entirely offset by an increase in noise. The negative contribution can interfere with the nonnegativity constraint of the MLEM algorithm, leading to loss of image detail in regions of high attenuation. The new NEG-ML algorithm avoids the problem by allowing negative pixel values. The algorithm is similar to MLEM in the suppression of the streak artifact but provides more anatomic information. In our department, it is in routine clinical use for reconstruction of PET whole-body images without attenuation correction. CONCLUSION: Ignoring attenuation may increase the tumor-to-background ratio, but this increase does not imply improved tumor detection. The NEG-ML algorithm reduces the adverse effect of the attenuation artifact on visual image quality.

Algorithms↗

PubMedDate not supplied

Image-derived input function for [11C]flumazenil kinetic analysis in human brain.

PURPOSE: We describe a method for analysis of [11C]flumazenil data using an input curve directly derived from the positron emission tomography (PET) images. PROCEDURE: The shape of the tracer plasma curve was obtained from the product of the intact flumazenil fraction in plasma in six arterial samples and the internal carotid artery time-activity curve (TAC). The resulting curve was calibrated using the [11C]flumazenil concentration in three of the six samples. The curve peak was recovered by adding an exponential function to the scaled curve whose parameters were estimated from simultaneous fittings of several tissue TACs assuming that all regions share the same input. RESULTS: Good agreement was found between the image-derived and the experimental plasma curves in six subjects. Distribution volumes were highly correlated with linear regression slope and intercept values between [0.94, 1.03] and [-0.10, 0.16], respectively. CONCLUSION: The proposed method is suitable for benzodiazepine receptor quantification requiring only a few blood samples.

Brain↗