Biomedical subjects

Henri Tochon-Danguy

Publications and source records attributed to Henri Tochon-Danguy.

7 recordsLinked to original sources

PubMed2006

A GABAA receptor mutation causing generalized epilepsy reduces benzodiazepine receptor binding.

Understanding the consequences of newly discovered single gene mutations causing human epilepsy has the potential to yield new insights into the underlying mechanisms of this disorder. A mutation of the gamma2 subunit of the GABA(A) receptor, which substitutes glutamine for arginine at position 43 (R43Q) has been found in a familial generalized epilepsy. We tested the hypothesis that individuals affected by the GABRG2(R43Q) mutation have reduced binding to the GABA(A) receptor complex using positron emission tomography (PET) and the benzodiazepine receptor ligand [(11)C]-flumazenil. Fourteen subjects with the GABRG2(R43Q) mutation and 20 controls were studied. Benzodiazepine receptor binding was reduced in subjects with the mutation (mean whole brain binding potential for [(11)C]-flumazenil: GABA(A) mutation 0.66+/-0.1; controls 0.89+/-0.1; P<0.003). The greatest change in benzodiazepine binding occurred anteriorly, with peak differences in insular and anterior cingulate cortices revealed by statistical parametric mapping. Our findings provide in vivo evidence of reduced benzodiazepine receptor binding in subjects with the mutation. As synaptic inhibition in the human brain is largely mediated by the GABA(A) receptor, these findings are likely to represent an important clue to the mechanisms linking this gene defect and the epilepsy phenotype.

Adult↗

PubMed2005

Increased serotonin receptor availability in human sleep: evidence from an [18F]MPPF PET study in narcolepsy.

Data from animal studies suggest that serotonin release promotes wakefulness and suppresses REM sleep, but there are dangers in extrapolating these findings to humans. Binding of the radioligand [18F]MPPF to 5HT1A receptors is sensitive to levels of endogenous serotonin. In this study, we aimed to demonstrate changes in serotonin receptor availability in the human brain in wakefulness and sleep using [18F]MPPF and positron emission tomography. 14 subjects with narcolepsy cataplexy underwent [18F]MPPF PET scans in wakefulness and in sleep. Subjects who used the stimulant methylphenidate took their normal medication for the wake scan but omitted it prior to the sleep scan. The change in binding potential (BP) between the sleep and wake scans was examined using paired t test. Methylphenidate is thought to have little or no effect on serotonergic neurotransmission, and in order to confirm the absence of an effect on [18F]MPPF binding, a concurrent study was performed using a beta-microprobe technique to examine the effect of methylphenidate administration on [18F]MPPF binding in Sprague-Dawley rats. The human study showed a significant increase in [18F]MPPF binding in sleep compared to wakefulness in the whole brain and all regions of interest examined (temporal cortex, mesial temporal region and cingulate cortex). The beta-microprobe study confirmed that methylphenidate administration had no effect on [18F]MPPF binding. These findings indicate that serotonin receptor availability is increased in sleep compared to wakefulness in narcoleptic humans.

Adult↗

PubMed2005

Simplified quantification of nicotinic receptors with 2[18F]F-A-85380 PET.

INTRODUCTION: Neuronal nicotinic acetylcholine receptors (nAChRs), widely distributed in the human brain, are implicated in various neurophysiological processes as well as being particularly affected in neurodegenerative conditions such as Alzheimer's disease. We sought to evaluate a minimally invasive method for quantification of nAChR distribution in the normal human brain, suitable for routine clinical application, using 2[(18)F]F-A-85380 and positron emission tomography (PET). METHODS: Ten normal volunteers (four females and six males, aged 63.40+/-9.22 years) underwent a dynamic 120-min PET scan after injection of 226 MBq 2[(18)F]F-A-85380 along with arterial blood sampling. Regional binding was assessed through standardized uptake value (SUV) and distribution volumes (DV) obtained using both compartmental (DV(2CM)) and graphical analysis (DV(Logan)). A simplified approach to the estimation of DV (DV(simplified)), defined as the region-to-plasma ratio at apparent steady state (90-120 min post injection), was compared with the other quantification approaches. RESULTS: DV(Logan) values were higher than DV(2CM). A strong correlation was observed between DV(simplified), DV(Logan) (r=.94) and DV(2CM) (r=.90) in cortical regions, with lower correlations in thalamus (r=.71 and .82, respectively). Standardized uptake value showed low correlation against DV(Logan) and DV(2CM). CONCLUSION: DV(simplified) determined by the ratio of tissue to metabolite-corrected plasma using a single 90- to 120-min PET acquisition appears acceptable for quantification of cortical nAChR binding with 2[(18)F]F-A-85380 and suitable for clinical application.

Azetidines↗

PubMed2004

The resistance to ischemia of white and gray matter after stroke.

A contributing factor to the failure of trials of neuroprotectants in acute ischemic stroke may be the differing vulnerability to ischemia of white compared with gray matter. To address this issue, we determined to establish the existence of potentially viable tissue in white matter and its evolution to infarction or salvage in both gray and white matter compartments in patients with ischemic stroke. Twenty-seven patients (mean age, 73.4 years) at a median of 16.5 hours after symptom onset were studied using the hypoxic marker 18F-misonidazole with positron emission tomography (PET). Tissue was segmented using an magnetic resonance probabilistic map. Although there was a greater volume of initially "at-risk tissue" in gray matter (58.3 cm3, 29.9-93.0 cm3 than white matter (42.0 cm3, 15.8-74.0 cm3; p <0.001) at the time of PET imaging, a higher proportion of this was still potentially viable in white matter (41.4%, 4.6-74.5%) than in gray matter (23.6%, 3.2-61.1%; p <0.05). However, a similar proportion in each compartment spontaneously survived. These data provide evidence for the existence of potentially salvageable tissue in human white matter and is consistent with it having a similar or even greater resistance to ischemia than gray matter. For the latter possibility, alternative therapeutic strategies may be required for its salvage.

Adult↗

PubMed2003

A novel method for determining hepatic sinusoidal oxygen permeability in the isolated perfused rat liver using [15O]O2.

Measurement of hepatic sinusoidal permeability of oxygen and other substrates may help elucidate the mechanisms responsible for impaired liver function in cirrhosis. However studies of sinusoidal oxygen permeability in normal liver and various disease states have been limited due to the considerable technical difficulties involved in the use of standard techniques. We have developed a new method for measuring sinusoidal oxygen permeability in the isolated perfused rat liver that overcomes the difficulties of previous methods by using [(15)O]O(2) and an in-line fluid monitor. This method uses data obtained from impulse response curves of radiolabelled red cells, albumin and oxygen that are fitted mathematically using the axial dispersion model to yield rate constants that describe oxygen transit through the liver. We have demonstrated the utility and reproducibility of this method by comparing multiple injections and permeability determinations in the same preparation. This approach could be used in isolated perfused organs to study oxygen permeability in a range of disease states.

Animals↗

PubMed2002

Evaluation of 18 F-fluorodeoxyglucose positron emission tomography and computed tomography with histopathologic correlation in the initial staging of head and neck cancer.

OBJECTIVE: To prospectively evaluate the use of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in the initial staging of squamous cell head and neck carcinoma. SUMMARY BACKGROUND DATA: The status of cervical lymph nodes is an important prognostic factor and determinant of management approach in squamous cell head and neck cancer. METHODS: FDG-PET findings were compared with those of computed tomography (CT) before removal of the primary tumor and/or neck dissection. Histopathologic analysis was used as the gold standard for assessment of the sensitivity and specificity of these modalities. RESULTS: FDG-PET correctly identified the primary tumor in 35 of 40 patients in whom the site of the primary was known clinically and still present (sensitivity 88%). None of four unknown primaries were detected. Tumors not detected by FDG-PET were generally superficial, with depths of less than 4 mm. CT correctly identified 18 of the 35 primary tumors (sensitivity 51%). Eleven of 17 CT false-negative tumors were detected by FDG-PET. The sensitivity and specificity for the presence of metastatic neck disease on FDG-PET were 82% and 100%, respectively; those for CT were 81% and 81%, respectively. FDG-PET was true positive for metastatic neck disease in two of the three CT false-negative patients. CONCLUSIONS: FDG-PET shows promise in the initial staging of head and neck cancer and provides additional accuracy to a conventional staging process using CT.

Adult↗

PubMed1999

Clinical Applications of [(15)O] H(2)O PET Activation Studies.

Localization of eloquent cortical regions is an important aspect of neurosurgical practice. When lesions lie close to or within areas such as somatosensory, motor or language cortex, the goal of surgical treatment is maximal resection without causing neurological deficit. Hence precise functional mapping combined with accurate delineation of the extent of pathology is important for deciding whether surgery is feasible at all and defining the safe limit of resection and the optimal operative approach. In addition, when the electroclinical pattern of intractable seizures suggests a specific localization in sensorimotor cortex (e.g., seizures originating in the face area), functional mapping may be of use in directing the surgical treatment at the seizure focus. Activation studies using positron emission tomography (PET) and the tracer [(15)O] labeled water ([(15)O]H(2)O) can be used in presurgical planning and in intraoperative surgical guidance in individual patients. The use of PET technology for these purposes is critically dependent on advances in registration or alignment of images acquired using different modalities; the development of neurosurgical guidance devices; and the development of methods of statistical analysis suitable for use in single subjects.

Journal Article↗