Dominique Vanderghinste

Abnormal Regional Brain Activity During Rest and (Anticipated) Gastric Distension in Functional Dyspepsia and the Role of Anxiety: A H 2 15 O-PET Study

OBJECTIVES:During gastric distension in hypersensitive functional dyspepsia (FD), activation was found in somatosensory cortex (SI/SII) and ventrolateral prefrontal cortex (vlPFC) but, contrary to controls, not in pregenual anterior cingulate (pACC). The aims of this article were to study (i) cortical activations and deactivations during distension and sham compared with baseline in FD, regardless of sensitivity status; (ii) differences in brain activity between health and FD during “no distension” conditions; and (iii) the relationship between anxiety and brain activity in FD.METHODS:Brain H215O-PET was performed in 25 FD patients (13 hypersensitive) during three conditions: baseline, distension at discomfort threshold, and sham. Brain activity was compared against healthy controls using SPM2.RESULTS:Discomfort threshold was lower; sensation scores in all conditions were higher in patients than controls. (i) Activations were similar to controls, except for a lack of pACC activation during distension in FD. Patients showed no dorsal pons and amygdala deactivation during distension and sham, respectively. (ii) Comparing baseline or sham activity showed the following differences: higher activity in SII/SI, insula, midcingulate (MCC), dorsolateral and ventrolateral PFC in controls; and higher activity in occipital cortex in FD. Differences in left lateral PFC were specific to sham. (iii) Anxiety correlated negatively with pACC and MCC and positively with dorsal pons activity.CONCLUSIONS:FD patients failed to activate pACC, to deactivate dorsal pons during distension, and to deactivate amygdala during sham; this may represent arousal–anxiety-driven failure of pain modulation. During baseline and sham, differences between patients and controls were found in sensory as well as affective–cognitive areas.

Regional Brain Activity in Functional Dyspepsia: A H215O-PET Study on the Role of Gastric Sensitivity and Abuse History

BACKGROUND & AIMS Differences in brain activity between health and functional dyspepsia (FD) have been reported; it is unclear whether this is influenced by gastric hypersensitivity or abuse history. Therefore, we aimed to determine the influence of gastric sensitivity and abuse history on gastric sensation scores and brain activity in homeostatic-afferent, emotional-arousal, and cortical-modulatory brain regions in FD. METHODS Abuse history was assessed using a validated self-report questionnaire. H(2)(15)O positron emission tomography was performed in 25 FD patients (13 hypersensitive and 8 abused) during 3 conditions, that is, no distension, gastric distension at discomfort threshold, and sham distension. Data were analyzed in SPM2. Region of interest analysis was used to confirm differences in prehypothesized regions. RESULTS No association between hypersensitivity and abuse history was found. Gastric hypersensitivity was associated with significantly higher gastric sensation scores during baseline and sham. A condition-independent difference in ventral posterior cingulate activity was found between groups, as well as distension and sham-specific differences in brainstem and cingulate areas. Abuse history was associated with higher gastric sensation scores in all conditions and with differences in insular, prefrontal, and hippocampus/amygdala activity. CONCLUSIONS Gastric sensitivity and abuse history independently influence gastric sensation as well as brain activity in FD.

Optimized multipinhole design for mouse imaging

To enhance high-sensitivity focused mouse imaging using multipinhole SPECT on a dual head camera, a fast analytical method was used to predict the contrast-to-noise ratio (CNR) in many points of a homogeneous cylinder for a large number of pinhole collimator designs with modest overlap. The design providing the best overall CNR, a configuration with 7 pinholes, was selected. Next, the pinhole pattern was made slightly irregular to reduce multiplexing artifacts. Two identical, but mirrored 7-pinhole plates were manufactured. In addition, the calibration procedure was refined to cope with small deviations of the camera from circular motion. First, the new plates were tested by reconstructing a simulated homogeneous cylinder measurement. Second, a Jaszczak phantom filled with 37 MBq 99mTc was imaged on a dual head gamma camera, equipped with the new pinhole collimators. The image quality before and after refined calibration was compared for both heads, reconstructed separately and together. Next, 20 short scans of the same phantom were performed with single and multipinhole collimation to investigate the noise improvement of the new design. Finally, two normal mice were scanned using the new multipinhole designs to illustrate the reachable image quality of abdomen and thyroid imaging. The simulation study indicated that the irregular patterns suppress most multiplexing artifacts. Using body support information strongly reduces the remaining multiplexing artifacts. Refined calibration improved the spatial resolution. Depending on the location in the phantom, the CNR increased with a factor of 1 to 2.5 using the new instead of a single pinhole design. The first proof of principle scans and reconstructions were successful, allowing the release of the new plates and software for preclinical studies in mice.

Micellar electrokinetic capillary chromatography for the separation of cefalexin and its related substances

Micellar electrokinetic capillary chromatography (MEKC) was examined for analysis of cefalexin and its related substances. Good selectivity was obtained with two different buffer solutions: a sodium acetate buffer (50 mM, pH 5.25) containing sodium dodecyl sulfate (50 mM SDS) or sodium phosphate buffer (40 mM, pH 7.0) containing 100 mM SDS. Both methods permit cefalexin to be completely separated from its ten related substances within 20 min. The robustness of the method, using pH 5.25 acetate buffer, was examined by means of a full‐fraction factorial design to test the influence of buffer pH, concentration of SDS and buffer concentration. The parameters for validation such as linearity, precision, limit of detection and limit of quantitation are also reported. The results show that method 1 is suitable for the analysis of cefalexin.

Different regional brain activity during physiological gastric distension compared to balloon distension: a H215O‐PET study

Background  Stepwise gastric balloon distension progressively activates a ‘visceral pain neuromatrix’, ultimately inducing discomfort and pain. On the other hand, normal meal ingestion requires gastric volume expansion without induction of pain. The aim was to test the hypothesis that physiological gastric distension (liquid meal infusion) until maximal satiation elicits brain responses similar to balloon distension at discomfort threshold.

S-Trityl protection of bis-amino bis-thiol (BAT) chelator enables flexible derivatisation and facile labelling with technetium-99m

Abstract We have coupled S , S ′-bis-trityl N -BOC protected 1,2-ethylenedicysteamine, a bis-amino bis-thiol (BAT) tetraligand, via a propylene or ethylene spacer to several biologically active molecules including 2-nitroimidazole, desethylflumazenil, a beta-CIT analogue, glucose and 2-(2′-hydroxy-4′-aminophenyl)-1,3-benzothiazole. The conjugates were efficiently labelled with technetium-99m by consecutive heating of the S , S ′-bis-trityl protected ligand in hydrochloric acid followed by neutralisation and heating in the presence of 99m Tc-tartrate. The S , S ′-bis-trityl BAT chelator is an interesting synthon that allows both flexible derivatisation with various biologically active molecules and facile labelling with technetium-99m.