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Methods Protocol: Previous studies [1, 2] have involved imaging of only a single central slice of the brain. The present study used a similar paradigm,

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Presentation on theme: "Methods Protocol: Previous studies [1, 2] have involved imaging of only a single central slice of the brain. The present study used a similar paradigm,"— Presentation transcript:

1 Methods Protocol: Previous studies [1, 2] have involved imaging of only a single central slice of the brain. The present study used a similar paradigm, but in a multi-slice implementation. Images were obtained using a 1.5 T Philips MRI scanner, using a T2-weighted EPI sequence (3 mm slice thickness, 2 mm × 2 mm in-plane resolution, TR = 10 s, 40 axial slices). Subjects: A group of 7 healthy individuals aged 25–40 years attended on 2 separate occasions. Each visit, following an overnight fast, involved 30 minutes of continuous scanning. The first 5 minutes acted as a baseline. After 5 minutes, the subject began to drink either 150 ml of water or 75 gm of glucose within a 150 ml solution (average drinking time 90 s). Scanning continued for a further 25 minutes from the start of drinking. Subsequently, a separate 3D high-resolution T1-weighted image was obtained at the same orientation to provide additional structural information. Data Analysis: Single-subject analysis involved motion correction of the EPI image set, followed by either (a) registration to a standard template, after which the hypothalamus was located via known Talairach co-ordinates, or (b) location of the hypothalamus by direct observation of the unregistered EPI images, using anatomical markers in a midline sagittal slice [anterior commissure ac, mammillary body mm, optic chiasm oc – see example structural image (top right)]. Due to problems that were identified with registration, subsequent analysis was undertaken on the basis of areas determined via method (b) only: a line was drawn between mm and ac and a second line drawn perpendicular to the first, at its midpoint (see example image). Two regions of interest were then specified: region A in the upper anterior hypothalamus, an area intended to include the paraventricular nucleus; region B in the lower posterior hypothalamus. Each region was then further subdivided into nine overlapping sub-regions of size 20 voxels (Δx = 10 mm, Δy = 4 mm, Δz = 6 mm), and the time course of the fMRI signal was determined for each of these sub regions. For each subject, and for both the “glucose” and “water” data sets, the subregion within region A that showed the greatest rms deviation from baseline, and the subregion within region B that showed the greatest rms deviation from baseline, were selected for further analysis. Results The graph (bottom left) shows the mean signal change over all subjects for the selected sub-regions in region A, and the mean signal change over all subjects for the selected sub-regions in region B, with water and glucose cases shown separately. Data are displayed with 5-point smoothing, i.e., with a 50-second running average. There is a suggestion of higher signal levels for the glucose case than for the water case, but none of the trends reaches significance. Discussion Two earlier studies [1, 2] have produced conflicting results. The data from the present pilot study do not correspond to the findings of either previous study. Following analyses of the techniques used in the present investigation, and the results obtained, it is clear that there are a number of limiting factors. Signal loss due to susceptibility artefacts is apparent in brain regions close to the hypothalamus, and this appears to be associated with instability or drift of signals from the hypothalamus itself. An imaging protocol is required which minimises such artefacts. The use of SENSE (parallel acquisition) and multi-shot rather than single-shot EPI techniques has subsequently been investigated and found to offer significant improvement, even at an enhanced resolution of (1.6 mm) 3. Movement artefact associated with drinking, in particular, tipping the head to assist in swallowing, has been identified as an additional problem. Attempts to restrain this movement with padding fitted specifically to each subject have been partially successful. However, to completely remove any movement artefacts it may be necessary to introduce the appropriate solutions intravenously. Introduction The regulation of glucose levels in the body is of intrinsic interest, but also has implications for the management of patients with diabetes, for whom tight control of blood glucose is proven to reduce the risk of complications. Some studies using fMRI have implicated the hypothalamus as the centre responsible for regulation of plasma glucose concentration, energy intake and feeding behaviour. Data from Matsuda et al. [1] show a reduction in the fMRI signal at 4-10 min after glucose ingestion followed by a return of the signal to baseline. In contrast, the results of Smeets et al. [2] show a prolonged signal decrease (1–2.5%) in the hypothalamus area. The aim of the present study is to further investigate the measurement of fMRI signal within the hypothalamus following glucose ingestion, with a view to determining the time course of this signal. A Benattayallah1, D Flanagan2, B Krishnan2, C Ball1, J Fulford1, KM Macleod1, IR Summers1, AC Shore1 1Peninsula MR Research Centre, University of Exeter, Exeter, UK; 2Department of Diabetes and Endocrinology, Derriford Hospital, Plymouth, UK References: [1] Matsuda et al. Altered Hypothalamic Function in Response to Glucose Ingestion in Obese Humans. DIABETES, (1999) [2] Smeets et al. Functional MRI of human hypothalamic responses following glucose ingestion. NeuroImage, – 368 (2005). Funded by Diabetes UK and the Juvenile Diabetes Research Foundation. The authors thank Philips Medical Systems for scientific support. fMRI: A USEFUL TOOL FOR THE ASSESSMENT OF HYPOTHALAMUS FUNCTION


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