SummaryObesity is a major public health issue worldwide. Understanding how the brain controls appetite offers promising inroads toward new therapies for obesity. Peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) are coreleased postprandially and reduce appetite and inhibit food intake when administered to humans. However, the effects of GLP-1 and the ways in which PYY and GLP-1 act together to modulate brain activity in humans are unknown. Here, we have used functional MRI to determine these effects in healthy, normal-weight human subjects and compared them to those seen physiologically following a meal. We provide a demonstration that the combined administration of PYY3-36 and GLP-17-36 amide to fasted human subjects leads to similar reductions in subsequent energy intake and brain activity, as observed physiologically following feeding.

Parkinson’s disease (PD) is associated with increased iron levels in the substantia nigra (SNc). This study evaluated whether the iron chelator, deferiprone, is well tolerated, able to chelate iron from various brain regions and improve PD symptomology. In a randomised double-blind, placebo controlled trial, 22 early onset PD patients, were administered deferiprone, 10 or 15 mg/kg BID or placebo, for 6 months. Patients were evaluated for PD severity, cognitive function, depression rating and quality of life. Iron concentrations were assessed in the substantia nigra (SNc), dentate and caudate nucleus, red nucleus, putamen and globus pallidus by T2* MRI at baseline and after 3 and 6 months of treatment. Deferiprone therapy was well tolerated and was associated with a reduced dentate and caudate nucleus iron content compared to placebo. Reductions in iron content of the SNc occurred in only 3 patients, with no changes being detected in the putamen or globus pallidus. Although 30 mg/kg deferiprone treated patients showed a trend for improvement in motor-UPDRS scores and quality of life, this did not reach significance. Cognitive function and mood were not adversely affected by deferiprone therapy. Such data supports more extensive clinical trials into the potential benefits of iron chelation in PD.

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Geometric distortions and poor image resolution are well known shortcomings of single-shot echo-planar imaging (ss-EPI). Yet, due to the motion immunity of ss-EPI, it remains the most common sequence for diffusion-weighted imaging (DWI). Moreover, both navigated DW interleaved EPI (iEPI) and parallel imaging (PI) methods, such as sensitivity encoding (SENSE) and generalized autocalibrating parallel acquisitions (GRAPPA), can improve the image quality in EPI. In this work, DW-EPI accelerated by PI is proposed as a self-calibrated and unnavigated form of interleaved acquisition. The PI calibration is performed on the b ‫؍‬ 0 s/mm 2 data and applied to each shot in the rest of the DW data set, followed by magnitude averaging. Central in this study is the comparison of GRAPPA and SENSE in the presence of off-resonances and motion. The results show that GRAPPA is more robust than SENSE against both off-resonance and motion-related artifacts. The SNR efficiency was also investigated, and it is shown that the SNR/scan time ratio is equally high for one-to three-shot high-resolution diffusion scans due to the shortened EPI readout train length. The image quality improvements without SNR efficiency loss, together with motion tolerance, make the GRAPPAdriven DW-EPI sequence clinically attractive. Magn Reson Med 57:881-890, 2007.

BackgroundThe compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.MethodsIn a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level–dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.ResultsMarked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.ConclusionsThe MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.

In this study, a spin- and gradient-echo echo-planar imaging (SAGE EPI) MRI pulse sequence is presented that allows simultaneous measurements of gradient-echo and spin-echo dynamic susceptibility-contrast perfusion-weighted imaging (DSC-PWI) data. Following signal excitation, five EPI readout trains were acquired using SAGE EPI, all of them with echo times of less than 100 ms. Contrast agent concentrations in brain tissue were determined based on absolute R2* and R2 estimates rather than relative changes in the signals of individual echo trains, producing T1-independent DSC-PWI data. Moreover, this acquisition technique enabled vessel size imaging through the simultaneous quantification of R2* and R2, without an increase in acquisition time. In this work, the concepts of the SAGE EPI pulse sequence and results in stroke and tumor imaging are presented. Overall, SAGE EPI combined the advantages of higher sensitivity of gradient-echo DSC-PWI acquisitions to the contrast agent passage with the better selectivity of spin-echo DSC-PWI measurements to the microvasculature.

Readout segmentation (RS-EPI) has been suggested as a promising variant to echo-planar imaging (EPI) for high-resolution imaging, particularly when combined with parallel imaging. This work details some of the technical aspects of diffusionweighted (DW)-RS-EPI, outlining a set of reconstruction methods and imaging parameters that can both minimize the scan time and afford high-resolution diffusion imaging with reduced distortions. These methods include an efficient generalized autocalibrating partially parallel acquisition (GRAPPA) calibration for DW-RS-EPI data without scan time penalty, together with a variant for the phase correction of partial Fourier RS-EPI data. In addition, the role of pulsatile and rigid-body brain motion in DW-RS-EPI was assessed. Corrupt DW-RS-EPI data arising from pulsatile nonlinear brain motion had a prevalence of ϳ7% and were robustly identified via k-space entropy metrics. For DW-RS-EPI data corrupted by rigid-body motion, we showed that no blind overlap was required. Although multishot echo-planar imaging (EPI) reduces blurring and geometric distortions over single-shot EPI, a shortcoming of this method for diffusion imaging is that even minuscule physiologic motion can cause nonlinear phase errors that usually result in profound ghosting artifacts. Although navigator-based nonlinear phase correction ameliorates the ghosting problem, residual nonequidistant sampling with regionally undersampled k-space still exists and requires excessive oversampling or averaging (1). While parallel imaging can also be used to accelerate k-space traversal and reduce distortions in EPI (2,3), the net acceleration for EPI is currently limited to realistic values of 3 and 4, producing images that still suffer from distortion artifacts, especially at high field strengths or higher spatial resolution.Instead of interleaving EPI trajectories along the phaseencoding dimension (k PE ) to increase k-space velocity, another variant of multishot EPI for diffusion-weighted (DW) imaging is readout-segmented EPI (RS-EPI) (4-11). In RS-EPI, adjacent 'blinds' are acquired (each accompanied with a navigator) to produce the combined k-space data that support the desired resolution along the readout dimension (k RO ). RS-EPI increases the k-space velocity compared with EPI by shortening the trajectory along k RO , thus diminishing distortions. Further distortion reduction can be achieved in RS-EPI via parallel imaging methods (7,9,10). Here, the net gain in acceleration of k-space traversal compared with standard single-shot EPI is governed by the blind width, the GRAPPA-acceleration factor, and slew rate constraints (shown in Table 1). Ignoring slew rate limitations, an RS-EPI scan theoretically offers an N/#blinds-fold distortion reduction over a conventional single-shot EPI scan.Due to its greater data consistency within the blind, in practice, DW-RS-EPI is much more manageable for motion and phase correction than interleaved DW-EPI (9). However, despite the consistency of each blind, a potential problem can ari...

PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used 18 F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. Methods: 18 F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. Results: 18 F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P , 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher 18 F-PBR111 binding in MS lesions (P , 0.05) and in perilesional (P , 0.05) and nonlesional white matter with reduced MTR (P , 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean 18 F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ 5 0.62, P , 0.05). Conclusion: This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune response in MS for differentiation of antiinflammatory effects of new medicines and their longer term impact on clinical outcome.