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Magnetic Resonance Imaging (MRI) motion artefacts frequently complicate structural and diffusion MRI analyses. While diffusion imaging is easily 'scrubbed' of motion affected volumes, the same is not true for T1w or T2w 'structural' images. Structural images are critical to most diffusion-imaging pipelines thus their corruption can lead to disproportionate data loss. To enable diffusion-image processing when structural images are missing or have been corrupted, we propose a means by which synthetic structural images can be generated from diffusion MRI. This technique combines multi-tissue constrained spherical deconvolution, which is central to many existing diffusion analyses, with the Bloch equations that allow simulation of MRI intensities for given scanner parameters and magnetic resonance (MR) tissue properties. We applied this technique to 32 scans, including those acquired on different scanners, with different protocols and with pathology present. The resulting synthetic T1w and T2w images were visually convincing and exhibited similar tissue contrast to acquired structural images. These were also of sufficient quality to drive a Freesurfer-based tractographic analysis. In this analysis, probabilistic tractography connecting the thalamus to the primary sensorimotor cortex was delineated with Freesurfer, using either real or synthetic structural images. Tractography for real and synthetic conditions was largely identical in terms of both voxels encountered (Dice 0.88-0.95) and mean fractional anisotropy (intrasubject absolute difference 0.00-0.02). We provide executables for the proposed technique in the hope that these may aid the community in analysing datasets where structural image corruption is common, such as studies of children or cognitively impaired persons.

SRT2104 has been developed as a selective small molecule activator of SIRT1, a NAD(+)-dependent deacetylase involved in the regulation of energy homeostasis and the modulation of various metabolic pathways, including glucose metabolism, oxidative stress and lipid metabolism. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. We report the first clinical trial of SRT2104 in elderly volunteers.Oral doses of 0.5 or 2.0 g SRT2104 or matching placebo were administered once daily for 28 days. Pharmacokinetic samples were collected through 24 hours post-dose on days 1 and 28. Multiple pharmacodynamic endpoints were explored with oral glucose tolerance tests (OGTT), serum lipid profiles, magnetic resonance imaging (MRI) for assessment of whole body visceral and subcutaneous fat, maximal aerobic capacity test and muscle 31P magnetic resonance spectroscopy (MRS) for estimation of mitochondrial oxidative capacity.SRT2104 was generally safe and well tolerated. Pharmacokinetic exposure increased less than dose-proportionally. Mean Tmax was 2-4 hours with elimination half-life of 15-20 hours. Serum cholesterol, LDL levels and triglycerides decreased with treatment. No significant changes in OGTT responses were observed. 31P MRS showed trends for more rapid calculated adenosine diphosphate (ADP) and phosphocreatine (PCr) recoveries after exercise, consistent with increased mitochondrial oxidative phosphorylation.SRT2104 can be safely administered in elderly individuals and has biological effects in humans that are consistent with SIRT1 activation. The results of this study support further development of SRT2104 and may be useful in dose selection for future clinical trials in patients.ClinicalTrials.gov NCT00964340.