Robust estimation of quantitative perfusion from multi-phase pseudo-continuous arterial spin labeling.

PURPOSE: Multi-phase PCASL has been proposed as a means to achieve accurate perfusion quantification that is robust to imperfect shim in the labeling plane. However, there exists a bias in the estimation process that is a function of noise in the data. In this work, this bias is characterized and then addressed in animal and human data. METHODS: The proposed algorithm to overcome bias uses the initial biased voxel-wise estimate of phase tracking error to cluster regions with different off-resonance phase shifts, from which a high-SNR estimate of regional phase offset is derived. Simulations were used to predict the bias expected at typical SNR. Multi-phase PCASL in 3 rat strains (n = 21) at 9.4 T was considered, along with 20 human subjects previously imaged using ASL at 3 T. The algorithm was extended to include estimation of arterial blood flow velocity. RESULTS: Based on simulations, a perfusion estimation bias of 6-8% was expected using 8-phase data at typical SNR. This bias was eliminated when a high-precision estimate of phase error was available. In the preclinical data, the bias-corrected measure of perfusion (107 ± 14 mL/100g/min) was lower than the standard analysis (116 ± 14 mL/100g/min), corresponding to a mean observed bias across strains of 8.0%. In the human data, bias correction resulted in a 15% decrease in the estimate of perfusion. CONCLUSIONS: Using a retrospective algorithmic approach, it was possible to exploit common information found in multiple voxels within a whole region of the brain, offering superior SNR and thus overcoming the bias in perfusion quantification from multi-phase PCASL.

High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study.

AIMS/HYPOTHESIS: High-dose supplements of thiamine prevent the development of microalbuminuria in experimental diabetes. The aim of this pilot study was to assess whether oral supplements of thiamine could reverse microalbuminuria in patients with type 2 diabetes. METHODS: Type 2 diabetic patients (21 male, 19 female) with microalbuminuria were recruited at the Diabetes Clinic, Sheikh Zayed Hospital, Lahore, Pakistan, and randomised to placebo and treatment arms. Randomisation was by central office in sequentially numbered opaque, sealed envelopes. Participants, caregivers and those assessing the outcomes were blinded to group assignment. Patients were given 3 x 100 mg capsules of thiamine or placebo per day for 3 months with a 2 month follow-up washout period. The primary endpoint was change in urinary albumin excretion (UAE). Other markers of renal and vascular dysfunction and plasma concentrations of thiamine were determined. RESULTS: UAE was decreased in patients receiving thiamine therapy for 3 months with respect to baseline (median -17.7 mg/24 h; p < 0.001, n = 20). There was no significant decrease in UAE in patients receiving placebo after 3 months of therapy (n = 20). UAE was significantly lower in patients who had received thiamine therapy compared with those who had received placebo (30.1 vs 35.5 mg/24 h, p < 0.01) but not at baseline. UAE continued to decrease in the 2 month washout period in both groups, but not significantly. There was no effect of thiamine treatment on glycaemic control, dyslipidaemia or BP. There were no adverse effects of therapy. CONCLUSIONS/INTERPRETATION: In this pilot study, high-dose thiamine therapy produced a regression of UAE in type 2 diabetic patients with microalbuminuria. Thiamine supplements at high dose may provide improved therapy for early-stage diabetic nephropathy. TRIAL REGISTRATION: CTRI (India) CTRI/2008/091/000112. FUNDING: Pakistan Higher Education Commission.

Sex reversal in Betta splendens Regan with emphasis on the problem of sex determination.

To gain insight into the sex-determining mechanism of the Siamese fighting fish, Betta splendens, sex-reversed individuals were bred and the ratios of the spawnings were examined. Sex-reversal of 245 females was undertaken by ovariectomizing them; of these, 104 became sex-reversed. Twenty-three of these latter fish were mated to normal females and eleven spawnings were raised to maturity. These spawnings resulted in all female broods or mixed broods. Were the male fish heterogametic, a view currently held by some authors, no males would be produced in these spawnings. Thus, male heterogamety was not substaintiated in this study. Contrary to other studies, the experimental sex reversal of females is not a rare event since nearly two-thirds of the fish that survived the surgery became sex-reversed. Gross dissection and histological observation of sex-reversed fish revealed a regenerated, unpaired duct which remained after the ovaries had been removed. The tissue of the regenerate was testicular and contained active spermatogenesis. Some alterative methods of sex determination which may apply to the Betta are examined. These include the possibility of two different sex-determining races, the effects of exogenous factors, and a polygenic system of sex determination.