Bioluminescence imaging of point sources implanted in small animals post mortem: evaluation of a method for estimating source strength and depth.

The performance of a simple approach for the in vivo reconstruction of bioluminescent point sources in small animals was evaluated. The method uses the diffusion approximation as a forward model of light propagation from a point source in a homogeneous tissue to find the source depth and power. The optical properties of the tissue are estimated from reflectance images obtained at the same location on the animal. It was possible to localize point sources implanted in mice, 2-8 mm deep, to within 1 mm. The same performance was achieved for sources implanted in rat abdomens when the effects of tissue surface curvature were eliminated. The source power was reconstructed within a factor of 2 of the true power for the given range of depths, even though the apparent brightness of the source varied by several orders of magnitude. The study also showed that reconstructions using optical properties measured in situ were superior to those based on data in the literature.

Quantification of bioluminescence images of point source objects using diffusion theory models.

A simple approach for estimating the location and power of a bioluminescent point source inside tissue is reported. The strategy consists of using a diffuse reflectance image at the emission wavelength to determine the optical properties of the tissue. Following this, bioluminescence images are modelled using a single point source and the optical properties from the reflectance image, and the depth and power are iteratively adjusted to find the best agreement with the experimental image. The forward models for light propagation are based on the diffusion approximation, with appropriate boundary conditions. The method was tested using Monte Carlo simulations, Intralipid tissue-simulating phantoms and ex vivo chicken muscle. Monte Carlo data showed that depth could be recovered within 6% for depth 4-12 mm, and the corresponding relative source power within 12%. In Intralipid, the depth could be estimated within 8% for depth 4-12 mm, and the relative source power, within 20%. For ex vivo tissue samples, source depths of 4.5 and 10 mm and their relative powers were correctly identified.

In vivo measurement of bone aluminium: recent developments.

A biomarker of aluminium accumulation in the human body can play a valuable role in determining health effects of chronic aluminium exposure, complementing other human and environmental monitoring data. In vivo neutron activation provides such a non-invasive biomarker. To date, the best in vivo neutron activation system used thermalised neutrons from a nuclear reactor at Brookhaven National Laboratory, which suffered only slightly from interference from other elements, primarily phosphorus, and from the disadvantage of restricted accessibility. At McMaster, we use a nuclear reaction on an accelerator to select neutron energy, which eliminates the interferences. Spectral decomposition analysis improved sensitivity. A new 4pi detection system also enhanced sensitivity. Together these improvements yield a minimum detection limit of 0.24 mgAl in a hand, slightly better than at Brookhaven and equivalent to "normal" levels. Further improvements should result from a new irradiation cavity and from using a higher proton current on the accelerator to shorten irradiation times. The system is now ready for pilot human studies.

Application of spectral decomposition analysis to in vivo quantification of aluminum by neutron activation analysis.

The toxic effects of aluminum are cumulative and result in painful forms of renal osteodystrophy, most notably adynamic bone disease and osteomalacia, but also other forms of disease. The Trace Element Group at McMaster University has developed an accelerator-based in vivo procedure for detecting aluminum body burden by neutron activation analysis (NAA). Further refining of the method was necessary for increasing its sensitivity. In this context, the present study proposes an improved algorithm for data analysis, based on spectral decomposition. A new minimum detectable limit (MDL) of (0.7+/-0.1)mg Al was reached for a local dose of (20+/-1)mSv. The study also addresses the feasibility of a new data acquisition technique, the electronic rejection of the coincident events detected by a NaI(Tl) system. It is expected that the application of this technique, together with spectral decomposition analysis, would provide an acceptable MDL for the method to be valuable in a clinical setting.