Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via¹H₂O MRI: implications for boron neutron capture therapy of malignant brain tumours

Abstract

In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against gamma-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 +/- 2% (p-value <0.001) was observed in the rat brain-this may account for neurological and behavioural abnormalities found in mammals drinking highly deuterated water. In addition to characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this report also estimates the impact of oedema on thermal neutron enhancement and effective dose reduction factors using simple linear transport calculations. While body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as approximately 10% in the presence of a 9% water volume increase (oedema).

Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo

“…[1] iron term for most brain regions, the field dependence of brain 1 H 2 O R 1 primarily arises from the B 0 dependence of r 1M . In other work involving in vivo 2 H‐substitution titration rodent studies (44), we found that an increasing 2 H proportion increases 1 H 2 O T 1 not only because the less competent 2 H replaces 1 H, but also because it induces cerebral edema and thus decreases f M .…”

Evaluating retinal toxicity of a new heavy intraocular dye, using a model of perfused and isolated retinal cultures of bovine and human origin

“…Since most of the toxic effects are centralized in neuronal tissue, toxic effects upon direct contact with the retinal cells are possible. It has been shown that mammals can tolerate a concentration of up to 30 % of D2O in drinking water, and that a short exposure to a blood serum deuterium fraction of up to 0.23 ml/ml seems to be safe [14][15][16][17][18]. The tested concentration in this study is 0.13 ml/ml.…”

Large-Scale User Facility Imaging and Scattering Techniques to Facilitate Basic Medical Research

“…One method to ameliorate the attenuation problem is to change the water composition from normal water to deuterated water (also referred to as heavy water) (Slatkin, Stoner et al 1983;Nakagawa, Hatanaka et al 1994;Kushner, Baker et al 1999;Medina, Li et al 2005). Studies have shown that approximately 20% of total body water (TBW) can be replaced with deuterated water without deleterious effects (Kushner, Baker et al 1999).…”