Unfortunately, isotopically enriched

83Kr is costly (approximately € 4000/L) at the current low demand for production. (2) There are little toxicological concerns for future clinical applications as krypton is chemically inert and does not exhibit anesthetic properties at ambient gas pressure [34] and [35]. This work was supported in part by the Medical Research Council under Grant No. G0900785 and by the Royal Society through the Paul Instrument Fund. “
“The blood–brain barrier (BBB) is commonly studied using dynamic contrast-enhanced MRI (DCE-MRI) in diseases such as brain tumors [1], [2] and [3] and multiple sclerosis [4], [5] and [6] where a relatively large focally abnormal Bortezomib clinical trial BBB is observed. There is increasing interest in using this imaging technique to identify more subtle BBB abnormalities, such as those which occur with normal ageing [7], dementia [7], [8], [9], [10], [11] and [12], Alzheimer’s disease [13], type II diabetes [14], cerebral microvascular disease [7] and [15] and in nonenhancing multiple sclerosis lesions [16] and [17]. These initial results suggest that DCE-MRI of subtle BBB disorders may provide useful

information. However, maximum post-contrast signal differences are small, typically about 5% in gray matter and 1–2% in white matter, with changes over the imaging period being on the order of 1–2%, and differences between patient groups on the order of a few percent at most. These results contrast with conventional DCE-MRI applications where signal enhancement find more may be on the order of 100% or greater in tumors [1] and [18] and 50% in multiple sclerosis [6]. The small changes associated with subtle BBB disorders will be significantly influenced by scanner noise, thereby requiring large sample sizes to minimize random noise and identify differences between groups, if present. Pregnenolone The effects of noise on concentration estimation in DCE-MRI have been extensively investigated by Schabel and Parker [19], but they do not explicitly present results for the very low concentrations

found in subtle BBB abnormalities, although their methods are equally valid for this situation. Other factors such as scanner drift and differences in background signal characteristics of different tissues might also contribute to observed signal differences and their influences need to be investigated. Furthermore, all of the DCE-MRI studies investigating these more subtle BBB disorders have used relatively simple analytical approaches, typically measuring signal enhancement over time in brain regions and inferring a direct relationship to BBB breakdown, i.e., assuming that greater signal enhancement equates to greater contrast agent concentration indicating a more abnormal BBB. This is a somewhat simplistic approach compared with established methodologies [6] that attempt to model the relationship between signal, contrast agent concentration and pharmacokinetics in order to quantify BBB abnormalities.