Cerebral development involves a complex cascade of events which are difficult to visualize and quantify in vivo. In this study we combine information from Diffusion Tensor Imaging (DTI) and Quantitative Susceptibility Mapping (QSM) to analyze developing mouse brains at five stages up to 56days postnatal. Susceptibility maps were calculated using frequency shifts in gradient echo MR images acquired at 9.4T. The mean apparent magnetic susceptibility and magnetic susceptibility anisotropy of major white matter tracts were evaluated as a function of age. During the first two weeks, susceptibility of white matter appeared paramagnetic relative to surrounding gray matter; it then gradually became more diamagnetic. While diffusion anisotropy was already apparent and high at postnatal day 2, susceptibility anisotropy only became significant during the third week. This mismatch indicated different microstructural underpinnings for diffusion anisotropy and susceptibility anisotropy. Histological exams were also performed to evaluate myelin and iron content. It is confirmed that the main source of susceptibility contrast in WM is the myelin content. The ability to quantify the magnetic properties of white matter will provide valuable information on the architecture of the brain during development and potentially a more specific indicator for myelin degenerative diseases.

Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk tissues. We report that two heat-activated transient receptor potential (TRP) ion channels, TRPV1 and TRPV4, were present in neural crest cells during critical windows of heart and face development. TRPV1 antagonists protected against the development of hyperthermia-induced defects in chick embryos. Treatment with chemical agonists of TRPV1 or TRPV4 replicated hyperthermia-induced birth defects in chick and zebrafish embryos. To test whether transient TRPV channel permeability in neural crest cells was sufficient to induce these defects, we engineered iron-binding modifications to TRPV1 and TRPV4 that enabled remote and noninvasive activation of these channels in specific cellular locations and at specific developmental times in chick embryos with radio-frequency electromagnetic fields. Transient stimulation of radio frequency-controlled TRP channels in neural crest cells replicated fever-associated defects in developing chick embryos. Our data provide a previously undescribed mechanism for congenital defects, whereby hyperthermia activates ion channels that negatively affect fetal development.