BackgroundNeurite orientation dispersion and density imaging (NODDI) is a diffusion magnetic resonance imaging (MRI) technique with the potential to visualize the microstructure of the brain. Revolutionary histological methods to render the mouse brain transparent have recently been developed, but verification of NODDI by these methods has not been reported.PurposeTo confirm the concordance of NODDI with histology in terms of density and orientation dispersion of neurites of the brain.Material and MethodsWhole brain diffusion MRI of a thy-1 yellow fluorescent protein mouse was acquired with a 7-T MRI scanner, after which transparent brain sections were created from the same mouse. NODDI parameters calculated from the MR images, including the intracellular volume fraction (Vic) and the orientation dispersion index (ODI), were compared with histological findings. Neurite density, Vic, and ODI were compared between areas of the anterior commissure and the hippocampus containing crossing fibers (crossing areas) and parallel fibers (parallel areas), and the correlation between fiber density and Vic was assessed.ResultsThe ODI was significantly higher in the crossing area compared to the parallel area in both the anterior commissure and the hippocampus (P = 0.0247, P = 0.00022, respectively). Neurite density showed a similar tendency, but was significantly different only in the hippocampus (P = 7.91E−07). There was no significant correlation between neurite density and Vic.ConclusionNODDI was verified by histology for quantification of the orientation dispersion of neurites. These results indicate that the ODI is a suitable index for understanding the microstructure of the brain in vivo.

Summary Thalidomide is a teratogen that causes multiple malformations in the developing baby through its interaction with cereblon (CRBN), a substrate receptor subunit of the CRL4 E3 ubiquitin ligase complex. CRBN was originally reported as a gene associated with autosomal recessive non-syndromic mild mental retardation. However, the function of CRBN during brain development remains largely unknown. Here we demonstrate that CRBN promotes brain development by facilitating the proliferation of neural stem cells (NSCs). Knockdown of CRBN in zebrafish embryos impaired brain development and led to small brains, as did treatment with thalidomide. By contrast, overexpression of CRBN resulted in enlarged brains, leading to the expansion of NSC regions and increased cell proliferation in the early brain field and an expanded expression of brain region-specific genes and neural and glial marker genes. These results demonstrate that CRBN functions in the determination of brain size by regulating the proliferation of NSCs during development.

We report a methodology which enables the preparation of dendrimeric contrast agents sensitive to Ca(2+) when starting from the monomeric analogue. The Ca-triggered longitudinal relaxivity response of these agents is not compromised by undertaking synthetic transformations, despite structural changes. The in vivo MRI studies in the rat cerebral cortex indicate that diffusion properties of dendrimeric contrast agents have great advantages as compared to their monomeric equivalents.

Three lipid-oligonucleotides (ODN) carrying TEMPO were prepared and formed a micelle with a diameter of ca. 10 nm. The double strand ODN, lipid-polyT in DS, incorporating TEMPO near the core of the micelle showed the largest water-proton relaxivity, r 1 , value of 2.4 (25 MHz, 0.59 T) and 6.8 mM 21 s 21 (42 MHz, 1.0 T) per TEMPO.DNA derivatives carrying stable aminoxyls through various types of linkers have previously been prepared, revealing not only the conformation of various DNA strands but also their dynamics. 1 Such DNA double strands carrying organic spins could be expected to function as metal-free and large-size MRI agents, 2 taking advantage of the unique properties of the DNA strand, which binds to many water molecules in major and minor grooves for structural stabilization. 3 Recently, we reported that the double strand incorporating 5-uridine-TEMPO, UST, had relatively large water-proton relaxivity, r 1 , which is an indicative value for the contrast. 4 To increase the molecular size and further improve of the r 1 value, in this study DNA-micelles 5 carrying TEMPO, 2,2,6,6tetramethylpiperidine-N-oxyl, were prepared. The 15-mer of thymidine (polyT) and TEMPO-uridine (TDU) directly attached to the TEMPO radical without a linker, were selected as the base sequence and a spin source, respectively. We report the rotational correlation time, t R , and the relaxivities, r 1 , for their single-strand and double-strand micelles with complimentary strand (polyA), in addition to T 1 -weighted images in vitro (Fig. 1).The TDU monomer, was prepared by Suzuki coupling reaction; 5-iodo-29-deoxyuridine reacted with 4-borate TEMPO in the presence of tetrakis(triphenylphosphine)palladium(0). After pro-

The reduction of Cho on (1) H-MRS might be a common marker for hypomyelinating disorders. A normal tNAA level in the thalamus of shiverer mice might be explained by the presence of mature oligodendrocytes, which enable neuron-to-oligodendrocyte NAA transport or NAA catabolism.