One model, two brains: Automatic fetal brain extraction from MR images of twins.

Fetal brain extraction from magnetic resonance (MR) images is of great importance for both clinical applications and neuroscience studies. However, it is a challenging task, especially when dealing with twins, which are commonly existing in pregnancy. Currently, there is no brain extraction method dedicated to twins, raising significant demand to develop an effective twin fetal brain extraction method. To this end, we propose the first twin fetal brain extraction framework, which possesses three novel features. First, to narrow down the region of interest and preserve structural information between the two brains in twin fetal MR images, we take advantage of an advanced object detector to locate all the brains in twin fetal MR images at once. Second, we propose a Twin Fetal Brain Extraction Network (TFBE-Net) to further suppress insignificant features for segmenting brain regions. Finally, we propose a Two-step Training Strategy (TTS) to learn correlation features of the single fetal brain for further improving the performance of TFBE-Net. We validate the proposed framework on a twin fetal brain dataset. The experiments show that our framework achieves promising performance on both quantitative and qualitative evaluations, and outperforms state-of-the-art methods for fetal brain extraction.

Environmental Nanoparticles Reach Human Fetal Brains.

Anthropogenic ultrafine particulate matter (UFPM) and industrial and natural nanoparticles (NPs) are ubiquitous. Normal term, preeclamptic, and postconceptional weeks(PCW) 8-15 human placentas and brains from polluted Mexican cities were analyzed by TEM and energy-dispersive X-ray spectroscopy. We documented NPs in maternal erythrocytes, early syncytiotrophoblast, Hofbauer cells, and fetal endothelium (ECs). Fetal ECs exhibited caveolar NP activity and widespread erythroblast contact. Brain ECs displayed micropodial extensions reaching luminal NP-loaded erythroblasts. Neurons and primitive glia displayed nuclear, organelle, and cytoplasmic NPs in both singles and conglomerates. Nanoscale Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si were detected in placentas and fetal brains. Preeclamptic fetal blood NP vesicles are prospective neonate UFPM exposure biomarkers. NPs are reaching brain tissues at the early developmental PCW 8-15 stage, and NPs in maternal and fetal placental tissue compartments strongly suggests the placental barrier is not limiting the access of environmental NPs. Erythroblasts are the main early NP carriers to fetal tissues. The passage of UFPM/NPs from mothers to fetuses is documented and fingerprinting placental single particle composition could be useful for postnatal risk assessments. Fetal brain combustion and industrial NPs raise medical concerns about prenatal and postnatal health, including neurological and neurodegenerative lifelong consequences.

Characterization of Epigenetic Histone Activation/Repression Marks in Sequences of Genes by Chromatin Immunoprecipitation-Quantitative Polymerase Chain Reaction (ChIP-qPCR).

Chromatin immunoprecipitation (ChIP) is widely used to measure protein-DNA interactions. This protocol outlines a ChIP method used to identify the association of a protein or protein modification (such as a specific histone modification-methylation, acetylation, etc.) of interest with a specific DNA sequence in a target gene in fetal mouse brains on gestational day (GD) 17. Briefly, DNA and proteins are cross-linked (via formaldehyde), and chromatin is sonicated into fragments between 200 and 1000 base pair (bp) long, with an average length of 500 bp. The DNA-protein complexes are captured using antibodies directed toward the protein or protein modification of interest. These immunoprecipitated complexes are retrieved using agarose beads. The DNA-protein cross-links are reversed (via heat and via presence of high salt concentrations), and the ChIP DNA is purified and measured via a quantitative polymerase chain (qPCR) reaction. The results show the association of histone modifications at unknown sites of specific genes of interest, indicating which epigenetic modifications of specific genes may be responsible for the outcome of interest.

Quantifying Activity for Repair of the DNA Lesion 8-Oxoguanine by Oxoguanine Glycosylase 1 (OGG1) in Mouse Adult and Fetal Brain Nuclear Extracts Using Biotin-Labeled DNA.

The reactive oxygen species (ROS)-initiated DNA lesion 8-oxoguanine (8-oxoG) is commonly used as a biomarker to measure oxidative stress levels in tissue samples from animals and humans. This lesion also can play a pathogenic role in cancer, birth defects, and neurodegeneration, among other disorders. The level of 8-oxoG may be enhanced due to ROS-initiating environmental factors (e.g., drugs, gamma radiation, microbial infection) or due to a decrease in the activity of oxoguanine glycosylase 1 (OGG1), an enzyme that repairs this lesion. Measurement of the activity of OGG1 can be useful in elucidating mechanisms and complements measurements of 8-oxoG levels in tissues of interest. This protocol describes an assay for measuring the activity of 8-oxoG in mouse adult and fetal brain tissues. Briefly, a synthetic duplex containing the 8-oxoG residue in one of the nucleotides (49-mer), labeled with biotin at the 3'-end, is incubated with protein extract from the tissue of interest containing OGG1, which cleaves the 8-oxoG residue producing a cleavage product of ~27-mer. The percent cleavage quantifies the activity of OGG1 in that tissue. The biotin tag allows rapid and sensitive detection of the cleavage product via chemiluminescence, avoiding the problems of safety and short half-lives of radionuclides encountered in assays employing a radioactively-labeled substrate.