Mild mutations in BRCA2 (FANCD1) cause Fanconi anemia (FA) when homozygous, while severe mutations cause common cancers including breast, ovarian, and prostate cancers when heterozygous. Here we report a zebrafish brca2 insertional mutant that shares phenotypes with human patients and identifies a novel brca2 function in oogenesis. Experiments showed that mutant embryos and mutant cells in culture experienced genome instability, as do cells in FA patients. In wild-type zebrafish, meiotic cells expressed brca2; and, unexpectedly, transcripts in oocytes localized asymmetrically to the animal pole. In juvenile brca2 mutants, oocytes failed to progress through meiosis, leading to female-to-male sex reversal. Adult mutants became sterile males due to the meiotic arrest of spermatocytes, which then died by apoptosis, followed by neoplastic proliferation of gonad somatic cells that was similar to neoplasia observed in ageing dead end (dnd)-knockdown males, which lack germ cells. The construction of animals doubly mutant for brca2 and the apoptotic gene tp53 (p53) rescued brca2-dependent sex reversal. Double mutants developed oocytes and became sterile females that produced only aberrant embryos and showed elevated risk for invasive ovarian tumors. Oocytes in double-mutant females showed normal localization of brca2 and pou5f1 transcripts to the animal pole and vasa transcripts to the vegetal pole, but had a polarized rather than symmetrical nucleus with the distribution of nucleoli and chromosomes to opposite nuclear poles; this result revealed a novel role for Brca2 in establishing or maintaining oocyte nuclear architecture. Mutating tp53 did not rescue the infertility phenotype in brca2 mutant males, suggesting that brca2 plays an essential role in zebrafish spermatogenesis. Overall, this work verified zebrafish as a model for the role of Brca2 in human disease and uncovered a novel function of Brca2 in vertebrate oocyte nuclear architecture.

The compact 3T MRI system has been in continuous operation at the Mayo Clinic since March 2016. To date, over 200 patient studies have been completed, including 96 comparison studies with a clinical 3T whole-body MRI. The increased gradient performance has reliably resulted in consistently improved image quality.

Purpose: To derive a noniterative gridding-type reconstruction framework for nonCartesian magnetic resonance imaging (MRI) that prospectively accounts for gradient nonlinearity (GNL)-induced image geometrical distortion during MR image reconstruction, as opposed to the standard, image-domain based GNL correction that is applied after reconstruction; to demonstrate that such framework is able to reduce the image blurring introduced by the conventional GNL correction, while still offering effective correction of GNL-induced geometrical distortion and compatibility with off-resonance correction. Methods: After introducing the nonCartesian MRI signal model that explicitly accounts for the effects of GNL and off-resonance, a noniterative gridding-type reconstruction framework with integrated GNL correction based on the type-III nonuniform fast Fourier transform (NUFFT) is derived. A novel type-III NUFFT implementation is then proposed as a numerically efficient solution to the proposed framework. The incorporation of simultaneous B 0 off-resonance correction to the proposed framework is then discussed. Several phantom and in vivo data acquired via various 2D and 3D nonCartesian acquisitions, including 2D Archimedean spiral, 3D shells with integrated radial and spiral, and 3D radial sampling, are used to compare the results of the proposed and the standard GNL correction methods. Results: Various phantom and in vivo data demonstrate that both the proposed and the standard GNL correction methods are able to correct the coarse-scale geometric distortion and blurring induced by GNL and off-resonance. However, the standard GNL correction method also introduces blurring effects to corrected images, causing blurring of resolution inserts in the phantom images and loss of small vessel clarity in the angiography examples. On the other hand, the results after the proposed GNL correction show better depiction of resolution inserts and higher clarity of small vessel. Conclusions: The proposed GNL-integrated nonCartesian reconstruction method can mitigate the resolution loss that occurs during standard image-domain GNL correction, while still providing effective correction of coarse-scale geometric distortion and blurring induced by GNL and off-resonance. C 2015 American Association of Physicists in Medicine. [http://dx

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One of the major concerns associated with high-performance gradients is peripheral nerve stimulation (PNS) of the subject during MRI exams. Since the installation, more than 680 volunteer subjects (patients and controls) have been scanned on a compact 3 T MRI system with high-performance gradients, capable of 80 mT m−1 gradient amplitude and 700 T m−1 s−1 slew rate simultaneously. Despite PNS concerns associated with the high-performance gradients, due to the smaller physical dimensions of the gradient coils, minimal or no PNS sensation was reported with most pulse sequences. The exception was PNS reported by only five of 252 subjects (about 2%) scanned with a specific 3D fast spin echo pulse sequence (3DFLAIR). Rather than derating the entire system performance across all pulse sequences and all gradient lobes, we addressed reported PNS effect with a simple and specific modification to the targeted lobes of the problematic pulse sequence. in addition, the PNS convolutional model was adapted to predict sequence-specific PNS threshold level and its reduction after derating. The effectiveness of the targeted pulse sequence modification was demonstrated by successfully re-scanning four of the subjects who previously reported PNS sensations without further reported PNS. The pulse sequence modification did not result in noticeable degradation of image quality or substantial increase in scan time. The results demonstrated that PNS was rarely reported on the compact 3 T, and when it was, utilizing a specific modification of the gradient waveform causing PNS was an effective strategy, rather than derating the performance of the entire gradient system.