We have used magnetic resonance microscopy to compare the cardiac anatomy of normal and NFATc knockout mice at an age of 13 days post conception. The embryos were injected with a contrast agent (Gd-DTPA conjugated to albumin), fixed in paraformaldehyde and then imaged at a field strength of 9.4 Tesla. The injection of contrast material allows us to make large (256x128x128), high resolution (60x40x40 microns voxel size) data sets in a reasonably short period of time (2 hours for four averages). We are then able to quantitatively assess the volumes of the fetal hearts. The NFATc knockout is embryonically lethal, with death occurring at 14.5 dpc, due to the failure of both pulmonary and aortic valves to develop. This should lead to regurgitation of the blood into the chambers, enlarging them. Preliminary results are that the left ventricle is actually smaller in the knockout relative to homozygote or heterozygote littermates. and analyzing the data sets using specialized software developed with the IDL programming language. We are proceeding to characterize other stages. Mice with genetic defects, specifically the knockouts of the NFATc, VCAM-1, and connexin43 genes, all of which have been shown to develop cardiac defects, will be studied in embryos at a variety of stages in order to delineate clearly the developmental process and understand the nature of the defects caused by the mutations. This knowledge will act as an important guide for future work in vivo.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
United States
Zip Code
Pang, Henry; Bow, Cora; Cheung, Jason Pui Yin et al. (2018) The UTE Disc Sign on MRI: A Novel Imaging Biomarker Associated With Degenerative Spine Changes, Low Back Pain, and Disability. Spine (Phila Pa 1976) 43:503-511
Ferraro, Pilar M; Jester, Charles; Olm, Christopher A et al. (2018) Perfusion alterations converge with patterns of pathological spread in transactive response DNA-binding protein 43 proteinopathies. Neurobiol Aging 68:85-92
Ercan, Altan; Kohrt, Wendy M; Cui, Jing et al. (2017) Estrogens regulate glycosylation of IgG in women and men. JCI Insight 2:e89703
Ban, H Y; Schweiger, M; Kavuri, V C et al. (2016) Heterodyne frequency-domain multispectral diffuse optical tomography of breast cancer in the parallel-plane transmission geometry. Med Phys 43:4383
Xie, Long; Dolui, Sudipto; Das, Sandhitsu R et al. (2016) A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment. Neuroimage Clin 11:388-397
Yadav, Santosh K; Kathiresan, Nagarajan; Mohan, Suyash et al. (2016) Gender-based analysis of cortical thickness and structural connectivity in Parkinson's disease. J Neurol 263:2308-2318
Finkelstein, Joel S; Lee, Hang; Leder, Benjamin Z et al. (2016) Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. J Clin Invest 126:1114-25
Rosenbaum, Michael; Leibel, Rudolph L (2016) Models of energy homeostasis in response to maintenance of reduced body weight. Obesity (Silver Spring) 24:1620-9
Machida, Manabu; Panasyuk, George Y; Wang, Zheng-Min et al. (2016) Radiative transport and optical tomography with large datasets. J Opt Soc Am A Opt Image Sci Vis 33:551-8
McCarthy, Ann L; Winters, Madeline E; Busch, David R et al. (2015) Scoring system for periventricular leukomalacia in infants with congenital heart disease. Pediatr Res 78:304-9

Showing the most recent 10 out of 414 publications