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My research centers on advancing the state-of-the-art of magnetic resonance imaging (MRI) and using these techniques to visualize development, connectivity, function, and pathology of the vertebrate nervous system. Extremely-high resolution MRI, or magnetic resonance microscopy (MRM), is an emerging technique that can observe the inner workings of intact living animals in three-dimensions at near-cellular resolution. Tissue morphological changes, progression of disease states, and biochemical changes may all be visualized with MRM. Small animal models of human development and disease are often the subject, and these capabilities make MRM an ideal complement to optical microscopy. Currently my lab focuses on understanding early events associated with the onset of autoimmune disease in the central nervous system (CNS). For these studies, we employ a prototypical animal disease model called experimental allergic encephalomyelitis (EAE). Many aspects of EAE mimic the human disease multiple sclerosis. Both diseases are characterized by the presence of lymphocyte infiltrates in white matter of the CNS. Also, demyelination is often observed. Our emphasis is understanding the mechanisms of the early lymphocyte entry into the CNS. Towards this goal, MRM is used to conduct in vivo longitudinal investigations using numerous imaging modalities. We employ anatomical image analyses, quantitative biophysical measurements, intra-cellular contrast reagents, and functional imaging. The studies are conducted at the Pittsburgh NMR Center for Biomedical Research. In parallel with this project, we are working on advancing MRM technology. We are devising new strategies for improving the sensitivity and resolution of MRM using cryogenically-cooled detection hardware. Also, in collaboration with the Computer Graphics Group at Brown University, we are developing novel software visualization tools for three-dimensional rendering of MR images. Selected Publications Srinivas M, Morel PA, Ernst LA, Laidlaw DH, Ahrens ET. Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. Magn Reson Med. 2007 Oct;58(4):725-3. Eagleson KL, Schlueter McFadyen-Ketchum LJ, Ahrens ET, Mills PH, Does MD, Nickols J, Levitt P. Disruption of Foxg1 expression by knock-in of Cre recombinase: Effects on the development of the mouse telencephalon. Neuroscience. 2007 Aug 24;148(2):385-99. Epub 2007 Jul 19. Ahrens, ET, Goins, WF, Robison, CS. Genetic approaches for modulating MRI contrast. In: Molecular and Cellular MRI, eds. J.W.M. Bulte and M. Modo, CRC Press, San Diego, p. 123-140. 2007. Mills PH, Ahrens ET. Theoretical MRI contrast model for exogenous T2 agents. Magn Reson Med. 2007 Feb; 57(2):442-7. Ahrens ET, Srinivas M, Capuano S, Simhan HN, Schatten GP.
Magnetic resonance imaging of embryonic and fetal development in model systems.
Methods Mol Med. 2006;124:87-101. Review. Ahrens, ET, Flores, R, Xu, HY, Morel, PA. In vivo imaging platform for tracking immunotherapeutic cells. Nat. Biotech. 2005; 23: 983-987. Koshibu, K, Ahrens, ET, Levitt, P. (2005) Postpubertal sex differentiation of forebrain structures and functions depend on transforming growth factor-alpha. J. Neurosci. 2005; 25: 3870-3880. Genove G, DeMarco U, Xu H, Goins WF, Ahrens ET. A novel transgene reporter for in vivo magnetic resonance imaging. Nat. Med. 2005; 11(4):450-454. Koshibu K, Levitt P, Ahrens ET. Sex-specific, post-puberty changes in mouse brain structures revealed by three-dimensional magnetic resonance microscopy. Neuroimage 2004; 22:1636-1645. Ahrens ET, Feili-Hariri M, Xu H, Genove G, Morel PA. Receptor-mediated endocytosis of iron-oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging. Mag. Reson. Med. 2003; 49:1006-1013. Ahrens ET, Narasimhan PT, Nakada T, Jacobs RE. Small animal neuro-imaging using magnetic resonance microscopy. Prog. Nucl. Mag. Res. Sp. 2002; 40(4):275-306. Sadun AA, Carelli V, Bose S, Ross-Cisneros FN, Barboni P, Ahrens ET. First application of extremely high resolution magnetic resonance imaging to study microscopic features of normal and LHON human optic nerve. Ophthalmology 2002; 109:1085-1091. Ahrens ET, Dubowitz DJ. Peripheral somatosensory fMRI in mouse at 11.7 T. NMR Biomed. 2001; 14:318-324.
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