Eric T. Ahrens
Professor & Director, NMR Center
601 Mellon Institute
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
Ph.D., University of California, Los Angeles
Postdoctoral Appointment, California Institute of Technology
My laboratory conducts interdisciplinary research utilizing leading-edge nuclear magnetic resonance tools to explore molecular and cellular events in vivo. There are two areas of research focus.
1. In vivo cytometry
Non-invasive imaging of the dynamic trafficking patterns of phenotypically-defined populations of immune cells can play a key role in elucidating the pathogenesis of major diseases such as cancer and autoimmune disorders. Our lab has developed a new field of in vivo cell tracking called ‘in vivo cytometry.’ In this approach, cell populations of interest, such as immune, tumor or stem cells, are tracked and quantified in vivo. We formulate novel perfluorocarbon (PFC) emulsions to label cells ex vivo. Labeled cells are introduced into the subject and cell migration is monitored using 19F MRI. The 19F images are extremely selective for the labeled cells, with no background signal from the host’s tissues. Moreover, the absolute number of labeled cells in regions of interest can be estimated directly from the in vivo 19F images. Alternatively, cell biodistribution can be rapidly and quantitatively assayed using conventional 19F NMR in intact tissue samples. These unique tools are being used to elucidate the etiology and dynamics of inflammatory events in cancer and autoimmune diseases, such as type-1 diabetes, experimental allergic encephalomyelitis (MS-model), and irritable bowel disease. In vivo cytometry is also being used to evaluate the modes of action of live-cell immunotherapeutic interventions in these disease models. Additionally, the PFC emulsion reagents have bio-sensing properties that report on the absolute level of intracellular oxygen and can potentially monitor cell activation, differentiation or apoptosis in vivo. We are currently using oxygen sensing to investigate, longitudinally, CNS glioma perfusion and metabolism in response to anti-tumor, T-cell immunotherapy. We are also collaborating with the Molecular Biosensors and Imaging Center (MBIC) to develop new generations of intracellular PFC probes that can be dually detected by MRI and fluorescence, or report on various intracellular functions. To maximize the potential of in vivo 19F MRI cell tracking, we are applying principles of nuclear spin physics, image processing, and computational modeling to improve data acquisition schemes and cell quantification accuracy. In collaboration with clinicians, we are actively pursuing translation of in vivo cytometry to monitor the delivery and modes of action of emerging immunotherapeutic cell therapies used in leading-edge human cancer treatments. We believe that in vivo cytometry will have a major impact in the clinical development of new generations of cellular therapeutics.
2. Vector-mediated biomagnetism
A second focus of the lab is the development and characterization of new generations of nucleic-acid based MRI reporters. We combine molecular biology tools and MRI to modulate contrast in targeted cells via the expression of novel iron-binding, paramagnetic, metalloproteins in the ferritin family. Following ferritin transgene expression in situ, the ferritin shells sequester physiologically available iron, and biomineralization of the ferritin core renders the complex paramagnetic, producing a contrasting effect in MRI. By uniting an MRI reporter with a gene of interest, a multitude of applications exist, including labeling stem cells for long-term tracking, or imaging transgene expression in genetically-manipulated animals. Our laboratory is actively designing recombinant ferritin molecules and characterizing their structure and function using NMR/MRI and biochemistry. We are also using these studies to garner insights into normal iron metabolism and its dysregulation in disease, particularly in the context of CNS disorders.
Kadayakkara DKK, Rangarajan S, Young WB, Ahrens ET. Assaying macrophage activity in a murine model of inflammatory bowel disease using fluorine-19 MRI. Lab. Invest. 92(4): 636-645, 2012.
Iordanova B, Ahrens ET. In vivo magnetic resonance imaging of ferritin-based reporter visualizes native neuroblast migration. Neuroimage 59: 1004-1012, 2012.
Mills PH, Hitchens TK, Foley LM, Link T, Ye Q, Weiss CR, Thompson JD, Gilson WD, Arepally A, Melick JA, Kochanek PM, Ho C, Bulte JWM, Ahrens ET. Automated detection and characterization of SPIO-labeled cells and capsules using magnetic field perturbations. Magn. Reson. Med. 67(1): 278-289, 2012.
Kadayakkara DKK, Janjic JM, Pusateri LB, Young WB, Ahrens ET. In vivo observation of intracellular oximetry in perfluorocarbon-labeled glioma cells and chemotherapeutic response in the CNS using fluorine-19 MRI. Magn. Reson. Med. 64(5): 1252-1259, 2010.
Janjic JM, Srinivas M, Kadayakkara DK, Ahrens ET. Self-delivering nanoemulsions for dual fluorine-19 MRI and fluorescence detection. J Am Chem Soc., 130(9):2832-2841, 2008 Mar 5.
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, 58(4):725-734, 2007 Oct.
Ahrens ET, Flores R, Xu HY, Morel PA. In vivo imaging platform for tracking immunotherapeutic cells. Nat. Biotech. 23: 983-987, 2005.
Genove G, DeMarco U, Xu H, Goins WF, Ahrens ET. A novel transgene reporter for in vivo magnetic resonance imaging. Nat. Med. 11: 450-454, 2005.
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. 49: 1006-101, 2003.
Louie AY, Huber MM, Ahrens ET, Fraser SE, Jacobs RE, Meade TJ. In vivo visualization of gene expression using magnetic resonance imaging. Nat. Biotech. 18: 321-325, 2000.