Jasanoff Lab is developing a new generation of functional magnetic resonance imaging (fMRI) methods to study the neural mechanisms of behavior.The Lab’s focus is on the design and application of new contrast agents that may help define spatiotemporal patterns of neural activity with far better precision and resolution than current techniques allow. Experiments using the new agents will combine the specificity of cellular neuroimaging with the whole brain coverage and noninvasiveness of conventional fMRI.
Lab Website: web.mit.edu/jasanofflab/
Address: MIT Rm. 16-560 | 77 Massachusetts Avenue | Cambridge, MA 02139
Our laboratory is developing a new generation of functional magnetic resonance imaging (fMRI) methods to study the neural mechanisms of behavior. Our principal focus is on the design and application of new contrast agents that may help define spatiotemporal patterns of neural activity with far better precision and resolution than current techniques allow. Experiments using the new agents will combine the specificity of cellular neuroimaging with the whole brain coverage and noninvasiveness of conventional fMRI. Introduction of these technologies will have far-reaching consequences in neuroscience, because the new imaging methods will be applicable to studies of any neural system in vivo. Our own goal is to use the methods to build explanatory models of neural network function in animals, with current emphasis on brain circuitry involved in instrumental learning behavior.
Contrast agents for “molecular fMRI”
Contrast agents required for functional molecular imaging experiments are roughly analogous to fluorescent dyes used widely in cellular neuroscience. They differ in chemistry—MRI contrast agents are generally paramagnetic, and the structural or electronic changes that allow them to be used as sensors must affect their magnetic properties in some way. We work largely with iron oxide nanoparticles, a potent form of contrast agent whose effects can be regulated through controlled aggregation or the construction of nanoassemblies. We recently created a family of calcium sensors by conjugating iron oxides to calcium sensing proteins, and we are using similar approaches to make sensors for both intra- and extracellular neuronal signaling events. In collaboration with other laboratories at MIT and elsewhere, we are also exploring genetically encodable or small synthetic contrast agents for molecular neuroimaging.
Functional imaging in animals
We use high resolution MRI in animals to test our new contrast agents. In collaboration with David Cory, we built an MRI microscopy system capable of 20-40 µm resolution imaging of small animals like the blowfly Sarcophaga bullata. In this system, we can combine visual stimulation and injection of contrast agents to determine response properties of the agents at the single neuron level. We also use conventional fMRI techniques, in combination with behavioral measures and electrophysiology, to study instrumental learning and plasticity phenomena in rodents. Significant effort is devoted to experiments that address dynamics of distributed brain pathways in awake, behaving animals. Our new sensors will be applied in these studies once effective delivery strategies are established.
|ALAN JASANOFF, Ph.D. (PI)
Alan initiated the laboratory’s research in “molecular fMRI,” ultrahigh resolution neuroimaging, and behavioral neuroscience. He joined the MIT faculty in 2004.
|ALI BARANDOV, Ph.D.
Ali is interested in the design and development of small molecule sensors for intracellular signal transduction events.
|BENJAMIN BARTELLE, Ph.D.
Ben is developing MRI sensor proteins meant to explore the function of the brain in vivo. He has previously developed a suite of MRI reporter proteins for studies of functional and developmental genetics of the mouse.
Graduate Student (Biology)
Sarah is investigating neural mechanisms of rewarding and aversive stimulus processing using fMRI approaches in rats
|MITUL DESAI, Ph.D.
Mitul studies how neural circuit dynamics give rise to aspects of brain function related to decision-making. He also works on a novel approach for high-sensitivity molecular imaging of neural signaling events.
Graduate Student (BE)
Souparno is working on a project that applies protein-engineering principles to develop protein based contrast agents for studying neural activity using fMRI.
|AVIAD HAI, Ph.D.
Aviad is using his knowledge in cell biology, electrophysiology and electrical engineering to develop novel MRI nanosensors for in vivo imaging of neural activity.
Grad Student (ChemE)
Vivian works on developing neurotransmitter-specific contrast agents based on biological molecules and nanoparticles. She applied protein bioengineering methods and bioconjugation chemistry to investigate novel contrast mechanisms and improve sensor properties.
Tehya is examining the capabilities of MRI sensors in vivo. She is also working on using fMRI to examine neural networks which mediate responses to affective stimuli, and how intersection and activation of these pathways influences behavior.
|NAN LI, Ph.D.
Nan is working on investigating reward neuronal circuits in vivo by utilizing dopamine dependent molecular fMRI, blood oxygenation level dependent fMRI, optogenetics and electrophysiological approaches.
Graduate Student (BE)
Yuri is interested in improving the properties of existing protein-based MRI contrast agents. She uses protein bioengineering approaches to identify molecular variants that generate optimized contrast in model systems.
|SATOSHI OKADA, Ph.D.
Satoshi is interested in rational design of contrast agents based on the collaboration of nanotechnology, molecular biology, and computer science and the application of them to in vivo imaging.
Graduate Student (BE)
Jacob is developing novel nanoscale neurotransmitter sensors with increased sensitivity relative to previous MRI probes. He is also engineering metalloproteins to detect intracellular signal transduction.
Graduate Student (BE)
Adrian uses protein and genetic engineering to develop a novel platform for molecular imaging of physiological events with unprecedented sensitivity and resolution. He is also working on new enzyme sensors for molecular fMRI.
Graduate Student (HST)
Agata works on improving delivery techniques of contrast agents into the brain. She is developing a novel device for intracranial injection to large brain regions, and investigating techniques for delivery via the bloodstream using focused ultrasound.
Articles in Peer-Reviewed Journals
Barch M, Okada S, Bartelle BB, Jasanoff A. (2014) “Screen-based analysis of magnetic nanoparticle libraries formed using peptidic iron oxide ligands.” J Am Chem Soc. 2014 Aug 26. (Epub ahead of print). [PubMed]
Lee T, Cai LX, Lelyveld VS, Hai A, Jasanoff A. (2014) “Molecular-level functional magnetic resonance imaging of dopaminergic signaling.” Science. 2014 May 2;344(6183):533-5. [PubMed]
Westmeyer GG, Emer Y, Lintelmann J, Jasanoff A. (2014) “MRI-based detection of alkaline phosphatase gene reporter activity using a porphyrin solubility switch.” Chem Biol. 2014 Mar 20;21(3):422-9. [PubMed]
Rodriguez E, Lelyveld VS, Atanasijevic T, Okada S, Jasanoff A. (2014) “Magnetic nanosensors optimized for rapid and reversible self-assembly.” Chem Commun (Camb). 2014 Apr 7;50(27):3595-8. [PubMed]
Jackson WS, Borkowski AW, Watson NE, King OD, Faas H, Jasanoff A, Lindquist S. (2013) “Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases.” Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14759-64. [PubMed]
Romero PA, Shapiro MG, Arnold FH, Jasanoff A. (2013) “Directed evolution of protein-based neurotransmitter sensors for MRI.” Methods Mol Biol. 2013;995:193-205.[PubMed]
Devor A, Bandettini PA, Boas DA, Bower JM, Buxton RB, Cohen LB, Dale AM, Einevoll GT, Fox PT, Franceschini MA, Friston KJ, Fujimoto JG, Geyer MA, Greenberg JH, Halgren E, Hämäläinen MS, Helmchen F, Hyman BT, Jasanoff A, Jernigan TL, Judd LL, Kim SG, Kleinfeld D, Kopell NJ, Kutas M, Kwong KK, Larkum ME, Lo EH, Magistretti PJ, Mandeville JB, Masliah E, Mitra PP, Mobley WC, Moskowitz MA, Nimmerjahn A, Reynolds JH, Rosen BR, Salzberg BM, Schaffer CB, Silva GA, So PT, Spitzer NC, Tootell RB, Van Essen DC, Vanduffel W, Vinogradov SA, Wald LL, Wang LV, Weber B, Yodh AG. (2013) “The challenge of connecting the dots in the B.R.a.I.N.” Neuron. 2013 Oct 16;80(2):270-4. [PubMed]
Matsumoto Y, Jasanoff A. (2013) “Metalloprotein-based MRI probes.” FEBS Lett. 2013 Apr 17;587(8):1021-9. [PubMed]
Brustad E.M., Lelyveld V.S., Snow C.D., Crook N., Jung S.T., Martinez F.M., Scholl T.J., Jasanoff A., Arnold F.H. (2012) “Structure-guided directed evolution of highly selective P450-based magnetic resonance imaging sensors for dopamine and serotonin.” J Mol Biol. 422(2):245-62. [PubMed]
Hsieh V., Jasanoff A. (2012) “Bioengineered probes for molecular magnetic resonance imaging in the nervous system. ACS Chem Neurosci.” 3(8):593-602. [PubMed]
Jasanoff A. (2012) “Adventures in neurobioengineering.” ACS Chem Neurosci. 2012 Aug 15;3(8):575. [PubMed]
Lelyveld, V. S., Brustad, E., Arnold, F. H., & Jasanoff, A. (2011) “Metal-substituted protein MRI contrast agents engineered for enhanced relaxivity and ligand sensitivity,” J. Am. Chem. Soc., 133(4): 649–651 [PubMed]
Lee, T., Zhang, X. A., Dhar, S., Faas, H., Lippard, S. J., & Jasanoff, A. (2010) “In vivo imaging with a cell-permeable porphyrin-based MRI contrast agent,” Chem. Biol. 17: 665-73. [PubMed]
You, Y., Tomat, E., Hwang, K., Atanasijevic, T., Nam, W., Jasanoff, A., & Lippard, S. J. (2010) Chem. Commun. (Camb.) 46: 4139-41. [PubMed]
Westmeyer, G. G., Durocher, Y., & Jasanoff, A. (2010) “A secreted enzyme reporter system for MRI,” Angew. Chem. Int. Ed. Engl. 49: 1-4. [PubMed]
Shapiro, M. G., Westmeyer, G. G., Romero, P. A., Szablowski, J. O., Küster, B., Shah, A., Otey, C. R., Langer, R., Arnold, F. H., & Jasanoff, A. (2010) “Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine,” Nat. Biotechnol. 28: 264-70. [PubMed]
Atanasijevic, T., Zhang, X. A., Lippard, S. J., & Jasanoff, A. (2010) “MRI sensing based on the displacement of paramagnetic ions from chelated complexes,” Inorg. Chem. 49: 2589-91. [PubMed]
Lelyveld, V. S., Atanasijevic, T., & Jasanoff, A. (2010) “Challenges for molecular neuroimaging with MRI,” Int. J. Imaging Syst. Technol. 20: 71-9. [PubMed]
Faas, H., Jackson, W. S., Borkowski, A. W., Wang, X., Ma, J., Lindquist, S., & Jasanoff, A. (2010) “Context-dependent perturbation of neural systems in transgenic mice expressing a cytosolic prion protein,” Neuroimage 49: 2607-17. [PubMed]
Shapiro, M. G., Szablowski, J. O., Langer, R., & Jasanoff, A. (2009) “Protein nanoparticles engineered to sense kinase activity in MRI,” J. Am. Chem. Soc. 131: 2484-6. [PubMed]
Jackson WS, Borkowski AW, Faas H, Steele AD, King OD, Watson N, Jasanoff A, Lindquist S. (2009) “Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice.” Neuron. 2009 Aug 27;63(4):438-50. [PubMed]
Matsumoto, Y., & Jasanoff, A. (2008) “T2 relaxation induced by clusters of superparamagnetic nanopar-ticles: Monte Carlo simulations,” Magn. Reson. Imaging 26: 994-8. [PubMed]
Colonnese, M. T., Phillips, M. A., Constantine-Paton, M., Kaila, K., & Jasanoff, A. (2008) Nat. Neurosci. 11: 72-9. [PubMed]
Jasanoff, A. (2007) “MRI contrast agents for functional molecular imaging of brain activity,” Curr. Opin. Neurobiol. 17: 593-600. [PubMed]
Atanasijevic, T. & Jasanoff, A. (2007) “Preparation of iron oxide-based calcium sensors for MRI,” Nat. Protoc. 2: 2582-9. [PubMed]
Jasanoff, A. (2007) “Bloodless fMRI,” Trends Neurosci. 30: 603-10. [PubMed]
Zhang, X. A., Lovejoy, K. S., Jasanoff, A., & Lippard, S. J. (2007) “Water-soluble porphyrins as dual-function molecular imaging platform for MRI and fluorescence zinc sensing,” Proc. Natl. Acad. Sci. USA 104: 10780-5. [PubMed]
Westmeyer, G. G. & Jasanoff, A. (2007) “Genetically controlled MRI contrast mechanisms and their prospects in systems neuroscience research,” Magn. Reson. Imaging 25: 1004-10. [PubMed]
Green, D. F., Dennis, A. T., Fam, P. S., Tidor, B., & Jasanoff, A. (2006) “Rational design of new binding specificity by simultaneous mutagenesis of calmodulin and a target peptide,” Biochemistry 45: 12547-59. [PubMed]
Atanasijevic, T., Shusteff, M., Fam, P., & Jasanoff, A. (2006) “Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin,” Proc. Natl. Acad. Sci. USA 103: 14707-12. [PubMed]
Shapiro, M. G., Atanasijevic, T., Faas, H., Westmeyer, G. G., & Jasanoff, A. (2006) “Dynamic imaging with MRI contrast agents: quantitative considerations.” Magn. Reson. Imaging 24: 449-62. [PubMed]
Kim, S. W., Kim, S., Tracy, J. B., Jasanoff, A., & Bawendi, M. G. (2005) “Phosphine oxide polymer for water-soluble nanoparticles,” J. Am. Chem. Soc. 127: 4556-7.[PubMed]
Jasanoff, A. (2005) “Functional MRI Using Molecular Imaging Agents,” Trends Neurosci. 28: 120-6. [PubMed]
Sun, P.Z. & Jasanoff, A. (2003) “In Vivo Oxygen Detection Using Exogenous Hemoglobin as a Contrast Agent in Magnetic Resonance Microscopy,” Magn. Reson. Med. 49: 609-14. [PubMed]
Jasanoff, A. & Sun, P. Z. (2002) “In Vivo Magnetic Resonance Microscopy of Brain Structure in Unanesthetized Flies,” J. Magn. Reson. 158: 79-85. [PubMed]