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Senior Investigator

Afonso C. Silva, Ph.D.

Cerebral Microcirculation Section


Building 10 Room B1D106
10 Center Drive MSC 1065
Bethesda MD 20892-1065
Office: (301) 402-9703
Lab: (301) 402-9703
Fax: (301) 480-2558
silvaa@ninds.nih.gov

Dr. Silva received his Bachelor's Degree in Electrical Engineering from Universidade Federal de Pernambuco in Recife, Brazil, and his Ph.D. in Bioengineering from Carnegie Mellon University, where he worked on non-invasive MRI measurements of cerebral blood flow using the arterial spin labeling technique. He then went on to do post-doctoral training in the Center for Magnetic Resonance Research at the University of Minnesota, where he studied the temporal and spatial characteristics of functional brain hemodynamics under the supervision of Prof. Seong-Gi Kim. Dr. Silva joined NINDS as a Staff Scientist in 1999, and became an investigator in 2004. His laboratory combines modern neuroimaging techniques (functional MRI, and optical imaging) with electrophysiological recordings aimed at understanding the mechanisms of regulation of cerebral blood flow during normal and stimulation-induced brain activity.



Unlike any other organ of the body, the brain is critically dependent on a continuous blood supply. Due to its high energy demands, the brain operates under a tight coupling of neuronal electrical activity to the hemodynamic regulation of energy supply and waste removal. The 'neurovascular coupling' entails a complex, highly redundant array of signaling mechanisms aimed at maintaining homeostasis of the brain parenchyma by regulating CBF on a precise spatial and temporal domain. There is increased evidence that such mechanisms result from an integrated action of neurons, glia and blood vessels, which form a 'neurovascular unit' acting at the cellular level to regulate local CBF. Disruption of these mechanisms causes brain dysfunction and disease.

Our laboratory is interested in understanding the mechanisms of CBF regulation during normal and pathological brain states. The fundamental questions related to cerebral blood flow regulation are:

  1. What is the smallest vascular unit that adapts independently to brain activity?
  2. How is this elemental vascular unit related to the cortical architecture?
  3. What are the major signaling pathways, and the key molecules, that translate a change in brain activity into a vascular response?

To address the above questions, we are working on well-defined rodent and non-human primate models of localized functional brain activation, using modern neuroimaging techniques (fMRI or optical microscopy), in combination with electrophysiology recordings of cortical activity. The cerebrovascular coupling will be tested under the presence of agonists and antagonists of several different known mediators or modulators of CBF. Complimentary information on the cerebrovascular coupling will be studied under pathophysiological brain conditions, such as the ones obtained using experimental animal models of brain stroke. More detailed information about our research can be found in our laboratory's webpage: Cerebral Microcirculation Unit



Functional reactivity of cerebral capillaries




Left Panels: Three-dimensional images of the cerebral vasculature in rat somatosensory cortex, obtained during electrical stimulation of the rat forepaw. Colored vessels show examples of volumetric segmentation of individual capillaries, arterioles, and venules. Middle Panels: Histograms of stimulation-induced volume changes of small vessels and medium vessels show a robust positive mean CBV increase across vessels of all sizes, the smallest vessels showing the largest changes in CBV in response to stimulation. Right Panels: Vessel-wise blood volume changes show heterogeneous reactivity of capillaries, in comparison with a net positive blood volume increase in arterioles and venules (left). Plot of the flux of red blood cells (RBC) show an increase consistent with increased RCB velocity and vessel volume during stimulation (right). For further info please refer to:www.nature.com/

Our current studies focus on using two-photon laser scanning microscopy (2PLSM) to measure the hemodynamic response to somatosensory stimulation in anesthetized rats. The goal of these experiments is to investigate whether the observed dissociation between increases in red blood cell (RBC) velocities and capillary dilatation in response to mild hypercapnia are also present during increased hyperemia induced by neuronal activation. We use bolus tracking methods to estimate vascular transit times. We then measure transit times at rest and during somatosensory stimulation, and use their variation to validate the selection of the region of interest. However, because of a reported evidence for focal, rather than distributed, regulation of capillary diameter, we improved on the methodology to now measure intraluminar vessel volumes, rather than relying on single point estimates of capillary diameter to establish its volumetric reactivity to increased neural activity.

Staff Image
  • Sang-ho Choi, Ph.D.
    Research Fellow
    (301) 402-3753

  • Julie Mackel
    Contractor
    301-402-1457

  • Daniel Papoti, Ph.D.
    Visiting Fellow
    (301) 594-3032

  • Cecil Chern-Chyi Yen, Ph.D.
    Visiting Fellow
    (301) 594-3031

  • Renshu Zhang
    Contractor
    301-451-7223

  • Lisa (Xianfen) Zhang
    Contractor
    301-594-2537

  • 1) Lee J, Hirano Y, Fukunaga M, Silva AC, Duyn JH (2009)
  • On the contribution of deoxy-hemoglobin to MRI gray-white matter phase contrast at high field.
  • Neuroimage, July, 17
  • 2) Chuang KH, Lee JH, Silva AC, Belluscio L, Koretsky AP (2009)
  • Manganese enhanced MRI reveals functional circuitry in response to odorant stimuli
  • Neuroimage, Jan 15;44(2), 363-72
  • 3) J. Tucciarone, K-H Chuang, S.J. Dodd, A. Silva, G. Pelled, and A.P. Koretsky (2009)
  • Layer Specific Tracing of Corticocortical and Thalamocortical Connectivity in the Rodent Using Manganese Enhanced MRI
  • Neuroimage, 44, 923-931
  • 4) Silva AC, Paiva FF (2009)
  • Dynamic magnetic resonance imaging of cerebral blood flow using arterial spin labeling
  • Methods Mol Biol, 489, 277-95
  • 5) Bock NA, Kocharyan A, Silva AC (2009)
  • Manganese-enhanced MRI visualizes V1 in the non-human primate visual cortex
  • NMR Biomed, Mar, 25
  • 6) Silva AC, Lee JH, Wu CW, Tucciarone J, Pelled G, Aoki I, Koretsky AP (2008)
  • Detection of cortical laminar architecture using manganese-enhanced MRI
  • J Neurosci Meth, 167(2), 246-57
  • 7) Bock NA, Paiva FF, Nascimento GC, Newman JD, Silva AC (2008)
  • Cerebrospinal fluid to brain transport of manganese in a non-human primate revealed by MRI
  • Brain Res, 1198, 160-70
  • 8) Silva AC, Bock NA (2008)
  • Manganese-enhanced MRI: an exceptional tool in translational neuroimaging
  • Schizophr Bull, 34(4), 595-604
  • 9) Goloshevsky AG, Silva AC, Dodd SJ, Koretsky AP (2008)
  • BOLD fMRI and somatosensory evoked potentials are well correlated over a broad range of frequency content of somatosensory stimulation of the rat forepaw
  • Brain Res, 1195, 67-76
  • 10) Stefanovic B, Hutchinson E, Yakovleva V, Schram V, Russell JT, Belluscio L, Koretsky AP, Silva AC (2008)
  • Functional reactivity of cerebral capillaries
  • J Cereb Blood Flow Metab, 28(5), 961-72
  • 11) Paiva FF, Tannus A, Talagala SL, Silva AC (2008)
  • Arterial spin labeling of cerebral perfusion territories using a separate labeling coil
  • J Magn Reson Imaging, 27(5), 970-7
  • 12) Bock NA, Paiva FF, Silva AC (2008)
  • Fractionated manganese-enhanced MRI
  • NMR Biomed, 21(5), 473-8
  • 13) Paiva FF, Tannus A, Silva AC (2007)
  • Measurement of cerebral perfusion territories using arterial spin labelling
  • NMR Biomed, 20(7), 633-42
  • 14) Silva AC, Koretsky AP, Duyn JH (2007)
  • Functional MRI impulse response for BOLD and CBV contrast in rat somatosensory cortex
  • Magn Reson Med, 57(6), 1110-8
  • 15) de Sousa PL, de Souza SL, Silva AC, de Souza RE, de Castro RM (2007)
  • Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl2: changes in T1 relaxation times during postnatal development
  • J Magn Reson Imaging, 25(1), 32-8
  • 16) Stefanovic B, Schwindt W, Hoehn M, Silva AC (2007)
  • Functional uncoupling of hemodynamic from neuronal response by inhibition of neuronal nitric oxide synthase
  • J Cereb Blood Flow Metab, 27(4), 741-54
  • 17) Hutchinson EB, Stefanovic B, Koretsky AP, Silva AC (2006)
  • Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia
  • Neuroimage, 32(2), 520-30
  • 18) Petridou N, Plenz D, Silva AC, Loew M, Bodurka J, Bandettini PA (2006)
  • Direct magnetic resonance detection of neuronal electrical activity
  • Proc Natl Acad Sci USA, 103(43), 16015-20
  • 19) Stefanovic B, Bosetti F, Silva AC (2006)
  • Modulatory role of cyclooxygenase-2 in cerebrovascular coupling
  • Neuroimage, 32(1), 23-32
  • 20) I. Aoki, Y. Takahashi, K.-H. Chuang, A. C. Silva, T. Igarashi, C. Tanaka, R. W. Childs, A. P. Koretsky (2006)
  • Cell labeling for magnetic resonance imaging with the T1 agent manganese chloride
  • NMR in Biomedicine, 19(1), 50-59
  • 21) S. D. Keilholz, A. C. Silva, M. Raman, H. Merkle, A. P. Koretsky (2006)
  • BOLD and CBV-Weighted Functional Magnetic Resonance Imaging of the Rat Somatosensory System
  • Magnetic Resonance in Medicine, 55(2), 316–324
  • 23) Chen Z, Silva AC, Yang J, Shen J. (2005)
  • Elevated endogenous GABA level correlates with decreased fMRI signals in the rat brain during acute inhibition of GABA transaminase
  • J Neurosci Res., 79(3), 383-391
  • 24) J. A. de Zwart, A. C. Silva, P. van Gelderen, P. Kellman, M. Fukunaga, R. Chu, A. P. Koretsky, J. A. Frank, J. H. Duyn (2005)
  • Temporal dynamics of the BOLD fMRI impulse response
  • Neuroimage, 24(3), 667-677
  • 25) J. H. Lee, A. C. Silva, H. Merkle, A. P. Koretsky (2005)
  • Manganese-enhanced magnetic resonance imaging of mouse brain after systemic administration of MnCl2: dose-dependent and temporal evolution of T1 contrast
  • Magnetic Resonance in Medicine, 53(3), 640-648
  • 26) A. P. Koretsky and A. C. Silva (2004)
  • Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)
  • NMR in Biomedicine, 17(8), 527-531
  • 27) A. C. Silva, J. H. Lee, I. Aoki, and A. P. Koretsky (2004)
  • Manganese-Enhanced Magnetic Resonance Imaging (MEMRI): Methodological and Practical Considerations
  • NMR in Biomedicine, 17(8), 532-534
  • 28) S. Keilholz, A. C. Silva, M. Raman, H. Merkle, and A. P. Koretsky (2004)
  • Functional MRI of the Rodent Somatosensory Pathway Using Multi-slice Echo Planar Imaging
  • Magn. Reson. Med, 52(1), 89-99
  • 29) Aoki I, Wu YJ, Silva AC, Lynch RM, Koretsky AP. (2004)
  • In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI.
  • Neuroimage, 22(3), 1046-1059
  • 30) Hinds KA, Hill JM, Shapiro EM, Laukkanen MO, Silva AC, Combs CA, Varney TR, Balaban RS, Koretsky AP, Dunbar CE. (2003)
  • Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells.
  • Blood, 102(3), 867-872
  • 31) C. Grabill, A. C. Silva, S. S. Smith, A.P. Koretsky and T. A. Rouault (2003)
  • MRI detection of iron distribution and associated neuronal pathology in iron regulatory protein-2 knockout mice
  • Brain Res, 971 (1), 95-106
  • 32) Lee SP, Silva AC, Kim SG. (2002)
  • Comparison of diffusion-weighted high-resolution CBF and spin-echo BOLD fMRI at 9.4 T.
  • Magn Reson Med, 47(4), 736-741
  • 33) Aoki I, Tanaka C, Takegami T, Ebisu T, Umeda M, Fukunaga M, Fukuda K, Silva AC, Koretsky AP, Naruse S. (2002)
  • Dynamic activity-induced manganese-dependent contrast magnetic resonance imaging (DAIM MRI).
  • Magn Reson Med., 48(6), 927-933
  • 34) A. C. Silva and A. P. Koretsky (2002)
  • Laminar specificity of fMRI onset times during somatosensory stimulation in rat
  • Proc. Natl. Acad. Sci., 99 (23), 15182-15187
  • 35) A. C. Silva, S.-P. Lee, C. Iadecola and S.-G. Kim (2000)
  • Early temporal characteristics of CBF and deoxyhemoglobin changes during somatosensory stimulation
  • J. Cereb. Blood Flow Metab, 20(1), 201-206
  • 36) T. Duong, A. C. Silva, S.-P. Lee, and S.-G. Kim (2000)
  • Functional MRI of calcium-dependent synaptic activity: cross correlation with CBF and BOLD measurements
  • Magn. Reson. Med, 43(3), 383-392
  • 37) A. C. Silva, S.-G. Kim and M. Garwood (2000)
  • Imaging Blood Flow in Brain Tumors Using Arterial Spin Labeling
  • Magn. Reson. Med, 44(2), 169-173
  • 38) Lee SP, Silva AC, Ugurbil K, Kim SG. (1999)
  • Diffusion-weighted spin-echo fMRI at 9.4 T: microvascular/tissue contribution to BOLD signal changes.
  • Magn Reson Med. , 42(5), 919-928
  • 39) E. L. Barbier, A. C. Silva, H. J. Kim, D. S. Williams and A. P. Koretsky (1999)
  • Perfusion analysis using dynamic arterial spin labeling (DASL)
  • Magn. Reson. Med, 41, 299-308
  • 40) A. C. Silva, S.-P. Lee, G. Yang, C. Iadecola and S.-G. Kim (1999)
  • Simultaneous BOLD and CBF based functional MRI during forepaw stimulation in rat.
  • J. Cereb. Blood Flow Metab, 19(8), 871-879
  • 41) A. C. Silva and S.-G. Kim (1999)
  • Pseudo-continuous arterial spin labeling technique for measuring CBF dynamics with high temporal resolution
  • Magn. Reson. Med, 43(2), 425-429
  • 42) Barbier EL, Silva AC, Kim HJ, Williams DS, Koretsky AP. (1999)
  • Perfusion analysis using dynamic arterial spin labeling (DASL).
  • Magn Reson Med, 41(2), 299-308
  • 43) Forman SD, Silva AC, Dedousis N, Barbier EL, Fernstrom JD, Koretsky AP. (1998)
  • Simultaneous glutamate and perfusion fMRI responses to regional brain stimulation.
  • J Cereb Blood Flow Metab, 18(10), 1064-1070
  • 44) A. C. Silva, E. L. Barbier, I. J. Lowe, and A. P. Koretsky (1998)
  • Radial Echo-Planar Imaging (rEPI)
  • J. Magn. Reson. Med, 135, 242-247
  • 45) R. G. Pautler, A. C. Silva and A. P. Koretsky (1998)
  • In vivo neuronal tract tracing using manganese enhanced magnetic resonance imaging
  • Magn. Reson. Med., 40, 740-748
  • 46) Silva AC, Zhang W, Williams DS, Koretsky AP. (1997)
  • Estimation of water extraction fractions in rat brain using magnetic resonance measurement of perfusion with arterial spin labeling.
  • Magn Reson Med, 37(1), 58-68
  • 47) Silva AC, Williams DS, Koretsky AP. (1997)
  • Evidence for the exchange of arterial spin-labeled water with tissue water in rat brain from diffusion-sensitized
  • Magn Reson Med, 38(2), 232-237
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