title: Optical Coherence Tomography angiography reveals laminar microvascular hemodynamics in the rat somatosensory cortex during activation.
abstract: The BOLD (blood-oxygen-level dependent) fMRI (functional Magnetic Resonance Imaging) signal is shaped, in part, by changes in red blood cell (RBC) content and flow across vascular compartments over time. These complex dynamics have been challenging to characterize directly due to a lack of appropriate imaging modalities. In this study, making use of infrared light scattering from RBCs, depth-resolved Optical Coherence Tomography (OCT) angiography was applied to image laminar functional hyperemia in the rat somatosensory cortex. After defining and validating depth-specific metrics for changes in RBC content and speed, laminar hemodynamic responses in microvasculature up to cortical depths of >1mm were measured during a forepaw stimulus. The results provide a comprehensive picture of when and where changes in RBC content and speed occur during and immediately following cortical activation. In summary, the earliest and largest microvascular RBC content changes occurred in the middle cortical layers, while post-stimulus undershoots were most prominent superficially. These laminar variations in positive and negative responses paralleled known distributions of excitatory and inhibitory synapses, suggesting neuronal underpinnings. Additionally, the RBC speed response consistently returned to baseline more promptly than RBC content after the stimulus across cortical layers, supporting a "flow-volume mismatch" of hemodynamic origin.
authors.affiliation: Department of Biomedical Engineering, University of California at Davis, 451 E. Health Sciences Dr. GBSF 2303, Davis, CA 95616, USA. Electronic address: vjsriniv@ucdavis.edu.
authors.forename: Vivek J
authors.initials: VJ
authors.lastname: Srinivasan
authors.affiliation: Department of Biomedical Engineering, University of California at Davis, 451 E. Health Sciences Dr. GBSF 2303, Davis, CA 95616, USA.
authors.forename: Harsha
authors.initials: H
authors.lastname: Radhakrishnan
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D006439:Hemodynamics; D008297:Male; D055806:Microvessels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000502:physiology*; D041623:Tomography, Optical Coherence
keywords: Blood volume; Blood-oxygen-level-dependent; Forepaw; Hematocrit; Hemodynamics; Laminar; Neurovascular coupling; Optical Coherence Tomography; Scattering; Somatosensory cortex; Three-dimensional microscopy; functional Magnetic Resonance Imaging
references.citation: Neuroimage. 2011 Jan 15;54(2):1021-30
references.pmid: 20858545
references.citation: J Cereb Blood Flow Metab. 1997 Dec;17(12):1326-36
references.pmid: 9397032
references.citation: Nat Photonics. 2013 Mar 1;7(3):
references.pmid: 24353743
references.citation: J Neurosci Methods. 2003 Mar 30;124(1):83-92
references.pmid: 12648767
references.citation: Neuroimage. 2008 Jun;41(2):189-203
references.pmid: 18420425
references.citation: Opt Express. 2003 Apr 21;11(8):889-94
references.pmid: 19461802
references.citation: J Neurosci. 2004 Apr 14;24(15):3850-61
references.pmid: 15084666
references.citation: J Cereb Blood Flow Metab. 2009 Jan;29(1):19-24
references.pmid: 18766196
references.citation: J Neurosci. 2005 Mar 2;25(9):2233-44
references.pmid: 15745949
references.citation: Nature. 2008 Jun 12;453(7197):869-78
references.pmid: 18548064
references.citation: Neuroimage. 2012 Jan 16;59(2):1451-60
references.pmid: 21851857
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15182-7
references.pmid: 12407177
references.citation: Proc Natl Acad Sci U S A. 1990 Aug;87(16):6082-6
references.pmid: 2117272
references.citation: J Neurosci. 2004 Jan 21;24(3):634-41
references.pmid: 14736849
references.citation: Neuroimage. 2000 Dec;12(6):664-75
references.pmid: 11112398
references.citation: Opt Lett. 1994 Apr 15;19(8):590-2
references.pmid: 19844382
references.citation: Magn Reson Med. 1999 Sep;42(3):591-8
references.pmid: 10467305
references.citation: Neuroimage. 2005 Aug 15;27(2):279-90
references.pmid: 15925522
references.citation: Phys Med Biol. 2000 Dec;45(12):3749-64
references.pmid: 11131197
references.citation: PLoS One. 2011 Apr 29;6(4):e18914
references.pmid: 21559482
references.citation: Nat Med. 2009 Oct;15(10):1219-23
references.pmid: 19749772
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13081-6
references.pmid: 14569029
references.citation: Nat Methods. 2014 Jan;11(1):55-8
references.pmid: 24240320
references.citation: Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5951-5
references.pmid: 1631079
references.citation: Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5675-9
references.pmid: 1608978
references.citation: Nat Neurosci. 2013 Jul;16(7):889-97
references.pmid: 23749145
references.citation: J Neurosci. 2004 Oct 13;24(41):8940-9
references.pmid: 15483113
references.citation: Opt Express. 2008 Aug 4;16(16):12350-61
references.pmid: 18679512
references.citation: Opt Express. 2007 Apr 2;15(7):4083-97
references.pmid: 19532651
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15741-6
references.pmid: 9861040
references.citation: Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15115-20
references.pmid: 23980158
references.citation: Brain Res. 2004 Jan 2;995(1):66-75
references.pmid: 14644472
references.citation: Neuroimage. 2006 Feb 1;29(3):879-87
references.pmid: 16194614
references.citation: J Cereb Blood Flow Metab. 2007 Jun;27(6):1248-61
references.pmid: 17213863
references.citation: Neuron. 2002 Jul 18;35(2):227-42
references.pmid: 12160742
references.citation: Neuroimage. 2007 Feb 1;34(3):1084-92
references.pmid: 17161623
references.citation: Proc Natl Acad Sci U S A. 2011 May 17;108(20):8473-8
references.pmid: 21536897
references.citation: Neuroimage. 2009 Jul 1;46(3):559-68
references.pmid: 19303450
references.citation: J Cereb Blood Flow Metab. 2012 Jul;32(7):1233-47
references.pmid: 22510601
references.citation: Brain. 1980 Jun;103(2):245-58
references.pmid: 6772267
references.citation: J Neurophysiol. 2007 Mar;97(3):2174-90
references.pmid: 17182911
references.citation: Opt Express. 2009 Aug 3;17(16):13354-64
references.pmid: 19654740
references.citation: Exp Brain Res. 1986;63(3):607-19
references.pmid: 3758272
references.citation: Magn Reson Med. 2004 Nov;52(5):1060-8
references.pmid: 15508149
references.citation: Biomed Opt Express. 2013 Jul 02;4(8):1255-68
references.pmid: 24009990
references.citation: Science. 1991 Nov 22;254(5035):1178-81
references.pmid: 1957169
references.citation: J Cereb Blood Flow Metab. 2008 May;28(5):961-72
references.pmid: 18059431
references.citation: Neuroimage. 2013 Jun;73:113-20
references.pmid: 23384528
references.citation: Neuron. 2002 Dec 19;36(6):1195-210
references.pmid: 12495632
references.citation: J Neurosci Methods. 2009 Mar 30;178(1):162-73
references.pmid: 19121336
references.citation: Opt Lett. 2008 Jul 1;33(13):1530-2
references.pmid: 18594688
references.citation: Neuroimage. 2004 Jan;21(1):144-53
references.pmid: 14741651
references.citation: Magn Reson Med. 1999 Nov;42(5):944-51
references.pmid: 10542354
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14826-31
references.pmid: 9405698
references.citation: Neuroimage. 2001 Jun;13(6 Pt 1):953-8
references.pmid: 11352601
references.citation: J Magn Reson Imaging. 2008 Mar;27(3):599-606
references.pmid: 18219630
references.citation: Hum Brain Mapp. 1999;8(2-3):109-14
references.pmid: 10524601
references.citation: J Cereb Blood Flow Metab. 2011 Oct;31(10):1999-2008
references.pmid: 21505479
references.citation: Neuroimage. 2006 May 1;30(4):1149-60
references.pmid: 16414284
references.citation: Opt Express. 2007 Oct 1;15(20):12636-53
references.pmid: 19550532
references.citation: Biomed Opt Express. 2012 Mar 1;3(3):612-29
references.pmid: 22435106
references.citation: Neuroimage. 2008 Oct 15;43(1):1-9
references.pmid: 18655837
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15246-51
references.pmid: 20696904
references.citation: Trends Neurosci. 1989 Mar;12(3):94-101
references.pmid: 2469224
references.citation: Appl Phys Lett. 2012 Jun 4;100(23):233702-2337024
references.pmid: 22904572
references.citation: Magn Reson Med. 1998 Apr;39(4):615-24
references.pmid: 9543424
references.citation: Opt Express. 2012 Jan 30;20(3):2220-39
references.pmid: 22330462
references.citation: J Neurophysiol. 2012 Jun;107(11):3116-34
references.pmid: 22402650
references.citation: Magn Reson Imaging. 2006 May;24(4):381-92
references.pmid: 16677944
references.citation: Annu Rev Neurosci. 2006;29:449-76
references.pmid: 16776593
references.citation: J Cereb Blood Flow Metab. 2006 May;26(5):634-44
references.pmid: 16222242
references.citation: Neuron. 2012 Nov 8;76(3):629-39
references.pmid: 23141073
references.citation: Neuroimage. 2007 Mar;35(1):89-104
references.pmid: 17222567