title: Compartment-resolved imaging of activity-dependent dynamics of cortical blood volume and oximetry.
abstract: Optical imaging, positron emission tomography, and functional magnetic resonance imaging (fMRI) all rely on vascular responses to image neuronal activity. Although these imaging techniques are used successfully for functional brain mapping, the detailed spatiotemporal dynamics of hemodynamic events in the various microvascular compartments have remained unknown. Here we used high-resolution optical imaging in area 18 of anesthetized cats to selectively explore sensory-evoked cerebral blood-volume (CBV) changes in the various cortical microvascular compartments. To avoid the confounding effects of hematocrit and oximetry changes, we developed and used a new fluorescent blood plasma tracer and combined these measurements with optical imaging of intrinsic signals at a near-isosbestic wavelength for hemoglobin (565 nm). The vascular response began at the arteriolar level, rapidly spreading toward capillaries and venules. Larger veins lagged behind. Capillaries exhibited clear blood-volume changes. Arterioles and arteries had the largest response, whereas the venous response was smallest. Information about compartment-specific oxygen tension dynamics was obtained in imaging sessions using 605 nm illumination, a wavelength known to reflect primarily oximetric changes, thus being more directly related to electrical activity than CBV changes. Those images were radically different: the response began at the parenchyma level, followed only later by the other microvascular compartments. These results have implications for the modeling of fMRI responses (e.g., the balloon model). Furthermore, functional maps obtained by imaging the capillary CBV response were similar but not identical to those obtained using the early oximetric signal, suggesting the presence of different regulatory mechanisms underlying these two hemodynamic processes.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel. ivo.vanzetta@incm.cnrs-mrs.fr
authors.forename: Ivo
authors.initials: I
authors.lastname: Vanzetta
authors.forename: Rina
authors.initials: R
authors.lastname: Hildesheim
authors.forename: Amiram
authors.initials: A
authors.lastname: Grinvald
mesh_terms: D000818:Animals; D001931:Brain Mapping; D002415:Cats; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003952:Diagnostic Imaging / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D017711:Nonlinear Dynamics; D010092:Oximetry; D010100:Oxygen / Q000097:blood*; D010775:Photic Stimulation / Q000379:methods; D015203:Reproducibility of Results; D013997:Time Factors; D014793:Visual Cortex / Q000098:blood supply* / Q000502:physiology
chemical_list: D010100:Oxygen
references.citation: Science. 1996 Apr 26;272(5261):551-4
references.pmid: 8614805
references.citation: J Neurosci. 2003 May 15;23(10):3963-71
references.pmid: 12764080
references.citation: J Neurosci. 1993 Oct;13(10):4157-80
references.pmid: 8410182
references.citation: Hum Brain Mapp. 2001 Dec;14(4):210-7
references.pmid: 11668652
references.citation: Neuron. 2001 Oct 25;32(2):359-74
references.pmid: 11684004
references.citation: J Neurosci Methods. 1991 Feb;36(2-3):127-37
references.pmid: 1905769
references.citation: Neuroimage. 2003 Jul;19(3):884-94
references.pmid: 12880817
references.citation: J Neurosci. 2004 Apr 14;24(15):3850-61
references.pmid: 15084666
references.citation: Science. 1997 Jun 27;276(5321):2034-7
references.pmid: 9197264
references.citation: Proc Natl Acad Sci U S A. 1990 Aug;87(16):6082-6
references.pmid: 2117272
references.citation: Magn Reson Med. 2003 Apr;49(4):655-64
references.pmid: 12652536
references.citation: J Neurosci. 2004 Jan 21;24(3):634-41
references.pmid: 14736849
references.citation: Neuroimage. 2004;23 Suppl 1:S220-33
references.pmid: 15501093
references.citation: Neuroimage. 2000 Apr;11(4):302-12
references.pmid: 10725186
references.citation: Phys Med Biol. 2000 Dec;45(12):3749-64
references.pmid: 11131197
references.citation: J Neurophysiol. 1997 May;77(5):2780-7
references.pmid: 9163392
references.citation: J Physiol. 1949 May;108(3):278-81
references.pmid: 18149764
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13081-6
references.pmid: 14569029
references.citation: Nat Neurosci. 2003 Jan;6(1):5-6
references.pmid: 12494240
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10904-9
references.pmid: 11526212
references.citation: Magn Reson Med. 2000 Aug;44(2):231-42
references.pmid: 10918322
references.citation: Neurosci Lett. 2001 Jun 22;306(1-2):106-10
references.pmid: 11403969
references.citation: J Neurosci. 1997 Mar 15;17(6):2112-27
references.pmid: 9045738
references.citation: Neuroimage. 2001 Nov;14(5):977-94
references.pmid: 11697930
references.citation: Science. 1999 Jan 22;283(5401):496-7
references.pmid: 9988650
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15741-6
references.pmid: 9861040
references.citation: Magn Reson Med. 1998 Jun;39(6):855-64
references.pmid: 9621908
references.citation: News Physiol Sci. 1999 Oct;14:177-182
references.pmid: 11390847
references.citation: Science. 1996 Jun 14;272(5268):1665-8
references.pmid: 8658144
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16000-5
references.pmid: 14673091
references.citation: J Physiol. 1982 Dec;333:269-91
references.pmid: 7182467
references.citation: Microvasc Res. 1998 Jul;56(1):43-53
references.pmid: 9683562
references.citation: Nat Neurosci. 2000 May;3(5):413-4
references.pmid: 10769371
references.citation: Science. 1999 Nov 19;286(5444):1555-8
references.pmid: 10567261
references.citation: Neuroimage. 2002 Sep;17(1):1-18
references.pmid: 12482064
references.citation: Brain Res. 1981 Mar 9;208(1):35-58
references.pmid: 7470927
references.citation: Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1294-8
references.pmid: 10749727
references.citation: Neuroimage. 2001 Jun;13(6 Pt 1):975-87
references.pmid: 11352604
references.citation: Cerebrovasc Brain Metab Rev. 1995 Fall;7(3):240-76
references.pmid: 8519605
references.citation: Science. 2003 Feb 14;299(5609):1070-2
references.pmid: 12586942
references.citation: J Physiol. 1890 Jan;11(1-2):85-158.17
references.pmid: 16991945
references.citation: Neuroimage. 1999 Sep;10(3 Pt 1):304-26
references.pmid: 10458944
references.citation: J Neurosci. 1985 Jul;5(7):1886-95
references.pmid: 4020423
references.citation: J Cereb Blood Flow Metab. 1993 Nov;13(6):899-913
references.pmid: 8408316
references.citation: Nature. 1996 Feb 22;379(6567):725-8
references.pmid: 8602218
references.citation: Brain Res. 1983 Dec 19;289(1-2):65-70
references.pmid: 6661656
references.citation: J Physiol. 1973 Jun;231(2):365-83
references.pmid: 4352767
references.citation: Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10625-9
references.pmid: 7938003
references.citation: J Neurosci. 1996 Nov 1;16(21):6945-64
references.pmid: 8824332
references.citation: J Cereb Blood Flow Metab. 2002 Mar;22(3):353-60
references.pmid: 11891441
references.citation: Proc Natl Acad Sci U S A. 2001 May 22;98(11):6417-22
references.pmid: 11344262
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4239-44
references.pmid: 12655065
references.citation: Neuroscientist. 2004 Feb;10(1):53-62
references.pmid: 14987448
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14826-31
references.pmid: 9405698
references.citation: Nat Neurosci. 2003 Jan;6(1):43-50
references.pmid: 12469126
references.citation: Trends Neurosci. 2003 Feb;26(2):108-14
references.pmid: 12536134
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12456-61
references.pmid: 14530410
references.citation: Neuroimage. 2001 Jun;13(6 Pt 1):959-67
references.pmid: 11352602
references.citation: Magn Reson Med. 2001 May;45(5):791-800
references.pmid: 11323805
references.citation: Nat Neurosci. 2000 Feb;3(2):105-7
references.pmid: 10649563
references.citation: Cereb Cortex. 2002 Mar;12(3):225-33
references.pmid: 11839597
references.citation: Nature. 1986 Nov 27-Dec 3;324(6095):361-4
references.pmid: 3785405
references.citation: J Neurophysiol. 2002 Sep;88(3):1545-58
references.pmid: 12205174
references.citation: Magn Reson Med. 1997 Jun;37(6):877-84
references.pmid: 9178239
references.citation: Ren Physiol Biochem. 1994 May-Aug;17(3-4):168-71
references.pmid: 7518950
references.citation: Neuroimage. 1998 May;7(4 Pt 1):326-36
references.pmid: 9626673
references.citation: J Neurosci. 1991 May;11(5):1458-69
references.pmid: 1851222
references.citation: Nature. 1991 Oct 3;353(6343):429-31
references.pmid: 1896085
references.citation: Neuron. 2004 Jun 10;42(5):843-54
references.pmid: 15182722
references.citation: Nat Neurosci. 2000 Feb;3(2):164-9
references.pmid: 10649572
references.citation: Neuroimage. 2001 Jun;13(6 Pt 1):988-1001
references.pmid: 11352605
references.citation: J Cereb Blood Flow Metab. 1997 Jan;17(1):64-72
references.pmid: 8978388