Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy.
The combination of intravital microscopy and animal models of disease has propelled studies of disease mechanisms and treatments. However, many disorders afflict tissues inaccessible to light microscopy in live subjects. Here we introduce cellular-level time-lapse imaging deep within the live mammalian brain by one- and two-photon fluorescence microendoscopy over multiple weeks. Bilateral imaging sites allowed longitudinal comparisons within individual subjects, including of normal and diseased tissues. Using this approach, we tracked CA1 hippocampal pyramidal neuron dendrites in adult mice, revealing these dendrites' extreme stability and rare examples of their structural alterations. To illustrate disease studies, we tracked deep lying gliomas by observing tumor growth, visualizing three-dimensional vasculature structure and determining microcirculatory speeds. Average erythrocyte speeds in gliomas declined markedly as the disease advanced, notwithstanding significant increases in capillary diameters. Time-lapse microendoscopy will be applicable to studies of numerous disorders, including neurovascular, neurological, cancerous and trauma-induced conditions.
James H. Clark Center for Biomedical Engineering & Sciences, Stanford University, Stanford, California, USA.
Robert P J
RP
Barretto
Tony H
TH
Ko
Juergen C
JC
Jung
Tammy J
TJ
Wang
George
G
Capps
Allison C
AC
Waters
Yaniv
Y
Ziv
Alessio
A
Attardo
Lawrence
L
Recht
Mark J
MJ
Schnitzer
D000818:Animals; D001927:Brain Diseases / Q000473:pathology*; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000098:blood supply / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D008856:Microscopy, Fluorescence / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000473:pathology; D017966:Pyramidal Cells / Q000473:pathology; D059008:Time-Lapse Imaging / Q000379:methods*
Cancer Res. 1994 Sep 1;54(17):4564-8
8062241
Nature. 2004 Mar 18;428(6980):328-32
15029197
J Neurosci. 2003 Mar 15;23(6):2212-7
12657680
Nat Med. 2005 Dec;11(12):1355-60
16286922
Nat Neurosci. 2004 Nov;7(11):1181-3
15475950
Nat Med. 2005 May;11(5):572-7
15821747
Nat Methods. 2005 Dec;2(12):941-50
16299479
Nat Med. 2008 Mar;14(3):255-7
18278052
Nat Rev Neurosci. 2006 Jun;7(6):449-63
16715054
Nature. 2008 Aug 7;454(7205):784-8
18600262
Neuro Oncol. 2007 Jul;9(3):319-25
17522333
Opt Lett. 2003 Jun 1;28(11):902-4
12816240
J Neurosurg. 2008 Apr;108(4):782-90
18377259
Nat Med. 2008 Apr;14(4):454-8
18345013
Neuro Oncol. 2007 Oct;9(4):424-9
17622647
Nat Neurosci. 2009 Feb;12(2):116-8
19151711
J Neurosci. 2004 Mar 31;24(13):3147-51
15056694
J Comp Neurol. 1998 Feb 16;391(3):335-52
9492204
J Neurosci. 2008 Nov 12;28(46):11970-9
19005062
Nature. 2002 Dec 19-26;420(6917):812-6
12490949
PLoS Biol. 2006 Feb;4(2):e29
16366735
Curr Top Dev Biol. 2009;87:149-74
19427519
Nature. 2008 Feb 7;451(7179):720-4
18256671
Nat Methods. 2005 Dec;2(12):932-40
16299478
J Neurophysiol. 2004 Nov;92(5):3121-33
15128753
Nat Methods. 2009 Jul;6(7):511-2
19525959
Nat Neurosci. 2007 May;10(5):549-51
17417634
Nat Rev Neurosci. 2007 Aug;8(8):610-22
17643088
Nat Methods. 2008 Nov;5(11):935-8
18836457
J Neurophysiol. 2004 Apr;91(4):1908-12
14668300
Microvasc Res. 1995 Jul;50(1):35-44
7476578
Nature. 2002 Dec 19-26;420(6917):788-94
12490942
J Neurosci. 1987 Apr;7(4):1215-22
3572477
Cancer Sci. 2006 Jun;97(6):546-53
16734735
J Neurol Sci. 2007 Sep 15;260(1-2):49-56
17475281
Genes Brain Behav. 2006;5 Suppl 2:48-60
16681800
Annu Rev Pathol. 2006;1:97-117
18039109
Neuron. 2000 Oct;28(1):41-51
11086982
J Neurophysiol. 2007 Sep;98(3):1791-805
17634346
Nat Rev Drug Discov. 2008 Jan;7(1):54-67
18079755
Epilepsia. 2008 Jun;49 Suppl 5:13-8
18522596