Early diagnosis of ischemic stroke is crucial for timely intervention and saving brain function. The mechanisms of stroke are complex, involving multiple parameters such as blood flow perfusion, tissue status, and oxygenation levels. These parameters interact with each other, necessitating multiple systems to evaluate. The animal model must be moved among systems for various systems monitoring, which complicates the operation and may induce additional interference. Here, we propose a non-contact all-optic OCT-PAM dual-mode imaging system for monitoring rat cortex states. The compact probe enables facilitating long-term multi-parameter observation. Using the system, we quantitatively monitored the state of the rat cortex of ischemic stroke during the acute phase, including blood perfusion density, vessel diameter, vessel length, optical attenuation coefficient, and photoacoustic absorption. We observed reduced perfusion in the affected cortex, contralateral perfusion increases, and vasodilation, suggesting collateral circulation activation. Additionally, increased optical attenuation and photoacoustic absorption in the stroke area were linked to blood-brain barrier changes. This OCT-PAM system and its quantitative analysis method offer a promising tool for early ischemic stroke diagnosis and exploring underlying molecular and cellular mechanisms.
StrongKMathersCBonitaR.Preventing stroke: saving lives around the world. Lancet Neurol2007;
6: 182–187.
2.
FeiginVLForouzanfarMHKrishnamurthiR, et al.
Global and regional burden of stroke during 1990–2010: findings from the global burden of disease study 2010. Lancet2014;
383: 245–254.
3.
FeiginVLNorrvingBMensahGA.Global burden of stroke. Circ Res2017;
120: 439–448.
GoASMozaffarianDRogerVL, et al.
Executive summary: heart disease and stroke statistics – 2014 update A. Rep Am Heart Assoc Circul2014;
129: 399–410.
6.
ChoiWJLiYDWangRKK.Monitoring acute stroke progression: multi-parametric OCT imaging of cortical perfusion, flow, and tissue scattering in a mouse model of permanent focal ischemia. IEEE Trans Med Imaging2019;
38: 1427–1437.
7.
BaronJC.Perfusion thresholds in human cerebral ischemia: historical perspective and therapeutic implications. Cerebrovasc Dis2001;
11: 2–8.
8.
ZinkstokSMRoosYBInvestigatorsA.Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet2012;
380: 731–737.
9.
KleindorferDLindsellCJBrassL, et al.
National US estimates of recombinant tissue plasminogen activator use – ICD-9 codes substantially underestimate. Stroke2008;
39: 924–928.
10.
PaciaroniMBandiniFAgnelliG, et al.
Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: time to initiation of oral anticoagulant therapy and outcomes. J Am Heart Assoc2018;
7: e010133.
11.
SchaeferPWHunterGJHeJ, et al.
Predicting cerebral ischemic infarct volume with diffusion and perfusion MR imaging. Am J Neuroradiol2002;
23: 1785–1794.
12.
AdusumilliGChristensenSYuenN, et al.
CT perfusion to measure venous outflow in acute ischemic stroke in patients with a large vessel occlusion. J Neurointerv Surg2024;
16: 1046–1052.
13.
GuehlNJDhaynautMHanseeuwBJ, et al.
Measurement of cerebral perfusion indices from the early phase of [18F]MK6240 dynamic tau PET imaging. J Nucl Med2023;
64: 968–975.
14.
ProvostCSoudantMLegrandL, et al.
Magnetic resonance imaging or computed tomography before treatment in acute ischemic stroke effect on workflow and functional outcome. Stroke2019;
50: 659–664.
15.
SakohMOstergaardLGjeddeA.Comparison of multitracer PET and functional MRI in a pig MCAO model for acute ischemic stroke. Keio Univ Symp Life2001;
6: 226–231.
16.
SchoknechtKPragerOVazanaU, et al.
Monitoring stroke progression: imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model. J Cereb Blood Flow Metab2014;
34: 1791–1801.
17.
SchrandtCJKazmiSMSJonesTA, et al.
Chronic monitoring of vascular progression after ischemic stroke using multiexposure speckle imaging and two-photon fluorescence microscopy. J Cereb Blood Flow Metab2015;
35: 933–942.
18.
WangRKJacquesSLMaZ, et al.
Three dimensional optical angiography. Opt Express2007;
15: 4083–4097.
19.
HuangDSwansonEALinCP, et al.
Optical coherence tomography. Science1991;
254: 1178–1181.
LiuJDingNYuY, et al.
Optimized depth-resolved estimation to measure optical attenuation coefficients from optical coherence tomography and its application in cerebral damage determination. J Biomed Opt2019;
24: 1–11.
22.
WangLHVHuS.Photoacoustic tomography: in vivo imaging from organelles to organs. Science2012;
335: 1458–1462.
KimJKweonJYChoiS, et al.
Non-invasive photoacoustic cerebrovascular monitoring of early-stage ischemic strokes. In Vivo, Adv Sci2024;
25.
JeonSKimJLeeD, et al.
Review on practical photoacoustic microscopy. Photoacoustics2019;
15: 100141.
26.
ZhuXYHuangQDiSpiritoA, et al.
Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy. Light-Sci Appl2022;
11: 138.
27.
SeongDHanSKimY, et al.
Precise ischemic stroke model inducing method with minimal tissue damage using localized photoacoustic microscopy. Pro Biomed Opt Imag2024;
12828.
28.
SeongDYiSHanS, et al.
Target ischemic stroke model creation method using photoacoustic microscopy with simultaneous vessel monitoring and dynamic photothrombosis induction. Photoacoustics2022;
27: 100376.
29.
LvJLiSZhangJD, et al.
Photoacoustic imaging dynamically monitors the structural and functional changes of ischemic stroke at a very early stage. Theranostics2020;
10: 816–828.
30.
YangSSLiuKZDingHJ, et al.
Longitudinal intrinsic optical imaging of cortical blood perfusion and tissue damage in focal photothrombosis stroke model. J Cereb Blood Flow Metab2019;
39: 1381–1393.
31.
DolezyczekHTamborskiSMajkaP, et al.
In vivo brain imaging with multimodal optical coherence microscopy in a mouse model of thromboembolic photochemical stroke. Neurophotonics2020;
7: 015002.
32.
LiangXQuanXGengX, et al.
A promising approach for quantifying focal stroke modeling and assessing stroke progression: optical resolution photoacoustic microscopy photothrombosis. Neural Regen Res2025;
20: 2029–2037.
33.
DingNJiangHWXiangB, et al.
Probe fusion all-optic OCT-PAM dual-mode imaging system for biomedical imaging. Photoacoustics2024;
38: 100631.
34.
Percie Du SertNHurstVAhluwaliaA, et al.
The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol2020;
18: e3000410.
35.
MaZHDingNLiZ, et al.
Spectral interference contrast based non-contact photoacoustic microscopy realized by SDOCT. Opt Lett2022;
47: 2895–2898.
36.
MaZHDingNYuY, et al.
Quantification of cerebral vascular perfusion density via optical coherence tomography based on locally adaptive regional growth. Appl Opt2018;
57: 10117–10124.
37.
YuYZhangNXiangB, et al.
Ma, characterization of cerebrovascular impairment induced by amyloid β peptide overload in glymphatic clearance system using swept-source optical coherence tomography. Neurophotonics2023;
10: 015005.
38.
BioseIJDewarDMacraeIM, et al.
Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke. J Cereb Blood Flow Metab2020;
40: 978–990.
39.
ProtzmannJJungFJakobssonL, et al.
Analysis of ischemic stroke-mediated effects on blood-brain barrier properties along the arteriovenous axis assessed by intravital two-photon imaging. Fluids Barriers Cns2024;
21: 35.
40.
UzdenskyAB.Photothrombotic stroke as a model of ischemic stroke. Transl Stroke Res2018;
9: 437–451.
41.
IshikawaMSekizukaEOshioC, et al.
Platelet adhesion and arteriolar dilation in the photothrombosis: observation with the rat closed cranial and spinal windows. J Neurol Sci2002;
194: 59–69.
42.
WatsonBDDietrichWDBustoR, et al.
Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol1985;
17: 497–504.
WangYYenSIan ShihYY, et al.
Topiramate suppresses peri-infarct spreading depolarization and improves outcomes in a rat model of photothrombotic stroke. iScience2024;
27: 110033.
45.
SenersPWoutersAMaïerB, et al.
Role of brain imaging in the prediction of intracerebral hemorrhage following endovascular therapy for acute stroke. Stroke2023;
54: 2192–2203.
46.
WangYLiuGHongD, et al.
White matter injury in ischemic stroke. Prog Neurobiol2016;
141: 45–60.
47.
KnezicABroughtonBRSWiddopRE, et al.
Optimising the photothrombotic model of stroke in the C57BI/6 and FVB/N strains of mouse. Sci Rep2022;
12: 7598.
48.
SommerCJ.Ischemic stroke: experimental models and reality. Acta Neuropathol2017;
133: 245–261.
49.
LiuNWKeCCZhaoYH, et al.
Evolutional characterization of photochemically induced stroke in rats: a multimodality imaging and molecular biological study. Transl Stroke Res2017;
8: 244–256.
50.
VenemaSMUDankbaarJWvan der LugtA, et al.
Cerebral collateral circulation in the era of reperfusion therapies for acute ischemic stroke. Stroke2022;
53: 3222–3234.
51.
RavindranAVKillingsworthMCBhaskarS.Cerebral collaterals in acute ischaemia: implications for acute ischaemic stroke patients receiving reperfusion therapy. Eur J Neurosci2021;
53: 1238–1261.
52.
DirnaglUIadecolaCMoskowitzMA.Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci1999;
22: 391–397.
53.
HossmannKA.Viability thresholds and the penumbra of focal ischemia. Ann Neurol1994;
36: 557–565.
54.
GrefkesCFinkGR.Connectivity-based approaches in stroke and recovery of function. Lancet Neurol2014;
13: 206–216.
55.
CocquytEMDe LeyLSantensP, et al.
The role of the right hemisphere in the recovery of stroke-related aphasia: a systematic review. J Neurolinguist2017;
44: 68–90.
56.
CholletFDiPieroVWiseRJ, et al.
The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. Ann Neurol1991;
29: 63–71.
57.
WittenbergGFChenRIshiiK, et al.
Constraint-induced therapy in stroke: magnetic-stimulation motor maps and cerebral activation. Neurorehabil Neural Repair2003;
17: 197.
58.
TakatsuruYNabekuraJKoibuchiN.Contribution of neuronal and glial circuit in intact hemisphere for functional remodeling after focal ischemia. Neurosci Res2014;
78: 38–44.
59.
SbarbatiAPietraCBaldassarriAM, et al.
The microvascular system in ischemic cortical lesions. Acta Neuropathol1996;
92: 56–63.
60.
ChenSChenYJXuL, et al.
Venous system in acute brain injury: Mechanisms of pathophysiological change and function. Exp Neurol2015;
272: 4–10.
61.
TongLSGuoZNOuYB, et al.
Cerebral venous collaterals: a new fort for fighting ischemic stroke?Prog Neurobiol2018;
163-164: 172–193.
62.
HeitkampCWinkelmeierLHeitJJ, et al.
Unfavorable cerebral venous outflow is associated with futile recanalization in acute ischemic stroke patients. Eur J Neurol2023;
30: 2684–2692.
63.
LiXLinLZhangJ, et al.
Microvascular dysfunction associated with unfavorable venous outflow in acute ischemic stroke patients. J Cereb Blood Flow Metab2023;
43: 106–115.
64.
LiuJLiYLinY, et al.
Quantitative research on the interaction between cerebral edema and peripheral cerebral blood perfusion using swept-source optical coherence tomography. Quant Imaging Med Surg2021;
11: 939–947.
65.
XuCYSchmittJMCarlierSG, et al.
Characterization of atherosclerosis plaques by measuring both backscattering and attenuation coefficients in optical coherence tomography. J Biomed Opt2008;
13: 034003.
66.
ScolaroLMcLaughlinRAKlyenBR, et al.
Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography. Biomed Opt Express2012;
3: 366–379.
67.
CaubergECCde BruinDMFaberDJ, et al.
Quantitative measurement of attenuation coefficients of bladder biopsies using optical coherence tomography for grading urothelial carcinoma of the bladder. J Biomed Opt2010;
15: 066013.
68.
ZhaoQZhouCWeiH, et al.
Ren, determination of glucose permeability and optical attenuation coefficient in normal and adenomatous human colon tissues using spectral domain optical coherence tomography. J Biomed Opt2012;
17: 105004.
69.
YuYMengZYLiA, et al.
Monitoring of edema progression in permanent and transient MCAO model using SS-OCT. J Innov Opt Heal Sci2021;
14.
70.
LiuJLiYYuY, et al.
Cerebral edema detection after middle cerebral artery occlusion using swept-source optical coherence tomography. Neurophotonics2019;
6: 045007.
71.
HowellsDWPorrittMJRewellSSJ, et al.
Different strokes for different folks: the rich diversity of animal models of focal cerebral ischemia. J Cereb Blood Flow Metab2010;
30: 1412–1431.
72.
DemyanenkoSUzdenskyA.Profiling of signaling proteins in penumbra after focal photothrombotic infarct in the rat brain cortex. Mol Neurobiol2017;
54: 6839–6856.
73.
LeeVMBurdettNGCarpenterTA, et al.
Evolution of photochemically induced focal cerebral ischemia in the rat – magnetic resonance imaging and histology. Stroke1996;
27: 2110–2118.
74.
LiuCChenJBZhangYC, et al.
Five-wavelength optical-resolution photoacoustic microscopy of blood and lymphatic vessels. Adv Photon2021;
3: 016002.
