Summary

Cerebral blodflow-baseret hviletilstand funktionel forbindelse af den menneskelige hjerne ved hjælp af optisk diffus korrelation spektroskopi

Published: May 27, 2020
doi:

Summary

Denne protokol viser, hvordan man måler hviletilstand funktionelle tilslutningsmuligheder i den menneskelige præfrontale cortex ved hjælp af en skræddersyet diffus korrelation spektroskopi instrument. Rapporten diskuterer også praktiske aspekter af eksperimentet samt detaljerede trin til analyse af dataene.

Abstract

For at opnå en omfattende forståelse af den menneskelige hjerne, udnyttelse af cerebral blodgennemstrømning (CBF) som en kilde til kontrast er ønsket, fordi det er en vigtig hæmodynamisk parameter relateret til cerebral iltforsyning. Hviletilstand lavfrekvente udsving baseret på iltning kontrast har vist sig at give sammenhænge mellem funktionelt forbundne regioner. Den præsenterede protokol bruger optisk diffus korrelation spektroskopi (DCS) til at vurdere blodgennemstrømning-baserede hviletilstand funktionelle tilslutningsmuligheder (RSFC) i den menneskelige hjerne. Resultater af CBF-baseret RSFC i human frontal cortex viser, at intra-regionale RSFC er betydeligt højere i venstre og højre cortices sammenlignet med inter-regionale RSFC i begge cortices. Denne protokol bør være af interesse for forskere, der anvender multimodale billeddannelse teknikker til at studere menneskelige hjernefunktion, især i den pædiatriske befolkning.

Introduction

Når hjernen er i hviletilstand, viser det en høj synkronisering af spontan aktivitet i funktionelt relaterede regioner, som kan være placeret tæt på eller på afstand. Disse synkroniseringsområder kaldes funktionelle netværk1,2,3,4,5,6,7,8,9. Dette fænomen blev først afsløret af en funktionel magnetisk resonans imaging (fMRI) undersøgelse ved hjælp af blod ilt-afhængige (FED) signaler, der indikerer iltning niveauer af cerebralt blod5,10, også kendt som hviletilstand funktionelle tilslutningsmuligheder (RSFC). Abnormiteter i RSFC har været forbundet med hjernesygdomme såsom autisme11, Alzheimers12, og depression13. RSFC er således et værdifuldt værktøj til at studere patienter med lidelser, der har problemer med at udføre opgavebaserede vurderinger. Men mange patienter, såsom unge autistiske børn, er dårlige kandidater til vurdering af fMRI, da det kræver at forblive stadig inde i et lukket rum i længere tid14,15. Optisk billedbehandling er hurtig og bærbar; Det er således velegnet til et flertal af patienter, især den pædiatriske befolkning16,17,18,19,20,21,22,23,24. Udnytte disse fordele, funktionelle nær-infrarød spektroskopi (fNIRS), som kan kvantificere hæmoglobin koncentration og ilt mætning parametre i hjernen, bruges til at måle RSFC hos mennesker (herunder den pædiatriske befolkning4,8,25 og patienter med autisme11).

Optisk diffus korrelation spektroskopi (DCS), en forholdsvis ny optisk teknik, kan kvantificere cerebral blodgennemstrømning, som er et vigtigt parameter, der forbinder iltforsyning med stofskiftet6,17,26,27,28,29. Optisk flow kontrast kvantificeret af DCS har vist sig at have højere følsomhed i hjernen sammenlignet med iltning kontrast30. Det er således fordelagtigt at bruge DCS-afledte CBF-parametre til vurdering af RSFC.

DCS er følsom over for bevægelige blodlegemer. Når sprede fotoner scatter fra bevægelige blodlegemer, dette forårsager intensiteten af detekterede lys til at svinge over tid. DCS måler en tidsbaseret intensitet autokorrelationsfunktion og dens henfaldshastighed er afhængig af de optiske parametre og blodgennemstrømningen. Disse værdier er i sidste ende bruges til at opnå cerebral blodgennemstrømning indeks (CBFi). Med hurtigere bevægelige blodlegemer henfalder intensitetsfunktionen autokorrelationsfunktionen hurtigere. Derfor kan oplysninger om bevægelse dybt under vævsoverfladen udledes (f.eks. i hjernen) fra målinger af forskellige lysudsving over tid27,31,32,33,34,35. DCS er en teknik, der supplerer de almindeligt kendte fNIRS , der måler iltning i blodet17,36. Da både fNIRS og DCS er optiske hjernebilleddannelseteknikker med høj tidsmæssig opløsning inden for millisekunder, er de optiske billedopbygninger langt mindre følsomme over for bevægelsesartefakter end fMRI. De er også blevet anvendt med succes til funktionel hjernescanning i pædiatriske populationer, herunder meget unge spædbørn16. Tidligere er der anvendt overfladiske blodgennemstrømningsmålinger til vurdering af RSFC i prækliniske undersøgelser hos mus37. Her anvendes blodgennemstrømningsparametre til kvantificering af RSFC hos ni raske voksne som en proof-of-concept-undersøgelse38,39.

I denne undersøgelse anvendes et kommercielt FD-fNIRS-system og brugerdefineret DCS-system (se Materialetabel). DCS, der blev bygget in-house består af to 785 nm, 100 mW, lang kohærens længde kontinuerlig-bølge lasere, der er koblet til en FC-stik og otte enkelt-foton tælle maskiner (SPCM) forbundet til en auto-korrelator. En brugerdefineret software grafisk brugergrænseflade (GUI) blev også lavet specielt til dette system til at vise og gemme foton tæller, autokorrelation kurver, og semi-kvantitative blodgennemstrømningen af hver SPCM kanal i realtid. Delene i dette system anvendes almindeligvis til DCS16,17,31,32,40,42,43,44, og de opnåede resultater er også blevet kontrolleret internt og anvendt i en nylig undersøgelse39.

Protocol

Protokollen blev godkendt af Institutional Review Board på Wright State University, og der blev indhentet informeret samtykke fra hver deltager forud for eksperimentet. 1. Forberedelse af emnet Tænd for FD-fNIRS- og DCS-systemet for at varme op i mindst 10 min (se afsnit 2 og 3 for at få flere oplysninger), før du starter målinger af motivet. Et eksempel på motivmåling med det kompakte DCS-instrument er vist i figur 1. Brug først et må…

Representative Results

Muligheden for at anvende DCS til at måle funktionel konnektivitet blev demostraterated39. Den hvilende tilstand funktionelle tilslutningsmuligheder i præfrontale cortices af ni emner blev målt. Resultaterne (gennemsnit ± SD) viste en højere korrelation i den intraregionale region for venstre (0,64 ± 0,25) og højre (0,62 ± 0,23) cortices sammenlignet med den interregionale region til venstre (0,32 ± 0,32), (0,34 ± 0,27) og højre (0,34 ± 0,29), (0,34 ± 0,26) cortices. (<strong class="x…

Discussion

For at afgøre, om CBF målt ved DCS nøjagtigt detekterede RSFC, blev to områder af hjernen med kendte RSFC-egenskaber undersøgt. Funktionel forbindelse mellem DLFC-områder og mellem DLFC og IFC antages at eksistere57,58,59. Der blev valgt forbindelse mellem to steder i venstre og højre DLFC, fordi den intraregionale forbindelse normalt er højere. Der blev også valgt konnektivitet mellem IFC og DLFC, da den interregionale…

Disclosures

The authors have nothing to disclose.

Acknowledgements

Forfatterne vil gerne anerkende finansiel støtte fra Ohio Third Frontier til Ohio Imaging Research and Innovation Network (OIRAIN, 667750), og National Natural Science Foundation of China (Nr. 81771876).

Materials

3D Printed Probe In-house N/A 3D printed PLA probe (Craftbot, Craft unique)
785nm, 100mW, CW, FC coupled Laser CrystaLaser DL785-100-S DCS component (light source)
Auto-correlator Correlator.com Flex05-8ch DCS component (output g2 curve to PC)
Data Acquisition GUI In-house N/A GUI coded in LabVIEW to run the DCS system
Data analysis software In-house N/A Matlab code used for obtaining RSFC results
EEG Electrode Cap OpenBCI N/A EEG mesh cap with standard 10/20 positions
Multi-mode fiber OZ Optics QMMJ-3,2.5-IRVIS-600/630-3PCBK-3 DCS component (source fiber)
Oxiplex calibration phantom ISS 75019, 75020 Set of 2 PDMS Calibration Phantom
Oxiplex muscle probe ISS 86010 4 channel muscle probe
Oxiplex Oximeter ISS 95205 FD-fNIRS (690nm, 830nm)
Power meter Thorlabs PM100D Laser light power adjuster
Sensor card Thorlabs F-IRC1-S laser IR beam viewer
Single-mode fiber OZ Optics SMJ-3S2.5-780-5/125-3PCBK-3 DCS component (detector fiber)
Single-Photon Counting Machine Excelitas SPMC-NIR-1×2-FC DCS component (detector)

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Cite This Article
Poon, C., Rinehart, B., Li, J., Sunar, U. Cerebral Blood Flow-Based Resting State Functional Connectivity of the Human Brain using Optical Diffuse Correlation Spectroscopy. J. Vis. Exp. (159), e60765, doi:10.3791/60765 (2020).

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