Non-invasive optical monitoring of brain haemodynamics and metabolism following acute brain injury

190 Pages·2017·19.91 MB·English

NON-INVASIVE OPTICAL MONITORING OF BRAIN
HAEMODYNAMICS AND METABOLISM FOLLOWING ACUTE BRAIN
INJURY
ARNAB GHOSH
BSc(Hons) MB,ChB MRCS
ThesisforawardofdegreeofPhD
DepartmentofBrainRepair&Rehabilitation
InstituteofNeurology
UCL
March2017
ArnabGhosh:Non-invasiveopticalmonitoringofbrainhaemodynamicsandmeta-
bolism following acute brain injury , Thesis for award of degree of PhD, © March
2017
DECLARATION
I, Arnab Ghosh, confirm that the work presented in this thesis is my own. Where
informationhasbeenderivedfromothersources,Iconfirmthatthishasbeenindicated
inthethesis.
London,March2017
ArnabGhosh
2differenceinarterial:venousoxygenconcentration
iv
ABSTRACT
Followingacutebraininjury(ABI),cellularhypoxia-ischaemia(CH-I)iscentraltothe
pathophysiologicalcascadesthatleadtodeathandneurologicaldisability.Thus,akey
tenetofneurocriticalcareistheavoidanceofCH-I,andakeyprerequisitetodoingso
istheavailabilityofabedsideclinicalmonitorthatcanidentifyCH-Iasitoccurs.
Thisthesisdescribesnormalcerebralphysiology,howthisisderangedandclinically
manipulatedfollowingABI,andtheuseofnearinfraredspectroscopy(NIRS),anon-
invasiveopticaltechnique,tomonitorforCH-Iinavarietyofclinicalcontexts.Ithen
presentmyworkinvestigatingtheuseofNIRS,withanemphasisonthemeasurement
oftheoxidationstateofcytochromecoxidase(CCO),inhealthyvolunteerswhoare
subjectedtoavarietyofchallengesdesignedtomanipulatecerebraloxygendelivery
withbothisovolaemicandhyper/hypovolaemicchallenges.
Finally, I describe experiments in a cohort of a patients who have suffered from
ABI,manipulatingcerebraloxygendeliverybymeansofnormobarichyperoxia.The
resultssuggestthatthemeasurementofCCOwithNIRSinpatientswithABIprovidesa
usefuladjuncttoestablishedmonitorsofcerebralhaemodynamicsandmetabolism;an
in-depthdiscussionoftheobservedchangesindifferenthaemodynamicandmetabolic
parameters,andtheirrelevancetonormalphysiologyandpathophysiologyofABIis
carriedout.
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PUBLICATIONS
Thefollowingpublicationshavearisenfromthiswork:
[1] Tachtsidis, I, Leung, T, Elwell, CE, Ghosh, A, Smith, M & Cooper, CE. Multi-
Wavelength,DepthResolved,ScatteringandPathlengthCorrectedinvivoNear-
InfraredSpectroscopyofBrainTissue. BiomedicalOptics(BIOMED),OSATech-
nicalDigest,p.BTuB,2010.
[2] Tachtsidis,I,Tisdall,MM,Pritchard,C,Leung,TS,Ghosh,A,Elwell,CE&Smith,
M. Analysisofthechangesintheoxidationofbraintissuecytochrome-c-oxidase
intraumaticbraininjurypatientsduringhypercapnoea:abroadbandNIRSstudy.
AdvancesinExperimentalMedicineandBiology,701:9–14,2011.
[3] Ghosh, A, Tachtsidis, I, Kolyva, C, Cooper, CE, Smith, M & Elwell, CE. Use of
ahybridopticalspectrometerforthemeasurementofchangesinoxidizedcyto-
chromecoxidaseconcentrationandtissuescatteringduringfunctionalactivation.
AdvancesinExperimentalMedicineandBiology,737:119–124,2012.
[4] Kolyva,C,Tachtsidis,I,Ghosh,A,Moroz,T,Cooper,CE,Smith,M&Elwell,CE.
Systematic investigation of changes in oxidized cerebral cytochrome c oxidase
concentrationduringfrontallobeactivationinhealthyadults. Biomedicaloptics
express,3(10):2550–2566,2012.
[5] Ghosh,A,Elwell,C&Smith,M. Cerebralnear-infraredspectroscopyinadults:a
workinprogress. Anesthesia&Analgesia,115(6):1373–1383,2012.
[6] Kolyva,C,Ghosh,A,Tachtsidis,I,Highton,D,Smith,M&Elwell,CE.Dependence
onNIRSSource-DetectorSpacingofCytochromeCOxidaseResponsetoHpoxia
and Hypercapnia in the Adult Brain. Advances in Experimental Medicine and
Biology,789(353-9),2013.
[7] Ghosh,A,Tachtsidis,I,Kolyva,C,Highton,D,Elwell,C&Smith,M. Normobaric
hyperoxiadoesnotchangeopticalscatteringorpathlengthbutdoesincreaseoxid-
isedcytochromeCoxidaseconcentrationinpatientswithbraininjury. Advances
inExperimentalMedicineandBiology,765:67–72,2013.
[8] Ghosh,A,Kolyva,C,Highton,D,Tachtsidis,I,Elwell,CE&Smith,M. Reduction
ofCytochromecOxidaseDuringVasovagalHypoxia-IschaemiainHumanAdult
Brain:aCaseStudy. AdvancesinExperimentalMedicineandBiology,789:21–27,
2013.
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[9] Kolyva, C, Ghosh, A, Tachtsidis, I, Highton, D, Cooper, CE, Smith, M & Elwell,
CE. Cytochrome c oxidase response to changes in cerebral oxygen delivery in
theadultbrainshowshigherbrain-specificitythanhaemoglobin. NeuroImage,
85(1):234–244,2014.
[10] Robertson,JL,Ghosh,A,Correia,T,Highton,D,Smith,M,Elwell,CE&Leung,TS.
Effectofbloodinthecerebrospinalfluidontheaccuracyofcerebraloxygenation
measuredbynearinfraredspectroscopy. AdvancesinExperimentalMedicineand
Biology,812:233–240,2014.
[11] Highton,D,Ghosh,A,Tachtsidis,I,Panovska-Griffiths,J,Elwell,CE&Smith,M.
MonitoringCerebralAutoregulationAfterBrainInjury:MultimodalAssessmentof
CerebralSlow-WaveOscillationsUsingNear-InfraredSpectroscopy. Anesthesia&
Analgesia,121(1):198–205,2015.
[12] Ghosh,A,Highton,D,Kolyva,C,Tachtsidis,I,Elwell,CE&Smith,M. Hyperoxia
resultsinincreasedaerobicmetabolismfollowingacutebraininjury. Journalof
cerebralbloodflowandmetabolism,p.271678X16679171,2016.
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“Geniusdepends...onrapidmetabolism,onthepossibilityofdrawingagainand
againongreat,eventremendousquantitiesofstrength“
—FriedrichNietsche
ACKNOWLEDGMENTS
It is no exaggeration to say that undertaking the work described in this thesis and
preparingthethesisitselfhasbeenthegreatestchallengeIhaveeverfaced.Fortunately,
itisnotachallengethatIhavefacedalone;Iamdeeplyindebtedtomanypeoplewho
havesupportedmeincompletingthiswork.
MartinSmith,myprimarysupervisor,hasbeenunfailinglyencouraging,whilstalso
insistingonadegreeofrigourthathasimprovedthisworktonoend,forwhichIam
verygrateful.DavidHighton,withwhomIhavesharedalab,hasbeenaconstantaid
inbothconceiving,performingandunderstandingtheexperimentsthataredescribed
here.
IntheDepartmentofMedicalPhysicsandBioengineering,ClareElwell,mysecondary
supervisor,hasshowedgreatpatienceintutoringmeinthesubjectofmedicaloptics,
andhasshownaninfectiousenthusiasmintakingthisworkintotheclinicalsetting.
Her colleague Ilias Tachtsidis is the creator of the primary apparatus used for the
experiments in this thesis, and is responsible for training me in the operation and
maintenanceofopticalspectrometerstotheextentthathehaskindlydescribedmeto
beascapableasanyengineeringdoctoralcandidate!ChristinaKolyvahasundertaken
anenormousamountofdataanalysis,inparticularonthedatadescribedinChapter4;
withoutherunfailinglymeticulousworkinthis,aswellasrevisingthemanypaperswe
haveco-authored,Icouldeasilyhavebeenoverwhelmed.
I am also indebted to the many nursing and medical staff of the Departments of
Neurosurgery,NeurocriticalCareandNeuroanaesthesiaintheNationalHospitalfor
NeurologyandNeurosurgeryatQueenSquare.Thereisnodoubtthatmyexperiments
wereanimpositionontheirtimeandspace,andIamgratefulfortheiraccommodations.
Iamalsogratefultotheverymanyofthemwhovolunteered(oftenafterbusynightshifts)
toundergotheexperimentsdescribedinChapter4.
MygirlfriendTessahasbeenaconstantsourceof(occasionallybadgering)encour-
agement,andforhersupportandunderstandinginallowingmetocompletethiswork,
Iowehermuch.
Finally, I am grateful to the families of the patients who provided assent for their
relativestobeincludedintheexperimentdescribedinChapter5.Inatimeofgreat
fearandapprehension,theyhaveshowngreatgenerosityinallowingtheirlovedones
tobeincludedinthesestudies.
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AndtothePea.
ix
CONTENTS
Declaration iii
Abstract v
Publications vi
ListofFigures xii
ListofTables xiv
Abbreviations xv
I 1
BACKGROUND AND PRINCIPLES
1 REVIEW OF CEREBRAL PHYSIOLOGY 2
1.1 Grossanatomicalandphysiologicalperspective . . . . . . . . . . . . . 2
1.2 Supplyofmetabolicsubstratetotissue . . . . . . . . . . . . . . . . . . 4
1.3 Cellularrespiration . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2 ACUTE BRAIN INJURY 20
2.1 Definitions&Epidemiology . . . . . . . . . . . . . . . . . . . . . . . 20
2.2 Pathophysiologyofacutebraininjury . . . . . . . . . . . . . . . . . . 21
2.3 NeurocriticalcaremanagementofABI . . . . . . . . . . . . . . . . . . 31
2.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
3 NEAR INFRARED SPECTROSCOPY 55
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3.2 PrinciplesofNIRS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3.3 ClinicaluseofNIRS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
3.4 TheHybridOpticalSpectrometer . . . . . . . . . . . . . . . . . . . . 70
3.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
II 81
EXPERIMENTAL STUDIES
4 CYTOCHROME c OXIDASE DURING MANIPULATION OF CEREBRAL OXYGEN
82
DELIVERY IN HEALTHY VOLUNTEERS
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
4.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
4.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
4.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
4.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
5 EFFECTS OF NORMOBARIC HYPEROXIA ON CYTOCHROME c OXIDASE
130
IN PATIENTS WITH ACUTE BRAIN INJURY
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
5.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
5.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
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