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U2-Net: A Bayesian U-Net Model with Epistemic Uncertainty Feedback for Photoreceptor Layer Segmentation in Pathological OCT Scans José Ignacio Orlando, Philipp Seeböck, Hrvoje Bogunović, Sophie Klimscha, Christoph Grechenig, Sebastian Waldstein, Bianca S. Gerendas, Ursula Schmidt-Erfurth

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Page 1: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

U2-Net:ABayesianU-NetModelwithEpistemicUncertaintyFeedbackforPhotoreceptorLayerSegmentationinPathologicalOCTScans

JoséIgnacioOrlando,PhilippSeeböck,Hrvoje Bogunović,SophieKlimscha,ChristophGrechenig,SebastianWaldstein,BiancaS.Gerendas,UrsulaSchmidt-Erfurth

Page 2: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million
Page 3: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

1.3billionpeoplesufferingsomeformofvisualimpairment

Page 4: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Age-RelatedMacularDegeneration(AMD)Maincauseofvisualdeficiencyinindustrializedcountries

Globalprevalenceof8.7%within45-85yearsoldpopulation

DiabeticMacularEdema(DME)In2017,425millionpeopleworldwideweresufferingfromdiabetes

~10%developedvision-threateningDME

RetinalVeinOcclusion(RVO)14-19millionpeopleaffectedworldwide

Page 5: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

AMD

DME

RVO

Photoreceptorcelldeath Visualacuityloss

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OpticalCoherenceTomography(OCT)State-of-the-artimagingmodalityinAMD,RVOandDME

Allowstoassessphotoreceptorintegrity

Page 7: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

InterdigitationZone(IZ)

Outersegmentofphoto-receptors

EllipsoidZone(IS/OS)

Page 8: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

InterdigitationZone(IZ)

Outersegmentofphoto-receptors

EllipsoidZone(IS/OS)

Page 9: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million
Page 10: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Normalphotoreceptors Normalphotoreceptors

Page 11: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Abnormalthinning

Page 12: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Pathologicaldisruption

Page 13: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Ourmid-termgoal

(i)Accuratesegmentation(ii)Interpretablefeedbacktocorrecttheresults

Understandthepathophysiologicalprocessesthatcause damageinphotoreceptorintegrity

Page 14: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Keychallenge

Pathologicalalterations

Ambiguousappearancesturndifficulttoproducereliablesegmentations

Unfeasibletocaptureeverypossiblepathologicalfeatureonatrainingset

Page 15: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Bayesiandeeplearning

Page 16: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

BayesiandeeplearningModeluncertainty

Aleatoric Taskuncertainty,whatwedon’tknowandwewillneverlearn

Epistemic Modeluncertainty,whatwedon’tknowbutwecanlearngivenmoretrainingdata

Page 17: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

BayesiandeeplearningModeluncertainty

Aleatoric

Epistemic

Taskuncertainty,whatwedon’tknowandwewillneverlearn

Modeluncertainty,whatwedon’tknowbutwecanlearngivenmoretrainingdata

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Epistemicuncertainty

BDLisusedtocomputeaposteriordistribution

Approximatedistributionlearnedbyvariational inference

(Galetal.,2015)

Bernoullidistributiontotheweightsofthei-thconvolutionallayerusingDropout

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Epistemicuncertainty

MonteCarlosamplingwith

dropoutintesttime

Page 20: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

MonteCarlosamplingwith

dropoutintesttime

Samplingmultipleslightlydifferent

outputs

Averagingtheoutcomesresultsinbetterperformance

Standarddeviationallowstoretrieveanepistemicuncertaintyestimate

Page 21: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

OurapproachUncertaintyU-shapedNetwork

Page 22: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

OurapproachUncertaintyU-shapedNetwork

Page 23: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

OurapproachU2-Net

Page 24: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

StandardU-Net+Nearestneighborupsampling +LeakyReLUs +Batchnorm+Dropout

MCsamplingwithdropoutintesttimetopredictaveragescoremap&epistemicuncertaintymap

Page 25: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Materials

Page 26: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

DatasetA

Trainingset Validation Test

AMD(early,CNV) 10volumes 490B-scans

DME 16volumes 784B-scans

RVO 24volumes 1176B-scans

Total 50volumes 2450B-scans

Splitatapatient-basispreservingdiseaseproportion

31volumes(1519B-scans)

4volumes(196B-scans)

15volumes(735B-scans)

Page 27: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

DatasetB

Test

LateAMD(GA) 10volumes 490B-scans

Separatetestset

10volumes(496B-scans)

Page 28: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Evaluationmetrics

Photoreceptors Disruptions- AreaunderPrecision/Recallcurve

- Diceindex- AreaunderPrecision/Recallcurve

(atanA-scanlevel)

Page 29: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Baselines

StandardU-Net(Ronneberger etal.,MICCAI2015)

Batchnormalization,NNupsampling,dropoutinbottleneck

BRU-Net(Apostolopoulos etal.,MICCAI2017)

BranchresidualU-Netwithdilatedconvolutionsandresidualconnections

BU-NetBayesianU2-Netwithaleatoric uncertaintyestimates

(InspiredinNairetal.,MICCAI2018)

Page 30: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Results

Page 31: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Quantitativeevaluation

Page 32: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

U2-Net

B-scan

Manual

TestsetA– Dice=0.9624(B-scanlevel)– Meanuncertainty:6.004e-4(B-scanlevel)

Page 33: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Manual / U2-Net

TestsetA– Dice=0.9624(B-scanlevel)– Meanuncertainty:6.004e-4(B-scanlevel)

Page 34: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

TestsetA– Dice=0.9624(B-scanlevel)– Meanuncertainty:6.004e-4(B-scanlevel)

Epistemicuncertaintyestimate

Page 35: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

B-scan

Manual U2-Net

TestsetA– Dice=0.9196(B-scanlevel)– Meanuncertainty:6.720e-4(B-scanlevel)

Page 36: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Manual / U2-Net

TestsetA– Dice=0.9196(B-scanlevel)– Meanuncertainty:6.720e-4(B-scanlevel)

Page 37: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Epistemicuncertaintyestimate

TestsetA– Dice=0.9196(B-scanlevel)– Meanuncertainty:6.720e-4(B-scanlevel)

Page 38: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

B-scan

Manual U2-Net

TestsetA– Dice=0.5400(B-scanlevel)– Meanuncertainty:0.0014(B-scanlevel)

Page 39: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Manual / U2-Net

TestsetA– Dice=0.5400(B-scanlevel)– Meanuncertainty:0.0014(B-scanlevel)

Page 40: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Epistemicuncertaintyestimate

TestsetA– Dice=0.5400(B-scanlevel)– Meanuncertainty:0.0014(B-scanlevel)

Page 41: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Uncertaintyestimatesareinverselycorrelatedwithperformance

TestsetA(earlyAMD,CNV,RVO,DME)

TestsetB(lateAMD,GA)

Page 42: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Uncertaintyestimatesareinverselycorrelatedwithperformance

TestsetA(earlyAMD,CNV,RVO,DME)

TestsetB(lateAMD,GA)

Page 43: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Conclusions

Page 44: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Firstdeeplearningapproach forphotoreceptorsegmentationinpathologicalOCTscans

AveragingmultipleMCsamples allowstoincreaseperformanceinabnormalareas withoutaffectingresultsinhealthyregions

Epistemicuncertaintycanbeusedtoassessresults’qualityandtoidentifyareasthatmightneedformanualcorrection

Page 45: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

https://ignaciorlando.github.io

Thanksforyourattention!Doyouhaveanyquestions?

[email protected]

@ignaciorlando

Page 46: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

U2-Net:ABayesianU-NetModelwithEpistemicUncertaintyFeedbackforPhotoreceptorLayerSegmentationinPathologicalOCTScans

JoséIgnacioOrlando,PhilippSeeböck,Hrvoje Bogunović,SophieKlimscha,ChristophGrechenig,SebastianWaldstein,BiancaS.Gerendas,UrsulaSchmidt-Erfurth

Page 47: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

HowmanyMCsamplesarenecessary?ValidationsetA

Photoreceptors Disruptions

Page 48: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

Quantitativeevaluation

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1Recall

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Prec

isio

n

Standard U-Net - AUC = 0.8946BRU-Net - AUC = 0.879BU-Net (T=1) - AUC = 0.8316BU-Net (T=10) - AUC = 0.8289U2-Net (T=1) - AUC = 0.9201U2-Net (T=10) - AUC = 0.9249

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1Recall

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Prec

isio

n

Standard U-Net - AUC = 0.9566BRU-Net - AUC = 0.9593BU-Net (T=1) - AUC = 0.9466BU-Net (T=10) - AUC = 0.9505U2-Net (T=1) - AUC = 0.9653U2-Net (T=10) - AUC = 0.9669

Onecentralmillimeter FullOCTvolume

TestsetA

Page 49: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1Recall

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Prec

isio

n

Standard U-Net - AUC = 0.4428BRU-Net - AUC = 0.1894BU-Net (T=1) - AUC = 0.1461BU-Net (T=10) - AUC = 0.1495U2-Net (T=1) - AUC = 0.5151U2-Net (T=10) - AUC = 0.5047

Quantitativeevaluation

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1Recall

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Prec

isio

n

Standard U-Net - AUC = 0.939BRU-Net - AUC = 0.9295BU-Net (T=1) - AUC = 0.8969BU-Net (T=10) - AUC = 0.8998U2-Net (T=1) - AUC = 0.95U2-Net (T=10) - AUC = 0.9472

Onecentralmillimeter FullOCTvolume

TestsetB

Page 50: U2-NetDiabetic Macular Edema (DME) In 2017, 425 million people worldwide were suffering from diabetes ~10% developed vision-threatening DME Retinal Vein Occlusion (RVO) 14-19 million

InterdigitationZone(IZ)

Outersegmentofphoto-receptors

EllipsoidZone(IS/OS)

Retinalpigment

Epithelium(RPE)

Myoidzone

Externallimiting

membrane(ELM)