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Quantitative analysis of radiologic images: Image segmentation and registration, statistical atlases Christos Davatzikos, Ph.D. Professor of Radiology

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  • Quantitative analysis of radiologic images:Image segmentation and registration, statistical atlases

    Christos Davatzikos, Ph.D. Professor of RadiologySection of Biomedical Image Analysishttp://www.rad.upenn.edu/sbia

  • You can control a quantity if you can measure or weigh itLord Kelvin, 1824-1907 Need to develop tools that obtain accurate and precise measurement from image data

  • Expert 1: Total Lesion volume: 15,635 mm^3Expert 2: Total Lesion volume: 7,560 mm^3Human limitations in measuring: inter-rater differences

  • Major limitation for:

    Diagnosis of disease stageMonitoring the effect of treatments

  • Quantification/measurement: ~3% longitudinal atrophy of the hippocampus in early AD patients Contraction pattern of the cardiac muscle- a 5% change in radiologic signal could be indicative of evolving pathologyMore human limitations

  • Visually detecting morphological abnormalitiesScan 1Scan 2

  • Visually detecting morphological abnormalitiesScan 1Scan 230% atrophy!

  • Manual Drawing of anatomical structuresVisual evaluation of a 3% atrophy is practically impossible Laborious and not well-reproducible manual outlining is required

  • Evaluating complex spatio-temporal patterns of radiologic signal change, especially if the magnitude of the signal change is small and anatomical variability is largeKahneman and Tversky in their Nobel prize winninng careers studied human reasoning under uncertainty and demonstrated the limitations of human reasoning in evaluating conjunctions, i.e. A and B and C Even more fundamental limitations of human evaluation

  • Detecting spatially complex very subtle anatomical abnormalitiesNormalSchizophrenia patient?

  • HealthyMildly Cognitively impaired:Prodromal stage to AlzheimersDetecting spatially complex very subtle anatomical abnormalities?

  • Functional activity during truth telling and lyingLiesTruths

  • Brain and criminal behavior

    Chart1

    -1.5702933728

    -1.6775437162

    -1.7655135323

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    -1.4043580248

    -0.6274336139

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    label_volume_fantasm

    subjectlabel1234567891011121415161718192123252627293032333435363738394143455052535456575960616263646970727374758083858688909294959697989910010110210510811011211411811912512813013213313914014515415916517519620325125434817304557597383105108

    medial front-orbital gyrus rightmiddle frontal gyrus rightlateral ventricle leftinsula rightprecentral gyrus rightlateral front-orbital gyrus rightcingulate region rightlateral ventricle rightmedial frontal gyrus leftsuperior frontal gyrus rightglobus palladus rightglobus palladus leftputamen leftinferior frontal gyrus leftputamen rightfrontal lobe WM rightparahippocampal gyrus leftangular gyrus righttemporal pole rightsubthalamic nucleus rightnucleus accumbens rightuncus rightcingulate region leftfornix leftfrontal lobe WM leftprecuneus rightsubthalamic nucleus leftposterior limb of internal capsule inc. cerebral peduncle leftposterior limb of internal capsule inc. cerebral peduncle righthippocampal formation rightinferior occipital gyrus leftsuperior occipital gyrus rightcaudate nucleus leftsupramarginal gyrus leftanterior limb of internal capsule leftoccipital lobe WM rightmiddle frontal gyrus leftsuperior parietal lobule leftcaudate nucleus rightcuneus leftprecuneus leftparietal lobe WM lefttemporal lobe WM rightsupramarginal gyrus rightsuperior temporal gyrus leftuncus leftmiddle occipital gyrus rightmiddle temporal gyrus leftlingual gyrus leftsuperior frontal gyrus leftnucleus accumbens leftoccipital lobe WM leftpostcentral gyrus leftinferior frontal gyrus rightprecentral gyrus lefttemporal lobe WM leftmedial front-orbital gyrus leftperirhinal cortex rightsuperior parietal lobule rightlateral front-orbital gyrus leftperirhinal cortex leftinferior temporal gyrus lefttemporal pole leftentorhinal cortex leftinferior occipital gyrus rightsuperior occipital gyrus leftlateral occipitotemporal gyrus rightentorhinal cortex righthippocampal formation leftthalamus leftparietal lobe WM rightinsula leftpostcentral gyrus rightlingual gyrus rightmedial frontal gyrus rightamygdala leftmedial occipitotemporal gyrus leftparahippocampal gyrus rightanterior limb of internal capsule rightmiddle temporal gyrus rightoccipital pole rightcorpus callosumamygdala rightinferior temporal gyrus rightsuperior temporal gyrus rightmiddle occipital gyrus leftangular gyrus leftmedial occipitotemporal gyrus rightcuneus rightlateral occipitotemporal gyrus leftthalamus rightoccipital pole leftfornix rightFrontal Left GMFrontal RIGHT GMParietal LEFT GMParietal RIGHT GMTemporal LEFT GMTemporal RIGHT GMMedial LEFT GMMedial RIGHT GMOccipital LEFT GMOccipital RIGHT GMlateral ventricle leftinsula rightlateral ventricle rightfrontal lobe WM rightfrontal lobe WM leftoccipital lobe WM rightparietal lobe WM lefttemporal lobe WM rightoccipital lobe WM lefttemporal lobe WM leftparietal lobe WM rightinsula leftSUMTotal Frontal LeftTotal Frontal RightTotal Parietal LeftTotal Parietal RightTotal Temporal LeftTotal Temporal RightTotal Occipital LeftTotal Occipital RightMedial LEFT GMMedial RIGHT GMlateral ventricle leftinsula rightlateral ventricle rightinsula leftTOTAL

    Johnson_Rogermm^31999.552818147.23825843.07365732.147417344.82411472.93849628.97046066.366612920.74149767.2681544.32321119.34624586.870411848.9353965.971889553.45841917.438611009.06524115.794277.7924450.9078991.132810980.2532747.671493417.14762686.71976.35182271.82622780.3582702.56565478.60185622.66182531.13427129.52944964.307614260.499420077.642218700.42862708.3284778.47022536.896642581.254850416.67825246.665218567.89341166.8865703.335419816.89365320.13589977.5956332.778612991.330814362.78213718.833813341.396650871.90781702.78921149.598818556.368610712.30161910.235613038.87064063.9326939.27122192.59326249.322811658.77581308.06483396.93485873.326240222.99265727.825610545.1924612.801213442.2386455.22968570.12942646.38224066.813830167.60463882.41711447.0076613.695610061.150417699.21165747.9949627.52987249.09924598.395215078.76026668.53743736.9164429.2988999021.525680581.401685892.893852357.166448044.0188922.475690363.075656595.411653629.216254960.330645520.07885843.07365732.14746066.366689553.458493417.147614260.499442581.254850416.678212991.330850871.907840222.99265727.82561074550.74173998.5492175446.352294938.421288267.0026139794.3834140779.753867951.661459780.578256595.411653629.21625843.07365732.14746066.36665727.82561062641.3028

    fantasm_segmentation0.0749907830.07993377170.04872470350.04471078760.08275316560.08409381890.05266890560.04990850040.05114726410.0423619630.00543768980.00533445950.0056454910.08334037180.08693600390.0132711270.03962703030.04691884360.01209001150.047342490.03743238080.00533043750.16192678690.16327414350.08835173380.08214316840.13009565560.13101266250.06323727550.055633090.05266890560.04990850040.00543768980.00533445950.0056454910.00533043750.9889168192

    0

    0

    NC-AVE0.08503990690.08825154910.04996136780.04499161940.07978948110.08192181110.05909995620.05976205860.05050805720.04730526660.00555206250.00676255190.00556958010.07972768040.08027093390.01248215840.03444798830.03905998470.00975433990.03805144650.03447413550.00721606390.16531084080.16797922950.0844093560.07946575490.11784092760.12098179580.06026239710.0597874250.05960936520.05455870440.00559949210.00682061290.00561722160.00727798590.9843043953

    NC-STDEV0.00453648760.00423701920.00372240340.00270527170.00348540460.00313955850.00275723990.00250560390.00313671830.00231584120.00233743350.00060704110.00218122740.00410175470.00417146470.00161616960.00243323480.00279498660.0012206120.00246444290.00192460970.00055266630.00870795230.00833877380.00615563820.00462988130.00594984750.0059345450.00435733030.00393201080.00280719640.00240016380.00235701140.00061137790.00219860130.00055587790.0543805952

    0

    NC-AVE105289.710365854109290.51305259161886.704458841555704.456459603798826.4910442073101502.52477134173317.887766768374071.539157774462601.126619664658617.34470274396908.95341082328346.84403582326904.494569359898844.926638719599455.680735518315532.674352134142713.578982469548450.071455792712114.865186737847147.082221798842772.01552972568917.85442073171239217.34204745.391101372208135.439691311104600.28344131198476.4719893293145973.573266006149952.59622713474715.991806402474150.019054878173317.887766768374071.53915777446908.95341082328346.84403582326904.49456935988917.85442073171225403.89195884total Brain Vol

    NC-STDEV11310.435790359411554.44999490047456.22969195546060.900045821810169.861817682710557.35800820278743.65621749338113.1832818137456.8879451136483.59136874883028.8445402969830.14290172322684.016632431511540.527511253910963.39244128322957.1185309995385.87952044846277.5809565082116.337789545578.15551207485321.0874082476902.9766018663145492.6120498.620633230621152.863803791911887.360122727910353.012160280314768.936547669815872.43716712469210.50444235198930.28106375328743.65621749338113.1832818133028.8445402969830.14290172322684.0166324315902.9766018663120377.694654151Stdev of Tot Br. Vol

    zscores-2.1845585107-2.0249877115-1.278063908-1.2639123565-0.9738593918-1.0551360637-1.9125267223-2.5196426911-1.0246628454-2.0200634429-0.3519097123-3.1496946253-0.3122663098-0.8051164238-0.5507905667-0.4302076291-0.02456872310.31327461290.41414258990.6677521934-0.4790417323-3.5327923383-1.4999468721-1.5453740824-0.8127845158-0.9861351683-0.418390982-0.5779101426-0.7344147597-1.6090692725-1.9125267223-2.5196426911-0.3519097123-3.1496946253-0.3122663098-3.5327923383-1.3520992375

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    1999.552818147.23825843.07365732.147417344.82411472.93849628.97046066.366612920.74149767.2681544.32321119.34624586.870411848.9353965.971889553.45841917.438611009.06524115.794277.7924450.9078991.132810980.2532747.671493417.14762686.71976.35182271.82622780.3582702.56565478.60185622.66182531.13427129.52944964.307614260.499420077.642218700.42862708.3284778.47022536.896642581.254850416.67825246.665218567.89341166.8865703.335419816.89365320.13589977.5956332.778612991.330814362.78213718.833813341.396650871.90781702.78921149.598818556.368610712.30161910.235613038.87064063.9326939.27122192.59326249.322811658.77581308.06483396.93485873.326240222.99265727.825610545.1924612.801213442.2386455.22968570.12942646.38224066.813830167.60463882.41711447.0076613.695610061.150417699.21165747.9949627.52987249.09924598.395215078.76026668.53743736.9164429.2988999021.525680581.401685892.893852357.166448044.0188922.475690363.075656595.411653629.216254960.330645520.07885843.07365732.14746066.366689553.458493417.147614260.499442581.254850416.678212991.330850871.907840222.99265727.82561074550.74173998.5492175446.352294938.421288267.0026139794.3834140779.753867951.661459780.578256595.411653629.21625843.07365732.14746066.36665727.82561062641.3028

    0.0749907830.07993377170.04872470350.04471078760.08275316560.08409381890.05266890560.04990850040.05114726410.0423619630.00543768980.00533445950.0056454910.08334037180.08693600390.0132711270.03962703030.04691884360.01209001150.047342490.03743238080.00533043750.16192678690.16327414350.08835173380.08214316840.13009565560.13101266250.06323727550.055633090.05266890560.04990850040.00543768980.00533445950.0056454910.00533043750.9889168192

    0

    0

    NC-AVE0.08503990690.08825154910.04996136780.04499161940.07978948110.08192181110.05909995620.05976205860.05050805720.04730526660.00555206250.00676255190.00556958010.07972768040.08027093390.01248215840.03444798830.03905998470.00975433990.03805144650.03447413550.00721606390.16531084080.16797922950.0844093560.07946575490.11784092760.12098179580.06026239710.0597874250.05960936520.05455870440.00559949210.00682061290.00561722160.00727798590.9843043953

    NC-STDEV0.00453648760.00423701920.00372240340.00270527170.00348540460.00313955850.00275723990.00250560390.00313671830.00231584120.00233743350.00060704110.00218122740.00410175470.00417146470.00161616960.00243323480.00279498660.0012206120.00246444290.00192460970.00055266630.00870795230.00833877380.00615563820.00462988130.00594984750.0059345450.00435733030.00393201080.00280719640.00240016380.00235701140.00061137790.00219860130.00055587790.0543805952

    0

    NC-AVE105289.710365854109290.51305259161886.704458841555704.456459603798826.4910442073101502.52477134173317.887766768374071.539157774462601.126619664658617.34470274396908.95341082328346.84403582326904.494569359898844.926638719599455.680735518315532.674352134142713.578982469548450.071455792712114.865186737847147.082221798842772.01552972568917.85442073171239217.34204745.391101372208135.439691311104600.28344131198476.4719893293145973.573266006149952.59622713474715.991806402474150.019054878173317.887766768374071.53915777446908.95341082328346.84403582326904.49456935988917.85442073171225403.89195884

    NC-STDEV11310.435790359411554.44999490047456.22969195546060.900045821810169.861817682710557.35800820278743.65621749338113.1832818137456.8879451136483.59136874883028.8445402969830.14290172322684.016632431511540.527511253910963.39244128322957.1185309995385.87952044846277.5809565082116.337789545578.15551207485321.0874082476902.9766018663145492.6120498.620633230621152.863803791911887.360122727910353.012160280314768.936547669815872.43716712469210.50444235198930.28106375328743.65621749338113.1832818133028.8445402969830.14290172322684.0166324315902.9766018663120377.694654151

    zscores-2.1845585107-2.0249877115-1.278063908-1.2639123565-0.9738593918-1.0551360637-1.9125267223-2.5196426911-1.0246628454-2.0200634429-0.3519097123-3.1496946253-0.3122663098-0.8051164238-0.5507905667-0.4302076291-0.02456872310.31327461290.41414258990.6677521934-0.4790417323-3.5327923383-1.4999468721-1.5453740824-0.8127845158-0.9861351683-0.418390982-0.5779101426-0.7344147597-1.6090692725-1.9125267223-2.5196426911-0.3519097123-3.1496946253-0.3122663098-3.5327923383-1.3520992375

    -2.2151772062-1.9631200843-0.3322219805-0.10380911250.85031289940.6918195257-2.332423331-3.93260804470.2037820345-2.1345606808-0.0489309077-2.35254646550.03480192560.8807673021.59777690960.48817191892.12845955752.81176978331.91352500643.77003801471.5370624719-3.4118715089-0.3886164918-0.56424195320.64044988130.5782898642.05967093931.69025032390.6827296139-1.0565421079-2.4723812674-1.9374527635-0.0686472346-2.43082638250.0128579093-3.5035541855

    0123456789101112131415161718192021

    label_volume_fsl

    subjectlabel1234567891011121415161718192123252627293032333435363738394143455052535456575960616263646970727374758083858688909294959697989910010110210510811011211411811912512813013213313914014515415916517519620325125434817304557597383105108

    medial front-orbital gyrus rightmiddle frontal gyrus rightlateral ventricle leftinsula rightprecentral gyrus rightlateral front-orbital gyrus rightcingulate region rightlateral ventricle rightmedial frontal gyrus leftsuperior frontal gyrus rightglobus palladus rightglobus palladus leftputamen leftinferior frontal gyrus leftputamen rightfrontal lobe WM rightparahippocampal gyrus leftangular gyrus righttemporal pole rightsubthalamic nucleus rightnucleus accumbens rightuncus rightcingulate region leftfornix leftfrontal lobe WM leftprecuneus rightsubthalamic nucleus leftposterior limb of internal capsule inc. cerebral peduncle leftposterior limb of internal capsule inc. cerebral peduncle righthippocampal formation rightinferior occipital gyrus leftsuperior occipital gyrus rightcaudate nucleus leftsupramarginal gyrus leftanterior limb of internal capsule leftoccipital lobe WM rightmiddle frontal gyrus leftsuperior parietal lobule leftcaudate nucleus rightcuneus leftprecuneus leftparietal lobe WM lefttemporal lobe WM rightsupramarginal gyrus rightsuperior temporal gyrus leftuncus leftmiddle occipital gyrus rightmiddle temporal gyrus leftlingual gyrus leftsuperior frontal gyrus leftnucleus accumbens leftoccipital lobe WM leftpostcentral gyrus leftinferior frontal gyrus rightprecentral gyrus lefttemporal lobe WM leftmedial front-orbital gyrus leftperirhinal cortex rightsuperior parietal lobule rightlateral front-orbital gyrus leftperirhinal cortex leftinferior temporal gyrus lefttemporal pole leftentorhinal cortex leftinferior occipital gyrus rightsuperior occipital gyrus leftlateral occipitotemporal gyrus rightentorhinal cortex righthippocampal formation leftthalamus leftparietal lobe WM rightinsula leftpostcentral gyrus rightlingual gyrus rightmedial frontal gyrus rightamygdala leftmedial occipitotemporal gyrus leftparahippocampal gyrus rightanterior limb of internal capsule rightmiddle temporal gyrus rightoccipital pole rightcorpus callosumamygdala rightinferior temporal gyrus rightsuperior temporal gyrus rightmiddle occipital gyrus leftangular gyrus leftmedial occipitotemporal gyrus rightcuneus rightlateral occipitotemporal gyrus leftthalamus rightoccipital pole leftfornix rightFrontal Left GMFrontal RIGHT GMParietal LEFT GMParietal RIGHT GMTemporal LEFT GMTemporal RIGHT GMMedial LEFT GMMedial RIGHT GMOccipital LEFT GMOccipital RIGHT GMlateral ventricle leftinsula rightlateral ventricle rightfrontal lobe WM rightfrontal lobe WM leftoccipital lobe WM rightparietal lobe WM lefttemporal lobe WM rightoccipital lobe WM lefttemporal lobe WM leftparietal lobe WM rightinsula leftSUMTotal Frontal LeftTotal Frontal RightTotal Parietal LeftTotal Parietal RightTotal Temporal LeftTotal Temporal RightTotal Occipital LeftTotal Occipital RightMedial LEFT GMMedial RIGHT GMlateral ventricle leftinsula rightlateral ventricle rightinsula leftTOTAL

    JohnsonRogermm^32887.2070312521145.6054687538257149.023437515816.79687514220.70312510984.57031254617.773437512710.74218759711.035156251123.24218751084.57031253775.7812513133.496093753867.187582973.144531251877.3437512041.894531254924.51171875114.2578125444.72656251039.7460937513067.578125536.132812589684.472656253046.289062559.7656252157.714843752345.800781252764.160156255865.82031255662.792968753290.6256822.07031254171.289062517182.617187521259.8632812514724.316406253227.343756626.074218753462.0117187536273.3398437541942.285156255749.804687517856.738281251568.847656254803.2226562517448.925781255227.7343759025.48828125359.4726562511876.6601562514266.4062513697.7539062512085.8398437547020.605468752860.839843751470.4101562513678.4179687511795.800781253189.5507812513015.722656253673.8281251374.6093751635.644531256894.14062511257.031251636.52343753322.2656255104.687537392.18756985.54687512131.542968755414.9414062512198.33984375905.27343759732.128906252084.7656253395.2148437524953.027343756098.7304687511258.78906251334.17968759436.8164062517284.57031254075.488281258064.843757533.9843757754.5898437514878.1255931.738281253760.83984375291.796875968435.1562582872.070312589677.4414062547339.648437546647.9492187588843.35937585719.72656256592560149.7070312557060.351562550160.937538257149.02343754617.773437582973.1445312589684.4726562517182.617187536273.3398437541942.2851562511876.6601562547020.6054687537392.18756985.5468751061318.85172556.54296875172650.585937583612.9882812584040.13671875135863.96484375127662.0117187568937.0117187567343.55468756592560149.7070312538257149.02343754617.77343756985.5468751052876.07421875

    fsl_segmentation0.07808404660.084496230.04460454890.04395281340.08371033790.08076717640.06211611160.05667449250.05376362790.04726283490.00360400650.00673598090.00435097660.07817928110.0845028550.01618987280.03417760830.03951902410.01119047320.0443039390.03523181330.00658194930.16258690150.16267551110.07878215720.07918462670.12801427690.12028620050.06495410110.06345270780.06211611160.05667449250.00360400650.00673598090.00435097660.00658194930.992045017

    0

    0

    NC-AVE0.08503990690.08825154910.04996136780.04499161940.07978948110.08192181110.05909995620.05976205860.05050805720.04730526660.00555206250.00676255190.00556958010.07972768040.08027093390.01248215840.03444798830.03905998470.00975433990.03805144650.03447413550.00721606390.16531084080.16797922950.0844093560.07946575490.11784092760.12098179580.06026239710.0597874250.05960936520.05455870440.00559949210.00682061290.00561722160.00727798590.9843043953

    NC-STDEV0.00453648760.00423701920.00372240340.00270527170.00348540460.00313955850.00275723990.00250560390.00313671830.00231584120.00233743350.00060704110.00218122740.00410175470.00417146470.00161616960.00243323480.00279498660.0012206120.00246444290.00192460970.00055266630.00870795230.00833877380.00615563820.00462988130.00594984750.0059345450.00435733030.00393201080.00280719640.00240016380.00235701140.00061137790.00219860130.00055587790.0543805952

    0

    NC-AVE105289.710365854109290.51305259161886.704458841555704.456459603798826.4910442073101502.52477134173317.887766768374071.539157774462601.126619664658617.34470274396908.95341082328346.84403582326904.494569359898844.926638719599455.680735518315532.674352134142713.578982469548450.071455792712114.865186737847147.082221798842772.01552972568917.85442073171239217.34204745.391101372208135.439691311104600.28344131198476.4719893293145973.573266006149952.59622713474715.991806402474150.019054878173317.887766768374071.53915777446908.95341082328346.84403582326904.49456935988917.85442073171225403.89195884total Brain Vol

    NC-STDEV11310.435790359411554.44999490047456.22969195546060.900045821810169.861817682710557.35800820278743.65621749338113.1832818137456.8879451136483.59136874883028.8445402969830.14290172322684.016632431511540.527511253910963.39244128322957.1185309995385.87952044846277.5809565082116.337789545578.15551207485321.0874082476902.9766018663145492.6120498.620633230621152.863803791911887.360122727910353.012160280314768.936547669815872.43716712469210.50444235198930.28106375328743.65621749338113.1832818133028.8445402969830.14290172322684.0166324315902.9766018663120377.694654151Stdev of Tot Br. Vol

    zscores-1.9820315034-1.6974474471-1.950993548-1.4942512123-0.9816388706-1.494957185-0.8455144602-1.7159518826-0.7430412121-1.3042782498-1.0181946844-1.4429089207-0.8519772583-1.375308199-0.89125771350.5579562733-1.1957636843-1.0366710274-0.112555298-0.0226735796-1.0110392138-2.1399309149-1.5702933728-1.6775437162-1.7655135323-1.3944091871-0.6845183734-1.4043580248-0.6274336139-0.7621780679-0.8455144602-1.7159518826-1.0181946844-1.4429089207-0.8519772583-2.1399309149-1.4332208158

    -1.5333140937-0.8863115898-1.4390753387-0.38399325331.1249359104-0.36776977381.0939039041-1.23226423811.0378906719-0.0183223483-0.8334166902-0.0437713962-0.5586779151-0.3774968031.01449283412.2941369846-0.11111956470.16423671751.17656827172.53708148140.3936786815-1.1473733508-0.3128105416-0.6360309769-0.9141536066-0.0607204051.7098504255-0.11721122231.07673820730.93216498320.89297151520.8815182249-0.8466168678-0.1384284246-0.5759321079-1.2521393301

    0123456789101112131415161718192021

    Total Frontal LeftTotal Frontal RightTotal Parietal LeftTotal Parietal RightTotal Temporal LeftTotal Temporal RightTotal Occipital LeftTotal Occipital Rightlateral ventricle leftlateral ventricle right

    -1.5702933728-1.6775437162-1.7655135323-1.3944091871-0.6845183734-1.4043580248-0.6274336139-0.7621780679-1.0181946844-0.8519772583

    3285240594352813417996161801249852541446211049127812344296149434400944052136137015603130506118314868610102041346668245526693145667464433744776247461955024189167533672753939394127147721654220317178554651985359481026940913513162321558513751534993255167315563134213629148094180156418617844128081862378058084254479481380361611387910301107323723863283916939128101518107371966646379176857288231692867494279332

    label_volume_fsl

    0

    0

    0

    0

    0

    0

    0

    0

    0

    0

    global_volume

    Segmentation Methodsfantasmfsl

    voxelvolume(mm^3)voxelvolume(mm^3)

    WM:324131466943.1186WM:343460494788.476

    GM:325442468831.7452GM:310775447702.465

    VN:724810441.4688VN:902412999.9744

  • Computers can complement and assist humans in many ways

  • Statistical anatomical atlases: from single-individual anatomical examples, to atlases capturing variability in a populationAnalogous to training of a human reader

  • Disease identification (learn variation of normal anatomy identify abnormality as a deviation from normal variation) Integration of data from multiple individuals in order to discover systematic relationships among radiologic and clinical measurements Does a lesion in a particular part of the brain correlate with a certain neurological deficit? Does prostate cancer appear uniformly throughout the prostate or does it tend to appear in certain regions more frequently what is the optimal way of biopsying/treating a patient in order to maximize probability of cancer detection/elimination?)-What is the normal variation of hippocampal size for a given age?- What is the normal variation of cardiac shape and deformation?

  • Image Registration: Integration and Comparative Analysis of Images from different individuals / modalities / times /conditions--Image integration and co-registration helps generalize from the individual to the group, and to construct normative data abnormalities can be distinguished from normal statistical variationUnderlying biological process that results in abnormal signal, or simply normal tissue whose normal variability, in terms of image properties, needs to be measuredOverlay/Comparison of such images?

  • Registration and Measurement of Biological Shape DArcy Thompson, 1917:

  • The deformation function measures the local deformation of the template:

    Deformation 1 Deformation 2Local structural measurements can be measured by analyzing the deformation functions with standard statistical methodologies Template Shape 1 Shape 2Red: ContractionGreen: Expansion

    High-Dimensional Shape TransformationsTemplateMR imageWarped template

  • Significant 4-year GM changes in 107 older adultsFrom the cover page of the Lancet, Neurology

  • RIGHTLEFTVoxel-based analysis of tissue density mapsEffect Size MapsNC > FTDNC > ADFTD > AD

  • Tissue atrophy map of an AD patient, relative to cognitively normal controlsTemplate SpacePatients scan

  • Regions of differences between schizophrenics and normal controlsAverage of 148 brain images, after deformable registration to the atlas

  • Atlas with optimal needle positionsApex Base Left Right 6 7 4 3 1 2 5 ApexBaseLeftRightTargeted Prostate Biopsy Using Mathematical Optimization100 SamplesTemplateSegmented 3D ProstateWarped Prostate AtlasUS prostate imageMRI prostate imageDeformable Segmentation of Prostate Images

  • 20 subjects, average age 64.7020 subjects, average age 83.05Quantitative analysis meets visual image interpretation40174 mm320564 mm3Younger Old Adult Average ModelOlder Old Adult Average ModelAverage age 64.7Average age 83

  • Using a statistical atlas to guide WM lesion segmentationSpatial distribution of WM abnormalities in 50 older adults (BLSA)

  • HAMMER: Hierarchical Attribute Matching Mechanism for Elastic Registration

  • Pattern Matching: Finding Anatomical CorrespondencesAttribute vector based on wavelet analysis of the anatomical context around each voxel morphological signature of each voxel

  • TemplateA brain MRI before warping and after warping

  • ModelMeasuring volumes of anatomical structures :An atlas with anatomical definitions is registered to the patients imagesSubject

  • To summarize:

    Anatomical definitions are used to create an atlas analogous to the knowledge of anatomy by humans Pattern matching performed hierachically at various scales is used to match the atlas to the individual

  • Can we use these quantitative image analysis tools as diagnostic tools?-Combine all morphological, physiological, and clinical measurements into a broader phenotypic profile-Use high-dimensional pattern classification and machine learning techniquesProblem: Potentially high statistical overlap for any single anatomical structure, if disease is not focal

  • Where is the problem?Data from Baltimore Longitudinal Study of Aging, Davatzikos et.al. Neurobiology of aging, in press

    plot

    0.00166956290.0016307283

    0.00163589540.0014632416

    0.00167819560.0011939015

    0.00137259830.0013760514

    0.00172135910.0020899751

    0.0015961850.0013380675

    0.00172999180.001250014

    0.00191214160.0013199388

    0.00174207760.0017722974

    0.0015512950.0019915624

    0.00181027580.0025949877

    0.00184825970.0012897244

    0.00128368150.0011809525

    0.00209429150.0010644111

    0.00159100540.0016963243

    Normal Controls

    MCI

    Hippocampus Volume

    Entorhinal Cortex Volume

    Sheet1

    label1013696100hippoentorhinal

    hippocampal formation lefthippocampal formation rightentorhinal cortex leftentorhinal cortex rightsum of hipposum of entorhinalICVTotal Hippo Nomalized by ICVtotal entorhinal normalized by ICV

    MCI dx0.5

    AE082673.63281253042.7734375897.81592.65716.406252490.41527170.361328130.00374313590.0016307283

    AN093141.6503906253272.167968751115.332031251119.2871093756413.8183593752234.6191406251247559.521484380.00419980540.0014632416

    AP082349.316406252676.26953125870.1171875953.1738281255025.58593751823.2910156251209337.646484380.00329078280.0011939015

    BF072366.4550781253115.283203125842.4316406251259.0332031255481.738281252101.464843751281190.869140630.0035894740.0013760514

    BJ082678.906253059.9121093751477.8808593751713.86718755738.8183593753191.7480468751370669.238281250.00375781150.0020899751

    BS092711.8652343753256.34765625858.2519531251185.2050781255968.2128906252043.457031251159929.49218750.00390802040.0013380675

    CI082634.082031252326.904296875888.574218751020.410156254960.9863281251908.9843751114465.869140630.00324848260.001250014

    CY032582.6660156253156.15234375954.49218751061.2792968755738.8183593752015.7714843751347125.97656250.00375781150.0013199388

    DL091241.894531251815.380859375841.11865.53057.2753906252706.61295545.166015630.00200192160.0017722974

    DR052986.0839843753381.5917968751103.4667968751937.988281256367.675781253041.4550781251349107.470703130.0041695910.0019915624

    DX043438.281253593.847656251782.4218752180.566406257032.128906253962.988281251368000.878906250.00460467870.0025949877

    ED062130.468752336.1328125655.2246093751314.4042968754466.60156251969.628906251139734.863281250.00292475660.0012897244

    EL032514.1113281252739.55078125813.427734375990.0878906255253.6621093751803.5156251268530.66406250.00344012840.0011809525

    EW012354.589843752971.58203125566.894531251058.6425781255326.1718751625.5371093751342004.150390630.00348760820.0010644111

    GN072048.730468752850.29296875971.6308593751618.94531254899.02343752590.5761718751145042.5781250.00320790890.0016963243

    Normal Control

    AD062689.4531253038.818359375885.93751663.769531255728.2714843752549.707031251267029.052734380.00375090540.0016695629

    AH092736.91406252910.9375835.839843751662.4511718755647.85156252498.2910156251326990.673828130.00369824590.0016358954

    AK093313.0371093752780.419921875987.4511718751575.4394531256093.457031252562.8906251268959.130859380.0039900310.0016781956

    AR0103348.63281253360.498046875834.5214843751261.6699218756709.1308593752096.191406251503177.53906250.00439317780.0013725983

    BA082876.660156253434.326171875991.406251637.402343756310.9863281252628.808593751131633.544921880.00413247040.0017213591

    BH062751.4160156253106.0546875986.13281251451.5136718755857.4707031252437.6464843751242892.529296880.00383550580.001596185

    BU072974.218753045.410156251059.96093751582.031256019.628906252641.99218751399911.767578130.00394168790.0017299918

    CA093762.597656253268.2128906251231.347656251688.8183593757030.8105468752920.1660156251263535.400390630.00460381550.0019121416

    CQ092834.472656252871.386718751132.4707031251527.9785156255705.8593752660.449218751358090.771484380.00373622980.0017420776

    DG092560.253906252616.943359375957.128906251411.9628906255177.1972656252369.0917968751122494.677734380.00339005880.001551295

    EB032510.156252880.6152343751187.8417968751576.75781255390.7714843752764.5996093751312542.77343750.00352990840.0018102758

    EV082437.6464843752649.90234375909.667968751912.9394531255087.5488281252822.6074218751284820.31250.00333135640.0018482597

    EX021717.8222656252896.435546875826.6113281251133.78906254614.25781251960.4003906251316259.228515630.00302144270.0012836815

    FF052661.7675781252721.093751215.527343751982.81255382.8613281253198.339843751398862.353515630.00352472880.0020942915

    FI083256.347656253923.43751016.4550781251413.281257179.785156252429.7363281251432588.623046880.00470136490.0015910054

    Sheet2

    Sheet3

  • Pattern ClassificationAbnormalityscoreA pattern is sampled by measuring brain volumes and blood flow in a number of brain regions Local tissue volumes and PET O15 are combined 15-20 brain regions (clusters) build a multi-parametric imaging profile

  • Abnormality ScoreMeasurement and Integration of Structural and Functional Patterns

    plot

    0.00166956290.0016307283

    0.00163589540.0014632416

    0.00167819560.0011939015

    0.00137259830.0013760514

    0.00172135910.0020899751

    0.0015961850.0013380675

    0.00172999180.001250014

    0.00191214160.0013199388

    0.00174207760.0017722974

    0.0015512950.0019915624

    0.00181027580.0025949877

    0.00184825970.0012897244

    0.00128368150.0011809525

    0.00209429150.0010644111

    0.00159100540.0016963243

    Normal Controls

    MCI

    Hippocampus Volume

    Entorhinal Cortex Volume

    Sheet1

    label1013696100hippoentorhinal

    hippocampal formation lefthippocampal formation rightentorhinal cortex leftentorhinal cortex rightsum of hipposum of entorhinalICVTotal Hippo Nomalized by ICVtotal entorhinal normalized by ICV

    MCI dx0.5

    AE082673.63281253042.7734375897.81592.65716.406252490.41527170.361328130.00374313590.0016307283

    AN093141.6503906253272.167968751115.332031251119.2871093756413.8183593752234.6191406251247559.521484380.00419980540.0014632416

    AP082349.316406252676.26953125870.1171875953.1738281255025.58593751823.2910156251209337.646484380.00329078280.0011939015

    BF072366.4550781253115.283203125842.4316406251259.0332031255481.738281252101.464843751281190.869140630.0035894740.0013760514

    BJ082678.906253059.9121093751477.8808593751713.86718755738.8183593753191.7480468751370669.238281250.00375781150.0020899751

    BS092711.8652343753256.34765625858.2519531251185.2050781255968.2128906252043.457031251159929.49218750.00390802040.0013380675

    CI082634.082031252326.904296875888.574218751020.410156254960.9863281251908.9843751114465.869140630.00324848260.001250014

    CY032582.6660156253156.15234375954.49218751061.2792968755738.8183593752015.7714843751347125.97656250.00375781150.0013199388

    DL091241.894531251815.380859375841.11865.53057.2753906252706.61295545.166015630.00200192160.0017722974

    DR052986.0839843753381.5917968751103.4667968751937.988281256367.675781253041.4550781251349107.470703130.0041695910.0019915624

    DX043438.281253593.847656251782.4218752180.566406257032.128906253962.988281251368000.878906250.00460467870.0025949877

    ED062130.468752336.1328125655.2246093751314.4042968754466.60156251969.628906251139734.863281250.00292475660.0012897244

    EL032514.1113281252739.55078125813.427734375990.0878906255253.6621093751803.5156251268530.66406250.00344012840.0011809525

    EW012354.589843752971.58203125566.894531251058.6425781255326.1718751625.5371093751342004.150390630.00348760820.0010644111

    GN072048.730468752850.29296875971.6308593751618.94531254899.02343752590.5761718751145042.5781250.00320790890.0016963243

    Normal Control

    AD062689.4531253038.818359375885.93751663.769531255728.2714843752549.707031251267029.052734380.00375090540.0016695629

    AH092736.91406252910.9375835.839843751662.4511718755647.85156252498.2910156251326990.673828130.00369824590.0016358954

    AK093313.0371093752780.419921875987.4511718751575.4394531256093.457031252562.8906251268959.130859380.0039900310.0016781956

    AR0103348.63281253360.498046875834.5214843751261.6699218756709.1308593752096.191406251503177.53906250.00439317780.0013725983

    BA082876.660156253434.326171875991.406251637.402343756310.9863281252628.808593751131633.544921880.00413247040.0017213591

    BH062751.4160156253106.0546875986.13281251451.5136718755857.4707031252437.6464843751242892.529296880.00383550580.001596185

    BU072974.218753045.410156251059.96093751582.031256019.628906252641.99218751399911.767578130.00394168790.0017299918

    CA093762.597656253268.2128906251231.347656251688.8183593757030.8105468752920.1660156251263535.400390630.00460381550.0019121416

    CQ092834.472656252871.386718751132.4707031251527.9785156255705.8593752660.449218751358090.771484380.00373622980.0017420776

    DG092560.253906252616.943359375957.128906251411.9628906255177.1972656252369.0917968751122494.677734380.00339005880.001551295

    EB032510.156252880.6152343751187.8417968751576.75781255390.7714843752764.5996093751312542.77343750.00352990840.0018102758

    EV082437.6464843752649.90234375909.667968751912.9394531255087.5488281252822.6074218751284820.31250.00333135640.0018482597

    EX021717.8222656252896.435546875826.6113281251133.78906254614.25781251960.4003906251316259.228515630.00302144270.0012836815

    FF052661.7675781252721.093751215.527343751982.81255382.8613281253198.339843751398862.353515630.00352472880.0020942915

    FI083256.347656253923.43751016.4550781251413.281257179.785156252429.7363281251432588.623046880.00470136490.0015910054

    Sheet2

    Sheet3

  • PET-post cingulateIndividual Diagnosis High-dimensional Pattern Classification (Machine learning) Evaluate spatial patterns of GM, WM, CSF, PET signal distribution Use these pattern to construct an image-based classifier, using support vector machinesL-ERCwAnterior L-hipp

  • Brain regions that collectively contributed to classificationImages in radiology convention

    AllGMEffect sizeWM Effect sizePETEffect size

  • Classification Rate vs. Number of Regions

  • Change of abnormality scores over time* Clinically normal, has now gone through autopsy with Braak 4 and moderate plaques meets AD pathology criteria*After removing this one participant

  • Normals: -0.3MCI at latest scan: 0.26MCI at year of conversion: 0.15Already significant structural abnormality on year of conversion to MCIAbnormality scores when converting from normal to MCI

  • Data from ADNIAD vs CN classifier applied to MCI: most MCIs have AD-like MRI profilesMMSE decline

  • fMRI for Lie Detection: A Card Concealment Experiment Experiments performed by the Brain and Behavior Laboratory (Psychiatry) Particiapnts were asked to lie about the possession of a card of their choice 22 participants, both true/lie responses Parameter images were created using the GLM with double gamma HRF

  • Most discriminative brain region: 63.1%

  • The power of true multi-variate analysis vs. mass-univariate

  • Pattern classification resultsIndividual imagesAverage images

    Chart1

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