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AAN –Toronto, April 11, 2010 Development of a harmonized protocol for hippocampal tracing An EADC-ADNI joint effort INTRODUCTION BACKGROUND Hippocampal volume as a diagnostic marker Structure: MR hippo volumetry Function: FDG PET Alzheimer CSF total tau Amyloid deposits: PET Biochemistry: CSF tau/Abeta Normal CSF Abeta42 Dubois, Feldman et al., Lancet Neurol 2007 BACKGROUND The effect of segmentation protocols on hippocampal volume Ref. Watson et al. Med border Mesial edge of temporal lobe Regional Zipursky outline at choroidal et al. fissure Norm. hippo vol (cm3) Left Right Lat border Inf border Temp horn of lat ventr Incl subicular complex & uncal cleft w/ border separating subicular complex from parahippo gyrus 4.903 5.264 Not mentioned The interface of hippocampal tissue and parahippocampal gyrus white matter 1.990 2.070 Geuze et al., Mol Psychiatry 2005;10:147-59 BACKGROUND Hippocampal volume as an outcome measure in trials of disease modifiers Drug Study Effect Segment. method Tramiprosate Alphase 68% (100 mg) 120% (150 mg) Not mentioned Gauthier et al., JNHA 2009 Atorvastatin ADCLT “CHV* mm³ -134±174 vs 583±354 p> .05” Manual protocol Insausti et al., 1998 AJNR; Machulda et al., 2001, Neuroimage Sparks et .a,l CCJM,2008 LEADe “significant at p<.05” MIDAS (semiautomated) “CHV* % 3.78±2.63 vs 2.86±3.19 p = 0.124” Manual protocol Watson et al., 1992, Neurology “significant atrophy” § Not mentioned “CHV* % -6.14±3.49vs 4.50±2.28 p= 0.07” ε4 carriers only Manual protocol Jack et al., 1989;Radiology Jack et al., 2004; Neurology AN1792 Xaliproden Donepezil SanofiAventis Trials * CHV= Change in hippocampal volume; § referenced link not working Ref Jones et al., Alz&Dem 2008 Feldman et al., Neurology 2010 Fox N et al., Neurology, 2005 From Vellas B et al. (Review), Lancet Neurol.,2008 Jack CR et al., Neurobiol. Aging, 2008 BACKGROUND Hippocampal volume (manual segmentation) as gold standard for automated segmentation algorithms Morey et al., NeuroImage 2009 AIMS To Harmonize Available Protocols for Manual Hippocampal Segmentation To Test the Validity of the Harmonized Protocol THE WORKGROUP EADC F Barkhof/P Scheltens B Dubois/S Leherici N Fox GB Frisoni H Hampel/J Pantel A Simmons H Soininen S Teipel LO Wahlund Amsterdam Paris London Brescia Frankfurt London Kuopio Rostock Stockholm THE WORKGROUP ADNI CR Jack Jr Rochester, MN G Barzokis UCLA, CA D Bennet Chicago, IL J Csernansky NorthW U, WA C DeCarli UC Davis, CA M De Leon New York, NY J Kaye Portland, OR R Killiany Boston USM, MA PM Thompson LoNI, UCLA, CA M Weiner/S Mueller UCSF/VAMC THE WORKGROUP other relevant hippo experts R Camicioli J O’Brien J Pruessner Univ Alberta, Canada NewCastle, UK McGill, QC, Canada THE WORKGROUP Advisory Boards EADC-ADNI P.I.s B Vellas B Winblad M Weiner Toulouse, France Stockholm, Sweden UCSF, US Population-based studies M Breteler / T Den Heijer P Sachdev / JJ Maller L Launer W Jagust Rotterdam Scan Study PATH through life NIA Bethesda Berkeley THE WORKGROUP Boards Statistical Board S Duchesne L Collins P Pasqualetti Laval Univ, Canada MNI, McGill, Montreal AFaR, Rome Clinical Advisor PJ Visser Maastricht, The Netherlands Dissemination/Education G Waldemar Copenhagen, Denmark THE WORKGROUP Personnel in Brescia Marina Boccardi Rossana Ganzola Enrica Cavedo psychologist, PhD psychologist psychologist Michela Pievani Anna Caroli Alberto Redolfi mathematician mathematician bioinformaticist AAN –Toronto, April 11, 2010 Development of a harmonized protocol for hippocampal tracing An EADC-ADNI joint effort METHODS METHODS Operationalization of protocols’ differences and extraction of tracing units Quantification of tracing units’ features Harmonized protocol OPERATIONALIZATION Selection of segmentation protocols Selection criteria i) Being based on 3D T1 MRI with field strength greater than 1 Tesla ii) Providing explicit description of landmarks for tracing of hippocampal borders iii) Being validated on AD/MCI samples, or being widely adopted in the literature about AD. OPERATIONALIZATION Protocols’ features extraction Areas explicitly included Areas explicitly excluded Andreas-Retzius CA regions, dentate gyrus (ARG), the part gyrus, subiculum, of the FG that is alveus, fimbria, part of adjacent to ARG, crus the fasciolar gyrus (FG) of fornix Most anterior slice Most posterior slice slice w here one of the follow ing is visible: alveus, temporal horn of lateral ventricle (uncal recess) or amygdala slice w here an ovoid mass of gray matter started to appear inferomedially to the trigone of the lateral ventricle Plane of tracing: AC-PC line; BOUNDARIES Normalization to the Talairach space HEAD Lateral border temporal horn of lateral ventricle (uncal recess) Inferior border Medial border Superior border CSF of ambient cistern temporal horn of lateral ventricle (uncal recess) and alveus Tracing start from the tail of hippocampus to the hippocampal head uncal cleft (if visible) In the following slices, you can find the BODY temporal horn of lateral ventricle (uncal recess) White matter of the parahippocampal gyrus CSF of ambient cistern superior excess of the quadrigeminal cistern TAIL hippocampal tracing on consecutive Discrimination of HT from FG and crus of fornix using arbitrary borders adjacent w hite matter atrium of lateral ventricle Discrimination of HT from ARG using arbitrary borders coronal slices (1.5T) of the control subject and AD patient according to Pruessner's criteria OPERATIONALIZATION Prototypical tracings Tracings carried out on a control and an AD subject from the ADNI dataset Tracings sent to the Authors for correction or approval CTRL Most posterior slice : slice where The fornix can be excluded by a an ovoid mass of gray matter (1) started to appear inferomedially of horizontal line (in fuchsia) from the superior border of the the atrium of lateral ventricle (2) quadrigeminal cistern (3) to the lateral ventricle (2). Part of gyrus fasciolaris (7) and of Sagittal Andreas-Retzius gyrus (8) can be excluded by a vertical line (in red) view from the medial end of the lateral ventricle (2) down to the parahippocampal gyrus (4). 2= Atrium of lateral ventricle 4= Parahippocampal gyrus 5= Gyrus dentatus 6= Cornu Ammonis 7= Gyrus fasciolaris 8= Gyrus of Andreas-Retzius 9= Isthmus AD Most posterior slice : slice where In AD subjects the cerebral structures are atrophic, lateral an ovoid mass of gray matter (1) started to appear inferomedially of ventricle (2) and ambient cistern (3) result enlarged. Therefore, the lines used to exclude the gyrus fasciolaris, the Andreasthe atrium of lateral ventricle (2) Retzius gyrus and the fornix do not intersect the hippocampal tail. That being so, is there another way to exclude the gyrus fasciolaris, the Andreas-Retzius gyrus and the fornix in these Sagittal subjects? view 2= Atrium of lateral ventricle 4= Parahippocampal gyrus 5= Gyrus dentatus 6= Cornu Ammonis 7= Gyrus fasciolaris 8= Gyrus of Andreas Retzius 9= Isthmus OPERATIONALIZATION Authors’ check For each protocol: features extraction, tracing and author’s certification CTRL Areas explicitly included Areas explicitly excluded Andreas-Retzius CA regions, dentate gyrus (ARG), the part gyrus, subiculum, of the FG that is alveus, fimbria, part of adjacent to ARG, crus the fasciolar gyrus (FG) of fornix Most anterior slice Most posterior slice slice w here one of the follow ing is visible: alveus, temporal horn of lateral ventricle (uncal recess) or amygdala slice w here an ovoid mass of gray matter started to appear inferomedially to the trigone of the lateral ventricle Inferior border Medial border Superior border temporal horn of lateral ventricle (uncal recess) uncal cleft (if visible) CSF of ambient cistern temporal horn of lateral ventricle (uncal recess) and alveus BODY AD temporal horn of lateral ventricle (uncal recess) White matter of the parahippocampal gyrus CSF of ambient cistern superior excess of the quadrigeminal cistern TAIL HEAD BOUNDARIES Lateral border Discrimination of HT from FG and crus of fornix using arbitrary borders adjacent w hite matter atrium of lateral ventricle Discrimination of HT from ARG using arbitrary borders X 10 OPERATIONALIZATION Extraction of similarities and differences Harmonized language Reduction of redundancy Tracing units and subunits Plane of tracing Axis of hippocampus [B,C,J,L,S] AC-PC line [H,K,M,Pa,Pr] Most posterior slice Areas explicitly included Areas explicitly excluded portion of subiculum, CA fields choroid plexis of inferior horn, amygdala Where inferior and superior colliculi are jointly visualized [B] Most posterior slice Most anterior slice Where crus of fornix is visible in full profile [C,K,L] Where the crura of the fornices are seen in full profile on both sides [J,S] Upper border of alveus/fimbria [C,J,L,M,Pr] Horizontal line from the superior border of the quadrigeminal cistern to the lateral ventricle (tail) [Pr] 45° line connecting the most inferior part of the subiculum medially to the cistern (head and body) [Pr] Oblique line with same inclination of parahippocampal WM, connecting the inferior part of the subiculum to the quadrigeminal cistern [K,L,M¥] slice in w hich the fornix level at w hich the alveus distinguishes the amygdala appeared as a solid w hite line through the collateral trigone from hippocampus Where gray matter is visible inferomedially to the trigone of the lateral ventricle [H,M•,Pa•,Pr] Superior border Inferior border Medial border Superior border HEAD inferior horn of the lateral ventricle w hite matter joining the parahippocampal gyrus angular bundle inferior horn of the lateral ventricle BODY Areas explicitly included Lateral border same as head same as head same as head same as head TAIL BOUNDARIES same as head Areas explicitly excluded Most anterior slice same as head Separation subiculum/enthor inal cortex Most posterior slice same as head same as head Andreas-Retzius slice w here one of the CA regions, dentate slice w here an ovoid mass of gyrus (ARG), the part follow ing is visible: alveus, gyrus, subiculum, gray matter started to appear Areas explicitly of the FG that Plane is tracing temporal horn lateralincluded Areasof explicitly anterior slice alveus, fimbria, part of inferomediallyexcluded to the trigone Most of the adjacent to ARG, crus ventricle (uncal recess) or the fasciolar gyrus (FG) lateral ventricle the separation of amygdala of fornix amygdala axial + coronal + sagittal Lower border of alveus/fimbria [B,H,K,Pa,S] Cornu Ammonis, subiculum, vertical digitation alveus and fimbria BOUNDARIES Most posterior slice coronal section in w hich the and hippocampal head w as hippocampus first appeared facilitated by sagittal and adjacent to the trigone of lateral transverse view s venticle Inferior border HEAD uncal cleft (if visible) BODY Medial border Medial border temporal horn of lateral ventricle (uncal recess) White matter of the parahippocampal gyrus Discrimination of HT from FG and crus of fornix using arbitrary borders adjacent w hite matter BODY HEAD Lateral border temporal horn of lateral ventricle (uncal recess) TAIL BOUDARIES Gyrus ambiens CSF of ambient cistern Inferior border Superior border identified by the contrast of the WM WM of parahippocampal identified by the contrast of the WM or CSF identified by the contrast of the WM or CSF WM of parahippocampal gyrus The medial border of the HC w as continued w ith a straight horizontal line (marking the inferior border of CA and subiculum) across the cortex of the PHG. The cortex below this line w as considered the PHG, and the cortex above this line w as included as a part of the HC CSF of ambient cistern TAIL Superior border Lateral border gyrus (PHG) temporal horn orofCSF lateral ventricle (uncal recess) and alveus The medial border of the HC w as continued w ith a straight horizontal line (marking the inferior border of CA and subiculum) across the cortex of the PHG. The cortex below this line w as considered the PHG, and the cortex above this line w as included as a part of the HC atrium of lateral ventricle identified by the contrast of the WM or CSF superior excess of the quadrigeminal cistern identified by the contrast of the WM or CSF WM of parahippocampal gyrus Discrimination of HT from ARG using arbitrary borders identified by the contrast of the WM or CSF, and Thalamus and caudate nucleus vertical line from the CA to the WM of the parahippocampal gyrus [C] Orizontal line from the highest medial point of the parahippocampal WM to the cistern [B,H,J¥] Line outlining the contour of white matter of parahippocamp al gyrus [Pa,S] OPERATIONALIZATION Extraction of similarities and differences Areas explicitly included Areas explicitly excluded portion of subiculum, CA fields choroid plexis of inferior horn, amygdala Most anterior slice Most posterior slice slice in w hich the fornix level at w hich the alveus distinguishes the amygdala appeared as a solid w hite line through the collateral trigone from hippocampus Inferior border Medial border Superior border HEAD inferior horn of the lateral ventricle w hite matter joining the parahippocampal gyrus angular bundle inferior horn of the lateral ventricle BODY BOUNDARIES Lateral border same as head same as head same as head same as head same as head Areas explicitly excluded same as head Most posterior slice Most anterior slice same as head Andreas-Retzius CA regions, dentate gyrus (ARG), the part gyrus, subiculum, of the FG that is alveus, fimbria, part of adjacent to ARG, crus the fasciolar gyrus (FG) of fornix same as head slice w here one of the follow ing is visible: alveus, temporal horn of lateral ventricle (uncal recess) or amygdala slice w here an ovoid mass of gray matter started to appear inferomedially to the trigone of the lateral ventricle Inferior border Medial border Superior border HEAD temporal horn of lateral ventricle (uncal recess) uncal cleft (if visible) CSF of ambient cistern temporal horn of lateral ventricle (uncal recess) and alveus BODY BOUNDARIES Lateral border temporal horn of lateral ventricle (uncal recess) White matter of the parahippocampal gyrus CSF of ambient cistern superior excess of the quadrigeminal cistern TAIL TAIL Areas explicitly included Discrimination of HT from FG and crus of fornix using arbitrary borders adjacent w hite matter atrium of lateral ventricle Discrimination of HT from ARG using arbitrary borders Plane of tracing Axis of hippocampus [B,C,J,L,S] AC-PC line [H,K,M,Pa,Pr] Where inferior and superior colliculi are jointly visualized [B] Where crus of fornix is visible in full profile [C,K,L] Lower border of alveus/fimbria [B,H,K,Pa,S] Upper border of alveus/fimbria [C,J,L,M,Pr] 45° line connecting the most inferior part of the subiculum medially to the cistern (head and body) [Pr] Oblique line with same inclination of parahippocampal WM, connecting the inferior part of the subiculum to the quadrigeminal cistern [K,L,M¥] Most posterior slice Where the crura of the fornices are seen in full profile on both sides [J•,S] Where gray matter is visible inferomedially to the trigone of the lateral ventricle [H,M•,Pa•,Pr] Superior border Horizontal line from the superior border of the quadrigeminal cistern to the lateral ventricle (tail) [Pr] Separation subiculum/enthorinal cortex vertical line from the CA to the WM of the parahippocampal gyrus [C] Orizontal line from the highest medial point of the parahippocampal WM to the cistern [B,H,J¥] Line outlining the contour of white matter of parahippocampal gyrus [Pa,S] METHODS Operationalization of protocols’ differences Quantification of tracing units’ features Harmonized protocol QUANTIFICATION OF TRACING UNITS’ FEATURES Contribution to hippo volume in control and AD Effect on re-test variability Contribution to differences between AD and controls METHODS Operationalization of protocols’ differences Quantification of tracing units’ features Harmonized protocol HARMONIZED PROTOCOL Participants to a Delphi panel based on: expertise in hippocampal anatomy manual tracing scientific production Assisted decisions based on: Low variability, highly informative.. ..included in harmonized protocol High variability, little informative.. ..excluded from harmonized prot HARMONIZED PROTOCOL Validation & implementation Validation with neuropathological data Comparison with currently used protocols Public tracings and probability maps Standard environment for tracing, learning, and certification AAN –Toronto, April 11, 2010 Development of a harmonized protocol for hippocampal tracing An EADC-ADNI joint effort EARLY RESULTS EARLY RESULTS Protocols’ features extraction & differences operationalization Modeling & computations of the operationalized differences Discussion PROTOCOLS’ FEATURES EXTRACTION B C H J K L M Pa Pr S Bartzokis G, et al. Convit A, et al. Haller JW, et al. Jack CR Jr. Killiany RJ, et al. Lehéricy S, et al. Malykhin NV, et al. Pantel J, et al. Pruessner JC, et al. Soininen HS, et al. Psychiatry Res 1998;82:11-24 Neurobiol Aging 1997;18:131-8 Radiology 1997;202:504-10 Epilepsia 1994;35 - Suppl 6:S21-9 Arch Neurol 1993;50:949-54 Am J Neuroradiol 1994;15:929-37 Psychiatry Res 2007;155:155-65 Hippocampus 2000;10:752-8 Cereb Cortex 2000;10:433-42 Neurology 1994;44:1660-8 PROTOCOLS’ FEATURES EXTRACTION http://www.hippocampal-protocol.net PROTOCOLS’ FEATURES EXTRACTION Harmonized language Reduction of redundancy Tracing units and subunits Plane of tracing Axis of hippocampus [B,C,J,L,S] AC-PC line [H,K,M,Pa,Pr] Most posterior slice Areas explicitly included Areas explicitly excluded portion of subiculum, CA fields choroid plexis of inferior horn, amygdala Where inferior and superior colliculi are jointly visualized [B] Most posterior slice Most anterior slice slice in w hich the fornix level at w hich the alveus distinguishes the amygdala appeared as a solid w hite line through the collateral trigone from hippocampus Where crus of fornix is visible in full profile [C,K,L] Where the crura of the fornices are seen in full profile on both sides [J,S] Upper border of alveus/fimbria [C,J,L,M,Pr] Horizontal line from the superior border of the quadrigeminal cistern to the lateral ventricle (tail) [Pr] 45° line connecting the most inferior part of the subiculum medially to the cistern (head and body) [Pr] Oblique line with same inclination of parahippocampal WM, connecting the inferior part of the subiculum to the quadrigeminal cistern [K,L,M¥] Where gray matter is visible inferomedially to the trigone of the lateral ventricle [H,M•,Pa•,Pr] Superior border Inferior border Medial border Superior border HEAD w hite matter joining the parahippocampal gyrus angular bundle inferior horn of the lateral ventricle BODY Areas explicitly included Lateral border inferior horn of the lateral ventricle same as head same as head same as head same as head TAIL BOUNDARIES same as head Areas explicitly excluded Most anterior slice same as head Separation subiculum/enthor inal cortex Most posterior slice same as head same as head Andreas-Retzius slice w here one of the CA regions, dentate slice w here an ovoid mass of gyrus (ARG), the part follow ing is visible: alveus, gyrus, subiculum, gray matter started to appear Areas explicitly of the FG that is lateralincluded Plane tracing temporal horn Areasof explicitly anterior slice alveus, fimbria, part of inferomediallyexcluded to the trigone Most of the adjacent to ARG, crus ventricle (uncal recess) or the fasciolar gyrus (FG) lateral ventricle the separation of amygdala of fornix amygdala axial + coronal + sagittal Lower border of alveus/fimbria [B,H,K,Pa,S] Cornu Ammonis, subiculum, vertical digitation alveus and fimbria BOUNDARIES Most posterior slice coronal section in w hich the and hippocampal head w as hippocampus first appeared facilitated by sagittal and adjacent to the trigone of lateral transverse view s venticle Inferior border HEAD uncal cleft (if visible) BODY Medial border Medial border temporal horn of lateral ventricle (uncal recess) White matter of the parahippocampal gyrus Discrimination of HT from FG and crus of fornix using arbitrary borders adjacent w hite matter BODY HEAD Lateral border temporal horn of lateral ventricle (uncal recess) TAIL BOUDARIES Gyrus ambiens CSF of ambient cistern Inferior border Superior border identified by the contrast of the WM WM of parahippocampal identified by the contrast of the WM or CSF identified by the contrast of the WM or CSF WM of parahippocampal gyrus The medial border of the HC w as continued w ith a straight horizontal line (marking the inferior border of CA and subiculum) across the cortex of the PHG. The cortex below this line w as considered the PHG, and the cortex above this line w as included as a part of the HC CSF of ambient cistern TAIL Superior border Lateral border gyrus (PHG) temporal horn orofCSF lateral ventricle (uncal recess) and alveus The medial border of the HC w as continued w ith a straight horizontal line (marking the inferior border of CA and subiculum) across the cortex of the PHG. The cortex below this line w as considered the PHG, and the cortex above this line w as included as a part of the HC atrium of lateral ventricle identified by the contrast of the WM or CSF superior excess of the quadrigeminal cistern identified by the contrast of the WM or CSF WM of parahippocampal gyrus Discrimination of HT from ARG using arbitrary borders identified by the contrast of the WM or CSF, and Thalamus and caudate nucleus vertical line from the CA to the WM of the parahippocampal gyrus [C] Orizontal line from the highest medial point of the parahippocampal WM to the cistern [B,H,J¥] Line outlining the contour of white matter of parahippocamp al gyrus [Pa,S] Plane of tracing Axis of hippocampus [B,C,J,L,S] AC-PC line [H,K,M,Pa,Pr] Most posterior slice Where inferior and superior colliculi are jointly visualized [B] Where crus of fornix is visible in full profile [C,K,L] Where the crura of the fornices are seen in full profile on both sides [J,S] Upper border of alveus/fimbria [C,J,L,M,Pr] Horizontal line from the superior border of the quadrigeminal cistern to the lateral ventricle (tail) [Pr] Where gray matter is visible inferomedially to the trigone of the lateral ventricle [H,M•,Pa•,Pr] Superior border Lower border of alveus/fimbria [B,H,K,Pa,S] Separation subiculum/enthorinal cortex vertical line from the CA to the WM of the parahippocampal gyrus [C] 45° line connecting the most inferior part of the subiculum medially to the cistern (head and body) [Pr] Oblique line with same inclination of parahippocampal WM, connecting the inferior part of the subiculum to the quadrigeminal cistern [K,L,M¥] Orizontal line from the highest medial point of the parahippocampal WM to the cistern [B,H,J¥] Line outlining the contour of white matter of parahippocamp al gyrus [Pa,S] PROTOCOLS’ FEATURES EXTRACTION Most anterior slice No longer an issue thanks to software for 3D navigation PROTOCOLS’ FEATURES EXTRACTION Plane of tracing Axis of hippocampus B. Bartzokis et al 1998 C. Convit et al 1997 J. Jack 1994 L. Lehéricy et al 1994 S. Soininen H et al 1994 AC-PC H. Haller-Csernansky et al 1997 K. Killiany et al 1993 M. Malykhin et al 2007 Pa. Pantel et al 2000 Pr. Pruessner et al 2000 PROTOCOLS’ FEATURES EXTRACTION Most posterior slice A. Level where the inferior (1) and superior (2) colliculi are jointly visualized [B] B. Slice where the crus of fornix is visible in full profile (3) [C, K, L] C. Slice where the crura of fornices on both sides are seen in full profile (4, 5) [J, S] D. Slice where an ovoid mass of gray matter (6) appears inferomedially to the trigone of the lateral ventricle (posterior to anterior) [H, M, Pa, Pr] PROTOCOLS’ FEATURES EXTRACTION Alveus Yellow = Alveus PROTOCOLS’ FEATURES EXTRACTION Fimbria Yellow = Fimbria PROTOCOLS’ FEATURES EXTRACTION Upper border PROTOCOLS’ FEATURES EXTRACTION Vertical line [C] Medial border 45° line [Pr] Line with same inclination WM [K, L, M] Horizontal line [B, H, J] Morphological details [Pa, S] EARLY RESULTS Protocols’ features extraction & differences operationalization Modeling & computations of the operationalized differences Discussion MODELING & COMPUTATIONS Plane of tracing Axis of hippocampus [B,C,J,L,S] AC-PC line [H,K,M,Pa,Pr] Where inferior and superior colliculi are jointly visualized [B] Where crus of fornix is visible in full profile [C,K,L] Most posterior slice Where the crura of the fornices are seen in full profile on both sides [J,S] Where gray matter is visible inferomedially to the trigone of the lateral ventricle [H,M•,Pa•,Pr] Superior border Lower border of alveus/fimbria [B,H,K,Pa,S] Upper border of alveus/fimbria [C,J,L,M,Pr] Separation subiculum/enthorinal cortex vertical line from the CA to the WM of the parahippocampal gyrus [C] 45° line connecting the most inferior part of the subiculum medially to the cistern (head and body) [Pr] Oblique line with same inclination of parahippocampal WM, connecting the inferior part of the subiculum to the quadrigeminal cistern [K,L,M¥] Orizontal line from the highest medial point of the parahippocampal WM to the cistern [B,H,J¥] Line outlining the contour of white matter of parahippocampal gyrus [Pa,S] Modeling by Simon Duchesne and Nicolas Robitaille Université Laval and Centre de Recherche Université Laval – Robert Giffard Quebec City, Canada MODELING & COMPUTATIONS Control subject MinHB (% of MaxHV) AD subject % diff from control 1768 (56) 1255 (57) - 29 175 (6) 150 (7) - 14 363 (11) 233 (10) - 36 45° line 161 (5) 112 (5) - 30 Oblique line 36 (1) 83 (4) +130 Morphology 121 (4) 30 (1) - 75 Horizontal line 45 (1) 8 (0.4) - 83 Alveus/Fimbria (%) Subiculum (%) Tail (%) MaxHV 838 (27) 571.5 (25.9) - 32 Colliculi 93 (3) 88 (4) - 12 Crus 108 (3) 137(6) + 27 Crura 109 (3) 184 (8) + 69 Caudal slices 529 (17) 163 (7) - 69 3144 2209 - 30 MODELING & COMPUTATIONS B J C K Pr L M S Pa H DISCUSSION Features operationalization: 4 tracing units, and subunits Preliminary info on contribution of units to total hippo volume 3D models may help Delphi panel for developing harmonized protocol Available: draft paper, and online material http://www.hippocampal-protocol.net April 14: Poster 24 PO3: Ageing and dementia imaging - other ACKNOWLEDGEMENTS Lilly International Wyeth International