- Email: [email protected]
Survey of segmentation protocols for manual hippocampal volumetry: Preparatory phase for an EADC-ADNI harmonization protocol
Alzheimer’s Imaging Consortium IC-03: Oral 3 - Magnetic Resonance for Early and Presymptomatic Diagnosis
S58
also excluded. The present study therefore included 337 subjects of whom 13 had developed AD (NINCDS-ADRDA criteria) and 25 SD (according to criteria of Erkinjuntti et al). MRI scans at 3 year follow-up were compared between groups. The CC was semi-automatically outlined on MRI images and quantified at baseline and follow-up. ARWMCs were visually scored using Fazekas scale (mild, moderate, severe) at baseline. Total CC area at follow-up was entered into ANCOVA analysis to test for differences between groups (AD, SD, non-demented). Subregional differences were analysed using repeated-measures ANCOVA, and significant results were further examined using univariate analysis. Results: Groups differed with regards to age, ARWMC-load and gender. Therefore the variables were entered into the ANCOVA analysis as covariates. AD, SD and non-demented elderly subjects did not differ in total CC area. AD and SD patients had smaller CC1 and CC5 compared to non-demented elderly subjects at 3 year follow-up, but did not differ in other CC subregions. No difference in subregional areas between the 2 patient groups. Conclusions: The presented results indicate that anterior and posterior CC atrophy is associated with dementia. No specific atrophy pattern was identified in dementia subtypes, although this may have been due to the relatively small number of subjects who developed dementia.
3 University of California, San Diego, La Jolla, CA, USA. Contact e-mail: [email protected]
Background: As treatments for AD develop, the field is moving toward identifying pre-dementia symptomatic individuals at the earliest stage possible. The large, longitudinal Alzheimer’s Disease Neuroimaging Initiative (ADNI) will be enrolling amnestic mild cognitive impairment (aMCI) subjects with a lesser degree of memory impairment. We used the National Alzheimer’s Coordinating Center (NACC) data to apply classifications of aMCI subjects to be used in ADNI studies. Methods: To characterize the clinical features of subjects with aMCI and a very mild level of memory impairment (designated as early MCI or EMCI), we applied the proposed ADNI criteria for MCI to the NACC Uniform Data Set (UDS). The NACC database is a repository for data from the National Institute on Aging Alzheimer’s Disease Centers Program and includes data necessary for classifying EMCI subjects according to the following criteria: clinical diagnosis of aMCI, CDR ¼ 0.5, CDR memory box > ¼ 0.5, MMSE >¼ 24 and education-specific cutoff scores on delayed recall of a single paragraph from Logical Memory II of Wechsler Memory Scale-Revised: 16 years, 9-11; 8-15 years, 5-9; 0-7 years, 3-6. NACC subjects were compared to those diagnosed with aMCI in the current ADNI project (now called late MCI or LMCI). Results: A total of 1334 subjects met criteria for aMCI outlined above. Of those, 371 met criteria for EMCI, 717 for LMCI, and 246 were classified as aMCI but did not conform to EMCI or LMCI criteria (other aMCI). The proportion of subjects who were ApoE4 carriers was as follows: EMCI 35.6%, LMCI 54.3%, other aMCI 37.4%. For the CDR sum of boxes, mean (SD) scores were: EMCI 1.3 (0.8), LMCI 1.6 (1.0) and other aMCI 1.1 (0.8). Annual rates of progression from aMCI to dementia were: EMCI 10.5%, LMCI 29.8% and other aMCI 9.3%. Conclusions: The category of EMCI can be characterized clinically and appears to represent a milder form of aMCI. The clinical definition of EMCI will be adopted in ADNI to assess the roles of imaging measures and fluid biomarkers in predicting progression. Support provided by the National Institute on Aging: U01 AG024904 and U01 AG016976, P50 AG016574, U01 AG006786.
IC-03-02
SURVEY OF SEGMENTATION PROTOCOLS FOR MANUAL HIPPOCAMPAL VOLUMETRY: PREPARATORY PHASE FOR AN EADC-ADNI HARMONIZATION PROTOCOL
Marina Boccardi1, Rossana Ganzola1, Simon Duchesne2, Alberto Redolfi1, George Bartzokis3, John Csernansky4, Mony de Leon5, Ronald Killiani6, Ste´phane Lehe´ricy7, Nikolai Malykhin8, Johannes Pantel9, Jens Pruessner10, Hilkka Soininen11, Clifford R. Jack, Jr,12, Giovanni B. Frisoni1, 1IRCCS Centro S. Giovanni di Dio Fatebenefratelli, Brescia, Italy; 2Universite´ Laval and Centre de Recherche Universite´ Laval e Robert Giffard, Quebec City, QC, Canada; 3David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 4Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5New York University School of Medicine, New York, NY, USA; 6 Boston University School of Medicine, Boston, MA, USA; 7Universite´ Pierre et Marie Curie, Paris, France; 8University of Alberta, Edmonton, AB, Canada; 9University of Frankfurt/Main, Frankfurt, Germany; 10McGill University, Montreal, QC, Canada; 11Kuopio University Hospital, Kuopio, Finland; 12Mayo Clinic and Foundation, Rochester, MN, USA. Contact e-mail: [email protected] SATURDAY, JULY 10, 2010 ALZHEIMER’S IMAGING CONSORTIUM IC-03 ORAL 3 - MAGNETIC RESONANCE FOR EARLY AND PRESYMPTOMATIC DIAGNOSIS IC-03-01
EARLY MCI AS AN IMAGING TARGET: DATA FROM THE NATIONAL ALZHEIMER’S COORDINATING CENTER
Ronald C. Petersen1, Dawn P. Gill2, Leslie E. Phillips2, Paul Aisen3, 1Mayo Clinic, Rochester, MN, USA; 2University of Washington, Seattle, WA, USA;
Background: Hippocampal atrophy is a key diagnostic marker for early and incipient Alzheimer’s disease (AD) but different procedures give rise to estimates of normal hippocampal volume that vary up to 2.5 times across laboratories. Internationally harmonized procedures are required to use hippocampal volume as a diagnostic marker in clinical settings, surrogate measure in clinical trials for AD drugs, and gold standard for automated segmentation algorithms. Methods: The 10 most frequently used segmentation protocols for hippocampal volumetry in the AD literature [1 to 10, see following] were surveyed to extract anatomical landmarks (anteriormost and posteriormost slice, dorsal, ventral, medial, and lateral borders). The hippocampi of one healthy control and one AD patient taken form the ADNI database were segmented by a single rater following each protocol.
Alzheimer’s Imaging Consortium IC-03: Oral 3 - Magnetic Resonance for Early and Presymptomatic Diagnosis Individual interactive web conferences were arranged with the primary authors to check correctness of interpretation. Semantically harmonized landmark differences among protocols were finally extracted. The protocols were [1] Bartzokis et al., 1998, [2] Convit et al., 1997, [3] Haller et al., 1997, [4] Jack et al., 1994, [5] Killiany 1993 et al., [6] Lehericy et al., 1994, [7] Malykhin et al., 2007 [8] Pantel et al., 2000, [9] Pruessner et al., 2000, and [10] Soininen et al., 1994. Results: The survey of anatomical landmarks of the protocols, and the hippocampi segmented following each of the protocols and checked with their authors can be found at http://www. centroalzheimer.it/public/SOPs/online. Landmark differences among protocols (available at the same http address) regard: (a) inclusion [#2,4,6,7,8,9] and exclusion [#1,3,5,10] of hippocampal white matter (alveus and fimbria); (b) specification of the most posterior slice: most restrictive [#1], most inclusive [#3,7,8,9] for a maximum linear difference of 9.6 mm; (c) separation between the subiculum and the parahippocampal gyrus, consisting of variable combinations of five criteria. Heterogeneities in the definition of the boundary with the amygdala, while a source of variance in the earlier protocols, are no longer an issue due to currently available visualization tools allowing 3D navigation. Conclusions: Operationalized differences among segmentation protocols for hippocampal volumetry constitute preparatory work for an international consensus for a harmonized protocol
IC-03-03
AMYLOID AND CEREBROVASCULAR DISEASE BOTH CONTRIBUTE TO COGNITIVE IMPAIRMENT IN INDIVIDUALS WITH HIGH VASCULAR RISK
Gil D. Rabinovici1, Adi Alkalay1, Natalie L. Marchant2, Charles DeCarli3, Helena C. Chui4, Bruce R. Reed3,5, William J. Jagust2,6, 1UCSF, San Francisco, CA, USA; 2UC Berkeley, Berkeley, CA, USA; 3UC Davis, Sacramento, CA, USA; 4USC, Los Angeles, CA, USA; 5VA Northern California Health Care System, Martinez, CA, USA; 6Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Contact e-mail: grabinovici@ memory.ucsf.edu Background: Autopsy studies suggest that cognitive impairment in late life is often due to a combination of Alzheimer’s disease (AD) and cerebrovascular disease (CVD), but in vivo studies relating both pathologies to cognition are lacking. We evaluated the relationship of amyloid and CVD to cognition in individuals with high vascular risk. Methods: Subjects enrolled in two vascular-focused studies of cognition at UC Davis underwent PIBPET (N ¼ 24) and MRI (N ¼ 17). PIB distribution volume ratio images (Logan, cerebellar reference) were classified as positive (PIB+, N ¼ 10) or negative (PIB-, N ¼ 14) based on visual reads blinded to clinical data. MRI scans were visually rated for the presence of infarcts (blinded to clinical history). Subjects were classified as having cerebrovascular disease (CVD+, N ¼ 17/24) if there was a clinical history of stroke, TIA or an infarct on imaging. Participants with a Clinical Dementia Rating (CDR) ¼ 0 were classified as cognitively normal (N ¼ 10), while individuals with CDR0.5 were considered cognitively impaired (total N ¼ 14, 11 with CDR ¼ 0.5). Results: The study population was old (mean age at PET 79.2 6 7.7 years), preponderantly male (79%), highly educated (mean 15.8 6 3.4 years) and most had vascular risk factors (92%). CVD was more frequent in cognitively impaired (13/14) versus non-impaired (4/10) subjects (c2 ¼ 7.89, p ¼ 0.005), and there was a trend for higher frequency of PIB+ scans in impaired (8/14) versus non-impaired (2/10) participants (c2 ¼ 3.31, p ¼ 0.07). Cognitive impairment was found in 3/5 patients with solely subcortical infarcts and in 6/7 subjects with cortical infarcts on MRI. Cognitive impairment was present in 2/7 CVD-/PIB-, 4/7 CVD+/PIB-, 0/1 CVD-/PIB+ and 8/9 CVD+/PIB+ subjects (c2 ¼ 7.41, p ¼ 0.06). Conclusions: Both amyloid and CVD contribute to cognitive impairment in individuals with high vascular risk. CVD is often viewed as a secondary factor in cognitive impairment, but these data suggest that it is not infrequently the primary cause. In this small, elderly cohort enriched for vascular disease, CVD was more strongly linked to cognition than was amyloid. Further studies are needed to determine the relative contributions of amyloid and CVD to cognitive decline and to changes in brain structure and function.
IC-03-04
S59
HIPPOCAMPAL NEUROPIL ATROPHY IN EARLY ALZHEIMER’S DISEASE: A 7T MRI STUDY
Geoffrey A. Kerchner1,2, Christopher P. Hess2, Kathryn HammondRosenbluth2, Duan Xu2, Douglas A. C. Kelley3, Daniel P. Vigneron2, Sarah J. Nelson2, Bruce L. Miller2, 1Stanford University, Stanford, CA, USA; 2 UCSF, San Francisco, CA, USA; 3GE Healthcare, San Francisco, CA, USA. Contact e-mail: [email protected] Background: In Alzheimer’s disease, mounting evidence points to a greater role for synaptic loss than neuronal loss. Supporting this notion, the hippocampal CA1 apical neuropil is one of the earliest sites of pathology, exhibiting atrophy before there is substantial loss of the CA1 pyramidal neurons themselves. To date, brain imaging technology has lacked sufficient resolution to reveal the laminar architecture of the hippocampus in living humans. Objective: To test the hypothesis that ultra-high field 7T MRI will reveal atrophy of the CA1 apical neuropil outpacing atrophy of the CA1 cell body layer or overall hippocampal volume in patients with mild AD relative to normal controls. Methods: Subjects with mild AD (n ¼ 14) and agematched normal controls (NC; n ¼ 16) were scanned on a 7T GE MRI. Two-dimensional T2*-weighted gradient-recalled echo images were obtained in crosssection to the mid-hippocampal body at an in-plane resolution of 195 mm, and linear measurements of the thickness of CA1 strata were made and normalized to total intracranial volume (TIV). Each subject also underwent conventional T1-weighted 3T MRI, and total hippocampal volume was assessed using an automated segmentation technique, and normalized to TIV. Results: Qualitatively, the hippocampi from AD and NC subjects appeared similar on 7T imaging. The cell body layer, or stratum pyramidale (SP) exhibited more intense signal than the apical neuropil, or stratum radiatum / lacunosum-moleculare (SRLM) (Figure 1: Cross-
S58
also excluded. The present study therefore included 337 subjects of whom 13 had developed AD (NINCDS-ADRDA criteria) and 25 SD (according to criteria of Erkinjuntti et al). MRI scans at 3 year follow-up were compared between groups. The CC was semi-automatically outlined on MRI images and quantified at baseline and follow-up. ARWMCs were visually scored using Fazekas scale (mild, moderate, severe) at baseline. Total CC area at follow-up was entered into ANCOVA analysis to test for differences between groups (AD, SD, non-demented). Subregional differences were analysed using repeated-measures ANCOVA, and significant results were further examined using univariate analysis. Results: Groups differed with regards to age, ARWMC-load and gender. Therefore the variables were entered into the ANCOVA analysis as covariates. AD, SD and non-demented elderly subjects did not differ in total CC area. AD and SD patients had smaller CC1 and CC5 compared to non-demented elderly subjects at 3 year follow-up, but did not differ in other CC subregions. No difference in subregional areas between the 2 patient groups. Conclusions: The presented results indicate that anterior and posterior CC atrophy is associated with dementia. No specific atrophy pattern was identified in dementia subtypes, although this may have been due to the relatively small number of subjects who developed dementia.
3 University of California, San Diego, La Jolla, CA, USA. Contact e-mail: [email protected]
Background: As treatments for AD develop, the field is moving toward identifying pre-dementia symptomatic individuals at the earliest stage possible. The large, longitudinal Alzheimer’s Disease Neuroimaging Initiative (ADNI) will be enrolling amnestic mild cognitive impairment (aMCI) subjects with a lesser degree of memory impairment. We used the National Alzheimer’s Coordinating Center (NACC) data to apply classifications of aMCI subjects to be used in ADNI studies. Methods: To characterize the clinical features of subjects with aMCI and a very mild level of memory impairment (designated as early MCI or EMCI), we applied the proposed ADNI criteria for MCI to the NACC Uniform Data Set (UDS). The NACC database is a repository for data from the National Institute on Aging Alzheimer’s Disease Centers Program and includes data necessary for classifying EMCI subjects according to the following criteria: clinical diagnosis of aMCI, CDR ¼ 0.5, CDR memory box > ¼ 0.5, MMSE >¼ 24 and education-specific cutoff scores on delayed recall of a single paragraph from Logical Memory II of Wechsler Memory Scale-Revised: 16 years, 9-11; 8-15 years, 5-9; 0-7 years, 3-6. NACC subjects were compared to those diagnosed with aMCI in the current ADNI project (now called late MCI or LMCI). Results: A total of 1334 subjects met criteria for aMCI outlined above. Of those, 371 met criteria for EMCI, 717 for LMCI, and 246 were classified as aMCI but did not conform to EMCI or LMCI criteria (other aMCI). The proportion of subjects who were ApoE4 carriers was as follows: EMCI 35.6%, LMCI 54.3%, other aMCI 37.4%. For the CDR sum of boxes, mean (SD) scores were: EMCI 1.3 (0.8), LMCI 1.6 (1.0) and other aMCI 1.1 (0.8). Annual rates of progression from aMCI to dementia were: EMCI 10.5%, LMCI 29.8% and other aMCI 9.3%. Conclusions: The category of EMCI can be characterized clinically and appears to represent a milder form of aMCI. The clinical definition of EMCI will be adopted in ADNI to assess the roles of imaging measures and fluid biomarkers in predicting progression. Support provided by the National Institute on Aging: U01 AG024904 and U01 AG016976, P50 AG016574, U01 AG006786.
IC-03-02
SURVEY OF SEGMENTATION PROTOCOLS FOR MANUAL HIPPOCAMPAL VOLUMETRY: PREPARATORY PHASE FOR AN EADC-ADNI HARMONIZATION PROTOCOL
Marina Boccardi1, Rossana Ganzola1, Simon Duchesne2, Alberto Redolfi1, George Bartzokis3, John Csernansky4, Mony de Leon5, Ronald Killiani6, Ste´phane Lehe´ricy7, Nikolai Malykhin8, Johannes Pantel9, Jens Pruessner10, Hilkka Soininen11, Clifford R. Jack, Jr,12, Giovanni B. Frisoni1, 1IRCCS Centro S. Giovanni di Dio Fatebenefratelli, Brescia, Italy; 2Universite´ Laval and Centre de Recherche Universite´ Laval e Robert Giffard, Quebec City, QC, Canada; 3David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 4Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5New York University School of Medicine, New York, NY, USA; 6 Boston University School of Medicine, Boston, MA, USA; 7Universite´ Pierre et Marie Curie, Paris, France; 8University of Alberta, Edmonton, AB, Canada; 9University of Frankfurt/Main, Frankfurt, Germany; 10McGill University, Montreal, QC, Canada; 11Kuopio University Hospital, Kuopio, Finland; 12Mayo Clinic and Foundation, Rochester, MN, USA. Contact e-mail: [email protected] SATURDAY, JULY 10, 2010 ALZHEIMER’S IMAGING CONSORTIUM IC-03 ORAL 3 - MAGNETIC RESONANCE FOR EARLY AND PRESYMPTOMATIC DIAGNOSIS IC-03-01
EARLY MCI AS AN IMAGING TARGET: DATA FROM THE NATIONAL ALZHEIMER’S COORDINATING CENTER
Ronald C. Petersen1, Dawn P. Gill2, Leslie E. Phillips2, Paul Aisen3, 1Mayo Clinic, Rochester, MN, USA; 2University of Washington, Seattle, WA, USA;
Background: Hippocampal atrophy is a key diagnostic marker for early and incipient Alzheimer’s disease (AD) but different procedures give rise to estimates of normal hippocampal volume that vary up to 2.5 times across laboratories. Internationally harmonized procedures are required to use hippocampal volume as a diagnostic marker in clinical settings, surrogate measure in clinical trials for AD drugs, and gold standard for automated segmentation algorithms. Methods: The 10 most frequently used segmentation protocols for hippocampal volumetry in the AD literature [1 to 10, see following] were surveyed to extract anatomical landmarks (anteriormost and posteriormost slice, dorsal, ventral, medial, and lateral borders). The hippocampi of one healthy control and one AD patient taken form the ADNI database were segmented by a single rater following each protocol.
Alzheimer’s Imaging Consortium IC-03: Oral 3 - Magnetic Resonance for Early and Presymptomatic Diagnosis Individual interactive web conferences were arranged with the primary authors to check correctness of interpretation. Semantically harmonized landmark differences among protocols were finally extracted. The protocols were [1] Bartzokis et al., 1998, [2] Convit et al., 1997, [3] Haller et al., 1997, [4] Jack et al., 1994, [5] Killiany 1993 et al., [6] Lehericy et al., 1994, [7] Malykhin et al., 2007 [8] Pantel et al., 2000, [9] Pruessner et al., 2000, and [10] Soininen et al., 1994. Results: The survey of anatomical landmarks of the protocols, and the hippocampi segmented following each of the protocols and checked with their authors can be found at http://www. centroalzheimer.it/public/SOPs/online. Landmark differences among protocols (available at the same http address) regard: (a) inclusion [#2,4,6,7,8,9] and exclusion [#1,3,5,10] of hippocampal white matter (alveus and fimbria); (b) specification of the most posterior slice: most restrictive [#1], most inclusive [#3,7,8,9] for a maximum linear difference of 9.6 mm; (c) separation between the subiculum and the parahippocampal gyrus, consisting of variable combinations of five criteria. Heterogeneities in the definition of the boundary with the amygdala, while a source of variance in the earlier protocols, are no longer an issue due to currently available visualization tools allowing 3D navigation. Conclusions: Operationalized differences among segmentation protocols for hippocampal volumetry constitute preparatory work for an international consensus for a harmonized protocol
IC-03-03
AMYLOID AND CEREBROVASCULAR DISEASE BOTH CONTRIBUTE TO COGNITIVE IMPAIRMENT IN INDIVIDUALS WITH HIGH VASCULAR RISK
Gil D. Rabinovici1, Adi Alkalay1, Natalie L. Marchant2, Charles DeCarli3, Helena C. Chui4, Bruce R. Reed3,5, William J. Jagust2,6, 1UCSF, San Francisco, CA, USA; 2UC Berkeley, Berkeley, CA, USA; 3UC Davis, Sacramento, CA, USA; 4USC, Los Angeles, CA, USA; 5VA Northern California Health Care System, Martinez, CA, USA; 6Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Contact e-mail: grabinovici@ memory.ucsf.edu Background: Autopsy studies suggest that cognitive impairment in late life is often due to a combination of Alzheimer’s disease (AD) and cerebrovascular disease (CVD), but in vivo studies relating both pathologies to cognition are lacking. We evaluated the relationship of amyloid and CVD to cognition in individuals with high vascular risk. Methods: Subjects enrolled in two vascular-focused studies of cognition at UC Davis underwent PIBPET (N ¼ 24) and MRI (N ¼ 17). PIB distribution volume ratio images (Logan, cerebellar reference) were classified as positive (PIB+, N ¼ 10) or negative (PIB-, N ¼ 14) based on visual reads blinded to clinical data. MRI scans were visually rated for the presence of infarcts (blinded to clinical history). Subjects were classified as having cerebrovascular disease (CVD+, N ¼ 17/24) if there was a clinical history of stroke, TIA or an infarct on imaging. Participants with a Clinical Dementia Rating (CDR) ¼ 0 were classified as cognitively normal (N ¼ 10), while individuals with CDR0.5 were considered cognitively impaired (total N ¼ 14, 11 with CDR ¼ 0.5). Results: The study population was old (mean age at PET 79.2 6 7.7 years), preponderantly male (79%), highly educated (mean 15.8 6 3.4 years) and most had vascular risk factors (92%). CVD was more frequent in cognitively impaired (13/14) versus non-impaired (4/10) subjects (c2 ¼ 7.89, p ¼ 0.005), and there was a trend for higher frequency of PIB+ scans in impaired (8/14) versus non-impaired (2/10) participants (c2 ¼ 3.31, p ¼ 0.07). Cognitive impairment was found in 3/5 patients with solely subcortical infarcts and in 6/7 subjects with cortical infarcts on MRI. Cognitive impairment was present in 2/7 CVD-/PIB-, 4/7 CVD+/PIB-, 0/1 CVD-/PIB+ and 8/9 CVD+/PIB+ subjects (c2 ¼ 7.41, p ¼ 0.06). Conclusions: Both amyloid and CVD contribute to cognitive impairment in individuals with high vascular risk. CVD is often viewed as a secondary factor in cognitive impairment, but these data suggest that it is not infrequently the primary cause. In this small, elderly cohort enriched for vascular disease, CVD was more strongly linked to cognition than was amyloid. Further studies are needed to determine the relative contributions of amyloid and CVD to cognitive decline and to changes in brain structure and function.
IC-03-04
S59
HIPPOCAMPAL NEUROPIL ATROPHY IN EARLY ALZHEIMER’S DISEASE: A 7T MRI STUDY
Geoffrey A. Kerchner1,2, Christopher P. Hess2, Kathryn HammondRosenbluth2, Duan Xu2, Douglas A. C. Kelley3, Daniel P. Vigneron2, Sarah J. Nelson2, Bruce L. Miller2, 1Stanford University, Stanford, CA, USA; 2 UCSF, San Francisco, CA, USA; 3GE Healthcare, San Francisco, CA, USA. Contact e-mail: [email protected] Background: In Alzheimer’s disease, mounting evidence points to a greater role for synaptic loss than neuronal loss. Supporting this notion, the hippocampal CA1 apical neuropil is one of the earliest sites of pathology, exhibiting atrophy before there is substantial loss of the CA1 pyramidal neurons themselves. To date, brain imaging technology has lacked sufficient resolution to reveal the laminar architecture of the hippocampus in living humans. Objective: To test the hypothesis that ultra-high field 7T MRI will reveal atrophy of the CA1 apical neuropil outpacing atrophy of the CA1 cell body layer or overall hippocampal volume in patients with mild AD relative to normal controls. Methods: Subjects with mild AD (n ¼ 14) and agematched normal controls (NC; n ¼ 16) were scanned on a 7T GE MRI. Two-dimensional T2*-weighted gradient-recalled echo images were obtained in crosssection to the mid-hippocampal body at an in-plane resolution of 195 mm, and linear measurements of the thickness of CA1 strata were made and normalized to total intracranial volume (TIV). Each subject also underwent conventional T1-weighted 3T MRI, and total hippocampal volume was assessed using an automated segmentation technique, and normalized to TIV. Results: Qualitatively, the hippocampi from AD and NC subjects appeared similar on 7T imaging. The cell body layer, or stratum pyramidale (SP) exhibited more intense signal than the apical neuropil, or stratum radiatum / lacunosum-moleculare (SRLM) (Figure 1: Cross-