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J. Schaerer , B. Singh , F. Roche , B. Belaroussi , E. Fletcher , L. Bracoud , C. Pachai and C. DeCarli

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BioClinica, Lyon, France & Newtown, PA, USA - email: Joel.Schaerer@BioClinica.com

University of California-Davis, Alzheimer's Disease Center, Sacramento, CA, USA


True positive rate

Hippocampal volume (HCV) has been proposed as a key biomarker in Alzheimers disease (AD) studies, both for improved subject selection and for monitoring treatment efficacy. Manual tracing of 3DT1 MR images may be considered as the gold standard for estimating HCV, as it represents the human knowledge of the hippocampus anatomy in a context of varying anatomy and acquisition conditions. However, manual tracing can lack reproducibility, even if the use of standardized protocols can somewhat mitigate this problem. During the past few years, automated methods for hippocampal volumetry have greatly improved through the use of multi-atlas and intensity-based refinement strategies. The purpose of this work was to compare manual and automated segmentations of the hippocampus in terms of reproducibility and clinical utility using data from the UC Davis Alzheimers Disease Center database . Clinical utility was assessed by measuring the ability of each method to discriminate normal and demented subjects.

Image analysis The manual hippocampal structures were traced by trained MR technicians following the previously described protocol, requiring about one hour per case. The automated hippocampal masks were obtained using the previously reported BMAS-HCV algorithm (BioClinica Multi-Atlas Segmentation). Statistical analysis Validation objectives included comparing the two volume estimations for each scan by computing the Pearsons correlation coefficient. The separation between normal and demented subjects using each method was also studied through a ROC analysis . This analysis was performed on 450 normal or demented subjects. MCI subjects were excluded.

Subject group separation The area under the ROC curve was substantially higher for the automated delineations (0.82 for the automated segmentations and 0.72 for the manual tracings), showing better ability for the automated multi-atlas algorithm to distinguish between subject groups (Figure 3).


Correlation between manual and automated masks The manual and automated volume estimations were found to be significantly correlated (r = 0.73, p < 0.001, see Figure 1).
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Normal vs. Demented

Manual Automated AUC = 0.72 AUC = 0.82

Population 669 subjects from the UC Davis Alzheimers Disease Center database were analyzed. These participants were recruited into the study through community outreach and memory clinic referrals. They were from diverse educational and ethnic origins. The subjects were evaluated as normal, MCI (Mild Cognitive Impairment), or demented using standardized diagnostic protocols that included clinical review of brain MRI. MRI Data MRI data were acquired on two 1.5T MRI scanners: a GE Signa machine and a Philips Eclipse machine. 3D T1-weighted sequences were performed for all subjects, using an axial-oblique 3D Fast Spoiled Gradient Recalled Echo (FSPGR) sequence with 1.5 mm thick slices and a 256x256 acquisition matrix over a square FOV of 25 cm. Analogous sequences were installed on both the GE and Philips scanners. Hippocampus definition For the manual masks, the hippocampus included the CA1-CA4 fields, Gyrus Dentatus and the subicular complex using a protocol described in [2]. For the automated masks, the hippocampal volume included the following structures: Cornu Ammonis, Gyrus Dentatus, Fimbria, Subiculum and Alveus [3]. The surrounding structures not included in the hippocampal volume were: Crus of Fornix, Choroid Plexus and Uncal Sulcus (when not partial volume).


False positive rate

Normal MCI Demented

Figure 3 - Group separation for each method


Figure 1 - Correlation between manual and automated methods

Comparison of the hippocampal volumes for both methods The median absolute volumes were clearly different (Figure 2), which was expected due to differences in hippocampal delineation protocols. The distribution was however similar between the two methods when converting the volumes into z-scores.

Automated multi-atlas hippocampal volumes were compared to manually traced hippocampal volumes in the UC Davis Alzheimers Disease Center patient cohort . The manual and automated methods were found to be strongly and significantly correlated. Both methods also demonstrated an ability to distinguish between normal and demented subjects. However the automated method was found to be superior to manual tracings according to this criterion. This suggests that automated multi-atlas methods are well suited for HCV measurement in large AD studies, even though the difference in tracing protocols does not allow a definitive conclusion.

[1] B. Belaroussi et al., Multi-Atlas Hippocampus Segmentation Refined With Intensity-Based Tissue Classification, Poster session, AAIC 2012 [2] C. DeCarli, B. R. Reed at al., Brain Behavior Relationships amongst African Americans, Caucasians and Hispanics, Alzheimer Dis Assoc Disord. 2008 [3] D. Hasboun, MR determination of hippocampal volume: comparison of three methods, American journal of radiology 1996 bioclinica.com/aaic2013-schaerer-poster

Figure 2 - Hippocampal volumes for each group and method (left: raw, right: z-scored )

Alzheimers Association International Conference (AAIC) July 13 18, 2013 Boston, USA