REPRODUCIBILITY OF INTRACRANIAL AND HIPPOCAMPAL VOLUME QUANTIFICATION AT 1.

5T AND 3T MRI: APPLICATION TO ADNI-1

F. Roche , B. Singh , J. Schaerer , B. Belaroussi , S. Gouttard , A. Istace , HJ. Yu , E. Fletcher , L. Bracoud , C. Pachai , C. DeCarli and the Alzheimer's Disease Neuroimaging Initiative 1 2 BioClinica, Lyon, France & Newtown, PA, USA - email: Florent.Roche@bioclinica.com, University of California-Davis, Alzheimer's Disease Center, Sacramento, CA, USA
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INTRODUCTION
Hippocampal volume (HCV) measured based on high-resolution T1 (3DT1) has been proposed as a key biomarker in Alzheimers Disease (AD) studies, both for improved subject selection and monitoring treatment efficacy. Intracranial volume (ICV) has also been used as a covariate for standardization of volumetric endpoints. In multicenter clinical trials, MRI data are usually acquired with different scanner types, models and field strengths (1.5T and 3T). The robustness of ICV and HCV segmentation algorithms in such multicenter context is therefore of major importance for the overall quality of volumetric assessments. The purpose of this work was to evaluate the reproducibility of two previously reported BioClinica Multi-Atlas Segmentation algorithms: BMAS-ICV and BMAS-HCV at 1.5T and 3T using ADNI-1 subjects.

RESULTS
Back-to-back 1.5T and 3T results (Table 1 and Figure 1) Back-to-back results were strongly and significantly correlated (r > 0.99) for ICV and HCV at each field strength. Mean values were nearly identical for both ICV and HCV. Unsigned RVE values were similar at both field strengths for both ICV and HCV. 1.5T vs 3T results (Table 1 and Figure 1) 1.5T and 3T results were strongly and significantly correlated (r > 0.97) for ICV and HCV. Mean values were nearly identical for both ICV and HCV. RVE values were higher when comparing across field strengths, but remained very low overall.
ICV ICV ICV HCV HCV HCV 1.5T back-to-back Volume (mL) r p-value RVE (%) - Signed RVE (%) - Unsigned 1449 151 0.9997 <0.001 -0.01 0.25 0.14 0.21 3T back-to-back 1450 150 0.9996 <0.001 -0.02 0.30 0.17 0.24 1.5T vs. 3T 1449 150 0.9842 <0.001 -0.08 1.90 1.49 1.17 1.5T back-to-back 6.782 1.211 0.9947 <0.001 0.04 1.94 1.47 1.26 3T back-to-back 6.848 1.200 0.9930 <0.001 0.29 2.17 1.65 1.43 1.5T vs. 3T 6.815 1.199 0.9784 <0.001 -1.01 3.72 3.03 2.36

Group separation for 1.5T and 3T (Figure 2) ROC analysis of normalized HCV aiming at separating NC and AD groups produced similar Areas Under the Curve (AUC) of 0.92 for both 1.5T and 3T field strengths. The AUC results of 1000 random combinations of 1.5T and 3T sequences gave similar results with a mean AUC of 0.92 (SD = 0.00) and an overall minimum of 0.91. HCV normalization slightly improved group separation.

METHODS
Population 153 3D T1-weighted MRI scans from the ADNI-1 database were analyzed in this study. It included 51 Normal Control (NC), 71 Mild Cognitive Impairment (MCI) and 31 AD subjects. Each subject was scanned at 1.5T and 3T a few days apart. During each of these imaging sessions, two back-to-back sequences were acquired (subject was not taken out of the scanner). Image analysis ICV and HCV were automatically quantified using 1.5T and 3T back-to-back sequences (4 measurements total). ICV and HCV were assessed using multi-atlas segmentation methods, BMAS-ICV [1] and BMAS-HCV [2]. Statistical analysis Pearsons correlation was computed for ICV and HCV between back-to-back sequences at each field strength (1.5T and 3T) and also between both field strengths. Signed and unsigned Relative Volume Error (RVE) were also assessed for the same combinations. V1 V2 V1 V2
RVE signed 2 V1 V2
RVEunsigned 2 V1 V2

HCV 1.5T (AUC = 0.891) HCV 3T (AUC = 0.891)

Normalized HCV 1.5T (AUC = 0.925) Normalized HCV 3T (AUC = 0.921)

Figure 2 - NC and AD group separation based on raw HCV (left) and normalized HCV (right)

Table 1 - Back-to-back 1.5T and 3T results

CONCLUSIONS

Sequences
1.5T #1 1.5T #2 3T #1 3T #2

ICV 1.5T #1

HCV 1.5T #1

MRI field strength did not impact the assessment of intracranial and hippocampal volumes. The observed volume differences were minor. Back-to-back and 1.5T vs. 3T measurements were highly correlated. Finally, the ability of normalized HCV to separate between normal controls and AD subjects was identical at both field strengths. Combining subjects scanned at 1.5T and 3T did not deteriorate normal vs. AD group separation. This suggests that clinical trials using hippocampal volume as a volumetric endpoint could allow scanners with either field strength to participate, as long as each subject is followed on the same scanner. Similar comparative analyses should be performed to study the potential impact of field strength on other common volumetric endpoints (brain and ventricles) as well as on longitudinal atrophy measurement.

ICV 1.5T #2

HCV 1.5T #2

A Receiver Operating Characteristic (ROC) analysis measuring the ability of normalized HCV (HCV/ICV) to separate NC and AD groups at 1.5T and 3T was performed, as well as 1000 random combinations of both field strengths, in order to simulate the context of a clinical trial mixing both field strengths.

REFERENCES
ICV 3T #1 HCV 3T #1 ICV 3T #2
Figure 1 - ICV (left) and HCV (right) results (top) and correlations (bottom) for each sequence

HCV 3T #2

[1] J. Schaerer et al., Accurate intra-cranial cavity delineation and volume measurement in the ADNI-1 MCI population using multi-atlas segmentation, Poster session, AAIC 2012 [2] Belaroussi et al., Multi-Atlas hippocampus segmentation refined with intensity-based tissue classification, Poster session, AAIC 2012 bioclinica.com/aaic2013-roche-poster

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