Fully Automatic MRI-Based Hippocampus Volumetry Using FSL-FIRST: Intra-Scanner Test-Retest Stability, Inter-Field Strength Variability, and Performance as Enrichment Biomarker for Clinical Trials Using Prodromal Target Populations at Risk for Alzheimer’s Disease

Article type: Research Article

Authors: Cavedo, Enrica^{a; b} | Suppa, Per^{c; d} | Lange, Catharina^c | Opfer, Roland^d | Lista, Simone^a | Galluzzi, Samantha^b | Schwarz, Adam J.^e | Spies, Lothar^d | Buchert, Ralph^{c; f; 1; *} | Hampel, Harald^{a; 1} | for the Alzheimer’s Disease Neuroimaging Initiative² | for the Alzheimer Precision Medicine Initiative (APMI)³

Affiliations: [a] AXA Research Fund and UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l’hôpital, F-75013, Paris, France | [b] IRCCS Centro San Giovanni di Dio, Brescia, Italy | [c] Department of Nuclear Medicine, Charité– Universitätsmedizin Berlin, Berlin, Germany | [d] Jung diagnostics GmbH, Hamburg, Germany | [e] Eli Lilly and Company, Indianapolis, IN, USA | [f] Department of Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Correspondence: [*] Correspondence to: Ralph Buchert, University Medical Center Hamburg-Eppendorf, Department of Radiology and Nuclear Medicine, Martinistr. 52, 20246 Hamburg, Germany. Tel.: +49 40 7410 54347; Fax: +49 40 7410 40265; E-mail: [email protected].

Note: [1] These authors contributed equally as senior authors.

Note: [2] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Note: [3] The APMI is an international network of leading interdisciplinary clinicians, scientists, and researchers (lead by Prof Hampel) devoted towards the transformation of Neurology and Psychiatry through the implementation of Precision Medicine, and the reintegration of Neuroscience and its clinical specialties into the theoretical framework of Medicine.

Abstract: Background:MRI-based hippocampus volume is a core clinical biomarker for identification of Alzheimer’s disease (AD). Objective:To assess robustness of automatic hippocampus volumetry with the freely available FSL-FIRST software with respect to short-term repeat and across field strength imaging. FSL-FIRST hippocampus volume (FIRST-HV) was also evaluated as enrichment biomarker for mild cognitive impairment (MCI) trials. Methods:Robustness of FIRST-HV was assessed in 51 healthy controls (HC), 74 MCI subjects, and 28 patients with AD dementia from ADNI1, each with two pairs of back-to-back scans, one at 1.5T one at 3T. Enrichment performance was tested in a second sample of 287 ADNI MCI subjects. Results:FSL-FIRST worked properly in all four scans in 147 out of 153 subjects of the first sample (49 HC, 72 MCI, 26 AD). In these subjects, FIRST-HV did not differ between the first and the second scan within an imaging session, neither at 1.5T nor at 3T (p≥0.302). FIRST-HV was on average 0.78% larger at 3T compared to 1.5T (p = 0.012). The variance of the FIRST-HV difference was larger in the inter-field strength setting than in the intra-scanner settings (p < 0.0005). Computer simulations suggested that the additional variability encountered in the inter-field strength scenario does not cause a relevant degradation of FIRST-HV’s prognostic performance in MCI. FIRST-HV based enrichment resulted in considerably increased effect size of the 2-years change of cognitive measures. Conclusion:The impact of intra-scanner test-retest and inter-field strength variability of FIRST-HV on clinical tasks is negligible. In addition, FIRST-HV is useful for enrichment in clinical MCI trials.

Keywords: Alzheimer’s disease, clinical trials, FSL-FIRST, hippocampus, mild cognitive impairment, reproducibility, test/retest

DOI: 10.3233/JAD-161108

Journal: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 151-164, 2017