Clinical applicability of quantitative atrophy measures on MRI in patients suspected of Alzheimer's disease

Abstract

Objectives: Neurodegeneration in suspected Alzheimer's disease can be determined using visual rating or quantitative volumetric assessments. We examined the feasibility of volumetric measurements of gray matter (GMV) and hippocampal volume (HCV) and compared their diagnostic performance with visual rating scales in academic and non-academic memory clinics.

Materials and methods: We included 231 patients attending local memory clinics (LMC) in the Netherlands and 501 of the academic Amsterdam Dementia Cohort (ADC). MRI scans were acquired using local protocols, including a T1-weighted sequence. Quantification of GMV and HCV was performed using FSL and FreeSurfer. Medial temporal atrophy and global atrophy were assessed with visual rating scales. ROC curves were derived to determine which measure discriminated best between cognitively normal (CN), mild cognitive impairment (MCI), and Alzheimer's dementia (AD).

Results: Patients attending LMC (age 70.9 ± 8.9 years; 47% females; 19% CN; 34% MCI; 47% AD) were older, had more cerebrovascular pathology, and had lower GMV and HCV compared to those of the ADC (age 64.9 ± 8.2 years; 42% females; 35% CN, 43% MCI, 22% AD). While visual ratings were feasible in > 95% of scans in both cohorts, quantification was achieved in 94-98% of ADC, but only 68-85% of LMC scans, depending on the software. Visual ratings and volumetric outcomes performed similarly in discriminating CN vs AD in both cohorts.

Conclusion: In clinical settings, quantification of GM and hippocampal atrophy currently fails in up to one-third of scans, probably due to lack of standardized acquisition protocols. Diagnostic accuracy is similar for volumetric measures and visual rating scales, making the latter suited for clinical practice. In a real-life clinical setting, volumetric assessment of MRI scans in dementia patients may require acquisition protocol optimization and does not outperform visual rating scales.

Key points: • In a real-life clinical setting, the diagnostic performance of visual rating scales is similar to that of automatic volumetric quantification and may be sufficient to distinguish Alzheimer's disease groups. • Volumetric assessment of gray matter and hippocampal volumes from MRI scans of patients attending non-academic memory clinics fails in up to 32% of cases. • Clinical MR acquisition protocols should be optimized to improve the output of quantitative software for segmentation of Alzheimer's disease-specific outcomes.

Keywords: Alzheimer’s disease; Gray matter volume (GMV); Hippocampal volume (HCV); Magnetic resonance imaging (MRI); Visual rating scales.

Fig. 1

Overview of the visual QC per pipeline and per cohort

Fig. 2

a–d Normalized HCV and GMV calculated with FSL and FreeSurfer pipelines per diagnostic group (CN, MCI, AD) and per cohort (ADC, LMC). Measures are displayed as residuals, corrected for age and sex

Fig. 3

Concordance between visual reads and volumetric outcomes of GMV (a, c, e, g, i, k) and HCV (b, d, f, h, j, l). GMV was assessed through GCA visual rating, FSL SIENAX, and FreeSurfer. Similarly, HCV was assessed through MTA, FSL FIRST, and FreeSurfer. HCV were averaged between left and right (L/R) hemispheres. Volumetric outcomes (FSL and FreeSurfer) were normalized for head size and they are reported in [mm³]

Fig. 4

ROC curves distinguishing CN vs AD (top, a–d) and CN vs MCI (bottom, e–h) on the base of visual rating (green), FSL (red), and FreeSurfer outcomes of GMV and HCV. Results are reported separately for the Amsterdam Dementia Cohort (ADC, left panel, a, b, e, f) and local memory clinics (LMC, right panel, c, d, g, h)