Measuring longitudinal change in the hippocampal formation from in vivo high-resolution T2-weighted MRI

Abstract

The hippocampal formation (HF) is a brain structure of great interest because of its central role in learning and memory, and its associated vulnerability to several neurological disorders. In vivo oblique coronal T2-weighted MRI with high in-plane resolution (~0.5 mm×0.5 mm), thick slices (~2.0 mm), and a field of view tailored to imaging the hippocampal formation (denoted HF-MRI in this paper) has been advanced as a useful imaging modality for detailed hippocampal morphometry. Cross-sectional analysis of volume measurements derived from HF-MRI has shown the modality’s promise to yield sensitive imaging-based biomarker for neurological disorders such as Alzheimer’s disease. However, the utility of this modality for making measurements of longitudinal change has not yet been demonstrated. In this paper, using an unbiased deformation-based morphometry (DBM) pipeline, we examine the suitability of HF-MRI for estimating longitudinal change by comparing atrophy rates measured in the whole hippocampus from this modality with those measured from more common isotropic (~1 mm3) T1-weighted MRI in the same set of individuals, in a cohort of healthy controls and patients with cognitive impairment. While measurements obtained from HF-MRI were largely consistent with those obtained from T1-MRI, HF-MRI yielded slightly larger group effect of greater atrophy rates in patients than in controls. The estimated minimum sample size required for detecting a 25% change in patients’ atrophy rate in the hippocampus compared to the control group with a statistical power β=0.8 was N=269. For T1-MRI, the equivalent sample size was N=325. Using a dataset of test–retest scans, we show that the measurements were free of additive bias. We also demonstrate that these results were not a confound of certain methodological choices made in the DBM pipeline to address the challenges of making longitudinal measurements from HF-MRI, using a region of interest (ROI) around the HF to globally align serial images, followed by slice-by-slice deformable registration to measure local volume change. Additionally, we present a preliminary study of atrophy rate measurements within hippocampal subfields using HF-MRI. Cross-sectional differences in atrophy rates were detected in several subfields.

Comparing 3T and 1.5T MRI for Mapping Hippocampal Atrophy in the Alzheimer's Disease Neuroimaging Initiative

“…It is possible that even higher magnetic field 57,58 strengths such as 7T or 11T may reveal finer scale features and provide superior power for detecting between-group differences. The future directions of this study include conducting longitudinal analyses to show the progressive atrophy that occurs with the disease with time.…”

In vivo Analysis of Hippocampal Subfield Atrophy in Mild Cognitive Impairment via Semi-Automatic Segmentation of T2-Weighted MRI

“…Another consideration is the slice angulation; though we attempt to align coronal slices to be orthogonal to the long axis of the hippocampus, there is some variability, which will have an effect on the apparent volume of a given slice. While the variance is not great enough to affect the number of slices, it can still impact volume measurements (see [61] for more detail).…”

Early Tau Burden Correlates with Higher Rate of Atrophy in Transentorhinal Cortex

“…Conventional approaches commonly choose one MRI scan as the fixed image and perform registration on the other one, which may introduce bias in longitudinal change estimation. Instead, the symmetric diffeomorphic registration brings the two MRI scans into a “middle” image space and was shown to be unbiased with respect to the ordering of the MRI scans and highly sensitive to small longitudinal changes [15]. …”