Elsevier

NeuroImage

Volume 82, 15 November 2013, Pages 393-402
NeuroImage

A new method for structural volume analysis of longitudinal brain MRI data and its application in studying the growth trajectories of anatomical brain structures in childhood

https://doi.org/10.1016/j.neuroimage.2013.05.065Get rights and content

Highlights

  • We propose a new longitudinal method to analyze longitudinal brain MRI datasets.

  • The method includes longitudinal registration and longitudinal classification steps.

  • We compare this method with cross-sectional methods.

  • A scan–rescan study shows that both longitudinal steps reduce variability.

  • The new method gives the best-fitted GM growth model using the NIH pediatric data.

Abstract

Cross-sectional analysis of longitudinal anatomical magnetic resonance imaging (MRI) data may be suboptimal as each dataset is analyzed independently. In this study, we evaluate how much variability can be reduced by analyzing structural volume changes in longitudinal data using longitudinal analysis. We propose a two-part pipeline that consists of longitudinal registration and longitudinal classification. The longitudinal registration step includes the creation of subject-specific linear and nonlinear templates that are then registered to a population template. The longitudinal classification step comprises a four-dimensional expectation-maximization algorithm, using a priori classes computed by averaging the tissue classes of all time points obtained cross-sectionally.

To study the impact of these two steps, we apply the framework completely (“LL method”: Longitudinal registration and Longitudinal classification) and partially (“LC method”: Longitudinal registration and Cross-sectional classification) and compare these with a standard cross-sectional framework (“CC method”: Cross-sectional registration and Cross-sectional classification).

The three methods are applied to (1) a scan–rescan database to analyze reliability and (2) the NIH pediatric population to compare gray matter growth trajectories evaluated with a linear mixed model.

The LL method, and the LC method to a lesser extent, significantly reduced the variability in the measurements in the scan–rescan study and gave the best-fitted gray matter growth model with the NIH pediatric MRI database. The results confirm that both steps of the longitudinal framework reduce variability and improve accuracy in comparison with the cross-sectional framework, with longitudinal classification yielding the greatest impact.

Using the improved method to analyze longitudinal data, we study the growth trajectories of anatomical brain structures in childhood using the NIH pediatric MRI database. We report age- and gender-related growth trajectories of specific regions of the brain during childhood that could be used as a reference in studying the impact of neurological disorders on brain development.

Introduction

Structural age-related change measurements from brain magnetic resonance imaging (MRI) are crucial to the study of normal brain growth and to understanding the biological process underlying brain development. They are also important in assessing the impact of neurological disorders and neurodegenerative diseases on brain growth.

Whereas a cross-sectional study involves only one structural measurement per subject, in a longitudinal study, multiple measurements are taken per subject. Indeed, subjects in cross-sectional MRI studies are scanned only once, while those in longitudinal studies are scanned repeatedly over time. Thus, longitudinal studies allow the observation of individual patterns of change.

To study age-related changes in cerebral structures during childhood, previous studies used either cross-sectional (Lange, 2011) or longitudinal brain MRI scans (Giedd et al., 1999, Lenroot and Giedd, 2006). In studies that used longitudinal pediatric brain MRI scans, each scan of a specific subject was analyzed independently. The structural brain measurements were computed without considering the longitudinal consistency between the scans of a single subject.

Recent methods reduce within-subject variability by taking into account longitudinal consistency whether for registration or tissue segmentation (Reuter et al., 2012, Wu et al., 2012).

Longitudinal registration was first proposed by Shen and Davatzikos (2004), who computed deformations between longitudinally acquired subject scans and a four-dimensional (4D) template. Thereafter, methods using consistent diffeomorphic registration of longitudinal images were presented (Durrleman et al., 2009, Lorenzi et al., 2010), and more recently, the creation of a subject-specific linear template was introduced (Reuter et al., 2012).

Regarding longitudinal classification, one proposed method incorporated longitudinal consistency constraints in a 3D fuzzy clustering segmentation (Xue et al., 2006), while another presented 4D image segmentation with a graph cut algorithm (Wolz et al., 2010).

Inspired by this previous work, we introduce a new method to measure structural volume changes in longitudinal MRI scans in which longitudinal information is used for both registration and segmentation. First, we propose the creation of linear and nonlinear subject-specific templates. Each time point is registered to the subject-specific template, which is registered to the population template, thus making the registration of time points to the population template more consistent. Second, we combine this registration with a 4D expectation-maximization (EM) algorithm for tissue classification, using a priori classes computed by averaging the tissue classes of all time points obtained cross-sectionally. This step allows us to take advantage of the longitudinal consistency of the classification.

The goal of the present paper is twofold. First, we study how longitudinal registration and longitudinal classification improve the longitudinal measurements. The longitudinal pipeline is compared with both a cross-sectional pipeline and a hybrid pipeline that combines longitudinal registration with cross-sectional tissue classification. These three pipelines are applied to a scan–rescan database to study the variability in the measurements and to the National Institutes of Health (NIH) MRI study of normal brain development (Evans, 2006) to study the impact of the variability in measurements on the gray matter (GM) growth curve models.

Second, we apply the longitudinal pipeline to report the growth trajectories of different anatomical brain structures in childhood using the NIH pediatric MRI database. We compare these growth trajectories with previously reported trajectories obtained from cross-sectional and longitudinal datasets.

Experimental results using the scan–rescan data as well as the longitudinal data from a large ensemble of subjects show that the variability of segmented volumes decreases by half as more consistent priors are used for tissue classification across all time points when using the proposed longitudinal image processing procedures.

Section snippets

Longitudinal method (LL)

The longitudinal pipeline (“LL method”: Longitudinal registration and Longitudinal classification) comprises the registration framework and classification framework defined below. Fig. 1 shows a flowchart detailing the steps involved in the LL method and the volume and registration notations used below.

Cross-sectional and hybrid methods

The LL method (longitudinal registration and classification) consists in applying the pipeline detailed above in its entirety. To study the impact of the longitudinal registration and classification steps, we compared the LL method with a standard cross-sectional framework (CC method: cross-sectional registration and cross-sectional classification) and a hybrid framework (LC method: longitudinal registration and cross-sectional classification).

The CC method is the standard pipeline. Each time

Data

A set of four scan–rescan datasets of T1w data from 20 young normal subjects was used (the 20NC-4 V database). The MRI data were acquired with a 1.5 T Siemens Sonata Vision clinical scanner (Siemens Medical Systems, Erlangen, Germany), using the standard head coil. Subjects were immobilized with a head restrainer. The protocol comprised four conventional whole-head high-resolution T1w scans. Scans were acquired using a 3D spoiled gradient echo sequence [TR = 22 ms, TE = 9.2 ms, α = 30 deg], providing

Scan–rescan reliability — 20NC-4 V database

Fig. 3 shows the GM classes obtained with the 3 methods (left:CC, middle:LC, right:LL) on two visits (V1 and V4) on the same subject (randomly chosen) of the 20NC-4 V database. In purple are the voxels of the GM class identical for the two scans, in blue are the voxels of the GM class in scan 1 but not in scan 4 and in red are the voxels of the GM class in scan 4 but not in scan 1. Ideally, given this scan–rescan data, no changes are expected, so no red and blue voxels should be found. We can

Discussion

The scan–rescan experiments with the 20NC-4 V data demonstrate that the LL pipeline, and the LC method to a lesser extent, give smaller variance and reduced bias in comparison with the CC pipeline. These results indicate that the processing pipeline is stable and reduces noise associated with cross-sectional analysis by taking advantage of the longitudinal consistency of the data. The within-subject alignments improve the registration consistency between each time point and the ICBM152 template.

Conclusion

We proposed a longitudinal method to analyze longitudinal brain MRI datasets and to measure structural age-related changes. The framework comprises two innovative parts: a longitudinal registration step and a longitudinal classification step. The results showed that both steps of the longitudinal framework reduce the variability in and improve the accuracy of the measurements. We also applied the method to the NIH pediatric dataset and reported growth trajectories of some brain structures that

Acknowledgments

Canadian Institutes of Health Research (MOP-111169 & 84360) and les Fonds de Recherche Santé Québec.

Data used in the preparation of this article were obtained from the NIH Pediatric MRI Data Repository created by the NIH MRI Study of Normal Brain Development. This is a multisite, longitudinal study of typically developing children from ages newborn through young adulthood conducted by the Brain Development Cooperative Group and supported by the National Institute of Child Health and Human

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