Purpose

Accurate classification and segmentation of brain tissue using MR imaging is a key challenge for automated volumetric assessment. Major limitations of MRI-based classification techniques arise from limited signal-to-noise (SNR) and contrast-to-noise ratios (CNR) as well as from partial-volume effects. As reported in [1], the uniform MP2RAGE series provides additional gray/white-matter contrast and reduced B1 bias and several groups have proposed strategies to perform automated morphometry based on MP2RAGE series [2,3]. In this work, we expand on our previous study, which compared skull-stripping performances across these strategies [4], by assessing the volumes of key neuroanatomical structures in a cohort of patients with clinical suspicion of anorexia nervosa, most of them with lower-than-normal body mass indices (BMI). We compare both strategies with regard to the detection of brain atrophy in anorexic patients, a finding that has previously been demonstrated by several groups [5-7].

Material and methods

This study was approved by the local ethical committee and included 16 patients (15 females, 1 male; mean age, 29.5 years, range, 16.2-74.5 years, BMI=14.9±3.2 kg/m²), presenting consecutively for brain MRI with clinical suspicion of anorexia nervosa. Three subgroups were formed: 1 (all patients, n=16), 2 (BMI<18.5 kg/m², n=13), and 3 (BMI<16 kg/m², n=10).
All patients were scanned at 3T (Magnetom Prisma, Siemens, Erlangen, Germany) using the MP2RAGE sequence (TI1/TI2=700/2500ms, TR=5000ms, voxel size=1x1x1.2mm³, TA=8:22min with a 64-channel coil).
Automated segmentation of brain structures was performed with the MorphoBox prototype [8] following two distinct strategies:
- Strategy 1 uses the product of the second inversion (Fig. 1A) and uniform (Fig. 1B) MP2RAGE images as suggested by Fujimoto et al. (2) for the skull-stripping step. Subsequently, it uses the uniform image for the tissue classification and brain segmentation steps.
- Strategy 2 uses the denoised uniform MP2RAGE image (Fig. 1C) as described in [3] using a regularization constant of 70 throughout the whole MorphoBox pipeline
Both strategies result in computing volumes of GM, WM and CSF, basal ganglia, hippocampus and lateral ventricles normalized by the total intracranial volume (TIV) (Fig. 1 D-E).
Finally, for the purpose of inter-subject comparison, all estimated volumes are transformed into z-scores adjusted for age and gender using a database of healthy controls as reference (306 subjects with normal BMI, 51% males; mean age, 66.4 years; range, 19-90 years).
Statistical significance of the difference between z-scores, absolute volumes and normalized volumes obtained by the two methods was assessed by paired t-tests.

Results

All normalized and absolute volumes obtained with Strategy 1 were significantly different from those obtained with Strategy 2. As shown in Fig. 2, Strategy 1 estimates significantly higher volumes of gray and white matter and lower CSF and ventricular volumes (p-value<0.001). Significant differences between z-scores obtained by the two strategies were found across all three groups for total GM (p-value=0.002, 0.002, 0.005 for group 1, 2, 3, respectively) but only for groups 2 and 3 for ventricle volumes (p-value<0.001) (see Fig. 3). As illustrated in Fig. 4, both strategies appear to detect brain atrophy, yet with different patterns: Strategy 1 detected a strong GM atrophy together with a moderate WM atrophy, while Strategy 2 detected a strong WM atrophy but no GM atrophy.

Discussion

Our results show both similarities and discrepancies between two MP2RAGE processing strategies for brain atrophy evaluation in anorexic patients, and stress the need to further develop the methodology of MP2RAGE-based brain morphometry. There are, however, two reasons to think that Strategy 1 is the most reliable. First, we previously showed that Strategy 1 achieves more accurate skull-stripping than Strategy 2 [4]. Secondly, the denoising step involved in Strategy 2 introduces some intensity bias, which is likely to confuse tissue classification, while Strategy 1 performs tissue classification from the uniform, bias-free image [1]. These facts help to explain the false perception, illustrated in Fig. 1 F-G, that Strategy 1 estimates larger cerebral volumes than Strategy 2. When compared to an age- and gender-matched group of controls, anorexic patients with abnormal BMI show decreased total brain and GM volumes which may be caused by loss of structural brain constituents and/or dehydration [6]. Since brain changes are completely or partially reversible when body weight returns to normal [5], further research will focus on assessing whether the MP2RAGE-based morphometry tool can reliably follow-up such patients.

Acknowledgements

No acknowledgement found.

References

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