Cortical thickness changes following spatial navigation training in adulthood and aging

A widespread network involving cortical and subcortical brain structures forms the neural substrate of human spatial navigation. Most studies investigating plasticity of this network have focused on the hippocampus. Here, we investigate age differences in cortical thickness changes evoked by four months of spatial navigation training in 91 men aged 20-30 or 60-70 years. Cortical thickness was automatically measured before, immediately after, and four months after termination of training. Younger as well as older navigators evidenced large improvements in navigation performance that were partly maintained after termination of training. Importantly, training-related cortical thickening in left precuneus and paracentral lobule were observed in young navigators only. Thus, spatial navigation training appears to affect cortical brain structure of young adults, but there is reduced potential for experience-dependent cortical alterations in old age.     

应用基于体素的形态测量学方法研究自发性正常压力脑积水

目的 研究自发性正常压力脑积水患者与正常人的颅脑结构形态学差异, 探讨有助于iNPH影像学诊断的指标。方法 应用3.0 TMR对10例iNPH患者及12名年龄相仿正常人行常规头颅MR扫描及全脑3D T1WI扫描。使用基于体素的形态测量学方法分析iNPH患者CSF分布、白质及灰质体积的变化。结果 VBM分析发现, 与正常人相比, iNPH患者侧脑室、3脑室、两侧侧裂池及鞍上池扩大, 内囊体积增大, 大脑纵裂旁以及额顶叶灰质体积增大;纵裂池及额顶叶脑沟变窄, 胼胝体压部、双侧侧脑室旁白质及额顶叶深部白质体积减小, 双侧颞叶灰质、尾状核、丘脑、海马体积缩小。结论 iNPH患者出现脑室系统、蛛网膜下腔的形态变化, 除此之外尚存在其他颅脑结构改变, 这些形态改变有助于iNPH的影像诊断。     

Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters

Multiple system atrophy (MSA) is a neurodegenerative disease affecting basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord. Clinically, a cerebellar (MSA-C) and a parkinsonian variant of MSA (MSA-P) are distinguished. We used voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) in 48 MSA patients (32 MSA-C, 16 MSA-P) and 46 controls. In MSA-C, VBM revealed gray matter loss in cerebellum, right thalamus, both putamina and several cortical regions including insular cortex. Gray matter loss in the cerebellum and insular cortex was correlated with disease duration and severity. There was white matter loss in the brainstem, which was correlated with disease duration and severity. VBR analysis in MSA-C showed decreased relaxation rate R2 in cerebellum, pontine brainstem and cortical regions including insular cortex. In MSA-P, gray matter was reduced in cerebellum, dorsal midbrain, both putamina, and several cortical regions including insular cortex. A correlation with disease duration and severity was detected only for some small cortical areas. Direct comparison of MSA-C and MSA-P showed differences only in infratentorial brain regions where structural abnormalities were more pronounced in MSA-C than in MSA-P. In MSA-C, there was a stronger reduction of gray matter in the basal parts of the cerebellum, of white matter in the brainstem and of the relaxation rate R2 in the cerebellum and brainstem.     

Grey matter volume alterations in CADASIL: a voxel-based morphometry study

CADASIL is a hereditary disease characterized by cerebral subcortical microangiopathy leading to early onset cerebral strokes and progressive severe cognitive impairment. Until now, only few studies have investigated the extent and localization of grey matter (GM) involvement. The purpose of our study was to evaluate GM volume alterations in CADASIL patients compared to healthy subjects. We also looked for correlations between global and regional white matter (WM) lesion load and GM volume alterations. 14 genetically proved CADASIL patients and 12 healthy subjects were enrolled in our study. Brain MRI (1.5 T) was acquired in all subjects. Optimized-voxel based morphometry method was applied for the comparison of brain volumes between CADASIL patients and controls. Global and lobar WM lesion loads were calculated for each patient and used as covariate-of-interest for regression analyses with SPM-8. Compared to controls, patients showed GM volume reductions in bilateral temporal lobes (p < 0.05; FDR-corrected). Regression analysis in the patient group revealed a correlation between total WM lesion load and temporal GM atrophy (p < 0.05; uncorrected), not between temporal lesion load and GM atrophy. Temporal GM volume reduction was demonstrated in CADASIL patients compared to controls; it was related to WM lesion load involving the whole brain but not to lobar and, specifically, temporal WM lesion load. Complex interactions between sub-cortical and cortical damage should be hypothesized.     

Automated voxel-based 3D cortical thickness measurement in a combined Lagrangian–Eulerian PDE approach using partial volume maps

Accurate cortical thickness estimation is important for the study of many neurodegenerative diseases. Many approaches have been previously proposed, which can be broadly categorised as mesh-based and voxel-based. While the mesh-based approaches can potentially achieve subvoxel resolution, they usually lack the computational efficiency needed for clinical applications and large database studies. In contrast, voxel-based approaches, are computationally efficient, but lack accuracy. The aim of this paper is to propose a novel voxel-based method based upon the Laplacian definition of thickness that is both accurate and computationally efficient. A framework was developed to estimate and integrate the partial volume information within the thickness estimation process. Firstly, in a Lagrangian step, the boundaries are initialized using the partial volume information. Subsequently, in an Eulerian step, a pair of partial differential equations are solved on the remaining voxels to finally compute the thickness. Using partial volume information significantly improved the accuracy of the thickness estimation on synthetic phantoms, and improved reproducibility on real data. Significant differences in the hippocampus and temporal lobe between healthy controls (NC), mild cognitive impaired (MCI) and Alzheimer’s disease (AD) patients were found on clinical data from the ADNI database. We compared our method in terms of precision, computational speed and statistical power against the Eulerian approach. With a slight increase in computation time, accuracy and precision were greatly improved. Power analysis demonstrated the ability of our method to yield statistically significant results when comparing AD and NC. Overall, with our method the number of samples is reduced by 25% to find significant differences between the two groups.     

Assessment of the cortical bone thickness using ultrasonic guided waves: modelling and in vitro study

Determination of cortical bone thickness is warranted, e.g., for assessing the level of endosteal resorption in osteoporosis or other bone pathologies. We have shown previously that the velocity of the fundamental antisymmetric (or flexural) guided wave, measured for bone phantoms and bones in vitro, correlates with the cortical thickness significantly better than those by other axial ultrasound methods. In addition, we have introduced an inversion scheme based on guided wave theory, group velocity filtering and 2-D fast Fourier transform, for determination of cortical thickness from the measured velocity of guided waves. In this study, the method was validated for tubular structures by using numerical simulations and experimental measurements on tube samples. In addition, 40 fresh human radius specimens were measured. For tubes with a thin wall, plate theory could be used to determine the wall thickness with a precision of 4%. For tubes with a wall thicker than 1/5 of the outer radius, tube theory provided the wall thickness with similar accuracy. For the radius bone specimens, tube theory was used and the ultrasonically-determined cortical thickness was found to be U-Th = 2.47 mm +/- 0.66 mm. It correlated strongly (r(2) = 0.73, p < 0.001) with the average cortical thickness, C-Th = 2.68 +/- 0.53 mm, and the local cortical thickness (r(2) = 0.81, p < 0.001), measured using peripheral quantitative computed tomography. We can conclude that the guided-wave inversion scheme introduced here is a feasible method for assessing cortical bone thickness.     

Adjusting for global effects in voxel-based morphometry: gray matter decline in normal aging

Results from studies that have examined age-related changes in gray matter based on structural MRI scans have not always been consistent. Reasons for this variability likely include small or unevenly-distributed samples, different methods for tissue class segmentation and spatial normalization, and the use of different statistical models. Particularly relevant to the latter is the method of adjusting for global (total) gray matter when making inferences about regionally-specific changes. In the current study, we use voxel-based morphometry (VBM) to explore the impact of these methodological choices in assessing age-related changes in gray matter volume in a sample of 420 adults evenly distributed between the ages of 18-77 years. At a broad level, we replicate previous findings, showing age-related gray matter decline in nearly all parts of the brain, with particularly rapid decline in inferior regions of frontal cortex (e.g., insula and left inferior frontal gyrus) and the central sulcus. Segmentation was improved by increasing the number of tissue classes and using less age-biased templates, and registration was improved by using a diffeomorphic flow-based algorithm (DARTEL) rather than a "constrained warp" approach. Importantly, different approaches to adjusting for global effects--not adjusting, Local Covariation, Global Scaling, and Local Scaling--significantly affected regionally-specific estimates of age-related decline, as demonstrated by ranking age effects across anatomical ROIs. Split-half cross-validation showed that, on average, Local Covariation explained a greater proportion of age-related variance across these ROIs than did Global Scaling. Nonetheless, the appropriate choice for global adjustment depends on one's assumptions and specific research questions. More generally, these results emphasize the importance of being explicit about the assumptions underlying key methodological choices made in VBM analyses and the inferences that follow.     

弱视儿童的MRI全脑皮层厚度分析

目的 利用皮层厚度分析技术探讨弱视患儿脑灰质发育的异常.方法 对11例弱视患儿和10名视力正常儿童行3D T1WI扫描,数据应用Freesurfer软件进行后处理,以双样本独立t检验进行病例组和对照组的全脑皮层厚度比较,将具有统计学意义(P<0.05)的像素在标准脑模板上生成伪彩图.选取像素阈值为500个相邻像素,分析弱视患者皮层厚度改变的区域.结果 弱视组在双侧中央前回、左侧距状回前部、左侧颞上回和右侧额中回、额上回皮层厚度大于对照组;而在双侧舌回、枕颞外侧回、顶上小叶的区域,对照组皮层厚度大于弱视组.结论 皮层厚度分析研究能够发现弱视患儿与视觉相关的大脑区域的灰质皮层发育异常,从而为探讨弱视相关的神经结构发育异常提供有用信息.     

Regional grey matter abnormalities in juvenile myoclonic epilepsy: a voxel-based morphometry study

Visual assessment of structural MRI is, by definition, normal in patients with juvenile myoclonic epilepsy (JME), a major subsyndrome of idiopathic generalized epilepsy (IGE). However, recent quantitative MRI studies have shown structural abnormalities in cortical and thalamic grey matter (GM) in JME. Voxel-based morphometry (VBM) is a fully automated, unbiased, operator-independent MRI analysis technique that detects regionally specific differences in brain tissue composition on a voxel-wise comparison between groups of subjects. Using VBM, we examined structural differences in cortical and subcortical GM volume (GMV) between 25 JME patients (15 women, mean age=22.7+/-5.1 years) and age- and sex-matched 44 control subjects (27 women, mean age=23.1+/-4.3 years). We also performed a correlation analysis to delineate a possible relationship between the GMV increases or reductions and the increasing duration of epilepsy. Group comparison showed GMV increases in the superior mesiofrontal region bilaterally and GMV reductions in the thalamus bilaterally in JME patients (P<0.05, corrected for multiple comparisons using false discovery rate). Correlation analysis revealed that bilateral thalamic GMV had negative correlations with the duration of epilepsy (P<0.05, corrected for multiple comparisons after small volume corrections; P<0.05, Pearson correlation test). Our findings of GMV increases in the superior mesiofrontal regions and progressive thalamic atrophy could further support the pathophysiological concept of the functional abnormalities in thalamocortical circuit in JME.     

Pain sensitisers exhibit grey matter changes after repetitive pain exposure: A longitudinal voxel-based morphometry study

Previous research in health and disease has shown that exposure to pain changes the density of cortical grey matter (GM). Such structural changes of the brain might, however, depend crucially on how this pain experience is evaluated and processed in the brain. In the present study we aimed to detect pain-rating patterns and underlying GM changes after the application of repetitive painful stimulation using voxel-based morphometry (VBM). Healthy volunteers were investigated (n = 27), receiving 8 noxious and 8 innocuous thermal stimuli on the right forearm for 11 consecutive working days. Data were compared with a control group without any intervention (n = 18). Behavioural data demonstrated that a subgroup of volunteers (n = 14) sensitised, whereas the others (n = 13) habituated over the stimulation days. The VBM analysis revealed no increase but a significant reduction of GM density, eg, in the anterior cingulate cortex, the insular cortex and the frontal cortex, exclusively in the group of sensitisers. By contrast, pain habituaters did not show any density changes in the GM.     

Structural gray matter differences between first-episode schizophrenics and normal controls using voxel-based morphometry

The aim of this study was to compare the gray matter segments from T1 structural MR images of the brain in first-episode schizophrenic subjects (n = 34) and normal control subjects (n = 36) using automated voxel-based morphometry (VBM). This study is novel in that few studies have examined subjects in their first episode of schizophrenia. The subjects were recruited for the Edinburgh High Risk project and regional brain volumes were previously measured using a semi-automated volumetric region of interest (ROI) method of analysis. The primary interest was to compare the results from the compatible parts of the ROI study and the primary VBM approach. Our secondary interest was to compare the results of a study-specific template that was constructed from the control group to those using the generic T1 template (152 Montreal Neurological Institute brains) supplied with SPM99 (statistical parametric mapping). The images were processed and statistically analyzed using the SPM99 program. VBM analysis identified significant decreases in gray matter in the schizophrenics relative to the normal control group at the corrected voxel level (P < 0.05) in the right anterior cingulate, right medial frontal lobe, left middle temporal gyrus, left postcentral gyrus, and the left limbic lobe. There were no increases in gray matter in the schizophrenics relative to the control group. The construction of a customized template appeared to improve the detection of structural abnormalities. The analyses were subsequently restricted to voxels within the amygdala-hippocampal complex using the SPM small-volume correction. This identified gray matter decreases in the schizophrenics, at the corrected voxel level (P < 0.05), in the left and right uncus and parahippocampal gyri and the right amygdala. These results are compatible with and extend the relevant findings of the previous volumetric ROI analysis, when allowing for the differences between the methods and interpretation of their results.     

Regional frontal cortical volumes decrease differentially in aging: an MRI study to compare volumetric approaches and voxel-based morphometry

Recent neuroimaging studies suggest that the frontal lobes are the part of the brain most profoundly affected by the aging process. The present study investigated whether subregions within the frontal cortex show different patterns of brain aging. Magnetic resonance images of 57 healthy participants between 21 and 81 years old were used to measure regional frontal gray matter volumes in three ways: a manual tracing method, a semiautomatic "Talairach boxes" volumetric method, and voxel-based morphometry. Seven regions within each hemisphere were manually traced: precentral gyrus, inferior frontal gyrus, dorsolateral frontal cortex, ventral medial region, lateral orbital region, anterior cingulate, and frontal pole. With the semiautomatic approach, four regions were measured: lateral, orbital, and medial frontal regions and frontal pole. Advancing age was strongly associated with decreases in the volume of the whole frontal cortex. Differential age effects on the volumes of frontal subregions were dependent on the method applied. According to the manual approach, age-related volume decreases were strongest in the lateral and orbital frontal gray matter. The semiautomatic and voxel-based analyses found that age effects were most prominent within the lateral frontal and cingulate regions. Overall, it was concluded that although semiautomated and voxel-based methods can provide a reasonable estimate of regional brain volume, they cannot serve as a substitute for manual volumetry.     

Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study

The striatum, a subcortical structure, is the principal target of the neurodegenerative process in Huntington's disease (HD). The measurement of striatal atrophy using the bicaudate ratio on CT scanner images has therefore been used for years to assess disease progression, but this measure only takes into account unidimensional changes in the head of the caudate nucleus. Recently, voxel-based morphometry (VBM), which permits automated statistical comparisons of whole-brain MRI images, has been proposed to quantify striatal atrophy. However, VBM was not originally designed to study subcortical structures, and severe deep brain deformations that occur in HD may hamper the automatic processing of VBM. Here, we validate the use of the optimised protocol of VBM to quantify subcortical atrophy in HD by comparing results obtained with this method to those provided by manual segmentation of subcortical structures. We studied 20 patients with early HD and 12 controls matched for age, sex and handedness using an improved T1-weighted sequence that eased grey matter segmentation. Both manual and automated methods evidenced the dorso-ventral gradient of striatal atrophy, a loss of grey matter in the globus pallidus and the thalamus, and similar correlations between clinical scores and subcortical atrophy. Furthermore, we were able to detect with VBM grey matter loss in the substantia nigra, the hypothalamus, the amygdala, the insular cortex and the premotor and sensorimotor cortices. Finally, VBM provided results consistent with previous post mortem results and proved to be a sensitive biomarker capable of correctly managing subcortical distortions throughout HD patients' brains.     

Pattern classification using principal components of cortical thickness and its discriminative pattern in schizophrenia

We proposed pattern classification based on principal components of cortical thickness between schizophrenic patients and healthy controls, which was trained using a leave-one-out cross-validation. The cortical thickness was measured by calculating the Euclidean distance between linked vertices on the inner and outer cortical surfaces. Principal component analysis was applied to each lobe for practical computational issues and stability of principal components. And, discriminative patterns derived at every vertex in the original feature space with respect to support vector machine were analyzed with definitive findings of brain abnormalities in schizophrenia for establishing practical confidence. It was simulated with 50 randomly selected validation set for the generalization and the average accuracy of classification was reported. This study showed that some principal components might be more useful than others for classification, but not necessarily matching the ordering of the variance amounts they explained. In particular, 40-70 principal components rearranged by a simple two-sample t-test which ranked the effectiveness of features were used for the best mean accuracy of simulated classification (frontal: (left(%)|right(%))=91.07|88.80, parietal: 91.40|91.53, temporal: 93.60|91.47, occipital: 88.80|91.60). And, discriminative power appeared more spatially diffused bilaterally in the several regions, especially precentral, postcentral, superior frontal and temporal, cingulate and parahippocampal gyri. Since our results of discriminative patterns derived from classifier were consistent with a previous morphological analysis of schizophrenia, it can be said that the cortical thickness is a reliable feature for pattern classification and the potential benefits of such diagnostic tools are enhanced by our finding.     

未受教育及受教育儿童语言处理脑区偏侧化的差异:基于体素的MR形态学分析

目的采用基于体素的形态学方法分析未受教育及受教育儿童语言处理相关脑区的偏侧化差异。方法对42名学龄儿童(未受教育组23名,6.0～7.8岁,中位年龄6.5岁;受教育组19名,5.8～7.6岁,中位年龄6.3岁)行高分辨力T1W扫描,采用VBM8软件包进行图像后处理,并采用LI-tools工具软件进行偏侧化分析,比较未受教育组与受教育组的灰质密度(GMD)偏侧化指数情况。结果受教育组的额下回(BA44)以及颞上回(BA22)的GMD偏侧化指数显著高于未受教育组。结论学校教育可能显著促进额下回和颞上回的GMD偏侧化。     

脑皮层厚度分析方法及其应用

本文系统描述了脑皮层厚度测量的后处理步骤以及相应的统计分析方法,并就该方法在脑发育和相关疾病中的具体应用进行了深入的讨论。最后,指出脑皮层厚度测量与分析方法的研究意义与潜在局限性。     

Susceptibility-resistant variable-flip-angle turbo spin echo imaging for reliable estimation of cortical thickness: a feasibility study

The thickness of the human cerebral cortex, which provides valuable information in the studies of normal and abnormal neuroanatomy, is commonly estimated using high-resolution, volumetric magnetization-prepared rapid gradient echo (MP-RAGE) magnetic resonance imaging due to its strong T₁-weighted contrast and high signal-to-noise ratio. However, the accuracy of cortical thickness estimates using MP-RAGE is potentially contaminated by susceptibility-induced signal loss particularly at regions in close proximity to air-filled cavities. The purpose of this work is to investigate the feasibility of susceptibility-resistant variable-flip-angle (VFA) three-dimensional turbo/fast spin echo imaging for reliable estimation of cortical thickness of the human brain, wherein 1) radio-frequency (RF) pulse refocuses susceptibility-induced spin de-phasing, 2) the VFA refocusing pulse train is applied for a tissue-specific prescribed signal evolution along the echo train, 3) the desired T₁-weighted contrast is achieved by composite restore pulses at the end of the refocusing pulse train, and 4) blood signals are suppressed using the VFA scheme combined with increasing moments of flow-sensitizing gradients while dura mater signals are attenuated due to short T₂ relaxation time, which alleviates potential failure in brain segmentation. Numerical simulations of the Bloch equation are performed in both MP-RAGE and the proposed method for comparison. In vivo studies are performed in 14 healthy volunteers at 3 T. Image processing is then performed using the Freesurfer, resulting in mean and standard deviations of cortical thickness for the entire cortical surfaces. Statistical analysis demonstrates that particularly in the inferior prefrontal and temporal regions heavily affected by susceptibility-induced signal loss conventional MP-RAGE, if compared with the proposed method, significantly under-estimates cortical thickness. It is expected that the proposed pulse sequence, which is resistant to susceptibility-induced signal loss and attenuates the signal intensity of blood and dura mater, can be a potentially promising alternative to conventional MP-RAGE in reliably estimating cortical thickness for the entire brain.     

Individual subject classification for Alzheimer's disease based on incremental learning using a spatial frequency representation of cortical thickness data

Patterns of brain atrophy measured by magnetic resonance structural imaging have been utilized as significant biomarkers for diagnosis of Alzheimer's disease (AD). However, brain atrophy is variable across patients and is non-specific for AD in general. Thus, automatic methods for AD classification require a large number of structural data due to complex and variable patterns of brain atrophy. In this paper, we propose an incremental method for AD classification using cortical thickness data. We represent the cortical thickness data of a subject in terms of their spatial frequency components, employing the manifold harmonic transform. The basis functions for this transform are obtained from the eigenfunctions of the Laplace-Beltrami operator, which are dependent only on the geometry of a cortical surface but not on the cortical thickness defined on it. This facilitates individual subject classification based on incremental learning. In general, methods based on region-wise features poorly reflect the detailed spatial variation of cortical thickness, and those based on vertex-wise features are sensitive to noise. Adopting a vertex-wise cortical thickness representation, our method can still achieve robustness to noise by filtering out high frequency components of the cortical thickness data while reflecting their spatial variation. This compromise leads to high accuracy in AD classification. We utilized MR volumes provided by Alzheimer's Disease Neuroimaging Initiative (ADNI) to validate the performance of the method. Our method discriminated AD patients from Healthy Control (HC) subjects with 82% sensitivity and 93% specificity. It also discriminated Mild Cognitive Impairment (MCI) patients, who converted to AD within 18 months, from non-converted MCI subjects with 63% sensitivity and 76% specificity. Moreover, it showed that the entorhinal cortex was the most discriminative region for classification, which is consistent with previous pathological findings. In comparison with other classification methods, our method demonstrated high classification performance in both categories, which supports the discriminative power of our method in both AD diagnosis and AD prediction.