Landmark‐guided region‐based spatial normalization for functional magnetic resonance imaging

As the size of the neuroimaging cohorts being increased to address key questions in the field of cognitive neuroscience, cognitive aging, and neurodegenerative diseases, the accuracy of the spatial normalization as an essential preprocessing step becomes extremely important. Existing spatial normalization methods have poor accuracy particularly when dealing with the highly convoluted human cerebral cortex and when brain morphology is severely altered (e.g., aging populations). To address this shortcoming, we propose a novel spatial normalization technique that takes advantage of the existing surface‐based human brain parcellation to automatically identify and match regional landmarks. To simplify the nonlinear whole brain registration, the identified landmarks of each region and its counterpart are registered independently with topology‐preserving deformation. Next, the regional warping fields are combined by an inverse distance weighted interpolation technique to have a global warping field for the whole brain. To ensure that the final warping field is topology‐preserving, we used simultaneously forward and reverse maps with certain symmetric constraints to yield bijectivity. We have evaluated our proposed solution using both simulated and real (structural and functional) human brain images. Our evaluation shows that our solution can enhance structural correspondence compared to the existing methods. Such improvement also increases the sensitivity and specificity of the functional imaging studies, reducing the required number of subjects and subsequent study costs. We conclude that our proposed solution can effectively substitute existing substandard spatial normalization methods to deal with the demand of large cohorts which is now common in clinical and aging studies.     

Assessment of spatial normalization of whole-brain magnetic resonance images in children

Commonly used frameworks for spatial normalization of brain imaging data (e.g., Talairach-space) are based on one or more adult brains. As pediatric brains are different in size and shape from adult brains and continue to develop through childhood, we aimed to assess the influence of age on various spatial normalization parameters. One hundred forty-eight healthy children aged 5-18 years were included in this study. The linear scaling parameters and the deformations from the non-linear spatial normalization to both a standard adult and a custom pediatric template were analyzed within SPM99. The effect of using a brain mask on the linear and of using different levels of constraint on the non-linear spatial normalization was assessed. Of the linear scaling factors, only the X-dimension (left-right) showed a significant age-correlation when based on brain tissue, whereas the overall scaling was not correlated with age. When based on the whole head, a very strong age-effect can be found in all dimensions. Non-linear deformations also show localized correlations with age, most pronounced in parietal and frontal areas. The total amount of volume change is significantly lower when using a pediatric template. It is also substantially influenced by the degree of regularization that is exerted on the spatial normalization parameters. Our results suggest that in the cortical areas showing a strong correlation of deformation with age, caution should be used in assigning imaging results in children to a specific morphological structure. Also, to minimize the amount of deformation during non-linear spatial normalization, a pediatric template should be used. Further implications of our findings on developmental neuroimaging studies are discussed.     

A modality-independent approach to spatial normalization of tomographic images of the human brain

A modality-independent approch for interactive spatial normalization of tomographic images of the human brain is described and its performance evaluated. Spatial normalization is accomplished using a nine-parameter affine transformation to interactively align and adjust the shape of a subject brain to the reference brain detailed in the 1988 atlas of Talairach et al. A user-friendly software application was developed using the X-windows Motif environment to guide the user through this process. This software supports data types from a wide variety of tomographic imagers and produces output in spatially concise formats. The parameters used for spatial alignment and shape normalization are presented and methods to apply them discussed. Where normalization parameters cannot be obtained directly from the image, as with positron emission tomography (PET), methods for estimating them are given. Evaluation of a new four-landmark method to fit the AC-PC line in 16 magnetic resonance imaging (MRI) studies indicated an average difference assessed as the distance between the true and fitted AC-PC line at four locations of 0.82 mm when using a 2-D weighted fit. The same landmarks were evaluated using lower spatial resolution PET-like images simulated from the 16 MRI studies. The difference between the PET and MR image volumes following alignment was minimal, with mean rotational differences of less than 0.2 deg and mean translational differences of generally less than 2 mm. Spatial normalization is illustrated for single photon emission computed tomography (SPECT), X-ray computed tomography (CT), PET, and MR image volumes. Modality-independent spatial normalization can be consistently and reliably performed with the methods and software presented. © 1995 Wiley-Liss, Inc.     

Comparison of spatial normalization procedures and their impact on functional maps

The alignment accuracy and impact on functional maps of four spatial normalization procedures have been compared using a set of high resolution brain MRIs and functional PET volumes acquired in 20 subjects. Simple affine (AFF), fifth order polynomial warp (WRP), discrete cosine basis functions (SPM), and a movement model based on full multi grid (FMG) approaches were applied on the same dataset for warping individual volumes onto the Human Brain Atlas (HBA) template. Intersubject averaged structural volumes and tissue probability maps were compared across normalization methods and to the standard brain. Thanks to the large number of degrees of freedom of the technique, FMG was found to provide enhanced alignment accuracy as compared to the other three methods, both for the grey and white matter tissues; WRP and SPM exhibited very similar performances whereas AFF had the lowest registration accuracy. SPM, however, was found to perform better than the other methods for the intra-cerebral cerebrospinal fluid (mainly in the ventricular compartments). Limited differences in terms of activation morphology and detection sensitivity were found between low resolution functional maps (FWHM approximately 10 mm) spatially normalized with the four methods, which overlapped in 42.8% of the total activation volume. These findings suggest that the functional variability is much larger than the anatomical one and that precise alignment of anatomical features has low influence on the resulting intersubject functional maps. When increasing the spatial resolution to approximately 6 mm, however, differences in localization of activated areas appear as a consequence of the different spatial normalization procedure used, restricting the overlap of the normalized activated volumes to only 6.2%.     

Nonrigid registration of multiple sclerosis brain images using lesion inpainting for morphometry or lesion mapping

Morphometric studies of medical images often include a nonrigid registration step from a subject to a common reference. The presence of white matter multiple sclerosis lesions will distort and bias the output of the registration. In this article, we present a method to remove this bias by filling such lesions to make the brain look like a healthy brain before the registration. We finally propose a dedicated method to fill the lesions and present numerical results showing that our method outperforms current state of the art method.     

MR‐PET head motion correction based on co‐registration of multicontrast MR images

Head motion is a major source of image artefacts in neuroimaging studies and can lead to degradation of the quantitative accuracy of reconstructed PET images. Simultaneous magnetic resonance‐positron emission tomography (MR‐PET) makes it possible to estimate head motion information from high‐resolution MR images and then correct motion artefacts in PET images. In this article, we introduce a fully automated PET motion correction method, MR‐guided MAF, based on the co‐registration of multicontrast MR images. The performance of the MR‐guided MAF method was evaluated using MR‐PET data acquired from a cohort of ten healthy participants who received a slow infusion of fluorodeoxyglucose ([18‐F]FDG). Compared with conventional methods, MR‐guided PET image reconstruction can reduce head motion introduced artefacts and improve the image sharpness and quantitative accuracy of PET images acquired using simultaneous MR‐PET scanners. The fully automated motion estimation method has been implemented as a publicly available web‐service.     

A rat brain MRI template with digital stereotaxic atlas of fine anatomical delineations in paxinos space and its automated application in voxel‐wise analysis

This study constructs a rat brain T₂‐weighted magnetic resonance imaging template including olfactory bulb and a compatible digital atlas. The atlas contains 624 carefully delineated brain structures based on the newest (2005) edition of rat brain atlas by Paxinos and Watson. An automated procedure, as an SPM toolbox, was introduced for spatially normalizing individual rat brains, conducting statistical analysis and visually localizing the results in the Atlas coordinate space. The brain template/atlas and the procedure were evaluated using functional images between rats with the right side middle cerebral artery occlusion (MCAO) and normal controls. The result shows that the brain region with significant signal decline in the MCAO rats was consistent with the occlusion position. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Impact of fiducial arrangement and registration sequence on target accuracy using a phantom frameless stereotactic navigation model

Modern frameless stereotactic techniques utilize scalp fiducial markers for registration. Anecdotal reports from surgeons indicate a variety of methods for improving accuracy using different fiducial arrangements and registration sequences. The few published studies on registration accuracy do not provide a simple and systematic method for determining target accuracy. Nine different arrangements of ten fiducial markers were attached to a model. Ten separate markers were designated as targets for evaluation of registration accuracy. We systematically registered each of the arrangements over multiple trials, in one of four sequences, and then measured the targets. The target coordinates were compared against the established target values, and a root-mean-square deviation (RMSD) was derived. A systematic multivariate analysis determined the effects of different variables on the RMSD. We found no correlation between the “Registration Accuracy” provided by Medtronic (Medtronic Navigation, Louisville, CO, USA) and our RMSD representing targeting accuracy (R = 0.008). RMSD did vary for different fiducial arrangements. We found no significant difference between the various sequences of fiducial arrangement. Thus, regardless of fiducial arrangement, registration sequence has no impact on accuracy. Fiducial arrangements distributed optimally across the skull, however, allowed for significantly improved accuracy. Further studies are required to determine which different arrangements of fiducials are relevant for specific procedures.     

Neuroimaging and presurgical evaluation of symptomatic epilepsies

The goal of presurgical evaluation of intractable epilepsy is to identify epileptogenic regions in the brain. From our experience of 38 cases of resective epilepsy surgery from the last 3 years, ictal SPECT was considered the most sensitive at detecting focal changes relating to seizures compared to other neuroimaging modalities, such as MRI, FDG-PET, SPECT and MEG. At interictal state, on the other hand, FDG-PET was most sensitive, especially in cases with focal cortical dysplasia, which is often MRI-invisible. In dysplastic tumors, MRI showed the highest concordance rate to clinically verified epileptogenic regions. Activation studies using functional neuroimaging such as PET and fMRI is useful to evaluate brain functions at epileptogenic regions presurgically. The role of functional brain imaging in epilepsy surgery is considered to be: (i). case selection for resective surgery, (ii). case selection for invasive EEG monitoring, and (iii). navigation of electrode placement and cortical resection.     

基于空间自动配准手术计划系统的设计和实现****

文章提出了一种基于手术空间和图像空间自动配准的手术计划系统设计和实现方法：①选取3个有一定间隔的横断面。②使用模板匹配法自动识别每一个横断面上的标志点。③用识别的数据建立手术空间和图像空间的刚体变换模型,再用最小二乘法解方程组得到两个空间的最优变换矩阵和平移矩阵。最后再通过建立脑空间和图像空间映射关系来计算功能靶点坐标。基于以上算法设计了手术计划系统软件,对比了手动和自动方法识别标志点的运行时间,并设计系统改进前后功能靶点计算值和手术空间实际测量值对比实验。结果证明以上方法有较好的靶点计算速度和精度。     

The SRI24 multichannel atlas of normal adult human brain structure

This article describes the SRI24 atlas, a new standard reference system of normal human brain anatomy, that was created using template‐free population registration of high‐resolution magnetic resonance images acquired at 3T in a group of 24 normal control subjects. The atlas comprises anatomical channels (T1, T2, and proton density weighted), diffusion‐related channels (fractional anisotropy, mean diffusivity, longitudinal diffusivity, mean diffusion‐weighted image), tissue channels (CSF probability, gray matter probability, white matter probability, tissue labels), and two cortical parcellation maps. The SRI24 atlas enables multichannel atlas‐to‐subject image registration. It is uniquely versatile in that it is equally suited for the two fundamentally different atlas applications: label propagation and spatial normalization. Label propagation, herein demonstrated using diffusion tensor image fiber tracking, is enabled by the increased sharpness of the SRI24 atlas compared with other available atlases. Spatial normalization, herein demonstrated using data from a young–old group comparison study, is enabled by its unbiased average population shape property. For both propagation and normalization, we also report the results of quantitative comparisons with seven other published atlases: Colin27, MNI152, ICBM452 (warp5 and air12), and LPBA40 (SPM5, FLIRT, AIR). Our results suggest that the SRI24 atlas, although based on 3T MR data, allows equally accurate spatial normalization of data acquired at 1.5T as the comparison atlases, all of which are based on 1.5T data. Furthermore, the SRI24 atlas is as suitable for label propagation as the comparison atlases and detailed enough to allow delineation of anatomical structures for this purpose directly in the atlas. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Functional dynamics of dopamine synthesis during monetary reward and punishment processing

The assessment of dopamine release with the PET competition model is thoroughly validated but entails disadvantages for the investigation of cognitive processes. We introduce a novel approach incorporating 6-[¹⁸F]FDOPA uptake as index of the dynamic regulation of dopamine synthesis enzymes by neuronal firing. The feasibility of this approach is demonstrated by assessing widely described sex differences in dopamine neurotransmission. Reward processing was behaviorally investigated in 36 healthy participants, of whom 16 completed fPET and fMRI during the monetary incentive delay task. A single 50 min fPET acquisition with 6-[¹⁸F]FDOPA served to quantify task-specific changes in dopamine synthesis. In men monetary gain induced stronger increases in ventral striatum dopamine synthesis than loss. Interestingly, the opposite effect was discovered in women. These changes were further associated with reward (men) and punishment sensitivity (women). As expected, fMRI showed robust task-specific neuronal activation but no sex difference. Our findings provide a neurobiological basis for known behavioral sex differences in reward and punishment processing, with important implications in psychiatric disorders showing sex-specific prevalence, altered reward processing and dopamine signaling. The high temporal resolution and magnitude of task-specific changes make fPET a promising tool to investigate functional neurotransmitter dynamics during cognitive processing and in brain disorders.     

Spatial and temporal analysis of fMRI data on word and sentence reading

Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level-dependent (BOLD) response estimates between regions. To avoid this problem, we parametrically varied linguistic task demands and compared only task-induced within-region BOLD response differences across areas. We reasoned that, in a hierarchical processing system, increasing task demands at lower processing levels induce delayed onset of higher-level processes in corresponding areas. The flow of activation is thus reflected in the size of task-induced delay increases. We estimated BOLD response delay and duration for each voxel and each participant by fitting a model function to the event-related average BOLD response. The GLM showed increasing activations with increasing linguistic demands dominantly in the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG). The combination of spatial and temporal analysis allowed a functional differentiation of IFG subregions involved in written language comprehension. Ventral IFG region (BA 47) and STG subserve earlier processing stages than two dorsal IFG regions (BA 44 and 45). This is in accordance with the assumed early lexical semantic and late syntactic processing of these regions and illustrates the complementary information provided by spatial and temporal fMRI data analysis of the same data set.     

Functional MRI mapping of stimulus rate effects across visual processing stages

Functional magnetic resonance imaging (fMRI) was used to record cortical activation across multiple stages in the visual system during single character visual search and reversing checkerboard stimulation. Scanning used T₂-weighted, gradient echo sequences with late echo times (TE = 36 ms) with a voxel size of 0.94 * 1.88 mm in-plane resolution, 4–5 mm deep, on a conventional scanner. A scout experiment recorded six slices to identify major regions of activation. Two slices were selected for extensive assessment. Character stimuli activated small (average 16 mm²), reliable, statistically defined regions of activation in the calcarine fissure, superior occipital cortex, and fusiform-lingual gyrus. The results include: (1) for character search, the MRI signal change increased linearly from 2.1 to 3.1% for stimulation from 1 to 8 Hz; (2) the character rate effect was equivalent across three levels of the visual system; (3) the checkerboard stimuli showed broader, more intense primary visual activation and less intense secondary visual activation than did character search. Issues relating to fMRI signal variability across the imagining plane, statistical data analysis, signal sensitivity, statistical power, fMRI experimental protocols, and comparisons with positron emission tomography (PET) data are discussed. © 1994 Wiley-Liss, Inc.     

Spatial coding of visual and somatic sensory information in body-centred coordinates

Because sensory systems use different spatial coordinate frames, cross-modal sensory integration and sensory-motor coordinate transformations must occur to build integrated spatial representations. Multimodal neurons using non-retinal body-centred reference frames are found in the posterior parietal and frontal cortices of monkeys. We used functional magnetic resonance imaging to reveal regions of the human brain using body-centred coordinates to code the spatial position of both visual and somatic sensory stimuli. Participants determined whether a visible vertical bar (visual modality) or a location touched by the right index finger (somatic sensory modality) lay to the left or to the right of their body mid-sagittal plane. This task was compared to a spatial control task having the same stimuli and motor responses and comparable difficulty, but not requiring body-centred coding of stimulus position. In both sensory modalities, the body-centred coding task activated a bilateral fronto-parietal network, though more extensively in the right hemisphere, to include posterior parietal regions around the intraparietal sulcus and frontal regions around the precentral and superior frontal sulci, the inferior frontal gyrus and the superior frontal gyrus on the medial wall. The occipito-temporal junction and other extrastriate regions exhibited bilateral activation enhancement related to body-centred coding when driven by visual stimuli. We conclude that posterior parietal and frontal regions of humans, as in monkeys, appear to provide multimodal integrated spatial representations in body-centred coordinates, and these data furnish the first indication of such processing networks in the human brain.     

Columnar specificity of microvascular oxygenation and blood flow response in primary visual cortex: evaluation by local field potential and spiking activity

The relation of cortical microcirculation, oxygen metabolism, and underlying neuronal network activity remains poorly understood. Anatomical distribution of cortical microvasculature and its relationship to cortical functional domains suggests that functional organizations may be revealed by mapping cerebral blood flow responses. However, there is little direct experimental evidence and a lack of electrophysiological evaluation. In this study, we mapped ocular-dominance columns in primary visual cortex (V1) of anesthetized macaques with capillary flow-based laser speckle contrast imaging and deoxyhemoglobin-based intrinsic optical imaging. In parallel, the local field potentials (LFPs) and spikes were recorded from a linear array of eight microelectrodes, carefully positioned into left and right eye columns in V1. We found differential activation maps of blood flow, after masking large superficial draining vessels, exhibited a column-like pattern similar as the oximetric maps. Both the activated spikes and γ-band LFP demonstrated corresponding eye preference, consistent with the imaging maps. Our results present direct support in favor of previous proposals that the regulation of microcirculation can be as fine as the submillimeter scale, suggesting that cortical vasculature is functionally organized at the columnar level in a manner appropriate for supplying energy demands of functionally specific neuronal populations.     

The impact of vascular factors on language localization in the superior temporal sulcus

The left superior temporal sulcus (STS) has been shown in numerous functional imaging studies to be a critical region for language processing, as it is reliably activated when language comprehension is compared with acoustically matched control conditions. Studies in non‐human primates have demonstrated several subdivisions in the STS, yet the precise region(s) within the STS that are important for language remain unclear, in large part because the presence of draining veins in the sulcus makes it difficult to determine whether neural activity is localized to the dorsal or ventral bank of the sulcus. We used functional MRI to localize language regions, and then acquired several additional sequences in order to account for the impact of vascular factors. A breath‐holding task was used to induce hypercapnia in order to normalize voxel‐wise differences in blood oxygen level‐dependent (BOLD) responsivity, and veins were identified on susceptibility‐weighted and T2*‐weighted BOLD images, and masked out. We found that the precise locations of language areas in individual participants were strongly influenced by vascular factors, but that these vascular effects could be ameliorated by hypercapnic normalization and vein masking. After these corrections were applied, the majority of regions activated by language processing were localized to the dorsal bank of the STS. Hum Brain Mapp 35:4049–4063, 2014. © 2014 Wiley Periodicals, Inc .     

Human brain atlas: For high-resolution functional and anatomical mapping

We present the new computerized Human Brain Atlas (HBA) for anatomical and functional mapping studies of the human brain. The HBA is based on many high-resolution magnetic resonance images of normal subjects and provides continuous updating of the mean shape and position of anatomical structures of the human brain. The structures are transformable by linear and nonlinear global and local transformations applied anywhere in 3-D pictures to fit the anatomical structures of individual brains, which, by reformatting, are transformed into a high-resolution standard anatomical format. The power of the HBA to reduce anatomical variations was evaluated on a randomized selection of anatomical landmarks in brains of 27 young normal male volunteers who were different from those on whom the standard brain was selected. The HBA, even when based only on standard brain surface and central structures, reduced interindividual anatomical variance to the level of the variance in structure position between the right and left hemisphere in individual brains. © 1994 Wiley-Liss, Inc.