Shape-constrained deformable brain segmentation: Methods and quantitative validation.

MRI-guided neuro interventions require rapid, accurate, and reproducible segmentation of anatomical brain structures for identification of targets during surgical procedures and post-surgical evaluation of intervention efficiency. Segmentation algorithms must be validated and cleared for clinical use. This work introduces a methodology for shape-constrained deformable brain segmentation, describes the quantitative validation used for its clinical clearance, and presents a comparison with manual expert segmentation and FreeSurfer, an open source software for neuroimaging data analysis. ClearPoint Maestro is software for fully-automatic brain segmentation from T1-weighted MRI that combines a shape-constrained deformable brain model with voxel-wise tissue segmentation within the cerebral hemispheres and the cerebellum. The performance of the segmentation was validated in terms of accuracy and reproducibility. Segmentation accuracy was evaluated with respect to training data and independently traced ground truth. Segmentation reproducibility was quantified and compared with manual expert segmentation and FreeSurfer. Quantitative reproducibility analysis indicates superior performance compared to both manual expert segmentation and FreeSurfer. The shape-constrained methodology results in accurate and highly reproducible segmentation. Inherent point based-correspondence provides consistent target identification ideal for MRI-guided neuro interventions.

Patient-Specific Sensor Registration for Electrical Source Imaging Using a Deformable Head Model.

OBJECTIVE: Electrical source imaging of brain activity is most accurate when using individualized bioelectric head models. Constructing these models requires identifying electrode positions on the scalp surface. Current methods such as photogrammetry involve significant user interaction that limits integration in clinical workflows. This work introduces and validates a new, fully-automatic method for sensor registration. METHODS: Average electrode coordinates are registered to the mean scalp mesh of a shape-constrained deformable head model used for tissue segmentation. Patient-specific electrode positions can be identified on the deformed scalp surface using point-based correspondence after model adaptation. RESULTS: The performance of the proposed method for sensor registration is evaluated with simulated and real data. Electrode variability is quantified for a photogrammetry-based solution and compared against the proposed sensor registration. CONCLUSION: A fully-automated model-based approach can identify electrode locations with similar accuracy as a current state-of-the-art photogrammetry system. SIGNIFICANCE: The new method for sensor registration presented in this work is rapid and fully automatic. It eliminates any user dependent inaccuracy introduced in sensor registration and ensures reproducible results. More importantly, it can more easily be integrated in clinical workflows, enabling broader adoption of electrical source imaging technologies.

Static and dynamic cocktail party listening in younger and older adults.

Verbal communication often takes place in situations with several simultaneous speakers ("cocktail party listening"). These situations can be static (only one listening target) or dynamic (with alternating targets). In particular, dynamic cocktail party listening is believed to generate extra cognitive load and appears to be particularly demanding for older listeners. Two groups of younger and older listeners with good hearing and normal cognition participated in the present study. Three different, spatially separated talker voices uttering matrix sentences were presented to each listener with varying types and probabilities of target switches. Moreover, several neuropsychological tests were conducted to investigate general cognitive characteristics that may be important for speech understanding in these situations. In a static condition with a priori knowledge of the target talker, both age groups revealed very high speech recognition performance. In comparison, dynamic conditions caused extra costs associated with the need to monitor different potential sound sources and to refocus attention when the target changed. The amount of costs depended on the probability and type of target talker alterations. Again, no significant age-group differences were found. No significant associations of cognitive characteristics and costs could be shown. However, a more fine-grained analysis based on the calculation of general and specific switch costs showed different mechanisms in older and younger listeners. This study confirms that dynamic cocktail party listening is associated with costs that depend on the type and probability of target switches. It extends previous research by showing that the effects of switching type and probability are similar for younger and older listeners with good hearing and good cognitive abilities. It further shows that, despite comparable costs of dynamic listening, mechanisms are different for the two age groups, as switching auditory attention may be preserved with aging, but monitoring different sound sources appears to be more difficult for older adults.

Normative brain volumetry derived from different reference populations: impact on single-subject diagnostic assessment in dementia.

Brain imaging data are increasingly made publicly accessible, and volumetric imaging measures derived from population-based cohorts may serve as normative data for individual patient diagnostic assessment. Yet, these normative cohorts are usually not a perfect reflection of a patient's base population, nor are imaging parameters such as field strength or scanner type similar. In this proof of principle study, we assessed differences between reference curves of subcortical structure volumes of normal controls derived from two population-based studies and a case-control study. We assessed the impact of any differences on individual assessment of brain structure volumes. Percentile curves were fitted on the three healthy cohorts. Next, percentile values for these subcortical structures for individual patients from these three cohorts, 91 mild cognitive impairment and 95 Alzheimer's disease cases and patients from the Alzheimer Center, were calculated, based on the distributions of each of the three cohorts. Overall, we found that the subcortical volume normative data from these cohorts are highly interchangeable, suggesting more flexibility in clinical implementation.

Rapid fully automatic segmentation of subcortical brain structures by shape-constrained surface adaptation.

This work presents a novel approach for the rapid segmentation of clinically relevant subcortical brain structures in T1-weighted MRI by utilizing a shape-constrained deformable surface model. In contrast to other approaches for segmenting brain structures, its design allows for parallel segmentation of individual brain structures within a flexible and robust hierarchical framework such that accurate adaptation and volume computation can be achieved within a minute of processing time. Furthermore, adaptation is driven by local and not global contrast, potentially relaxing requirements with respect to preprocessing steps such as bias-field correction. Detailed evaluation experiments on more than 1000 subjects, including comparisons to FSL FIRST and FreeSurfer as well as a clinical assessment, demonstrate high accuracy and test-retest consistency of the presented segmentation approach, leading, for example, to an average segmentation error of less than 0.5 mm. The presented approach might be useful in both, research as well as clinical routine, for automated segmentation and volume quantification of subcortical brain structures in order to increase confidence in the diagnosis of neuro-degenerative disorders, such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, or clinical applications for other neurologic and psychiatric diseases.

Differences in Regional Brain Volumes Two Months and One Year after Mild Traumatic Brain Injury.

Conventional structural imaging is often normal after mild traumatic brain injury (mTBI). There is a need for structural neuroimaging biomarkers that facilitate detection of milder injuries, allow recovery trajectory monitoring, and identify those at risk for poor functional outcome and disability. We present a novel approach to quantifying volumes of candidate brain regions at risk for injury. Compared to controls, patients with mTBI had significantly smaller volumes in several regions including the caudate, putamen, and thalamus when assessed 2 months after injury. These differences persisted but were reduced in magnitude 1 year after injury, suggesting the possibility of normalization over time in the affected regions. More pronounced differences, however, were found in the amygdala and hippocampus, suggesting the possibility of regionally specific responses to injury.

Construction and comparative evaluation of different activity detection methods in brain FDG-PET.

AIM: We constructed and evaluated reference brain FDG-PET databases for usage by three software programs (Computer-aided diagnosis for dementia (CAD4D), Statistical Parametric Mapping (SPM) and NEUROSTAT), which allow a user-independent detection of dementia-related hypometabolism in patients' brain FDG-PET. METHODS: Thirty-seven healthy volunteers were scanned in order to construct brain FDG reference databases, which reflect the normal, age-dependent glucose consumption in human brain, using either software. Databases were compared to each other to assess the impact of different stereotactic normalization algorithms used by either software package. In addition, performance of the new reference databases in the detection of altered glucose consumption in the brains of patients was evaluated by calculating statistical maps of regional hypometabolism in FDG-PET of 20 patients with confirmed Alzheimer's dementia (AD) and of 10 non-AD patients. Extent (hypometabolic volume referred to as cluster size) and magnitude (peak z-score) of detected hypometabolism was statistically analyzed. RESULTS: Differences between the reference databases built by CAD4D, SPM or NEUROSTAT were observed. Due to the different normalization methods, altered spatial FDG patterns were found. When analyzing patient data with the reference databases created using CAD4D, SPM or NEUROSTAT, similar characteristic clusters of hypometabolism in the same brain regions were found in the AD group with either software. However, larger z-scores were observed with CAD4D and NEUROSTAT than those reported by SPM. Better concordance with CAD4D and NEUROSTAT was achieved using the spatially normalized images of SPM and an independent z-score calculation. The three software packages identified the peak z-scores in the same brain region in 11 of 20 AD cases, and there was concordance between CAD4D and SPM in 16 AD subjects. CONCLUSION: The clinical evaluation of brain FDG-PET of 20 AD patients with either CAD4D-, SPM- or NEUROSTAT-generated databases from an identical reference dataset showed similar patterns of hypometabolism in the brain regions known to be involved in AD. The extent of hypometabolism and peak z-score appeared to be influenced by the calculation method used in each software package rather than by different spatial normalization parameters.

Voxel-based classification of FDG PET in dementia using inter-scanner normalization.

Statistical mapping of FDG PET brain images has become a common tool in differential diagnosis of patients with dementia. We present a voxel-based classification system of neurodegenerative dementias based on partial least squares (PLS). Such a classifier relies on image databases of normal controls and dementia cases as training data. Variations in PET image characteristics can be expected between databases, for example due to differences in instrumentation, patient preparation, and image reconstruction. This study evaluates (i) the impact of databases from different scanners on classification accuracy and (ii) a method to improve inter-scanner classification. Brain FDG PET databases from three scanners (A, B, C) at two clinical sites were evaluated. Diagnostic categories included normal controls (NC, nA=26, nB=20, nC=24 for each scanner respectively), Alzheimer's disease (AD, nA=44, nB=11, nC=16), and frontotemporal dementia (FTD, nA=13, nB=13, nC=5). Spatially normalized images were classified as NC, AD, or FTD using partial least squares. Supervised learning was employed to determine classifier parameters, whereby available data is sub-divided into training and test sets. Four different database setups were evaluated: (i) "in-scanner": training and test data from the same scanner, (ii) "x-scanner": training and test data from different scanners, (iii) "train other": train on both x-scanners, and (iv) "train all": train on all scanners. In order to moderate the impact of inter-scanner variations on image evaluation, voxel-by-voxel scaling was applied based on "ratio images". Good classification accuracy of on average 94% was achieved for the in-scanner setups. Accuracy deteriorated for setups with mismatched scanners (79-91%). Ratio-image normalization improved all results with mismatched scanners (85-92%). In conclusion, automatic classification of individual FDG PET in differential diagnosis of dementia is feasible. Accuracy can vary with respect to scanner or acquisition characteristics of the training image data. The adopted approach of ratio-image normalization has been demonstrated to effectively moderate these effects.

B-spline-based stereotactical normalization of brain FDG PET scans in suspected neurodegenerative disease: impact on voxel-based statistical single-subject analysis.

A b-spline-based method 'Lobster', originally designed as a general technique for non-linear image registration, was tailored for stereotactical normalization of brain FDG PET scans. Lobster was compared with the normalization methods of SPM2 and Neurostat with respect to the impact on the accuracy of voxel-based statistical analysis. (i) Computer simulation: Seven representative patterns of cortical hypometabolism served as artificial ground truth. They were inserted into 26 normal control scans with different simulated severity levels. After stereotactical normalization and voxel-based testing, statistical maps were compared voxel-by-voxel with the ground truth. This was done at different levels of statistical significance. There was a highly significant effect of the stereotactical normalization method on the area under the resulting ROC curve. Lobster showed the best average performance and was most stable with respect to variation of the severity level. (ii) Clinical evaluation: Statistical maps were obtained for the normal controls as well as patients with Alzheimer's disease (AD, n=44), Lewy-Body disease (LBD, 9), fronto-temporal dementia (FTD, 13), and cortico-basal dementia (CBD, 4). These maps were classified as normal, AD, LBD, FTD, or CBD by two experienced readers. The stereotactical normalization method had no significant effect on classification by of each of the experts, but it appeared to affect agreement between the experts. In conclusion, Lobster is appropriate for use in single-subject analysis of brain FDG PET scans in suspected dementia, both in early diagnosis (mild hypometabolism) and in differential diagnosis in advanced disease stages (moderate to severe hypometabolism). The computer simulation framework developed in the present study appears appropriate for quantitative evaluation of the impact of the different processing steps and their interaction on the performance of voxel-based single-subject analysis.

Association between FDG uptake, CSF biomarkers and cognitive performance in patients with probable Alzheimer's disease.

PURPOSE: Brain imaging of FDG uptake and cerebrospinal fluid (CSF) concentration of amyloid-beta 1-42 (Abeta(1-42)) or tau proteins are promising biomarkers in the diagnosis of Alzheimer's disease (AD). There is still uncertainty regarding any association between decreased FDG uptake and alterations in CSF markers. METHODS: The relationship between FDG uptake, CSF Abeta(1-42) and total tau (T-tau), as well as the Mini-Mental State Examination (MMSE) score was investigated in 34 subjects with probable AD using step-wise linear regression. FDG uptake was scaled to the pons. RESULTS: Scaled FDG uptake was significantly reduced in the probable AD subjects compared to 17 controls bilaterally in the precuneus/posterior cingulate area, angular gyrus/inferior parietal cortex, inferior temporal/midtemporal cortex, midfrontal cortex, and left caudate. Voxel-based single-subject analysis of the probable AD subjects at p < 0.001 (uncorrected) revealed a total volume of significant hypometabolism ranging from 0 to 452 ml (median 70 ml). The total hypometabolic volume was negatively correlated with the MMSE score, but it was not correlated with the CSF measures. VOI-based step-wise linear regression revealed that scaled FDG uptake in the precuneus/posterior cingulate was negatively correlated with CSF Abeta(1-42). Scaled FDG uptake in the caudate was positively correlated with CSF T-tau. CONCLUSION: The extent and local severity of the reduction in FDG uptake in probable AD subjects are associated with cognitive impairment. In addition, there appears to be a relationship between local FDG uptake and CSF biomarkers which differs between different brain regions.