Normative data for volumetric estimates of brain structures are necessary to adequately assess brain volume alterations in individuals with suspected neurological or psychiatric conditions. Although ...many studies have described age and sex effects in healthy individuals for brain morphometry assessed via magnetic resonance imaging, proper normative values allowing to quantify potential brain abnormalities are needed. We developed norms for volumetric estimates of subcortical brain regions based on cross-sectional magnetic resonance scans from 2790 healthy individuals aged 18 to 94years using 23 samples provided by 21 independent research groups. The segmentation was conducted using FreeSurfer, a widely used and freely available automated segmentation software. Models predicting subcortical regional volumes of each hemisphere were produced including age, sex, estimated total intracranial volume (eTIV), scanner manufacturer, magnetic field strength, and interactions as predictors. The mean explained variance by the models was 48%. For most regions, age, sex and eTIV predicted most of the explained variance while manufacturer, magnetic field strength and interactions predicted a limited amount. Estimates of the expected volumes of an individual based on its characteristics and the scanner characteristics can be obtained using derived formulas. For a new individual, significance test for volume abnormality, effect size and estimated percentage of the normative population with a smaller volume can be obtained. Normative values were validated in independent samples of healthy adults and in adults with Alzheimer's disease and schizophrenia.
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•Normative data for volumetric estimates of subcortical brain regions are provided.•Segmentation was performed using FreeSurfer's 5.3 default parameters.•Models include age, sex, intracranial volume and scanner's OEM and strength.•Effect size and test for volume abnormality can be produced for new individuals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Gray and white matter volume difference and change are important imaging markers of pathology and disease progression in neurology and psychiatry. Such measures are usually estimated from tissue ...segmentation maps produced by publicly available image processing pipelines. However, the reliability of the produced segmentations when using multi-center and multi-scanner data remains understudied. Here, we assess the robustness of six publicly available tissue classification pipelines across images acquired from different MR scanners and sites.
We used 90 T1-weighted images of a single individual, scanned in 73 sessions across 27 different sites to assess the robustness of the tissue classification tools. Variability in Dice similarity index values and tissue volumes was assessed for Atropos, BISON, Classify_Clean, FAST, FreeSurfer, and SPM12.
BISON had the highest overall Dice coefficient for GM, followed by SPM12 and Atropos; while Atropos had the highest overall Dice coefficient for WM, followed by BISON and SPM12. BISON had the lowest overall variability in its volumetric estimates, followed by FreeSurfer, and SPM12. All methods also had significant differences between some of their estimates across different scanner manufacturers (e.g. BISON had significantly higher GM estimates and correspondingly lower WM estimates for GE scans compared to Philips and Siemens), and different signal-to-noise ratio (SNR) levels (e.g. FAST and FreeSurfer had significantly higher WM volume estimates for high versus medium and low SNR tertiles as well as correspondingly lower GM volume estimates).
Our comparisons provide a benchmark on the reliability of the publicly used tissue classification techniques and the amount of variability that can be expected when using large multi-center and multi-scanner databases.
•Reliability comparison of six publicly available tissue classification pipelines.•90 T1-weighted images of a single individual across 27 sites used for evaluation.•Compared estimated volume differences across scanner manufacutrers•Assessed the impact of signal-to-noise ratio.•Our comparisons provide a benchmark on the reliability of each technique.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Sex differences play a vital role in human brain structure and physiology. Previous reports have proposed evidence hinting at a metabolic advantage in female brains across adulthood. It remained to ...be determined whether this advantage would be maintained across the spectrum of cognitive impairment, up to and including dementia due to Alzheimer's disease (AD). Here, using a machine-learning algorithm, we explore sex differences in metabolic brain-age derived from fluorodeoxyglucose positron emission tomography imaging among cognitively healthy individuals and those affected by mild cognitive impairment and clinically probable AD. First, we report that cognitively healthy male participants showed a persistently “older” looking brains when compared to healthy female participants in term of metabolic brain age, confirming earlier reports. However, this distinction disappeared among MCI individuals and probable AD patients, and this loss could not be explained by an accompanying neurodegeneration. This would seem to indicate that females have a higher rate of decline in brain glucose metabolism when cognitively impaired to negate their prior advantage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•We present a robust and simple bias-adjustment scheme for neuroimaging-based brain age frameworks.•The efficiency of proposed bias-adjustment scheme was assessed in the context of cognitively ...healthy aging and Alzheimer's disease.•The proposed bias-adjustment scheme was shown efficient and statistically improved results, making it a necessary part for future brain age frameworks.
The level of prediction error in the brain age estimation frameworks is associated with the authenticity of statistical inference on the basis of regression models. In this paper, we present an efficacious and plain bias-adjustment scheme using chronological age as a covariate through the training set for downgrading the prediction bias in a Brain-age estimation framework. We applied proposed bias-adjustment scheme coupled by a machine learning-based brain age framework on a large set of metabolic brain features acquired from 675 cognitively unimpaired adults through fluorodeoxyglucose positron emission tomography data as the training set to build a robust Brain-age estimation framework. Then, we tested the reliability of proposed bias-adjustment scheme on 75 cognitively unimpaired adults, 561 mild cognitive impairment patients as well as 362 Alzheimer's disease patients as independent test sets. Using the proposed method, we gained a strong R2 of 0.81 between the chronological age and brain estimated age, as well as an excellent mean absolute error of 2.66 years on 75 cognitively unimpaired adults as an independent set; whereas an R2 of 0.24 and a mean absolute error of 4.71 years was achieved without bias-adjustment. The simulation results demonstrated that the proposed bias-adjustment scheme has a strong capability to diminish prediction error in brain age estimation frameworks for clinical settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
We present a retrospective meta‐analysis of voxel‐based morphometry (VBM) of gray (GM) and white matter (WM) differences between patients with bipolar disorder (BD) and behaviorally healthy ...controls.
Methods
We used the activation likelihood estimation and Sleuth software for our meta‐analysis, considering P‐value maps at the cluster level inference of .05 with uncorrected P<.001. Results were visualized with the software MANGO.
Results
We included twenty‐five articles in the analysis, and separated the comparisons where BD patients had lower GM or WM concentrations than controls (573 subjects, 21 experiments, and 117 locations/180 subjects, five experiments, and 15 locations, respectively) and the comparisons where BD patients had greater GM concentrations than controls (217 subjects, nine experiments, and 49 locations). Higher WM concentrations in BD patients were not detected. We observed for BD reduced GM concentrations in the left medial frontal gyrus and right inferior/precentral gyri encompassing the insular cortex, and greater GM concentrations in the left putamen. Further, lower WM concentrations were detected in the left inferior longitudinal fasciculus, left superior corona radiata, and left posterior cingulum.
Conclusions
This meta‐analysis confirms deterioration of frontal and insular regions as already found in previous meta‐analysis. GM reductions in these regions could be related to emotional processing and decision making, which are typically impaired in BD. Moreover, we found abnormalities in precentral frontal areas and putamen that have been linked to more basic functions, which could point to sensory and specific cognitive deficits. Finally, WM reductions involved circuitry that may contribute to emotional dysregulation in BD.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Aetiological and clinical heterogeneity is increasingly recognized as a common characteristic of Alzheimer's disease and related dementias. This heterogeneity complicates diagnosis, treatment, and ...the design and testing of new drugs. An important line of research is discovery of multimodal biomarkers that will facilitate the targeting of subpopulations with homogeneous pathophysiological signatures. High-throughput 'omics' are unbiased data-driven techniques that probe the complex aetiology of Alzheimer's disease from multiple levels (e.g. network, cellular, and molecular) and thereby account for pathophysiological heterogeneity in clinical populations. This review focuses on data reduction analyses that identify complementary disease-relevant perturbations for three omics techniques: neuroimaging-based subtypes, metabolomics-derived metabolite panels, and genomics-related polygenic risk scores. Neuroimaging can track accrued neurodegeneration and other sources of network impairments, metabolomics provides a global small-molecule snapshot that is sensitive to ongoing pathological processes, and genomics characterizes relatively invariant genetic risk factors representing key pathways associated with Alzheimer's disease. Following this focused review, we present a roadmap for assembling these multiomics measurements into a diagnostic tool highly predictive of individual clinical trajectories, to further the goal of personalized medicine in Alzheimer's disease.
Aging is associated with structural alterations in many regions of the brain. Monitoring these changes contributes to increasing our understanding of the brain's morphological alterations across its ...lifespan, and could allow the identification of departures from canonical trajectories. Here, we introduce a novel and unique patch-based grading procedure for estimating a synthetic estimate of cortical aging in cognitively intact individuals. The cortical age metric is computed based on image similarity between an unknown (test) cortical label and known (training) cortical labels using machine learning algorithms. The proposed method was trained on a dataset of 100 cognitively intact individuals aged 19–61 years, within the 31 bilateral cortical labels of the Desikan-Killiany-Tourville parcellation, then tested on an independent test set of 78 cognitively intact individuals spanning a similar age range. The proposed patch-based framework yielded a R2 = 0.94, as well as a mean absolute error of 1.66 years, which compared favorably to the literature. These experimental results demonstrate that the proposed patch-based grading framework is a reliable and robust method to estimate brain age from image data, even with a limited training size.
•We presented a novel and unique patch-based framework for estimating brain age in cognitively intact individuals.•We assessed the efficiency of this patch-based metric against a region-wise metric.•The patch-based technique demonstrated a superior performance to state-of-the-art techniques for estimating brain age.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Alzheimer's disease is a complex, multi-factorial, and multi-parametric neurodegenerative etiology. Mathematical models can help understand such a complex problem by providing a way to explore and ...conceptualize principles, merging biological knowledge with experimental data into a model amenable to simulation and external validation, all without the need for extensive clinical trials. We performed a scoping review of mathematical models describing the onset and evolution of Alzheimer's disease as a result of biophysical factors following the PRISMA standard. Our search strategy applied to the PubMed database yielded 846 entries. After using our exclusion criteria, only 17 studies remained from which we extracted data, which focused on three aspects of mathematical modeling: how authors addressed continuous time (since even when the measurements are punctual, the biological processes underlying Alzheimer's disease evolve continuously), how models were solved, and how the high dimensionality and non-linearity of models were managed. Most articles modeled Alzheimer's disease at the cellular level, operating on a short time scale (e.g., minutes or hours), i.e., the micro view (12/17); the rest considered regional or brain-level processes with longer timescales (e.g., years or decades) (the macro view). Most papers were concerned primarily with amyloid beta (
= 8), few described both amyloid beta and tau proteins (
= 3), while some considered more than these two factors (
= 6). Models used partial differential equations (
= 3), ordinary differential equations (
= 7), and both partial differential equations and ordinary differential equations (
= 3). Some did not specify their mathematical formalism (
= 4). Sensitivity analyses were performed in only a small number of papers (4/17). Overall, we found that only two studies could be considered valid in terms of parameters and conclusions, and two more were partially valid. This puts the majority (
= 13) as being either invalid or with insufficient information to ascertain their status. This was the main finding of our paper, in that serious shortcomings make their results invalid or non-reproducible. These shortcomings come from insufficient methodological description, poor calibration, or the impossibility of experimentally validating or calibrating the model. Those shortcomings should be addressed by future authors to unlock the usefulness of mathematical models in Alzheimer's disease.
Studies using resting-state functional magnetic resonance imaging (rsfMRI) are increasingly collecting data at multiple sites in order to speed up recruitment or increase sample size. The main ...objective of this study was to assess the long-term consistency of rsfMRI connectivity maps derived at multiple sites and vendors using the Canadian Dementia Imaging Protocol (CDIP, www.cdip-pcid.ca). Nine to 10 min of functional BOLD images were acquired from an adult cognitively healthy volunteer scanned repeatedly at 13 Canadian sites on three scanner makes (General Electric, Philips and Siemens) over the course of 2.5 years. The consistency (spatial Pearson’s correlation) of rsfMRI connectivity maps for seven canonical networks ranged from 0.3 to 0.8, with a negligible effect of time, but significant site and vendor effects. We noted systematic differences in data quality (i.e. head motion, number of useable time frames, temporal signal-to-noise ratio) across vendors, which may also confound some of these results, and could not be disentangled in this sample. We also pooled the long-term longitudinal data with a single-site, short-term (1 month) data sample acquired on 26 subjects (10 scans per subject), called HNU1. Using randomly selected pairs of scans from each subject, we quantified the ability of a data-driven unsupervised cluster analysis to match two scans of the same subjects. In this “fingerprinting” experiment, we found that scans from the Canadian subject (Csub) could be matched with high accuracy intra-site (>95% for some networks), but that the accuracy decreased substantially for scans drawn from different sites and vendors, even falling outside of the range of accuracies observed in HNU1. Overall, our results demonstrate good multivariate stability of rsfMRI measures over several years, but substantial impact of scanning site and vendors. How detrimental these effects are will depend on the application, yet our results demonstrate that new methods for harmonizing multisite analysis represent an important area for future work.
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•Consistency of rsfMRI connectivity over 2.5 years, 13 sites and 3 scanner vendors.•Time elapsed between scans had negligible effect on consistency.•Consistency decreased due to site and vendor differences.•Accuracy of connectivity fingerprints decreased due to site and vendor differences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Identifying early signs of neurodegeneration due to Alzheimer's disease (AD) is a necessary first step towards preventing cognitive decline. Individual cortical thickness measures, available after ...processing anatomical magnetic resonance imaging (MRI), are sensitive markers of neurodegeneration. However, normal aging cortical decline and high inter-individual variability complicate the comparison and statistical determination of the impact of AD-related neurodegeneration on trajectories. In this paper, we computed trajectories in a 2D representation of a 62-dimensional manifold of individual cortical thickness measures. To compute this representation, we used a novel, nonlinear dimension reduction algorithm called Uniform Manifold Approximation and Projection (UMAP). We trained two embeddings, one on cortical thickness measurements of 6237 cognitively healthy participants aged 18-100 years old and the other on 233 mild cognitively impaired (MCI) and AD participants from the longitudinal database, the Alzheimer's Disease Neuroimaging Initiative database (ADNI). Each participant had multiple visits (Formula: see text), one year apart. The first embedding's principal axis was shown to be positively associated (Formula: see text) with participants' age. Data from ADNI is projected into these 2D spaces. After clustering the data, average trajectories between clusters were shown to be significantly different between MCI and AD subjects. Moreover, some clusters and trajectories between clusters were more prone to host AD subjects. This study was able to differentiate AD and MCI subjects based on their trajectory in a 2D space with an AUC of 0.80 with 10-fold cross-validation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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