A novel method for PET connectomics guided by fibre-tracking MRI: Application to Alzheimer's disease.

This study introduces a novel brain connectome matrix, track-weighted PET connectivity (twPC) matrix, which combines positron emission tomography (PET) and diffusion magnetic resonance imaging data to compute a PET-weighted connectome at the individual subject level. The new method is applied to characterise connectivity changes in the Alzheimer's disease (AD) continuum. The proposed twPC samples PET tracer uptake guided by the underlying white matter fibre-tracking streamline point-to-point connectivity calculated from diffusion MRI (dMRI). Using tau-PET, dMRI and T1-weighted MRI from the Alzheimer's Disease Neuroimaging Initiative database, structural connectivity (SC) and twPC matrices were computed and analysed using the network-based statistic (NBS) technique to examine topological alterations in early mild cognitive impairment (MCI), late MCI and AD participants. Correlation analysis was also performed to explore the coupling between SC and twPC. The NBS analysis revealed progressive topological alterations in both SC and twPC as cognitive decline progressed along the continuum. Compared to healthy controls, networks with decreased SC were identified in late MCI and AD, and networks with increased twPC were identified in early MCI, late MCI and AD. The altered network topologies were mostly different between twPC and SC, although with several common edges largely involving the bilateral hippocampus, fusiform gyrus and entorhinal cortex. Negative correlations were observed between twPC and SC across all subject groups, although displaying an overall reduction in the strength of anti-correlation with disease progression. twPC provides a new means for analysing subject-specific PET and MRI-derived information within a hybrid connectome using established network analysis methods, providing valuable insights into the relationship between structural connections and molecular distributions. PRACTITIONER POINTS: New method is proposed to compute patient-specific PET connectome guided by MRI fibre-tracking. Track-weighted PET connectivity (twPC) matrix allows to leverage PET and structural connectivity information. twPC was applied to dementia, to characterise the PET nework abnormalities in Alzheimer's disease and mild cognitive impairment.

Building a tissue-unbiased brain template of fiber orientation distribution and tractography with multimodal registration.

PURPOSE: Brain templates provide an essential standard space for statistical analysis of brain structure and function. Despite recent advances, diffusion MRI still lacks a template of fiber orientation distribution (FOD) and tractography that is unbiased for both white and gray matter. Therefore, we aim to build up a set of such templates for better white-matter analysis and joint structural and functional analysis. METHODS: We have developed a multimodal registration method to leverage the complementary information captured by T1 -weighted, T2 -weighted, and diffusion MRI, so that a coherent transformation is generated to register FODs into a common space and average them into a template. Consequently, the anatomically constrained fiber-tracking method was applied to the FOD template to generate a tractography template. Fiber-centered functional connectivity analysis was then performed as an example of the benefits of such an unbiased template. RESULTS: Our FOD template preserves fine structural details in white matter and also, importantly, clear folding patterns in the cortex and good contrast in the subcortex. Quantitatively, our templates show better individual-template agreement at the whole-brain scale and segmentation scale. The tractography template aligns well with the gray matter, which led to fiber-centered functional connectivity showing high cross-group consistency. CONCLUSION: We have proposed a novel methodology for building a tissue-unbiased FOD and anatomically constrained tractography template based on multimodal registration. Our templates provide a standard space and statistical platform for not only white-matter analysis but also joint structural and functional analysis, therefore filling an important gap in multimodal neuroimage analysis.

Network communication models narrow the gap between the modular organization of structural and functional brain networks.

Structural and functional brain networks are modular. Canonical functional systems, such as the default mode network, are well-known modules of the human brain and have been implicated in a large number of cognitive, behavioral and clinical processes. However, modules delineated in structural brain networks inferred from tractography generally do not recapitulate canonical functional systems. Neuroimaging evidence suggests that functional connectivity between regions in the same systems is not always underpinned by anatomical connections. As such, direct structural connectivity alone would be insufficient to characterize the functional modular organization of the brain. Here, we demonstrate that augmenting structural brain networks with models of indirect (polysynaptic) communication unveils a modular network architecture that more closely resembles the brain's established functional systems. We find that diffusion models of polysynaptic connectivity, particularly communicability, narrow the gap between the modular organization of structural and functional brain networks by 20-60%, whereas routing models based on single efficient paths do not improve mesoscopic structure-function correspondence. This suggests that functional modules emerge from the constraints imposed by local network structure that facilitates diffusive neural communication. Our work establishes the importance of modeling polysynaptic communication to understand the structural basis of functional systems.

Gradual changes in microarchitectural properties of cortex and juxtacortical white matter: Observed by anatomical and diffusion MRI.

PURPOSE: Characterization of cerebral cortex is challenged by the complexity and heterogeneity of its cyto- and myeloarchitecture. This study evaluates quantitative MRI metrics, measured across two cortical depths and in subcortical white matter (WM) adjacent to cortex (juxtacortical WM), indicative of myelin content, neurite density, and diffusion microenvironment, for a comprehensive characterization of cortical microarchitecture. METHODS: High-quality structural and diffusion MRI data (N = 30) from the Human Connectome Project were processed to compute myelin index, neurite density index, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from superficial cortex, deep cortex, and juxtacortical WM. The distributional patterns of these metrics were analyzed individually, correlated to one another, and were compared to established parcellations. RESULTS: Our results supported that myeloarchitectonic and the coexisting cytoarchitectonic structures influence the diffusion properties of water molecules residing in cortex. Full cortical thickness showed myelination patterns similar to those previously observed in humans. Higher myelin indices with similar distributional patterns were observed in deep cortex whereas lower myelin indices were observed in superficial cortex. Neurite density index and other diffusion MRI derived parameters provided complementary information to myelination. Reliable and reproducible correlations were identified among the cortical microarchitectural properties and fiber distributional patterns in proximal WM structures. CONCLUSION: We demonstrated gradual changes across the cortical sheath by assessing depth-specific cortical micro-architecture using anatomical and diffusion MRI. Mutually independent but coexisting features of cortical layers and juxtacortical WM provided new insights towards structural organizational units and variabilities across cortical regions and through depth.

Individual deviations from normative models of brain structure in a large cross-sectional schizophrenia cohort.

The heterogeneity of schizophrenia has defied efforts to derive reproducible and definitive anatomical maps of structural brain changes associated with the disorder. We aimed to map deviations from normative ranges of brain structure for individual patients and evaluate whether the loci of individual deviations recapitulated group-average brain maps of schizophrenia pathology. For each of 48 white matter tracts and 68 cortical regions, normative percentiles of variation in fractional anisotropy (FA) and cortical thickness (CT) were established using diffusion-weighted and structural MRI from healthy adults (n = 195). Individuals with schizophrenia (n = 322) were classified as either within the normative range for healthy individuals of the same age and sex (5-95% percentiles), infra-normal (<5% percentile) or supra-normal (>95% percentile). Repeating this classification for each tract and region yielded a deviation map for each individual. Compared to the healthy comparison group, the schizophrenia group showed widespread reductions in FA and CT, involving virtually all white matter tracts and cortical regions. Paradoxically, however, no more than 15-20% of patients deviated from the normative range for any single tract or region. Furthermore, 79% of patients showed infra-normal deviations for at least one locus (healthy individuals: 59 ± 2%, p < 0.001). Thus, while infra-normal deviations were common among patients, their anatomical loci were highly inconsistent between individuals. Higher polygenic risk for schizophrenia associated with a greater number of regions with infra-normal deviations in CT (r = -0.17, p = 0.006). We conclude that anatomical loci of schizophrenia-related changes are highly heterogeneous across individuals to the extent that group-consensus pathological maps are not representative of most individual patients. Normative modeling can aid in parsing schizophrenia heterogeneity and guiding personalized interventions.

A robust framework for characterising diffusion metrics of the median and ulnar nerves: Exploiting state-of-the-art tracking methods.

Diffusion-weighted imaging has been used to quantify peripheral nerve properties; however, traditional post-processing techniques have several limitations. Advanced neuroimaging techniques, which overcome many of these limitations, have not been applied to peripheral nerves. Here, we use state-of-the-art diffusion analysis tools to reconstruct the median and ulnar nerves and quantify their diffusion properties. Diffusion-weighted MRI scans were obtained from eight healthy adult subjects. Constrained spherical deconvolution was combined with probabilistic fibre tracking to compute track-weighted fibre orientation distribution (TW-FOD). The tensor was computed and used along with the tracks to estimate TW apparent diffusion coefficient (TW-ADC), TW fractional anisotropy (TW-FA), TW axial diffusivity (TW-AD), and TW radial diffusivity (TW-RD). Variability of TW measurements was used to estimate power size information. The population intersession mean (± SD) measurements for the median nerve were TW-FOD 1.30 (±0.17), TW-ADC 1.16 (±0.13) × 10-3  mm2 /s, TW-FA 0.60 (±0.05), TW-AD 2.05 (±0.16) × 10-3  mm2 /s, and TW-RD 0.72 (±0.12) × 10-3  mm2 /s. The corresponding measurements for the ulnar nerve were TW-FOD 1.25 (±0.14), TW-ADC 1.13 (±0.10) × 10-3  mm2 /s, TW-FA 0.56 (±0.06), TW-AD 1.93 (±0.01) × 10-3  mm2 /s, and TW-RD 0.74 (±0.12) × 10-3  mm2 /s. Based on these measurements, a sample size of 37 would be sufficient to detect a 10% difference in any of the measured TW metrics. A sample size of 20 would be large enough to detect within-subject differences as small as 2.9% (TW-AD, ulnar nerve) and between-subject differences as small as 3.8% (TW-AD, ulnar nerve).

IVIM-DKI for differentiation between prostate cancer and benign prostatic hyperplasia: comparison of 1.5 T vs. 3 T MRI.

OBJECTIVE: To implement an advanced spatial penalty-based reconstruction to constrain the intravoxel incoherent motion (IVIM)-diffusion kurtosis imaging (DKI) model and investigate whether it provides a suitable alternative at 1.5 T to the traditional IVIM-DKI model at 3 T for clinical characterization of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Thirty-two patients with biopsy-proven PCa were recruited for MRI examination (n = 16 scanned at 1.5 T, n = 16 scanned at 3 T). Diffusion-weighted imaging (DWI) with 13 b values (b = 0 to 2000 s/mm2 up to 3 averages, 1.5 T: TR = 5.774 s, TE = 81 ms and 3 T: TR = 4.899 s, TE = 100 ms), T2-weighted, and T1-weighted imaging were used on the 1.5 T and 3 T MRI scanner, respectively. The IVIM-DKI signal was modeled using the traditional IVIM-DKI model and a novel model in which the total variation (TV) penalty function was combined with the traditional model to optimize non-physiological variations. Paired and unpaired t-tests were used to compare intra-scanner and scanner group differences in IVIM-DKI parameters obtained using the novel and the traditional models. Analysis of variance with post hoc test and receiver operating characteristic (ROC) curve analysis were used to assess the ability of parameters obtained using the novel model (at 1.5 T) and the traditional model (at 3 T) to characterize prostate lesions. RESULTS: IVIM-DKI modeled using novel model with TV spatial penalty function at 1.5 T, produced parameter maps with 50-78% lower coefficient of variation (CV) than traditional model at 3 T. Novel model estimated higher D with lower D*, f and k values at both field strengths compared to traditional model. For scanner differences, the novel model at 1.5 T estimated lower D* and f values as compared to traditional model at 3 T. At 1.5 T, D and f values were significantly lower with k values significantly higher in tumor than BPH and healthy tissue. D (AUC: 0.98), f (AUC: 0.82), and k (AUC: 0.91) parameters estimated using novel model showed high diagnostic performance in cancer lesion detection at 1.5 T. DISCUSSION: In comparison with the IVIM-DKI model at 3 T, IVIM-DKI signal modeled with the TV penalty function at 1.5 T showed lower estimation errors. The proposed novel model can be utilized for improved detection of prostate lesions.

Automated Perfusion-Diffusion Magnetic Resonance Imaging in Childhood Arterial Ischemic Stroke.

Background and Purpose: Recent studies using automated perfusion imaging software have identified adults most likely to benefit from reperfusion therapies in extended time windows. The time course of penumbral tissue is poorly characterized in childhood arterial ischemic stroke (AIS). We explore the feasibility of using automated perfusion-diffusion imaging software to characterize penumbra in childhood AIS. Methods: An observational cohort study of children with acute unilateral AIS presenting to our institution. Diffusion-weighted imaging and dynamic susceptibility contrast perfusion magnetic resonance imaging performed within 72 hours of symptom onset were necessary for inclusion. Perfusion-diffusion mismatch was estimated using RAPID software. Ischemic core was defined as apparent diffusion coefficient <620×10−6 mm2/s and hypoperfusion as Tmax >6 seconds. Favorable mismatch profile was defined as core volume <70 mL, mismatch volume ≥15 mL, and a mismatch ratio ≥1.8. Results: Twenty-nine children (median 8 years old, interquartile range, 4.4­14.6) were included (26 unilateral middle cerebral artery and 3 unilateral cerebellar infarcts). Median Pediatric National Institutes of Health Stroke Scale was 4 (interquartile range, 3­11). Most cases had cryptogenic (n=11) or focal cerebral arteriopathy (n=9) causes. Median time-to-imaging =13.7 hours (interquartile range, 7.5­25.3). RAPID detected an ischemic core in 19 (66%) patients. In the remaining cases, the mean apparent diffusion coefficient values were mostly higher than the threshold as the majority of these presentations were delayed (median >21 hours) and infarct volumes were small (<3.5 mL). Overall, 3 children, imaged at 3.75, 11, and 23.5 hours had favorable mismatch profiles. Conclusions: This study demonstrates it is feasible to rapidly assess perfusion-diffusion mismatch in childhood AIS using automated software. Favorable mismatch profiles, using adult-based parameters, persisted beyond the standard 4.5 hours window for thrombolysis, suggesting potential therapeutic benefit of RAPID use. Further work is required to determine the utility of perfusion-based imaging to guide clinical decision making, whether adult thresholds require modification in childhood AIS, and to investigate the effect of time-delay and cause on mismatch characteristics.

Characterisation of white matter asymmetries in the healthy human brain using diffusion MRI fixel-based analysis.

The diffusion tensor model for diffusion MRI has been used extensively to study asymmetry in the human brain white matter. However, given the limitations of the tensor model, the nature of any underlying asymmetries remains uncertain, particularly in crossing fibre regions. Here, we provide a more robust characterisation of human brain white matter asymmetries based on fibre-specific diffusion MRI metrics and a whole-brain data-driven approach. We used high-quality diffusion MRI data (n = 100) from the Human Connectome Project, the spherical deconvolution model for fibre orientation distribution estimation, and the Fixel-Based Analysis framework to utilise crossing fibre information in registration, data smoothing and statistical inference. We found many significant asymmetries, widespread throughout the brain white matter, with both left>right and right>left dominances observed in different pathways. No influences of sex, age, or handedness on asymmetry were found. We also report on the relative contributions of microstructural and morphological white matter properties toward the asymmetry findings. Our findings should provide important information to future studies focussing on how these asymmetries are affected by disease, development/ageing, or how they correlate to functional/cognitive measures.

TractLearn: A geodesic learning framework for quantitative analysis of brain bundles.

Deep learning-based convolutional neural networks have recently proved their efficiency in providing fast segmentation of major brain fascicles structures, based on diffusion-weighted imaging. The quantitative analysis of brain fascicles then relies on metrics either coming from the tractography process itself or from each voxel along the bundle. Statistical detection of abnormal voxels in the context of disease usually relies on univariate and multivariate statistics models, such as the General Linear Model (GLM). Yet in the case of high-dimensional low sample size data, the GLM often implies high standard deviation range in controls due to anatomical variability, despite the commonly used smoothing process. This can lead to difficulties to detect subtle quantitative alterations from a brain bundle at the voxel scale. Here we introduce TractLearn, a unified framework for brain fascicles quantitative analyses by using geodesic learning as a data-driven learning task. TractLearn allows a mapping between the image high-dimensional domain and the reduced latent space of brain fascicles using a Riemannian approach. We illustrate the robustness of this method on a healthy population with test-retest acquisition of multi-shell diffusion MRI data, demonstrating that it is possible to separately study the global effect due to different MRI sessions from the effect of local bundle alterations. We have then tested the efficiency of our algorithm on a sample of 5 age-matched subjects referred with mild traumatic brain injury. Our contributions are to propose: 1/ A manifold approach to capture controls variability as standard reference instead of an atlas approach based on a Euclidean mean. 2/ A tool to detect global variation of voxels' quantitative values, which accounts for voxels' interactions in a structure rather than analyzing voxels independently. 3/ A ready-to-plug algorithm to highlight nonlinear variation of diffusion MRI metrics. With this regard, TractLearn is a ready-to-use algorithm for precision medicine.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

Increased cerebral blood flow with increased amyloid burden in the preclinical phase of alzheimer's disease.

BACKGROUND: Arterial spin labeling (ASL) is an emerging MRI technique for noninvasive measurement of cerebral blood flow (CBF) that has been used to show hemodynamic changes in the brains of people with Alzheimer's disease (AD). CBF changes have been measured using positron emission tomography (PET) across the AD spectrum, but ASL showed limited success in measuring CBF variations in the preclinical phase of AD, where amyloid ß (Aß) plaques accumulate in the decades prior to symptom onset. PURPOSE: To investigate the relationship between CBF measured by multiphase-pseudocontinuous-ASL (MP-PCASL) and Aß burden as measured by 11 C-PiB PET imaging in a study of cognitively normal (CN) subjects age over 65. STUDY TYPE: Cross-sectional. POPULATION: Forty-six CN subjects including 33 with low levels of Aß burden and 13 with high levels of Aß. FIELD STRENGTH/SEQUENCE: 3T/3D MP-PCASL. ASSESSMENT: The MP-PCASL method was chosen because it has a high signal-to-noise ratio. Furthermore, the data were analyzed using an efficient processing pipeline consisting of motion correction, ASL motion correction imprecision removal, temporal and spatial filtering, and partial volume effect correction. STATISTICAL TESTS: General Linear Model. RESULTS: In CN subjects positive for Aß burden (n = 13), we observed a positive correlation between CBF and Aß burden in the hippocampus, amygdala, caudate (P < 0.01), frontal, temporal, and insula (P < 0.05). DATA CONCLUSION: To the best of our knowledge, this is the first study using MP-PCASL in the study of AD, and the results suggest a potential compensatory hemodynamic mechanism that protects against pathology in the early stages of AD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:505-513.

Multi-stage automated local arterial input function selection in perfusion MRI.

OBJECTIVE: Cerebral blood flow (CBF) quantification using dynamic-susceptibility contrast MRI can be achieved via model-independent deconvolution, with local arterial input function (AIF) deconvolution methods identifying multiple arterial regions with unique corresponding arterial input functions. The clinical application of local AIF methods necessitates an efficient and fully automated solution. To date, such local AIF methods have relied on the computation of a singular surrogate measure of bolus arrival time or custom arterial scoring functions to infer vascular supply origins. This paper aims to introduce a new local AIF method that alternatively utilises a multi-stage approach to perform AIF selection. MATERIAL AND METHODS: A fully automated, multi-stage local AIF method is proposed, leveraging both signal-based cluster analysis and priority flooding to define arterial regions and their corresponding vascular supply origins. The introduced method was applied to data from four patients with cerebrovascular disease who showed significant artefacts when using a prevailing automated local AIF method. RESULTS: The immediately apparent image artefacts found using the pre-existing method due to poor AIF selection were found to be absent when using the proposed method. CONCLUSION: The results suggest the proposed solution provides a more robust approach to perfusion quantification than currently available fully automated local AIF methods.

Connectomes from streamlines tractography: Assigning streamlines to brain parcellations is not trivial but highly consequential.

When using diffusion MRI streamlines tractograms to construct structural connectomes, ideally, each streamline should connect exactly 2 regions-of-interest (i.e. network nodes) as defined by a given brain parcellation scheme. However, the ill-posed nature of termination criteria in many tractography algorithms can cause streamlines apparently being associated with zero, one, or more than two grey matter (GM) nodes; streamlines that terminate in white matter or cerebrospinal fluid may even end up being assigned to nodes if the definitions of these nodes are not strictly constrained to genuine GM areas, resulting in a misleading connectome in non-trivial ways. Based on both in-house MRI data and state-of-the-art data provided by the Human Connectome Project, this study investigates the actual influence of streamline-to-node assignment methods, and their interactions with fibre-tracking terminations and brain parcellations, on the construction of pairwise regional connectivity and subsequent connectomic measures. Our results show that the frequency of generating successful pairwise connectivity is heavily affected by the convoluted interactions between the applied strategies for connectome construction, and that minor changes in the mechanism can cause significant variations in the within- and between-module connectivity strengths as well as in the commonly-used graph theory metrics. Our data suggest that these fundamental processes should not be overlooked in structural connectomics research, and that improved data quality is not in itself sufficient to solve the underlying problems associated with assigning streamlines to brain nodes. We demonstrate that the application of advanced fibre-tracking techniques that are designed to correct for inaccuracies of track terminations with respect to anatomical information at the fibre-tracking stage is advantageous to the subsequent connectome construction process, in which pairs of parcellation nodes can be more robustly identified from streamline terminations via a suitable assignment mechanism.

Is removal of weak connections necessary for graph-theoretical analysis of dense weighted structural connectomes from diffusion MRI?

Recent advances in diffusion MRI tractography permit the generation of dense weighted structural connectomes that offer greater insight into brain organization. However, these efforts are hampered by the lack of consensus on how to extract topological measures from the resulting graphs. Here we evaluate the common practice of removing the graphs' weak connections, which is primarily intended to eliminate spurious connections and emphasize strong connections. Because this processing step requires arbitrary or heuristic-based choices (e.g., setting a threshold level below which connections are removed), and such choices might complicate statistical analysis and inter-study comparisons, in this work we test whether removing weak connections is indeed necessary. To this end, we systematically evaluated the effect of removing weak connections on a range of popular graph-theoretical metrics. Specifically, we investigated if (and at what extent) removal of weak connections introduces a statistically significant difference between two otherwise equal groups of healthy subjects when only applied to one of the groups. Using data from the Human Connectome Project, we found that removal of weak connections had no statistical effect even when removing the weakest ∼70-90% connections. Removing yet a larger extent of weak connections, thus reducing connectivity density even further, did produce a predictably significant effect. However, metric values became sensitive to the exact connectivity density, which has ramifications regarding the stability of the statistical analysis. This pattern persisted whether connections were removed by connection strength threshold or connectivity density, and for connectomes generated using parcellations at different resolutions. Finally, we showed that the same pattern also applies for data from a clinical-grade MRI scanner. In conclusion, our analysis revealed that removing weak connections is not necessary for graph-theoretical analysis of dense weighted connectomes. Because removal of weak connections provides no practical utility to offset the undesirable requirement for arbitrary or heuristic-based choices, we recommend that this step is avoided in future studies.

Robust Identification of Rich-Club Organization in Weighted and Dense Structural Connectomes.

The human brain is a complex network, in which some brain regions, denoted as 'hub' regions, play critically important roles. Some of these hubs are highly interconnected forming a rich-club organization, which has been identified based on the degree metric from structural connectomes constructed using diffusion tensor imaging (DTI)-based fiber tractography. However, given the limitations of DTI, the yielded structural connectomes are largely compromised, possibly affecting the characterization of rich-club organizations. Recent progress in diffusion MRI and fiber tractography now enable more reliable but also very dense structural connectomes to be achieved. However, while the existing rich-club analysis method is based on weighted networks, it is essentially built upon degree metric and, therefore, not suitable for identifying rich-club organizations from such dense networks, as it yields nodes with indistinguishably high degrees. Therefore, we propose a novel method, i.e. Rich-club organization Identification using Combined H-degree and Effective strength to h-degree Ratio (RICHER), to identify rich-club organizations from dense weighted networks. Overall, it is shown that more robust rich-club organizations can be achieved using our proposed framework (i.e., state-of-the-art fiber tractography approaches and our proposed RICHER method) in comparison to the previous method focusing on weighted networks based on degree, i.e., RC-degree. Furthermore, by simulating network attacks in 3 ways, i.e., attack to non-rich-club/non-rich-club edges (NRC2NRC), rich-club/non-rich-club edges (RC2NRC), and rich-club/rich-club edges (RC2RC), brain network damage consequences have been evaluated in terms of global efficiency (GE) reductions. As expected, significant GE reductions have been detected using our proposed framework among conditions, i.e., NRC2NRC < RC2NRC, NRC2NRC < RC2RC and RC2NRC < RC2RC, which however have not been detected otherwise.

Effect of combination and number of b values in IVIM analysis with post-processing methodology: simulation and clinical study.

OBJECTIVE: To investigate the effect of number and combination of b values used on the accuracy of estimated Intravoxel Incoherent Motion (IVIM) parameters using simulation and clinical data. MATERIALS AND METHODS: Simulations with seven combinations of b values were performed for 4, 6, 8, and 13 numbers of b values with six different values of D, D*, and f parameters. Two methodologies were implemented for IVIM analysis: standard biexponential model (BE) and biexponential model with total variation penalty function (BE + TV). Clinical data set of six patients with prostate cancer was retrospectively analyzed using 4, 8, and 13 b values. RESULTS: BE + TV method showed lesser error and lower variability in simulation and clinical data, respectively. 8 and 13 b values showed good agreement in the values of parameters estimated with high correlation coefficient (ρ = 0.83-0.93). Clinical data showed high spurious noise with lower b values [4 b values leading to high coefficient of variation (CV); however, substantially, lower CV was observed with 8 and 13 b values]. DISCUSSION: BE model with TV penalty function is robust to combination of b values used for IVIM analysis. Combination of 8 b values provided a reasonably good accuracy in IVIM parameters.

The role of whole-brain diffusion MRI as a tool for studying human in vivo cortical segregation based on a measure of neurite density.

PURPOSE: To investigate whether diffusion MRI can be used to study cortical segregation based on a contrast related to neurite density, thus providing a complementary tool to myelin-based MRI techniques used for myeloarchitecture. METHODS: Several myelin-sensitive MRI methods (e.g., based on T1 , T2 , and T2*) have been proposed to parcellate cortical areas based on their myeloarchitecture. Recent improvements in hardware, acquisition, and analysis methods have opened the possibility of achieving a more robust characterization of cortical microstructure using diffusion MRI. High-quality diffusion MRI data from the Human Connectome Project was combined with recent advances in fiber orientation modeling. The orientational average of the fiber orientation distribution was used as a summary parameter, which was displayed as inflated brain surface views. RESULTS: Diffusion MRI identifies cortical patterns consistent with those previously seen by MRI methods used for studying myeloarchitecture, which have shown patterns of high myelination in the sensorimotor strip, visual cortex, and auditory areas and low myelination in frontal and anterior temporal areas. CONCLUSION: In vivo human diffusion MRI provides a useful complementary noninvasive approach to myelin-based methods used to study whole-brain cortical parcellation, by exploiting a contrast based on tissue microstructure related to neurite density, rather than myelin itself. Magn Reson Med 79:2738-2744, 2018. © 2017 International Society for Magnetic Resonance in Medicine.