Free-breathing, fat-corrected T1 mapping of the liver with stack-of-stars MRI, and joint estimation of T1, PDFF, R 2 * , and B 1 + .

PURPOSE: Quantitative T1 mapping has the potential to replace biopsy for noninvasive diagnosis and quantitative staging of chronic liver disease. Conventional T1 mapping methods are confounded by fat and B 1 + $$ {B}_1^{+} $$ inhomogeneities, resulting in unreliable T1 estimations. Furthermore, these methods trade off spatial resolution and volumetric coverage for shorter acquisitions with only a few images obtained within a breath-hold. This work proposes a novel, volumetric (3D), free-breathing T1 mapping method to account for multiple confounding factors in a single acquisition. THEORY AND METHODS: Free-breathing, confounder-corrected T1 mapping was achieved through the combination of non-Cartesian imaging, magnetization preparation, chemical shift encoding, and a variable flip angle acquisition. A subspace-constrained, locally low-rank image reconstruction algorithm was employed for image reconstruction. The accuracy of the proposed method was evaluated through numerical simulations and phantom experiments with a T1/proton density fat fraction phantom at 3.0 T. Further, the feasibility of the proposed method was investigated through contrast-enhanced imaging in healthy volunteers, also at 3.0 T. RESULTS: The method showed excellent agreement with reference measurements in phantoms across a wide range of T1 values (200 to 1000 ms, slope = 0.998 (95% confidence interval (CI) [0.963 to 1.035]), intercept = 27.1 ms (95% CI [0.4 54.6]), r2 = 0.996), and a high level of repeatability. In vivo imaging studies demonstrated moderate agreement (slope = 1.099 (95% CI [1.067 to 1.132]), intercept = -96.3 ms (95% CI [-82.1 to -110.5]), r2 = 0.981) compared to saturation recovery-based T1 maps. CONCLUSION: The proposed method produces whole-liver, confounder-corrected T1 maps through simultaneous estimation of T1, proton density fat fraction, and B 1 + $$ {B}_1^{+} $$ in a single, free-breathing acquisition and has excellent agreement with reference measurements in phantoms.

Microstructural neural correlates of maximal grip strength in autistic children: the role of the cortico-cerebellar network and attention-deficit/hyperactivity disorder features.

Introduction: Maximal grip strength, a measure of how much force a person's hand can generate when squeezing an object, may be an effective method for understanding potential neurobiological differences during motor tasks. Grip strength in autistic individuals may be of particular interest due to its unique developmental trajectory. While autism-specific differences in grip-brain relationships have been found in adult populations, it is possible that such differences in grip-brain relationships may be present at earlier ages when grip strength is behaviorally similar in autistic and non-autistic groups. Further, such neural differences may lead to the later emergence of diagnostic-group grip differences in adolescence. The present study sought to examine this possibility, while also examining if grip strength could elucidate the neuro-motor sources of phenotypic heterogeneity commonly observed within autism. Methods: Using high resolution, multi-shell diffusion, and quantitative R1 relaxometry imaging, this study examined how variations in key sensorimotor-related white matter pathways of the proprioception input, lateral grasping, cortico-cerebellar, and corticospinal networks were associated with individual variations in grip strength in 68 autistic children and 70 non-autistic (neurotypical) children (6-11 years-old). Results: In both groups, results indicated that stronger grip strength was associated with higher proprioceptive input, lateral grasping, and corticospinal (but not cortico-cerebellar modification) fractional anisotropy and R1, indirect measures concordant with stronger microstructural coherence and increased myelination. Diagnostic group differences in these grip-brain relationships were not observed, but the autistic group exhibited more variability particularly in the cortico-cerebellar modification indices. An examination into the variability within the autistic group revealed that attention-deficit/hyperactivity disorder (ADHD) features moderated the relationships between grip strength and both fractional anisotropy and R1 relaxometry in the premotor-primary motor tract of the lateral grasping network and the cortico-cerebellar network tracts. Specifically, in autistic children with elevated ADHD features (60% of the autistic group) stronger grip strength was related to higher fractional anisotropy and R1 of the cerebellar modification network (stronger microstructural coherence and more myelin), whereas the opposite relationship was observed in autistic children with reduced ADHD features. Discussion: Together, this work suggests that while the foundational elements of grip strength are similar across school-aged autistic and non-autistic children, neural mechanisms of grip strength within autistic children may additionally depend on the presence of ADHD features. Specifically, stronger, more coherent connections of the cerebellar modification network, which is thought to play a role in refining and optimizing motor commands, may lead to stronger grip in children with more ADHD features, weaker grip in children with fewer ADHD features, and no difference in grip in non-autistic children. While future research is needed to understand if these findings extend to other motor tasks beyond grip strength, these results have implications for understanding the biological basis of neuromotor control in autistic children and emphasize the importance of assessing co-occurring conditions when evaluating brain-behavior relationships in autism.

Role of autonomic, nociceptive, and limbic brainstem nuclei in core autism features.

Although multiple theories have speculated about the brainstem reticular formation's involvement in autistic behaviors, the in vivo imaging of brainstem nuclei needed to test these theories has proven technologically challenging. Using methods to improve brainstem imaging in children, this study set out to elucidate the role of the autonomic, nociceptive, and limbic brainstem nuclei in the autism features of 145 children (74 autistic children, 6.0-10.9 years). Participants completed an assessment of core autism features and diffusion- and T1-weighted imaging optimized to improve brainstem images. After data reduction via principal component analysis, correlational analyses examined associations among autism features and the microstructural properties of brainstem clusters. Independent replication was performed in 43 adolescents (24 autistic, 13.0-17.9 years). We found specific nuclei, most robustly the parvicellular reticular formation-alpha (PCRtA) and to a lesser degree the lateral parabrachial nucleus (LPB) and ventral tegmental parabrachial pigmented complex (VTA-PBP), to be associated with autism features. The PCRtA and some of the LPB associations were independently found in the replication sample, but the VTA-PBP associations were not. Consistent with theoretical perspectives, the findings suggest that individual differences in pontine reticular formation nuclei contribute to the prominence of autistic features. Specifically, the PCRtA, a nucleus involved in mastication, digestion, and cardio-respiration in animal models, was associated with social communication in children, while the LPB, a pain-network nucleus, was associated with repetitive behaviors. These findings highlight the contributions of key autonomic brainstem nuclei to the expression of core autism features.

Neuroimaging of tissue microstructure as a marker of neurodegeneration in the AT(N) framework: defining abnormal neurodegeneration and improving prediction of clinical status.

BACKGROUND: Alzheimer's disease involves accumulating amyloid (A) and tau (T) pathology, and progressive neurodegeneration (N), leading to the development of the AD clinical syndrome. While several markers of N have been proposed, efforts to define normal vs. abnormal neurodegeneration based on neuroimaging have been limited. Sensitive markers that may account for or predict cognitive dysfunction for individuals in early disease stages are critical. METHODS: Participants (n = 296) defined on A and T status and spanning the AD-clinical continuum underwent multi-shell diffusion-weighted magnetic resonance imaging to generate Neurite Orientation Dispersion and Density Imaging (NODDI) metrics, which were tested as markers of N. To better define N, we developed age- and sex-adjusted robust z-score values to quantify normal and AD-associated (abnormal) neurodegeneration in both cortical gray matter and subcortical white matter regions of interest. We used general logistic regression with receiver operating characteristic (ROC) and area under the curve (AUC) analysis to test whether NODDI metrics improved diagnostic accuracy compared to models that only relied on cerebrospinal fluid (CSF) A and T status (alone and in combination). RESULTS: Using internal robust norms, we found that NODDI metrics correlate with worsening cognitive status and that NODDI captures early, AD neurodegenerative pathology in the gray matter of cognitively unimpaired, but A/T biomarker-positive, individuals. NODDI metrics utilized together with A and T status improved diagnostic prediction accuracy of AD clinical status, compared with models using CSF A and T status alone. CONCLUSION: Using a robust norms approach, we show that abnormal AD-related neurodegeneration can be detected among cognitively unimpaired individuals. Metrics derived from diffusion-weighted imaging are potential sensitive markers of N and could be considered for trial enrichment and as outcomes in clinical trials. However, given the small sample sizes, the exploratory nature of the work must be acknowledged.

How we get a grip: Microstructural neural correlates of manual grip strength in children.

Maximal grip strength is associated with a variety of health-related outcome measures and thus may be reflective of the efficiency of foundational brain-body communication. Non-human primate models of grip strength strongly implicate the cortical lateral grasping network, but little is known about the translatability of these models to human children. Further, it is unclear how supplementary networks that provide proprioceptive information and cerebellar-based motor command modification are associated with maximal grip strength. Therefore, this study employed high resolution, multi-shell diffusion and quantitative T1 imaging to examine how variations in lateral grasping, proprioception input, and cortico-cerebellar modification network white matter microstructure are associated with variations in grip strength across 70 children. Results indicated that stronger grip strength was associated with higher lateral grasping and proprioception input network fractional anisotropy and R1, indirect measures consistent with stronger microstructural coherence and increased myelination. No relationships were found in the cerebellar modification network. These results provide a neurobiological mechanism of grip behavior in children which suggests that increased myelination of cortical sensory and motor pathways is associated with stronger grip. This neurobiological mechanism may be a signature of pediatric neuro-motor behavior more broadly as evidenced by the previously demonstrated relationships between grip strength and behavioral outcome measures across a variety of clinical and non-clinical populations.

Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children.

BACKGROUND: Elevated or reduced responses to sensory stimuli, known as sensory features, are common in autistic individuals and often impact quality of life. Little is known about the neurobiological basis of sensory features in autistic children. However, the brainstem may offer critical insights as it has been associated with both basic sensory processing and core features of autism. METHODS: Diffusion-weighted imaging (DWI) and parent-report of sensory features were acquired from 133 children (61 autistic children with and 72 non-autistic children, 6-11 years-old). Leveraging novel DWI processing techniques, we investigated the relationship between sensory features and white matter microstructure properties (free-water-elimination-corrected fractional anisotropy [FA] and mean diffusivity [MD]) in precisely delineated brainstem white matter tracts. Follow-up analyses assessed relationships between microstructure and sensory response patterns/modalities and analyzed whole brain white matter using voxel-based analysis. RESULTS: Results revealed distinct relationships between brainstem microstructure and sensory features in autistic children compared to non-autistic children. In autistic children, more prominent sensory features were generally associated with lower MD. Further, in autistic children, sensory hyporesponsiveness and tactile responsivity were strongly associated with white matter microstructure in nearly all brainstem tracts. Follow-up voxel-based analyses confirmed that these relationships were more prominent in the brainstem/cerebellum, with additional sensory-brain findings in the autistic group in the white matter of the primary motor and somatosensory cortices, the occipital lobe, the inferior parietal lobe, and the thalamic projections. LIMITATIONS: All participants communicated via spoken language and acclimated to the sensory environment of an MRI session, which should be considered when assessing the generalizability of this work to the whole of the autism spectrum. CONCLUSIONS: These findings suggest unique brainstem white matter contributions to sensory features in autistic children compared to non-autistic children. The brainstem correlates of sensory features underscore the potential reflex-like nature of behavioral responses to sensory stimuli in autism and have implications for how we conceptualize and address sensory features in autistic populations.

Improving Imaging of the Brainstem and Cerebellum in Autistic Children: Transformation-Based High-Resolution Diffusion MRI (TiDi-Fused) in the Human Brainstem.

Diffusion-weighted magnetic resonance imaging (dMRI) of the brainstem is technically challenging, especially in young autistic children as nearby tissue-air interfaces and motion (voluntary and physiological) can lead to artifacts. This limits the availability of high-resolution images, which are desirable for improving the ability to study brainstem structures. Furthermore, inherently low signal-to-noise ratios, geometric distortions, and sensitivity to motion not related to molecular diffusion have resulted in limited techniques for high-resolution data acquisition compared to other modalities such as T1-weighted imaging. Here, we implement a method for achieving increased apparent spatial resolution in pediatric dMRI that hinges on accurate geometric distortion correction and on high fidelity within subject image registration between dMRI and magnetization prepared rapid acquisition gradient echo (MPnRAGE) images. We call this post-processing pipeline T1 weighted-diffusion fused, or "TiDi-Fused". Data used in this work consists of dMRI data (2.4 mm resolution, corrected using FSL's Topup) and T1-weighted (T1w) MPnRAGE anatomical data (1 mm resolution) acquired from 128 autistic and non-autistic children (ages 6-10 years old). Accurate correction of geometric distortion permitted for a further increase in apparent resolution of the dMRI scan via boundary-based registration to the MPnRAGE T1w. Estimation of fiber orientation distributions and further analyses were carried out in the T1w space. Data processed with the TiDi-Fused method were qualitatively and quantitatively compared to data processed with conventional dMRI processing methods. Results show the advantages of the TiDi-Fused pipeline including sharper brainstem gray-white matter tissue contrast, improved inter-subject spatial alignment for group analyses of dMRI based measures, accurate spatial alignment with histology-based imaging of the brainstem, reduced variability in brainstem-cerebellar white matter tracts, and more robust biologically plausible relationships between age and brainstem-cerebellar white matter tracts. Overall, this work identifies a promising pipeline for achieving high-resolution imaging of brainstem structures in pediatric and clinical populations who may not be able to endure long scan times. This pipeline may serve as a gateway for feasibly elucidating brainstem contributions to autism and other conditions.

Reduction of Motion Artifacts in Functional Connectivity Resulting from Infrequent Large Motion.

Introduction: Subject head motion is an ongoing challenge in functional magnetic resonance imaging, particularly in the estimation of functional connectivity. Infants (1-month old) scanned during nonsedated sleep often have occasional but large movements of several millimeters separated by periods with relatively little movement. This results in residual signal changes even after image realignment and can distort estimates of functional connectivity. A new motion correction technique, JumpCor, is introduced to reduce the effects of this motion and compared to other existing techniques. Methods: Different approaches for reducing residual motion artifacts after image realignment were compared both in actual and simulated data: JumpCor, regressing out the estimated subject motion, and regressing out the average white matter, cerebrospinal fluid (CSF), and global signals and their temporal derivatives. Results: Motion-related signal changes resulting from infrequent large motion were significantly reduced both by regressing out the estimated motion parameters and by JumpCor. Furthermore, JumpCor significantly reduced artifacts and improved the quality of functional connectivity estimates when combined with typical preprocessing approaches. Discussion: Motion-related signal changes resulting from occasional large motion can be effectively corrected using JumpCor and to a certain extent also by regressing out the estimated motion. This technique should reduce the data loss in studies where participants exhibit this type of motion, such as sleeping infants.

Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults.

INTRODUCTION: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. METHODS: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aß)42 /Aß40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. RESULTS: We observed a significant CSF Aß42 /Aß40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. DISCUSSION: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.

Edited magnetic resonance spectroscopy in the neonatal brain.

J-difference-edited spectroscopy is a valuable approach for the detection of low-concentration metabolites with magnetic resonance spectroscopy (MRS). Currently, few edited MRS studies are performed in neonates due to suboptimal signal-to-noise ratio, relatively long acquisition times, and vulnerability to motion artifacts. Nonetheless, the technique presents an exciting opportunity in pediatric imaging research to study rapid maturational changes of neurotransmitter systems and other metabolic systems in early postnatal life. Studying these metabolic processes is vital to understanding the widespread and rapid structural and functional changes that occur in the first years of life. The overarching goal of this review is to provide an introduction to edited MRS for neonates, including the current state-of-the-art in editing methods and editable metabolites, as well as to review the current literature applying edited MRS to the neonatal brain. Existing challenges and future opportunities, including the lack of age-specific reference data, are also discussed.

Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer's disease.

Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric-fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO-is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer's disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.

FreeSurfer based cortical mapping and T1-relaxometry with MPnRAGE: Test-retest reliability with and without retrospective motion correction.

A test-retest study of FreeSurfer derived cortical thickness, cortical surface area, and cortical volume, as well as quantitative R1 relaxometry assessed on the midpoint of the cortex, was performed on a cohort of pediatric subjects (6-12 years old) scanned without sedation using SNARE-MPnRAGE (self navigated retrospective motion corrected magnetization prepared with n rapid gradient echoes) imaging. Reliability was assessed with coefficients of variation (CoVs) and intraclass correlation coefficients (ICCs) and statistical tests were used to determine differences with and without SNARE motion correction. Comparison of the test-retest measures of SNARE-MPnRAGE with prospectively motion corrected PROMO MPRAGE were also performed. When SNARE motion correction was used all parameters had statistically significant improvements and demonstrated high reliability. Reliability varied depending on parameter, region, and measurement type (vertex or region of interest). For mean thickness/surface area/volume/mean R1 across the regions of FreeSurfer's DK Atlas, the mean CoVs (% x100) were (1.2/1.6/1.9/0.9) and the mean ICCs were (0.88/0.96/0.94/0.83). When assessed on a per-vertex basis, the CoVs and ICCs for thickness/R1 had mean values of (2.9/1.9) and (0.82/0.68) across the regions of the DK Atlas. Retrospectively motion corrected MPnRAGE had significantly lower CoVs and higher ICCs for the morphological measures than PROMO MPRAGE. Motion correction effectively removed motion related biases in nearly all regions for R1 and morphometric measures.

Three-dimensional motion-corrected T1 relaxometry with MPnRAGE.

PURPOSE: To test the performance of the MPnRAGE motion-correction algorithm on quantitative relaxometry estimates. METHODS: Twelve children (9.4 ± 2.6 years, min = 6.5 years, max = 13.8 years) were imaged 3 times in a session without sedation. Stabilization padding was not used for the second and third scans. Quantitative T1 values were estimated in each voxel on images reconstructed with and without motion correction. Mean T1 values were assessed in various regions determined from automated segmentation algorithms. Statistical tests were performed on mean values and the coefficient of variation across the measurements. Accuracy of T1 estimates were determined by scanning the High Precision Devices (Boulder, CO) MRI system phantom with the same protocol. RESULTS: The T1 values obtained with MPnRAGE agreed within 4% of the reference values of the High Precision Devices phantom. The best fit line was T1 (MPnRAGE) = 1.02 T1 (reference)-0.9 ms, R2  = 0.9999. For in vivo studies, motion correction reduced the coefficients of variation of mean T1 values in whole-brain tissue regions determined by FSL FAST by 74% ± 7%, and subcortical regions determined by FIRST and FreeSurfer by 32% ± 21% and 33% ± 26%, respectively. Across all participants, the mean coefficients of variation ranged from 0.8% to 2.0% for subcortical regions and 0.6% ± 0.5% for cortical regions when motion correction was applied. CONCLUSION: The MPnRAGE technique demonstrated highly accurate values in phantom measurements. When combined with retrospective motion correction, MPnRAGE demonstrated highly reproducible T1 values, even in participants who moved during the acquisition.

Test-retest of automated segmentation with different motion correction strategies: A comparison of prospective versus retrospective methods.

Test-retest of automated image segmentation algorithms (FSL FAST, FSL FIRST, and FREESURFER) are computed on magnetic resonance images from 12 unsedated children aged 9.4±2.6 years ([min,max] â€‹= â€‹[6.5 years, 13.8 years]) using different approaches to motion correction (prospective versus retrospective). The prospective technique, PROMO MPRAGE, dynamically estimates motion using specially acquired navigator images and adjusts the remaining acquisition accordingly, whereas the retrospective technique, MPnRAGE, uses a self-navigation property to retrospectively estimate and account for motion during image reconstruction. To increase the likelihood and range of motions, participants heads were not stabilized with padding during repeated scans. When motion was negligible both techniques had similar performance. When motion was not negligible, the automated image segmentation and anatomical labeling software tools showed the most consistent performance with the retrospectively corrected MPnRAGE technique (≥80% volume overlaps for 15 of 16 regions for FIRST and FREESURFER, with greater than 90% volume overlaps for 12 regions with FIRST and 11 regions with FREESURFER). Prospectively corrected MPRAGE with linear view-ordering also demonstrated lower performance than MPnRAGE without retrospective motion correction.

Optimizing the intrinsic parallel diffusivity in NODDI: An extensive empirical evaluation.

PURPOSE: NODDI is widely used in parameterizing microstructural brain properties. The model includes three signal compartments: intracellular, extracellular, and free water. The neurite compartment intrinsic parallel diffusivity (d∥) is set to 1.7 µm2⋅ms-1, though the effects of this assumption have not been extensively explored. This work investigates the optimality of d∥ = 1.7 µm2⋅ms-1 under varying imaging protocol, age groups, sex, and tissue type in comparison to other biologically plausible values of d∥. METHODS: Model residuals were used as the optimality criterion. The model residuals were evaluated in function of d∥ over the range from 0.5 to 3.0 µm2⋅ms-1. This was done with respect to tissue type (i.e., white matter versus gray matter), sex, age (infancy to late adulthood), and diffusion-weighting protocol (maximum b-value). Variation in the estimated parameters with respect to d∥ was also explored. RESULTS: Results show d∥ = 1.7 µm2⋅ms-1 is appropriate for adult brain white matter but it is suboptimal for gray matter with optimal values being significantly lower. d∥ = 1.7 µm2⋅ms-1 was also suboptimal in the infant brain for both white and gray matter with optimal values being significantly lower. Minor optimum d∥ differences were observed versus diffusion protocol. No significant sex effects were observed. Additionally, changes in d∥ resulted in significant changes to the estimated NODDI parameters. CONCLUSION: The default (d∥) of 1.7 µm2⋅ms-1 is suboptimal in gray matter and infant brains.

Topographic organization of connections between prefrontal cortex and mediodorsal thalamus: Evidence for a general principle of indirect thalamic pathways between directly connected cortical areas.

Our ability to act flexibly, according to goals and context, is known as cognitive control. Hierarchical levels of control, reflecting different levels of abstraction, are represented across prefrontal cortex (PFC). Although the mediodorsal thalamic nucleus (MD) is extensively interconnected with PFC, the role of MD in cognitive control is unclear. Tract tracer studies in macaques, involving subsets of PFC areas, have converged on coarse MD-PFC connectivity principles; but proposed finer-grained topographic schemes, which constrain interactions between MD and PFC, disagree in many respects. To investigate a unifying topographic scheme, we performed probabilistic tractography on diffusion MRI data from eight macaque monkeys, and estimated the probable paths connecting MD with each of all 19 architectonic areas of PFC. We found a connectional topography where the orderly progression from ventromedial to anterior to posterolateral PFC was represented from anteromedial to posterolateral MD. The projection zones of posterolateral PFC areas in MD showed substantial overlap, and those of ventral and anteromedial PFC areas in MD overlapped. The exception was cingulate area 24: its projection zone overlapped with projections zones of all other PFC areas. Overall, our data suggest that nearby, functionally related, directly connected PFC areas have partially overlapping projection zones in MD, consistent with a role for MD in coordinating communication across PFC. Indeed, the organizing principle for PFC projection zones in MD appears to reflect the flow of information across the hierarchical, multi-level PFC architecture. In addition, cingulate area 24 may have privileged access to influence thalamocortical interactions involving all other PFC areas.

Association of Prenatal Maternal Depression and Anxiety Symptoms With Infant White Matter Microstructure.

Importance: Maternal depression and anxiety can have deleterious and lifelong consequences on child development. However, many aspects of the association of early brain development with maternal symptoms remain unclear. Understanding the timing of potential neurobiological alterations holds inherent value for the development and evaluation of future therapies and interventions. Objective: To examine the association between exposure to prenatal maternal depression and anxiety symptoms and offspring white matter microstructure at 1 month of age. Design, Setting, and Participants: This cohort study of 101 mother-infant dyads used a composite of depression and anxiety symptoms measured in mothers during the third trimester of pregnancy and measures of white matter microstructure characterized in the mothers' 1-month offspring using diffusion tensor imaging and neurite orientation dispersion and density imaging performed from October 1, 2014, to November 30, 2016. Magnetic resonance imaging was performed at an academic research facility during natural, nonsedated sleep. Main Outcomes and Measures: Brain mapping algorithms and statistical models were used to evaluate the association between maternal depression and anxiety and 1-month infant white matter microstructure as measured by diffusion tensor imaging and neurite orientation dispersion and density imaging findings. Results: In the 101 mother-infant dyads (mean [SD] age of mothers, 33.22 [3.99] years; mean age of infants at magnetic resonance imaging, 33.07 days [range, 18-50 days]; 92 white mothers [91.1%]; 53 male infants [52.5%]), lower 1-month white matter microstructure (decreased neurite density and increased mean, radial, and axial diffusivity) was associated in right frontal white matter microstructure with higher prenatal maternal symptoms of depression and anxiety. Significant sex × symptom interactions with measures of white matter microstructure were also observed, suggesting that white matter development may be differentially sensitive to maternal depression and anxiety symptoms in males and females during the prenatal period. Conclusions and Relevance: These data highlight the importance of the prenatal period to early brain development and suggest that the underlying white matter microstructure is associated with the continuum of prenatal maternal depression and anxiety symptoms.

Robust Motion Correction Strategy for Structural MRI in Unsedated Children Demonstrated with Three-dimensional Radial MPnRAGE.

Purpose To develop and evaluate a retrospective method to minimize motion artifacts in structural MRI. Materials and Methods The motion-correction strategy was developed for three-dimensional radial data collection and demonstrated with MPnRAGE, a technique that acquires high-resolution volumetric magnetization-prepared rapid gradient-echo, or MPRAGE, images with multiple tissue contrasts. Forty-four pediatric participants (32 with autism spectrum disorder [mean age ± standard deviation, 13 years ± 3] and 12 age-matched control participants [mean age, 12 years ± 3]) were imaged without sedation. Images with and images without retrospective motion correction were scored by using a Likert scale (0-4 for unusable to excellent) by two experienced neuroradiologists. The Tenengrad metric (a reference-free measure of image sharpness) and statistical analyses were performed to determine the effects of performing retrospective motion correction. Results MPnRAGE T1-weighted images with retrospective motion correction were all judged to have good or excellent quality. In some cases, retrospective motion correction improved the image quality from unusable (Likert score of 0) to good (Likert score of 3). Overall, motion correction improved mean Likert scores from 3.0 to 3.8 and reduced standard deviations from 1.1 to 0.4. Image quality was significantly improved with motion correction (Mann-Whitney U test; P < .001). Intraclass correlation coefficients for absolute agreement of Tenengrad scores with reviewers 1 and 2 were 0.92 and 0.88 (P < .0005 for both), respectively. In no cases did the retrospective motion correction induce severe image degradation. Conclusion Retrospective motion correction of MPnRAGE data were shown to be highly effective for consistently improving image quality of T1-weighted MRI in unsedated pediatric participants, while also enabling multiple tissue contrasts to be reconstructed for structural analysis. © RSNA, 2018 Online supplemental material is available for this article.

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease.

IMPORTANCE: The accumulation of aggregated ß-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. OBJECTIVE: To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. DESIGN, SETTING, AND PARTICIPANTS: Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including ß-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. MAIN OUTCOMES AND MEASURES: Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. RESULTS: The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/ß-amyloid 42, suggesting that phosphorylated tau 181/ß-amyloid 42 levels modulate age-related changes in myelin water fraction. CONCLUSIONS AND RELEVANCE: These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease's course and lead to new markers of efficacy for prevention and treatment trials.

Alterations of Myelin Content in Parkinson's Disease: A Cross-Sectional Neuroimaging Study.

Alterations to myelin may be a core pathological feature of neurodegenerative diseases. Although white matter microstructural differences have been described in Parkinson's disease (PD), it is unknown whether such differences include alterations of the brain's myelin content. Thus, the objective of the current study is to measure and compare brain myelin content between PD patients and age-matched controls. In this cross-sectional study, 63 participants from the Longitudinal MRI in Parkinson's Disease study underwent brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) scoring, and cognitive asessments. Subjects were imaged with the mcDEPSOT (multi-component driven equilibrium single pulse observation of T1 and T2), a multicomponent relaxometry technique that quantifies longitudinal and transverse relaxation rates (R1 and R2, respectively) and the myelin water fraction (VFM), a surrogate for myelin content. A voxel-wise approach was used to compare R1, R2, and VFM measures between PD and control groups, and to evaluate relationships with age as well as disease duration, UPDRS scores, and daily levodopa equivalent dose. PD subjects had higher VFM than controls in frontal and temporal white matter and bilateral thalamus. Greater age was strongly associated with lower VFM in both groups, while an age-by-group interaction suggested a slower rate of VFM decline in the left putamen with aging in PD. Within the PD group, measures of disease severity, including UPDRS, daily levodopa equivalent dose, and disease duration, were observed to be related with myelin content in diffuse brain regions. The age-by-group interaction suggests that either PD or dopaminergic therapies allay observed age-related myelin changes. The relationships between VFM and disease severity measures suggests that VFM may provide a surrogate marker for microstructural changes related to Parkinson's disease.