Gray-white Matter Contrast Research Articles

Early childhood family threat and longitudinal amygdala-mPFC circuit development: Examining cortical thickness and gray matter-white matter contrast

Early threat-associated cortical thinning may be interpreted as accelerated cortical development. However, non-adaptive processes may show similar macrostructural changes. Examining cortical thickness (CT) together with grey/white-matter contrast (GWC), a proxy for intracortical myelination, may enhance the interpretation of CT findings. In this prospective study, we examined associations between early life family-related threat (harsh parenting, family conflict, and neighborhood safety) and CT and GWC development from late childhood to middle adolescence. MRI was acquired from 4200 children (2069 boys) from the Generation R study at ages 8, 10 and 14 years (in total 6114 scans), of whom 1697 children had >1 scans. Linear mixed effect models were used to examine family factor-by-age interactions on amygdala volume, caudal and rostral anterior cingulate (ACC) and medial orbitofrontal cortex (mOFC) CT and GWC. A neighborhood safety-by-age-interaction was found for rostral ACC GWC, suggesting less developmental change in children from unsafe neighborhoods. Moreover, after more stringent correction for motion, family conflict was associated with greater developmental change in CT but less developmental change in GWC. Results suggest that early threat may blunt ACC GWC development. Our results, therefore, do not provide evidence for accelerated threat-associated structural development of the amygdala-mPFC circuit between ages 8–14 years.

Large Numbers for Small Children-Up to What Age Do Infants Benefit from a Longer Echo Time in Cerebral T2 MRI Sequences?

In newborns, white matter shows a high T2-weighted (T2w) signal in MRI with poor grey-white matter contrast. To increase this contrast, an extremely long echo time (TE) is used in the examination of children. It is not known up to what age this long TE should be used. The purpose of this study was to find up to what age a long TE should be used in infants. In the prospective study, 101 infants (0-18 months) underwent cranial MRI at 3 Tesla. T2-weighted Fast Spin Echo sequences with long TE (200 ms) and medium TE (100 ms) were used. The signal intensities of the cortex and white matter were measured and the grey-white matter contrast (MC) was calculated. A cut-off age was determined. The T2w sequences with long TE had a statistically significantly higher MC until the age of six months (medium TE: 0.1 ± 0.05, Long TE: 0.19 ± 0.07; p < 0.001). After the tenth month, the T2w sequence with medium TE provided significantly better MC (Medium TE: 0.1 ± 0.05; long TE: 0.05 ± 0.4; p < 0.001). The use of a long TE is only helpful in the first six months of life. After the tenth month of life, a medium TE should be favored as is used in adult brain MRI.

Parental education and income are linked to offspring cortical brain structure and psychopathology at 9-11years.

A child's socioeconomic environment can shape central aspects of their life, including vulnerability to mental disorders. Negative environmental influences in youth may interfere with the extensive and dynamic brain development occurring at this time. Indeed, there are numerous yet diverging reports of associations between parental socioeconomic status (SES) and child cortical brain morphometry. Most of these studies have used single metric- or unimodal analyses of standard cortical morphometry that downplay the probable scenario where numerous biological pathways in sum account for SES-related cortical differences in youth. To comprehensively capture such variability, using data from 9758 children aged 8.9-11.1years from the ABCD Study®, we employed linked independent component analysis (LICA) and fused vertex-wise cortical thickness, surface area, curvature and grey-/white-matter contrast (GWC). LICA revealed 70 uni- and multimodal components. We then assessed the linear relationships between parental education, parental income and each of the cortical components, controlling for age, sex, genetic ancestry, and family relatedness. We also assessed whether cortical structure moderated the negative relationships between parental SES and child general psychopathology. Parental education and income were both associated with larger surface area and higher GWC globally, in addition to local increases in surface area and to a lesser extent bidirectional GWC and cortical thickness patterns. The negative relation between parental income and child psychopathology were attenuated in children with a multimodal pattern of larger frontal- and smaller occipital surface area, and lower medial occipital thickness and GWC. Structural brain MRI is sensitive to SES diversity in childhood, with GWC emerging as a particularly relevant marker together with surface area. In low-income families, having a more developed cortex across MRI metrics, appears beneficial for mental health.

Multiple Kernel Synthesis of Head CT Using a Task-Based Loss Function

In CT imaging of the head, multiple image series are routinely reconstructed with different kernels and slice thicknesses. Reviewing the redundant information is an inefficient process for radiologists. We address this issue with a convolutional neural network (CNN)-based technique, synthesiZed Improved Resolution and Concurrent nOise reductioN (ZIRCON), that creates a single, thin, low-noise series that combines the favorable features from smooth and sharp head kernels. ZIRCON uses a CNN model with an autoencoder U-Net architecture that accepts two input channels (smooth- and sharp-kernel CT images) and combines their salient features to produce a single CT image. Image quality requirements are built into a task-based loss function with a smooth and sharp loss terms specific to anatomical regions. The model is trained using supervised learning with paired routine-dose clinical non-contrast head CT images as training targets and simulated low-dose (25%) images as training inputs. One hundred unique de-identified clinical exams were used for training, ten for validation, and ten for testing. Visual comparisons and contrast measurements of ZIRCON revealed that thinner slices and the smooth-kernel loss function improved gray-white matter contrast. Combined with lower noise, this increased visibility of small soft-tissue features that would be otherwise impaired by partial volume averaging or noise. Line profile analysis showed that ZIRCON images largely retained sharpness compared to the sharp-kernel input images. ZIRCON combined desirable image quality properties of both smooth and sharp input kernels into a single, thin, low-noise series suitable for both brain and skull imaging.

Cortical gray-white matter contrast abnormalities in male children with attention deficit hyperactivity disorder.

Presently, research concerning alterations in brain structure among individuals with attention deficit hyperactivity disorder (ADHD) predominantly focuses on entire brain volume and cortical thickness. In this study, we extend our examination to the cortical microstructure of male children with ADHD. To achieve this, we employ the gray-white matter tissue contrast (GWC) metric, allowing for an assessment of modifications in gray matter density and white matter microstructure. Furthermore, we explore the potential connection between GWC and the severity of disorder in male children by ADHD. We acquired 3DT1 sequences from the public ADHD-200 database. In this study, we conducted a comparative analysis between 43 male children diagnosed with ADHD and 50 age-matched male controls exhibiting typical development trajectories. Our investigation entailed assessing differences in GWC and cortical thickness. Additionally, we explored the potential correlation between GWC and the severity of ADHD. To delineate the cerebral landscape, each hemisphere was subdivided into 34 cortical regions using freesurfer 7.2.0. For quantification, GWC was computed by evaluating the intensity contrast of non-normalized T1 images above and below the gray-white matter interface. Our findings unveiled elevated GWC within the bilateral lingual, bilateral insular, left transverse temporal, right parahippocampal and right pericalcarine regions in male children with ADHD when contrasted with their healthy counterparts. Moreover, the cortical thickness in the ADHD group no notable distinctions that of control group in all areas. Intriguingly, the GWC of left transverse temporal demonstrated a negative correlation with the extent of inattention experienced by male children with ADHD. Utilizing GWC as a metric facilitates a more comprehensive assessment of microstructural brain changes in children with ADHD. The fluctuations in GWC observed in specific brain regions might serve as a neural biomarker, illuminating structural modifications in male children grappling with ADHD. This perspective enriches our comprehension of white matter microstructure and cortical density in these children. Notably, the inverse correlation between the GWC of the left transverse temporal and inattention severity underscores the potential role of structural and functional anomalies within this region in ADHD progression. Enhancing our insight into ADHD-related brain changes holds significant promise in deciphering potential neuropathological mechanisms.

Improved gray-white matter contrast using magnetization prepared fast imaging with steady-state free precession (MP-FISP) brain imaging at 0.55 T.

To improve the gray/white matter contrast of magnetization prepared rapid gradient echo (MP-RAGE) MRI at 0.55 T by optimizing the acquisition and sequence kernel parameters. A segmented magnetization prepared rapid gradient echo prototype sequence was implemented with (MP-RAGE*) and without (MP-FISP*) radiofrequency spoiling. Optimized parameters were derived with the assistance of an extended phase graph signal simulation as a function of the relaxation times, the flip angle, the delay times, and the effective inversion time using segmentation. The resulting protocols were compared to the MP-RAGE product sequence offered by the vendor in terms of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). A tissue segmentation reproducibility study was performed on three volunteers for the product MP-RAGE and the MP-FISP*. The MP-RAGE simulation reproduced the parameters already used in the product MP-RAGE on the scanner. An average CNR improvement of 15% for the custom MP-RAGE* over the product MP-RAGE and additional 22% for the MP-FISP* over the MP-RAGE* were observed, which is in accordance with the simulation results. The total improvement, averaged over all volunteers and regions, was 41%. The reproducibility study did not yield a significant difference between MP-RAGE and MP-FISP*. We presented some easy-to-implement adjustments to the MP-RAGE sequence at 0.55 T, which can lead to an overall average improvement of 41% in CNR.

Cortical thickness, gray-white matter contrast, and intracortical myelin in first-episode schizophrenia patients treated with long-acting paliperidone palmitate versus oral antipsychotics

This longitudinal study evaluated the cortical thickness, gray-to-white matter contrast (GWC), and frontal lobe intracortical myelin (ICM) volume in first-episode schizophrenia (FES) patients treated with oral antipsychotics (OAP) versus a long-acting injectable antipsychotic, paliperidone palmitate (PP). 2D proton density and inversion recovery images, and 3D T1-weighted MPRAGE images were acquired at 3T from 68 FES patients in a randomized clinical trial with PP vs OAP. At baseline, no differences in GWC and ICM were observed between FES patients and HCs, but the thickness of the left precuneus, the right transverse temporal gyrus, and the bilateral superior temporal gyri was found to be thinner in FES patients relative to HCs. Following 9 months of antipsychotics, OAP treatment, compared to PP treatment, resulted in a more widespread cortical thickness reduction including the right lateral occipital and orbitofrontal gyri. No significant ICM and GWC changes were observed in the PP group, whereas OAP treatment led to a significant ICM volume decrease and GWC increase. A negative correlation was found between ICM changes and GWC changes within multiple frontal regions after 9 months of OAP treatment. These preliminary findings suggest that PP treatment might aid preservation of brain morphology.

Optimized flow compensation for contrast-enhanced T1-weighted Wave-CAIPI 3D MPRAGE imaging of the brain

Flow-related artifacts have been observed in highly accelerated T1-weighted contrast-enhanced wave-controlled aliasing in parallel imaging (CAIPI) magnetization-prepared rapid gradient-echo (MPRAGE) imaging and can lead to diagnostic uncertainty. We developed an optimized flow-mitigated Wave-CAIPI MPRAGE acquisition protocol to reduce these artifacts through testing in a custom-built flow phantom. In the phantom experiment, maximal flow artifact reduction was achieved with the combination of flow compensation gradients and radial reordered k-space acquisition and was included in the optimized sequence. Clinical evaluation of the optimized MPRAGE sequence was performed in 64 adult patients, who all underwent contrast-enhanced Wave-CAIPI MPRAGE imaging without flow-compensation and with optimized flow-compensation parameters. All images were evaluated for the presence of flow-related artifacts, signal-to-noise ratio (SNR), gray-white matter contrast, enhancing lesion contrast, and image sharpness on a 3-point Likert scale. In the 64 cases, the optimized flow mitigation protocol reduced flow-related artifacts in 89% and 94% of the cases for raters 1 and 2, respectively. SNR, gray-white matter contrast, enhancing lesion contrast, and image sharpness were rated as equivalent for standard and flow-mitigated Wave-CAIPI MPRAGE in all subjects. The optimized flow mitigation protocol successfully reduced the presence of flow-related artifacts in the majority of cases.Relevance statementAs accelerated MRI using novel encoding schemes become increasingly adopted in clinical practice, our work highlights the need to recognize and develop strategies to minimize the presence of unexpected artifacts and reduction in image quality as potential compromises to achieving short scan times.Key points• Flow-mitigation technique led to an 89–94% decrease in flow-related artifacts.• Image quality, signal-to-noise ratio, enhancing lesion conspicuity, and image sharpness were preserved with the flow mitigation technique.• Flow mitigation reduced diagnostic uncertainty in cases where flow-related artifacts mimicked enhancing lesions.Graphical

High spatial overlap but diverging age-related trajectories of cortical magnetic resonance imaging markers aiming to represent intracortical myelin and microstructure.

Statistical effects of cortical metrics derived from standard T1- and T2-weighted magnetic resonance imaging (MRI) images, such as gray-white matter contrast (GWC), boundary sharpness coefficient (BSC), T1-weighted/T2-weighted ratio (T1w/T2w), and cortical thickness (CT), are often interpreted as representing or being influenced by intracortical myelin content with little empirical evidence to justify these interpretations. We first examined spatial correspondence with more biologically specific microstructural measures, and second compared between-marker age-related trends with the underlying hypothesis that different measures primarily driven by similar changes in myelo- and microstructural underpinnings should be highly related. Cortical MRI markers were derived from MRI images of 127 healthy subjects, aged 18-81, using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Their gross spatial distributions were compared with gene expression-derived cell-type densities, histology-derived cytoarchitecture, and quantitative R1 maps acquired on a subset of participants. We then compared between-marker age-related trends in their shape, direction, and spatial distribution of the linear age effect. The gross anatomical distributions of cortical MRI markers were, in general, more related to myelin and glial cells than neuronal indicators. Comparing MRI markers, our results revealed generally high overlap in spatial distribution (i.e., group means), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers can be different from microstructural changes that affect these markers in aging.

Determination of optimal regularization factor in Bayesian penalized likelihood reconstruction of brain PET images using [18 F]FDG and [11 C]PiB.

The Bayesian penalized likelihood (BPL) reconstruction algorithm, Q.Clear, can achieve a higher signal-to-noise ratio on images and more accurate quantitation than ordered subset-expectation maximization (OSEM). The reconstruction parameter (β) in BPL requires optimization according to the radiopharmaceutical tracer. The present study aimed to define the optimal β value in BPL required to diagnose Alzheimer disease from brain positron emission tomography (PET) images acquired using 18 F-fluoro-2-deoxy-D-glucose ([18 F]FDG) and 11 C-labeled Pittsburg compound B ([11 C]PiB). Images generated from Hoffman 3D brain and cylindrical phantoms were acquired using a Discovery PET/computed tomography (CT) 710 and reconstructed using OSEM+time-of-flight (TOF) under clinical conditions and BPL+TOF (β=20-1000). Contrast was calculated from images generated by the Hoffman 3D brain phantom, and noise and uniformity were calculated from those generated by the cylindrical phantom. Five cognitively healthy controls and five patients with Alzheimer disease were assessed using [18 F]FDG and [11 C]PiB PET to validate the findings from the phantom study. The β values were restricted by the findings of the phantom study, then one certified nuclear medicine physician and two certified nuclear medicine technologists visually determined optimal β values by scoring the quality parameters of image contrast, image noise, cerebellar stability, and overall image quality of PET images from 1 (poor) to 5 (excellent). The contrast in BPL satisfied the Japanese Society of Nuclear Medicine (JSNM) criterion of ≥55% and exceeded that of OSEM at ranges of β=20-450 and 20-600 for [18 F]FDG and [11 C]PiB, respectively. The image noise in BPL satisfied the JSNM criterion of ≤15% and was below that in OSEM when β=150-1000 and 400-1000 for [18 F]FDG and [11 C]PiB, respectively. The phantom study restricted the ranges of β values to 100-300 and 300-500 for [18 F]FDG and [11 C]PiB, respectively. The BPL scores for gray-white matter contrast and image noise, exceeded those of OSEM in [18 F]FDG and [11 C]PiB images regardless of β values. Visual evaluation confirmed that the optimal β values were 200 and 450 for [18 F]FDG and [11 C]PiB, respectively. The BPL achieved better image contrast and less image noise than OSEM, while maintaining quantitative standardized uptake value ratios (SUVR) due to full convergence, more rigorous noise control, and edge preservation. The optimal β values for [18 F]FDG and [11 C]PiB brain PET were apparently 200 and 450, respectively. The present study provides useful information about how to determine optimal β values in BPL for brain PET imaging.

Decreased Gray—White Matter Contrast of [11C]-PiB Uptake in Cognitively Unimpaired Subjects with Severe Obstructive Sleep Apnea

BackgroundVery recently, cognitively normal, middle-aged adults with severe obstructive sleep apnea (OSA) were shown to have regional cortical amyloid-β deposits. In the normal brain, amyloid tracer (e.g., [11C]-PiB) uptake is observed in white matter (WM) but not in cortical gray matter (GM), resulting in clear GM—WM contrast. There are no reports on possible changes in this contrast in severe OSA.ObjectivesEvaluate changes in the global [11C]-PiB GM—WM contrast and study if factors reflecting clinical and imaging characteristics are associated with them.Design and SettingCross-sectional imaging study.Participants19 cognitively intact middle-aged (mean 44 years) patients with severe OSA (Apnea—Hypopnea Index >30/h), carefully selected to exclude any other possible factors that could alter brain health.MeasurementsDetailed neuroimaging (amyloid PET, MRI). Signs of possible alterations in amyloid tracer GM—WM contrast and kinetics were studied with static and dynamic [11C]-PiB PET and WM structures with detailed 3.0T MRI.ResultsStatic [11C]-PiB PET uptake showed significantly decreased GM—WM contrast in 5 out of 19 patients. This was already clearly seen in visual evaluation and also detected quantitatively using retention indexes. Dynamic imaging revealed decreased contrast due to alterations in trace accumulation in the late phase of [11C]-PiB kinetics. Decreased GM—WM contrast in the late phase was global in nature. MRI revealed no corresponding alterations in WM structures. Importantly, decreased GM—WM contrast was associated with smoking (p = 0.007) and higher Apnea—Hypopnea Index (p = 0.001).ConclusionsSevere OSA was associated with decreased GM—WM contrast in amyloid tracer uptake, with significant correlation with clinical parameters of smoking and AHI. The results support and further extend the current understanding of the deleterious effect of severe OSA on proper amyloid clearance, possibly reflecting dysfunction of the brain glymphatic system.

Association between gray/white matter contrast and white matter microstructural alterations in medication-naïve obsessive–compulsive disorder

Intracortical myelin is involved in speeding and synchronizing neural activity of the cerebral cortex and has been found to be disrupted in various psychiatric disorders. However, its role in obsessive–compulsive disorder (OCD) has remained unknown. In this study, we investigated the alterations in intracortical myelin and their association with white matter (WM) microstructural abnormalities in OCD. T1-weighted and diffusion-weighted brain images were obtained for 51 medication-naïve patients with OCD and 26 healthy controls (HCs). The grey/white matter contrast (GWC) was calculated from T1-weighted signal intensities to characterize the intracortical myelin profile in OCD. Diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), were extracted from diffusion-weighted images to examine the WM microstructure in OCD. Compared with HCs, patients with OCD showed increased GWC in the bilateral orbitofrontal, cuneus, lingual and fusiform gyrus, left anterior cingulate, left superior parietal, right inferior parietal, and right middle frontal cortices, suggesting reduced intracortical myelin. Patients with OCD also showed decreased FA in several WM regions, with a topology corresponding to the GWC alterations. In both groups, the mean GWC of the significant clusters in between-group GWC analysis was correlated negatively with the mean FA of the significant clusters in between-group FA analysis. In patients with OCD, the FA of a cluster in the right cerebellum correlated negatively with the Yale-Brown obsessive–compulsive scale scores. Our results suggest that abnormal intracortical and WM myelination could be the microstructural basis for the brain connectivity alterations and disrupted inhibitory control in OCD.

Estimating the effect of a scanner upgrade on measures of grey matter structure for longitudinal designs.

Longitudinal imaging studies are crucial for advancing the understanding of brain development over the lifespan. Thus, more and more studies acquire imaging data at multiple time points or with long follow-up intervals. In these studies changes to magnetic resonance imaging (MRI) scanners often become inevitable which may decrease the reliability of the MRI assessments and introduce biases. We therefore investigated the difference between MRI scanners with subsequent versions (3 Tesla Siemens Verio vs. Skyra) on the cortical and subcortical measures of grey matter in 116 healthy, young adults using the well-established longitudinal FreeSurfer stream for T1-weighted brain images. We found excellent between-scanner reliability for cortical and subcortical measures of grey matter structure (intra-class correlation coefficient > 0.8). Yet, paired t-tests revealed statistically significant differences in at least 67% of the regions, with percent differences around 2 to 4%, depending on the outcome measure. Offline correction for gradient distortions only slightly reduced these biases. Further, T1-imaging based quality measures reflecting gray-white matter contrast systematically differed between scanners. We conclude that scanner upgrades during a longitudinal study introduce bias in measures of cortical and subcortical grey matter structure. Therefore, before upgrading a MRI scanner during an ongoing study, researchers should prepare to implement an appropriate correction method for these effects.

Using Perfusion Contrast for Spatial Normalization of ASL MRI Images in a Pediatric Craniosynostosis Population.

Spatial normalization is an important step for group image processing and evaluation of mean brain perfusion in anatomical regions using arterial spin labeling (ASL) MRI and is typically performed via high-resolution structural brain scans. However, structural segmentation and/or spatial normalization to standard space is complicated when gray-white matter contrast in structural images is low due to ongoing myelination in newborns and infants. This problem is of particularly clinical relevance for imaging infants with inborn or acquired disorders that impair normal brain development. We investigated whether the ASL MRI perfusion contrast is a viable alternative for spatial normalization, using a pseudo-continuous ASL acquired using a 1.5 T MRI unit (GE Healthcare). Four approaches have been compared: (1) using the structural image contrast, or perfusion contrast with (2) rigid, (3) affine, and (4) nonlinear transformations – in 16 healthy controls [median age 0.83 years, inter-quartile range (IQR) ± 0.56] and 36 trigonocephaly patients (median age 0.50 years, IQR ± 0.30) – a non-syndromic type of craniosynostosis. Performance was compared quantitatively using the real-valued Tanimoto coefficient (TC), visually by three blinded readers, and eventually by the impact on regional cerebral blood flow (CBF) values. For both patients and controls, nonlinear registration using perfusion contrast showed the highest TC, at 17.51 (CI 6.66–49.38) times more likely to have a higher rating and 17.45–18.88 ml/100 g/min higher CBF compared with the standard normalization. Using perfusion-based contrast improved spatial normalization compared with the use of structural images, significantly affected the regional CBF, and may open up new possibilities for future large pediatric ASL brain studies.

Can 7T MPRAGE match MP2RAGE for gray-white matter contrast?

Ultra-High Field (UHF) MRI provides a significant increase in Signal-to-Noise Ratio (SNR) and gains in contrast weighting in several functional and structural acquisitions. Unfortunately, an increase in field strength also induces non-uniformities in the transmit field (B1+) that can compromise image contrast non-uniformly. The MPRAGE is one of the most common T1 weighted (T1w) image acquisitions for structural imaging. It provides excellent contrast between gray and white matter and is widely used for brain segmentation. At 7T, the signal non-uniformities tend to complicate this and therefore, the self-bias-field corrected MP2RAGE is often used there. In both MPRAGE and MP2RAGE, more homogeneous image contrast can be achieved with adiabatic pulses, like the TR-FOCI inversion pulse, or special pulse design on parallel transmission systems, like Universal Pulses (UP). In the present study, we investigate different strategies to improve the bias-field for MPRAGE at 7T, comparing the contrast and GM/WM segmentability against MP2RAGE. The higher temporal efficiency of MPRAGE combined with the potential of the user-friendly UPs was the primary motivation for this MPRAGE-MP2RAGE comparison. We acquired MPRAGE data in six volunteers, adding a k-space shutter to reduce scan time, a kt-point UP approach for homogeneous signal excitation, and a TR-FOCI pulse for homogeneous inversion. Our results show remarkable signal contrast improvement throughout the brain, including regions of low B1+ such as the cerebellum. The improvements in the MPRAGE were largest following the introduction of the UPs. In addition to the CNR, both SNR and GM/WM segmentability were also assessed. Among the MPRAGEs, the combined strategy (UP + TR-FOCI) yielded highest SNR and showed highest spatial similarity between GM segments to the MP2RAGE. Interestingly, the distance between gray and white matter peaks in the intensity histograms did not increase, as better pulses and higher SNR especially benefitted the (cerebellar) gray matter. Overall, the gray-white matter contrast from MP2RAGE is higher, with higher CNR and higher intensity peak distances, even when scaled to scan time. Hence, the extra acquisition time for MP2RAGE is justified by the improved segmentability.

Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder.

BackgroundRecent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD.Materials and MethodsWe used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n = 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD, n = 9; typical development, n = 8; non-typical development, n = 3).ResultsASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.LimitationsOur study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples.ConclusionThese preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

MRI brain templates of the male Yucatan minipig

The pig is growing in popularity as an experimental animal because its gyrencephalic brain is similar to humans. Currently, however, there is a lack of appropriate brain templates to support functional and structural neuroimaging pipelines. The primary contribution of this work is an average volume from an iterative, non-linear registration of 70 five- to seven-month-old male Yucatan minipigs. In addition, several aspects of this study are unique, including the comparison of linear and non-linear template generation, the characterization of a large and homogeneous cohort, an analysis of effective resolution after averaging, and the evaluation of potential in-template bias as well as a comparison with a template from another minipig species using a “left-out” validation set. We found that within our highly homogeneous cohort, non-linear registration produced better templates, but only marginally so. Although our T1-weighted data were resolution limited, we preserved effective resolution across the multi-subject average, produced templates that have high gray-white matter contrast and demonstrate superior registration accuracy compared to an alternative minipig template.

Maturational trajectories of pericortical contrast in typical brain development

In the last few years, a significant amount of work has aimed to characterize maturational trajectories of cortical development. The role of pericortical microstructure putatively characterized as the gray-white matter contrast (GWC) at the pericortical gray-white matter boundary and its relationship to more traditional morphological measures of cortical morphometry has emerged as a means to examine finer grained neuroanatomical underpinnings of cortical changes. In this work, we characterize the GWC developmental trajectories in a representative sample (n = 394) of children and adolescents (~4 to ~22 years of age), with repeated scans (1–3 scans per subject, total scans n = 819). We tested whether linear, quadratic, or cubic trajectories of contrast development best described changes in GWC. A best-fit model was identified vertex-wise across the whole cortex via the Akaike Information Criterion (AIC). GWC across nearly the whole brain was found to significantly change with age. Cubic trajectories were likeliest for 63% of vertices, quadratic trajectories were likeliest for 20% of vertices, and linear trajectories were likeliest for 16% of vertices. A main effect of sex was observed in some regions, where males had a higher GWC than females. However, no sex by age interactions were found on GWC. In summary, our results suggest a progressive decrease in GWC at the pericortical boundary throughout childhood and adolescence. This work contributes to efforts seeking to characterize typical, healthy brain development and, by extension, can help elucidate aberrant developmental trajectories.

A hypomyelinating leukodystrophy in German Shepherd dogs

BackgroundShaking puppy syndrome is commonly attributed to abnormal myelination of the central nervous system.Hypothesis/ObjectivesTo report the long‐term clinical course and the imaging characteristics of hypomyelinating leukodystrophy in German Shepherd dogs.Animals and MethodsThree related litters with 11 affected dogs.ResultsThe 11 affected dogs experienced coarse, side‐to‐side tremors of the head and trunk, which interfered with normal goal‐oriented movements and disappeared at rest. Signs were noticed shortly after birth. Nine dogs were euthanized, 3 dogs underwent pathological examination, and 2 littermates were raised by their breeder. Tremors improved gradually until 6 to 7 months of age. Adult dogs walked with severe residual pelvic limb ataxia. One dog developed epilepsy with tonic‐clonic seizures at 15 months of age. Conventional magnetic resonance imaging (MRI) disclosed homogenous hyperintense signal of the entire subcortical white matter in 3 affected 7‐week‐old dogs and a hypointense signal in a presumably unaffected littermate. Subcortical white matter appeared isointense to gray matter at 15 and 27 weeks of age on repeated MRI. Abnormal white matter signal with failure to display normal gray‐white matter contrast persisted into adulthood. Cerebellar arbor vitae was not visible at any time point. Clinical signs, MRI findings, and pathological examinations were indicative of a hypomyelinating leukodystrophy. All parents of the affected litters shared a common ancestor and relatedness of the puppies suggested an autosomal recessive mode of inheritance.ConclusionWe describe a novel hypomyelinating leukodystrophy in German Shepherd dogs with a suspected inherited origin.

Reduced gray-white matter contrast localizes the motor cortex on double inversion recovery (DIR) 3T MRI.

Reduced gray-white matter contrast along the central sulcus has been described on T1- and T2-weighted magnetic resonance imaging (MRI). The purpose of this study was to assess the gray-white matter contrast of the motor cortex on double inversion recovery (DIR), a sequence with superior gray-white matter differentiation. The gray-white matter signal on DIR was retrospectively compared to T1-weighted magnetization-prepared rapid gradient echo (T1-MPRAGE) using normal (n= 25) and abnormal (n = 25) functional MRI (fMRI) exams. Quantitative gray-white matter contrast ratios (CR) of the precentral and adjacent gyri were obtained on normal exams. Two neuroradiologists qualitatively rated reduced gray-white matter contrast of the hemispheres of both normal and abnormal exams. Hand motor functional mapping was used as a reference. In normal hemispheres (n= 50), the mean CR was significantly lower on DIR (0.44) vs T1-MPRAGE (0.63, p< 0.001). Reduced gray-white matter contrast was categorized as "definitely present" more frequently on DIR than T1-MPRAGE by reviewers in both normal (n = 50; reviewer 1 DIR 88% and MPRAGE 68%, p= 0.02; reviewer 2 DIR 86% and T1-MPRAGE 64%; p=0.01) and abnormal hemispheres (n = 50; reviewer 1 DIR 80% and T1-MPRAGE 38%, p < 0.001; reviewer 2 DIR 74% and T1-MPRAGE 46%, p= 0.005). Reduced gray-white matter contrast of the motor cortex is more pronounced on DIR compared to T1-MPRAGE on quantitative and qualitative assessments of normal MRI exams. In abnormal cases, reviewers more definitively identified the motor cortex on DIR. In cases with distorted brain anatomy, DIR may be a useful adjunct sequence to localize the motor cortex.