Diffusion-tensor-imaging 1-year-old and 2-year-old infant brain atlases with comprehensive gray and white matter labels.

Human infancy is marked by fastest postnatal brain structural changes. It also coincides with the onset of many neurodevelopmental disorders. Atlas-based automated structure labeling has been widely used for analyzing various neuroimaging data. However, the relatively large and nonlinear neuroanatomical differences between infant and adult brains can lead to significant offsets of the labeled structures in infant brains when adult brain atlas is used. Age-specific 1- and 2-year-old brain atlases covering all major gray and white matter (GM and WM) structures with diffusion tensor imaging (DTI) and structural MRI are critical for precision medicine for infant population yet have not been established. In this study, high-quality DTI and structural MRI data were obtained from 50 healthy children to build up three-dimensional age-specific 1- and 2-year-old brain templates and atlases. Age-specific templates include a single-subject template as well as two population-averaged templates from linear and nonlinear transformation, respectively. Each age-specific atlas consists of 124 comprehensively labeled major GM and WM structures, including 52 cerebral cortical, 10 deep GM, 40 WM, and 22 brainstem and cerebellar structures. When combined with appropriate registration methods, the established atlases can be used for highly accurate automatic labeling of any given infant brain MRI. We demonstrated that one can automatically and effectively delineate deep WM microstructural development from 3 to 38 months by using these age-specific atlases. These established 1- and 2-year-old infant brain DTI atlases can advance our understanding of typical brain development and serve as clinical anatomical references for brain disorders during infancy.

Alterations of large-scale functional network connectivity in patients with infantile esotropia before and after surgery.

BACKGROUND: Growing evidences have indicated neurodevelopmental disorders in infantile esotropia (IE). However, few studies have analyzed the characteristics of large-scale functional networks of IE patients or their postoperative network-level alterations. METHODS: Here, individuals with IE (n = 32) and healthy subjects (n = 30) accomplished the baseline clinical examinations and resting-state MRI scans. A total of 17 IE patients also underwent corrective surgeries and completed the longitudinal clinical assessments and resting-state MRI scans. Linear mixed effects models were applied for cross-sectional and longitudinal network-level analyses. Correlation analysis was performed to assess the relationship between longitudinal functional connectivity (FC) alterations and baseline clinical variables. RESULTS: In cross-sectional analyses, network-level FC were apparently aberrant in IE patients compared to controls. In longitudinal analyses, intra- and internetwork connectivity were observed with significant alterations in postoperative IE patients compared to the preoperative counterparts. Longitudinal FC changes are negatively correlated to the age at surgery in IE. CONCLUSIONS: Obviously, altered network-level FC benefiting from the corrective surgery serves as the neurobiological substrate of the observed improvement of stereovision, visuomotor coordination, and emotional management in postoperative IE patients. Corrective surgery should be performed as early as possible to obtain more benefits for IE in brain function recovery.

CT and MRI Features of Hairy Polyps in Neonates and Infants: A Retrospective Study of 14 Patients.

BACKGROUND: The typical imaging findings of hairy polyps have been described mostly in case reports. This study was conducted to describe the CT and MRI features of hairy polyps and their common associated abnormalities. METHODS: Medical records of 14 patients with pathological diagnosis of hairy polyps were collected for this study. For each patient, the medical records, including demographics, clinical manifestations, and imaging findings were reviewed. RESULTS: The female-to-male ratio was 3.7:1. The age at first episode varied from birth to 2.7 years. The masses were derived from the back side of the soft palate in seven (50.0%) cases, from the lateral pharyngeal wall in four (28.6%) cases, from the soft palate in one (7.1%) case, from the nasal vestibule in one (7.1%) case, and from the parapharyngeal space in one (7.1%) case. A total of 11 (78.6%) cases presented with pedicled masses containing fat and a central core of soft tissue, there were 3 (21.4%) cases whose imaging findings were atypical, and there were 6 (42.9%) patients who had other pathologies. CONCLUSIONS: Hairy polyps typically presented as pedicled masses containing fat and a central core of soft tissue, but sometimes their imaging findings can be atypical and they can be associated with other congenital abnormalities. CT and MRI are reliable methods for the diagnosis of hairy polyps and their associated abnormalities.

Infant brain regional cerebral blood flow increases supporting emergence of the default-mode network.

Human infancy is characterized by most rapid regional cerebral blood flow (rCBF) increases across lifespan and emergence of a fundamental brain system default-mode network (DMN). However, how infant rCBF changes spatiotemporally across the brain and how the rCBF increase supports emergence of functional networks such as DMN remains unknown. Here, by acquiring cutting-edge multi-modal MRI including pseudo-continuous arterial-spin-labeled perfusion MRI and resting-state functional MRI of 48 infants cross-sectionally, we elucidated unprecedented 4D spatiotemporal infant rCBF framework and region-specific physiology-function coupling across infancy. We found that faster rCBF increases in the DMN than visual and sensorimotor networks. We also found strongly coupled increases of rCBF and network strength specifically in the DMN, suggesting faster local blood flow increase to meet extraneuronal metabolic demands in the DMN maturation. These results offer insights into the physiological mechanism of brain functional network emergence and have important implications in altered network maturation in brain disorders.

Abnormal developmental trends of functional connectivity in young children with infantile esotropia.

Previous studies have shown that functional networks are present at birth and change dynamically throughout infancy and early childhood. However, the status of functional connectivity is still poorly understood in patients with infantile esotropia (IE). The aim of this study is to investigate the developmental trends of functional connectivity in patients with IE during a critical period of growth and development. A total of 17 patients with IE (9 males and 8 females; mean age: 3.36 ± 2.03 years, age range: 0.67-6.36 years) and 20 healthy subjects matched for age and gender were recruited and underwent resting-state functional magnetic resonance imaging. The whole-brain functional network connectivity was analyzed for the IE group and healthy control group. A general linear model was applied to assess the group-age interaction in terms of the functional connectivity. The discrepancy between the two groups in functional connectivity trajectories was also quantified across age and exhibited by the quadratic parabolic model. There were significant group-age interactions between the visual network and the default mode network, the visual network and the sensorimotor network, the limbic network and the default mode network, and within the limbic network in the functional connectivity. A U-shaped tendency across age, with an "inflection point" ranging from 3.1 to 4.0 years of age was exhibited in the difference between functional connectivity trajectories of the IE patients and normal controls. Abnormality in functional network connectivity could present in IE patients at birth, exhibiting aberrant developmental patterns over time. An abnormal functional network could reduce the ability of the cortex in visual information processing, further reactivating the subcortical visual information processing system, which is probably the pathogenesis of IE. Three to four years after birth is the critical time window for children with IE to establish normal network connections in the brain. Early surgery during this period may be helpful for affected children to have an opportunity to approach the normal development trajectory as early as possible.

Local structural-functional connectivity decoupling of caudate nucleus in infantile esotropia.

Abnormal brain structural and functional properties were demonstrated in patients with infantile esotropia (IE). However, few studies have investigated the interaction between structural and functional connectivity (SC-FC) in patients with IE. Structural network was generated with diffusion tensor imaging and functional network was constructed with resting-state functional magnetic resonance imaging for 18 patients with IE as well as 20 age- and gender- matched healthy subjects. The SC-FC coupling for global connectome, short connectome and long connectome were examined in IE patients and compared with those of healthy subjects. A linear mixed effects model was employed to examine the group-age interaction in terms of the coupling metrics. The Pearson correlation between coupling measures and strabismus degree was evaluated in IE patients, on which the regulatory effect of age was also investigated through hierarchical regression analysis. Significantly decreased SC-FC coupling score for short connections was observed in left caudate nucleus (CAU) in IE patients, whereas no brain regions exhibited altered coupling metrics for global connections or long connections. The group-age interaction was also evident in local coupling metrics of left CAU. The age-related regulatory effect on coupling-degree association was distinguishing between brain regions implicated in visual processing and cognition-related brain areas in IE patients. Local SC-FC decoupling in CAU was evident in patients with IE and was initiated in their early postnatal period, possibly interfering the visual cortico-striatal loop and subcortical optokinetic pathway subserving visual processing and nasalward optokinesis during neurodevelopment, which provides new insight into underlying neuropathological mechanism of IE.

Brain development in children with developmental delay using amide proton transfer-weighted imaging and magnetization transfer imaging.

IMPORTANCE: The process of brain development in children with developmental delay is not well known. Amide proton transfer-weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development. OBJECTIVE: To assess the contribution of amide proton transfer-weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD). METHODS: Fifty-one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1-8 months; median age: 4 months) in group A showed delayed myelination on MRI, while 21 patients (3 girls, 18 boys; age range: 12-36months; median age: 25months) in group B showed normal myelination on MRI. Fifty-one age- and sex-matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent-sample t-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05. RESULTS: For group A, the MTR values were lower in all regions (P = 0.004-0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004-0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05). INTERPRETATION: For DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.

IrCo alloy nanoparticles supported on N-doped carbon for hydrogen evolution electrocatalysis in acidic and alkaline electrolytes.

Designing efficient and low-cost electrocatalysts for the hydrogen evolution reaction (HER) is of great importance to advance water splitting technology towards practical applications. Herein, we report the preparation of IrCo nanoparticles supported on nitrogen-doped carbon (IrCo/NC) as a HER electrocatalyst in acidic and alkaline electrolytes. The IrCo/NC composite is obtained by pyrolyzing an Ir-doped Co(OH)2 precursor on g-C3N4, and is endowed with N-doped carbon and uniform IrCo alloy nanoparticles via a crystal confinement resulting from the Ir-doping into the Co(OH)2 layer. Electrocatalytic analysis shows that the IrCo/NC electrode requires low overpotentials of 32 mV at 10 mA cm-2 in 0.5 M H2SO4 and 33 mV in 1 M KOH, which are superior to those of the Co/NC and IrCo alloys that are free of Ir-doping or N-doped carbon. The results provide a strategy for designing and preparing active noble-transition bimetallic alloy electrocatalysts as efficient HER catalysts.

N-self-doped porous carbon derived from animal-heart as an electrocatalyst for efficient reduction of oxygen.

Biomass-derived nitrogen-self-doped carbon was prepared by a simple and green approach based on the direct pyrolysis of pork heart using KOH as an activation reagent at controlled temperatures (700-900 °C). The obtained samples displayed a specific surface area up to 1718.84 m2 g-1, high content of nitrogen (3.03%) and interconnected porous structure, which is able to expose abundant active sites and promote mass transfer. Electrochemical measurements showed that our catalyst possessed a high electrocatalytic activity for oxygen reduction reaction in alkaline solution that is equivalent to that of commercial Pt/C. The sample carbonized at 700 °C (PC-APHs-700) with the onset potential of 0.92 V and half-wave potential of 0.80 V possessed the highest concentrations of graphite and pyridine nitrogen and exhibited the best performance among the PC-APHs-T samples. In addition, PC-APHs-700 had a higher long-term stability and stronger methanol tolerance than commercial Pt/C. This work demonstrates that it is a promising approach to develop and utilize carbon materials with added value as effective metal-free cathode catalysts for alkaline fuel cells based on economic and environmental friendly renewable biomass.

Total Syntheses of Norrisolide-Type Spongian Diterpenes Cheloviolene†C, Seconorrisolide†B, and Seconorrisolide†C.

The first total syntheses of three unusual norrisolide-type rearranged spongian diterpenes, cheloviolene C, seconorrisolide B, and seconorrisolide C, have been accomplished via a common intermediate through late-stage ring-scissoring. The synthesis features a Wolff ring contraction for the synthesis of the trans-hydrindane system, and a crucial retro Diels-Alder reaction/intramolecular ene cyclization for the rapid stereoselective construction of the furo[2,3-b]furan system, which is commonly seen in rearranged spongian diterpenes.

Do magnetic resonance imaging manifestations of skeletal system improve after treatment of Gaucher disease?

OBJECTIVES: Skeletal lesions are the most serious complications of Gaucher disease (GD). The pathological changes of skeletal system are complex, which seriously affects the quality of life. The aim was to investigate whether the skeletal system improved in quantitative imaging after treatment with enzyme replacement therapy (ERT). METHODS: Magnetic resonance imaging (MRI) of the vertebrae and femur was performed in 40 patients and 34 healthy volunteers. The scan sequences include iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) and intravoxel incoherent motion imaging (IVIM). Statistical data were analyzed by using t-test. RESULTS: As for the fat fraction (FF) and R2*, there were significant differences in FF and R2* of vertebrae and left femur. As for the standard apparent diffusion coefficient (sADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*) and fraction of fast apparent diffusion coefficient (f) of vertebrae and femur. Only D of vertebrae, sADC and f of left femur and sADC of right femur had statistical difference. CONCLUSION: The quantitative imaging of skeletal system lesions have certain characteristics. The lesions in the skeletal system of patients treated with ERT has been improved to some extent, but it is still different from that in normal people.

Differential White Matter Maturation from Birth to 8 Years of Age.

Comprehensive delineation of white matter (WM) microstructural maturation from birth to childhood is critical for understanding spatiotemporally differential circuit formation. Without a relatively large sample of datasets and coverage of critical developmental periods of both infancy and early childhood, differential maturational charts across WM tracts cannot be delineated. With diffusion tensor imaging (DTI) of 118 typically developing (TD) children aged 0-8 years and 31 children with autistic spectrum disorder (ASD) aged 2-7 years, the microstructure of every major WM tract and tract group was measured with DTI metrics to delineate differential WM maturation. The exponential model of microstructural maturation of all WM was identified. The WM developmental curves were separated into fast, intermediate, and slow phases in 0-8 years with distinctive time period of each phase across the tracts. Shorter periods of the fast and intermediate phases in certain tracts, such as the commissural tracts, indicated faster earlier development. With TD WM maturational curves as the reference, higher residual variance of WM microstructure was found in children with ASD. The presented comprehensive and differential charts of TD WM microstructural maturation of all major tracts and tract groups in 0-8 years provide reference standards for biomarker detection of neuropsychiatric disorders.

Nickel-catalyzed intermolecular oxidative Heck arylation driven by transfer hydrogenation.

The conventional oxidative Heck reaction between aryl boronic acids and alkenes typically involved the PdII/Pd0/PdII catalytic cycle incorporating an external oxidant and often suffered C=C bond isomerization for internal alkyl-substituted alkenes via chain-walking. Herein, we demonstrate that the regioselectivity (γ-selectivity vs. δ-selectivity) and pathway selectivity (hydroarylation vs. oxidative Heck coupling) of a directed Ni-catalyzed alkene arylation can be controlled by judicious tuning of the coordination environment around the nickel catalyst via optimization of an appropriate phosphine ligand and directing group. In this way, the Ni(0)-catalyzed oxidative Heck arylation that relies on transfer hydrogenation of an acceptor olefin is developed with excellent E/Z selectivity and regioselectivity. Mechanistic investigations suggest that the addition of the acceptor is crucial for lowering the energy for carbometalation and for enabling catalytic turnover.

Altered brain functional network in children with type 1 Gaucher disease: a longitudinal graph theory-based study.

PURPOSE: Previous studies have investigated the brain structural abnormalities in children with type I Gaucher disease (GD). The purpose of our study is to investigate the topological efficiency of the brain functional network in children with type 1 GD. METHODS: Twenty-two children diagnosed with type 1 GD and 22 sex- and age-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) examination. For longitudinal study, the GD patients underwent rs-fMRI examination again after 4.6 years. Graph theoretical analysis was used to assess the brain network topological properties at the global and regional levels. RESULTS: Compared with the HCs, the children with type 1 GD showed a decreased efficiency in functional segregation with a decreased γ (normalized clustering coefficient). In addition, the balance between functional segregation and integration was disrupted with decreased small-worldness (σ). At the regional level, the children with type 1 GD showed significantly decreased nodal degree and efficiency in the right precentral gyrus (PreCG.R) and left postcentral gyrus (PoCG.L). The significantly altered γ, σ, and nodal degree in the PreCG.R and PoCG.L were negatively correlated with the disease duration. No significant alterations in the global and regional topological properties were identified in these patients over time. CONCLUSION: Compared with that of the HCs, the efficiency of the brain functional network in the children with type 1 GD was disrupted, and regional involvement was located in motor- and sensory-related regions. The efficiency of the brain functional network in these patients remained stable over time.

AgSbF6-Mediated Selective Thiolation and Selenylation at C-4 Position of Isoquinolin-1(2 H)-ones.

A new and facile AgSbF6-mediated protocol for the construction of C-4 thiolated or selenylated isoquinolin-1(2 H)-ones via a radical pathway was established. This reaction proceeded efficiently with excellent regioselectivity, a broad substrate scope, and good functional group tolerance. A radical reaction mechanism involving thiyl radicals as key intermediates is proposed for the present transformation.

Brain white matter microstructural alterations in children of type I Gaucher disease characterized with diffusion tensor MR imaging.

OBJECTIVES: To investigate white matter (WM) microstructural alterations in type I Gaucher disease (type I GD) pediatric patients and explore the correlation between the disease duration and WM changes. METHODS: Twenty-two GD patients and twenty-two sex- and age-matched typical development (TD) children were recruited. Changes in WM were investigated using diffusion tensor imaging (DTI) and applying atlas-based tract analysis. For all DTI measurements, independent-samples t-test was applied to report significant differences between type I GD and TD. Partial correlation was applied to determine whether the disease duration was correlated with DTI measurements. RESULTS: Bidirectional fractional anisotropy (FA) changes were found in the bilateral superior cerebellar peduncle, right posterior limb of the internal capsule, right posterior corona radiata, and right posterior thalamic radiation (p < 0.05). Higher mean diffusivity (MD)was found in the right superior corona radiata, middle cerebellar peduncle, right posterior thalamic radiation and right superior longitudinal fasciculus (p < 0.05) in type I GD. And higher radial diffusivity (RD) was also found in the left superior cerebellar peduncle (p < 0.05) in type I GD. The disease duration of type I GD patients is positively correlated with axial diffusivity and MD in multiple major WM tracts. CONCLUSION: DTI findings supported the microstructural alterations of multiple WM tracts in type I GD patients.

Short-range connections in the developmental connectome during typical and atypical brain maturation.

The human brain is remarkably complex with connectivity constituting its basic organizing principle. Although long-range connectivity has been focused on in most research, short-range connectivity is characterized by unique and spatiotemporally heterogeneous dynamics from infancy to adulthood. Alterations in the maturational dynamics of short-range connectivity has been associated with neuropsychiatric disorders, such as autism and schizophrenia. Recent advances in neuroimaging techniques, especially diffusion magnetic resonance imaging (dMRI), resting-state functional MRI (rs-fMRI), electroencephalography (EEG) and magnetoencephalography (MEG), have made quantification of short-range connectivity possible in pediatric populations. This review summarizes findings on the development of short-range functional and structural connections at the macroscale. These findings suggest an inverted U-shaped pattern of maturation from primary to higher-order brain regions, and possible "hyper-" and "hypo-" short-range connections in autism and schizophrenia, respectively. The precisely balanced short- and long-range connections contribute to the integration and segregation of the connectome during development. The mechanistic relationship among short-range connectivity maturation, the developmental connectome and emerging brain functions needs further investigation, including the refinement of methodological approaches.

Altered Spontaneous Brain Activity in Children with Early Tourette Syndrome: a Resting-state fMRI Study.

Tourette syndrome (TS) is a childhood-onset chronic disorder characterized by the presence of multiple motor and vocal tics. This study investigated the alterations of spontaneous brain activities in children with TS by resting-state functional magnetic resonance imaging (rs-fMRI). We obtained rs-fMRI scans from 21 drug-naïve and pure TS children and 29 demographically matched healthy children. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) of rs-fMRI data were calculated to measure spontaneous brain activity. We found significant alterations of ALFF or fALFF in vision-related structures including the calcarine sulcus, the cuneus, the fusiform gyrus, and the left insula in TS children. Decreased ReHo was found in the right cerebellum. Further analysis showed that the ReHo value of the right cerebellum was positively correlated with TS duration. Our study provides empirical evidence for abnormal spontaneous neuronal activity in TS patients, which may implicate the neurophysiological mechanism in TS children. Moreover, the right cerebellum can be potentially used as a biomarker for the pathophysiology of early TS in children.

BMI-for-Age and Weight-for-Length in Children 0 to 2 Years.

OBJECTIVES: To determine the agreement between weight-for-length and BMI-for-age in children 0 to <2 years by using research-collected data, examine factors that may affect agreement, and determine if agreement differs between research- and routinely collected data. METHODS: Cross-sectional data on healthy, term-born children (n = 1632) aged 0 to <2 years attending the TARGet Kids! practice-based research network in Toronto, Canada (December 2008-October 2014) were collected. Multiple visits for each child were included. Length (cm) and weight (kg) measurements were obtained by trained research assistants during research visits, and by nonresearch staff during all other visits. BMI-for-age z-scores were compared with weight-for-length z-scores (the criterion measure). RESULTS: The correlation between weight-for-length and BMI-for-age was strong (r = 0.986, P < .0001) and Bland-Altman plots revealed good agreement (difference = -0.08, SD = 0.20, P = .91). A small proportion (6.3%) of observations were misclassified and most misclassifications occurred near the percentile cutoffs. There were no differences by age and sex. Agreement was similar between research- and routinely collected data (r = 0.99, P < .001; mean difference -0.84, SD = 0.20, P = .67). CONCLUSIONS: Weight-for-length and BMI-for-age demonstrated high agreement with low misclassification. BMI-for-age may be an appropriate indicator of growth in the first 2 years of life and has the potential to be used from birth to adulthood. Additional investigation is needed to determine if BMI-for-age in children <2 years is associated with future health outcomes.

Amide Proton Transfer (APT) MR imaging and Magnetization Transfer (MT) MR imaging of pediatric brain development.

OBJECTIVES: To quantify the brain maturation process during childhood using combined amide proton transfer (APT) and conventional magnetization transfer (MT) imaging at 3 Tesla. METHODS: Eighty-two neurodevelopmentally normal children (44 males and 38 females; age range, 2-190 months) were imaged using an APT/MT imaging protocol with multiple saturation frequency offsets. The APT-weighted (APTW) and MT ratio (MTR) signals were quantitatively analyzed in multiple brain areas. Age-related changes in MTR and APTW were evaluated with a non-linear regression analysis. RESULTS: The APTW signals followed a decreasing exponential curve with age in all brain regions measured (R(2) = 0.7-0.8 for the corpus callosum, frontal and occipital white matter, and centrum semiovale). The most significant changes appeared within the first year. At maturation, larger decreases in APTW and lower APTW values were found in the white matter. On the contrary, the MTR signals followed an increasing exponential curve with age in the same brain regions measured, with the most significant changes appearing within the initial 2 years. There was an inverse correlation between the MTR and APTW signal intensities during brain maturation. CONCLUSIONS: Together with MT imaging, protein-based APT imaging can provide additional information in assessing brain myelination in the paediatric population. KEY POINTS: • APTW signals followed a decreasing exponential curve with age. • The most significant APTW changes appeared within the first year • At maturation, larger APTW decreases and lower APTW appeared in white matter • MTR signals followed an increasing exponential curve with age.