Age-related changes in the pediatric brain: quantitative MR evidence of maturational changes during adolescence.

PURPOSETo determine whether a quantitative MR imaging method to map spin-lattice relaxation time (T1) can be used to characterize maturational changes in the normal human brain.METHODSAn inversion-recovery technique was used to map T1 transversely at the level of the basal ganglia in a study population of 19 healthy children (4 to 10 years old) and 31 healthy adolescents (10 to 20 years old), and in a normative population of 20 healthy adults (20 to 30 years old).RESULTSNonparametric analysis of variance showed that T1 decreases with age in the genu, frontal white matter, caudate, putamen, anterior thalamus, pulvinar nucleus, optic radiation, cortical gray matter (all P < .0001), and occipital white matter. There was a significant reduction in T1 between childhood (mean age, 7.1 +/- 1.4) and adolescence (mean age, 13.5 +/- 2.6) in all brain structures, but there was also a significant reduction in T1 between adolescence (mean age, 13.5 +/- 2.6) and adulthood (mean age, 26.5 +/- 3.4) in all brain structures except occipital white matter. Regression shows that T1 declines to within the range (mean +/- 2 SD) of young adult T1 values by about 2 years in the occipital white matter, by about 4 years in the genu, by 11 years in the cortical gray matter, by 11 years in the frontal white matter, and by 13 years in the thalamus.CONCLUSIONBrain structures mature at strikingly different rates, yet the ratio of gray matter T1 to white matter T1 does not change significantly with age. Thus, conventional MR imaging methods based on inherent contrast are insensitive to these changes. Age-related changes tend to reach completion sooner in white matter than in gray matter tracts. Such normative data are essential for studies of specific pediatric disorders and may be useful for assessing brain maturation in cases of developmental delay.     

T2?值在健康成年人脑铁含量与年龄的相关性分析

目的：采用3.0T ESWAN 定量测量健康成年人额叶白质区及灰质核团的 T2?值,探讨额叶白质区及灰质核团与年龄的相关性。方法收集年龄20~85岁的157例健康成年人进行 MRI 常规及 ESWAN 扫描,按其年龄段分为6组。A 组：20~29岁;B 组：30~39岁;C 组：40~49岁;D 组：50~59岁;E 组：60~69岁;F 组：≥70岁。经后处理在 T2?图像上分别测量左右侧额叶白质区、红核、黑质网状带、黑质致密带、尾状核头、壳核、苍白球和丘脑的 T2?值,分析 T2?值与年龄的相关性。结果健康成年人在黑质网状带、苍白球的T2?值最低,额叶白质区的T2?值最高。红核、壳核、苍白球、尾状核头和丘脑的T2?值在部分年龄段间有统计学意义(P <0.05),有一定规律性。而黑质网状带、黑质致密带、额叶白质区的 T2?值在不同年龄段间差异无统计学意义(P >0.05)。红核、黑质网状部、黑质致密部、壳核、苍白球、尾状核头的 T2?值与年龄呈明显负相关(r 值=-0.258、-0.229、-0.231、-0.584、-0.320、-0.437, P 值均<0.001),而丘脑、额叶白质区的 T2?值与年龄呈正相关(r 值=0.319、0.161,P <0.001及0.05)。结论ESWAN 能清晰显示脑内核团的结构,准确评估脑内的铁含量和随年龄变化的规律。     

采用磁敏感加权成像技术研究年龄相关的脑铁沉积现象

目的 采用磁敏感加权成像技术,探讨正常人大脑不同区域的铁含量随年龄变化的规律.方法 78名成年健康志愿者按照年龄分为青年组(≤35岁)27名、中年组(36～55岁)35名和老年组(≥56岁)16名,所有受试者均进行磁敏感加权成像,在校正相位图上分别测量苍白球、壳核、尾状核、黑质、红核、丘脑和额叶白质的相位值.30岁以上受试者各脑区的平均相位值和文献报道的脑铁实际含量进行Pearson相关分析,采用单因素方差分析比较各脑区不同年龄组之间的校正相位值差异.用线性回归分析法进一步研究由方差分析法所揭示的年龄相关的铁含量变化,并计算其变化率.结果 各脑区的平均相位值和文献报道的脑铁实际含量问存在负相关性(r=-0.796,P=0.032),铁含量多的脑区相位值的负值大.青年组、中年组和老年组壳核相位值的中位数分别是-0.0185、-0.0362和-0.0566,额叶白质相位值中位数分别是0.0034、-0.0031和-0.0021,各年龄组间的差异具有统计学意义(F值分别为20.115、3.536,P值分别＜0.01、＜0.05).线性回归分析表明,壳核、红核和额叶白质的铁含量随着年龄的增加而增加(回归系数分别为-0.001、-0.001、＜-0.001,P值均＜0.05),苍白球、尾状核、黑质和丘脑的铁含量不随年龄而变化.结论 研究结果证明并拓展了对年龄相关的脑铁沉积现象的认识,为全面、准确认识疾病相关的脑铁异常沉积现象提供了必要的基础.     

Precise and accurate measurement of proton T1 in human brain in vivo: Validation and preliminary clinical application

Precise and accurate inversion-recovery (PAIR) magnetic resonance (MR) measurements of T1 were obtained in eight brain regions and cerebrospinal fluid of 26 healthy volunteers. Accuracy of the technique was assessed by measuring T1 in small fluid volumes with the PAIR technique and with two independent spectroscopic techniques. The mean difference between T1 measured with PAIR and with the two spectroscopic techniques was 3.1% ± 1.3. The precision (reproducibility) of measurements with the PAIR technique was excellent. The coefficient of variation (CV) across 16 measurements in a head phantom was 2.0%, compared with a CV of 2.7% across 45 separate measurements in a single subject. The within-subject CV was 1.8% ± 0.6 in white matter and 1.4% ± 1.0 in basal ganglia. The between-subject CV in 26 healthy volunteers was 3.6% ± 0.6 in white matter and 4.1% ± 1.9 in basal ganglia. Comparison between a patient with an active recurrent brain tumor and an agematched patient with an inactive brain tumor showed that T1 was significantly elevated throughout the brain of the active-tumor patient, especially in white matter tracts, even though no tumor or edema was detected in the white matter on standard MR images. Comparisons between five brain tumor patients and four healthy volunteers of similar age showed that T1 was significantly and substantially elevated throughout the white matter tracts and in the caudate nucleus, putamen, and thalamus. These results are consistent with the hypothesis that white matter tracts are selectively vulnerable to edema and that T1 increases in white matter are a sensitive indicator of patient status or tumor aggressiveness.     

”Ecstasy”-induced changes of cerebral glucose metabolism and their correlation to acute psychopathology

The aim of this study was to determine the acute effects of the ”Ecstasy” analogue MDE (3,4-methylene dioxyethamphetamine) on cerebral glucose metabolism (rMRGlu) of healthy volunteers and to correlate neurometabolism with acute psychopathology. In a randomized double-blind trial, 15 healthy volunteers without a history of drug abuse were examined with fluorine-18-deoxyglucose (¹⁸FDG) positron emission tomography (PET) 110–120 min after oral administration of 2 mg/kg MDE (n=7) or placebo (n=8). Two minutes prior to radiotracer injection, constant cognitive stimulation was started and maintained for 32 min using a word repetition paradigm to ensure constant and comparable mental conditions during cerebral glucose uptake. Individual brain anatomy was represented using T1-weighted 3D flash magnetic resonance imaging (MRI), followed by manual regionalization into 108 regions of interest and PET/MRI overlay. After absolute quantification of rMRGlu and normalization to global metabolism, normalized rMRGlu under MDE was compared to placebo using the Mann-Whitney U-test. Acute psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and rMRGlu was correlated to PANSS scores according to Spearman. MDE subjects showed significantly decreased rMRGlu in the bilateral frontal cortex: left frontal posterior (–7.1%, P<0.05) and right prefrontal superior (–4.6%, P<0.05). On the other hand, rMRGlu was significantly increased in the bilateral cerebellum (right: +10.1%, P<0.05; left: +7.6%, P<0.05) and in the right putamen (+6.2%, P<0.05). There were positive correlations between rMRGlu in the middle right cingulate and grandiosity (r=0.87, P<0.05), both the right amygdala (r=0.90, P<0.01) and the left posterior cingulate (r=0.90, P<0.01) to difficulties in abstract thinking, and the right frontal inferior (r=0.85, P<0.05), right anterior cingulate (r=0.93, P<0.01), and left anterior cingulate (r=0.85, P<0.05) to attentional deficits. A negative correlation was found between the left frontal operculum (Broca’s area) and attentional deficits (r=–0.85, P<0.05). The present study revealed acute neurometabolic changes under the ”Ecstasy” analogue MDE, indicating a frontostriatocerebellar imbalance paralleling other psychotropic substances or various psychiatric disorders. Received 10 May and in revised form 16 August 1999     

Bilateral pre- and postcentral gyrus volume positively correlates with T2-SNR of putamen in healthy adults

Introduction

The aim of the present study was to investigate the correlation between local gray matter volume and signal-to-noise ratio on T2-weighted imaging (T2-SNR) of putamen in healthy adults using two tools: voxel-based morphometry (VBM) treating age as a confounding covariate to control for age-related gray matter volume changes and high spatial resolution T1-weighted imaging acquired with a 3.0-T magnetic resonance (3T-MR) scanner.

Methods

Contiguous sagittal T1-weighted images and axial T2-weighted images of the brain were obtained from 1,380 healthy participants. T2-SNR of putamen was defined as A/B, where A is the mean T2-weighted signal intensity (T2-SI) in the right and left sides of putamen, and B is the background noise. The software Statistical Parametric Mapping 5 was used for image segmentation. The association between T2-SNR of putamen and gray matter volume was assessed with VBM, treating age as a confounding covariate.

Results

A significant positive correlation was obtained between T2-SNR of putamen and bilateral pre- and postcentral gyrus volume.

Conclusion

To the best of our knowledge, this is the first VBM study to show an age-independent relationship between T2-SNR of putamen and bilateral pre- and postcentral gyrus volumes in healthy adults.     

Quantitative MR imaging of children with sickle cell disease: Striking T1 elevation in the thalamus

Nineteen patients with sickle cell disease (SCD) were examined with conventional MR imaging (cMRI), including T1- and T2-weighted sequences and MR angiography (MRA). qMRI mapping of T1 was also done using a precise and accurate inversion-recovery (PAIR) technique optimized and validated previously. In addition, 21 healthy African-American control subjects had the qMRI examination. Nonparametric Kruskal-Wallis analysis of variance of control subjects, of SCD patients without stroke, and of SCD patients with stroke showed that T1 increased with disease severity in the thalamus, frontal white matter, genu, and occipital white matter. T1 was significantly longer in SCD patients without stroke (n=13) than in control subjects (n=21) in the thalamus and frontal white matter. In addition, T1 values were significantly longer in SCD patients with stroke than in patients without stroke in the genu and frontal white matter. Abnormality of the thalamus was identified by qMRI in a substantial fraction of patients read as normal by both cMRI and MRA, suggesting that it may be possible to use T1 elevation to identify a subset of patients with SCD who are at elevated risk for stroke.     

Magnetic resonance fiber density mapping of age-related white matter changes

Objectives

To introduce fiber density mapping (FDM) for investigation of age-related white matter (WM) changes and to compare its capabilities with conventional diffusion tensor imaging (DTI) post-processing.

Methods

DTI data with 1.9 mm³ isotropic voxels were acquired from 44 healthy volunteers (18–88 years) at 3 T. FDM is a 3-step approach which includes diagonalization of the diffusion tensor, fiber reconstruction for the whole brain, and calculation of fiber density (FD) values. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were additionally calculated. Voxel-based analyses were performed to determine volume clusters of significant correlation with age. Bivariate linear regression models and Hotelling–Williams tests were used to detect significant differences between correlations.

Results

FDM detected a larger WM volume affected by age-related changes concomitant with fewer significant clusters compared to FA and MD. This indicates that WM alterations due to normal aging occur rather globally than locally. FD values showed a significant stronger correlation with age in frontal lobes (prefrontal and precentral gyrus), limbic lobes (cingulate and parahippocampal gyrus), the corpus callosum (genu) and temporal lobes.

Conclusions

FDM shows higher sensitivity for detection of age-related WM changes because it includes all surrounding fiber structures into the evaluation of each DTI data voxel.     

Detection of age related differences in CBF with PCASL using 2 post label delays

BackgroundThe brain is reliant on an abundant and uninterrupted CBF for normal neural function because it is an organ with high metabolic activity and limited ability to store energy.PurposeThis study aimed to compare age-related variations in CBF measured with PCASL.MethodsThis prospective study included healthy volunteers at the Radiology Department of Shanxi Cardiovascular Hospital between October 2018 and July 2019. The volunteers were divided into three groups (n = 30 per group): young (≤44 years), middle-aged (45–59 years) and elderly (≥60 years). CBF was measured by PCASL using 2 post label delays (PLD) (PLD = 1.5 s, 2.5 s), and compared between PLDs and groups. The relation between CBF value and age was assessed by Pearson correlation analysis.ResultsFor PLD = 1.5 s, CBF differed significantly between groups for all brain regions (P < 0.05), with higher values in the young group and lower values in the elderly group. For PLD = 2.5 s, the young and middle-aged groups had broadly comparable CBF values, whereas the elderly group had higher CBF values (P < 0.05) for most brain regions. For both PLDs, no brain regions showed significant differences in CBF values between males and females. The CBF of all brain regions was negatively correlated with age for PLD = 1.5 s (P < 0.05) but not PLD = 2.5 s. Compared with PLD = 1.5 s, PLD = 2.5 s yielded lower CBF values for the young group and higher CBF values for the elderly group.Conclusion3D-pCASL with dual PLDs can non-invasively evaluate age-related changes in CBF in healthy people.     

Quantitative multivoxel <Superscript>1</Superscript>H MR spectroscopy of the brain in children with acute liver failure

Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase).     

Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I

Objective

Dopamine transporter (DAT) density is considered as a marker of pre-synaptic function. Numerous neuroimaging studies have consistently demonstrated an age-related decrease in DAT density in normal human brain. However, the precise degree of the regional decline is not yet clear. The purpose of this study was to evaluate the effect of the normal aging process on DAT densities in human-specific brain regions including the substantia nigra and thalamus using positron emission tomography (PET) with [¹⁸F]FE-PE2I, a new PET radioligand with high affinity and selectivity for DAT.

Methods

Thirty-six healthy volunteers ranging in age from 22 to 80 years were scanned with PET employing [¹⁸F]FE-PE2I for measuring DAT densities. Region of interest (ROI)-based analysis was used, and ROIs were manually defined for the caudate, putamen, substantia nigra, thalamus, and cerebellar cortex. DAT binding was quantified using a simplified reference tissue model, and the cerebellum was used as reference region. Estimations of binding potential in the caudate, putamen, substantia nigra, and thalamus were individually regressed according to age using simple regression analysis. Estimates of DAT loss per decade were obtained using the values from the regression slopes.

Results

There were 7.6, 7.7, and 3.4 % per-decade declines in DAT in the caudate, putamen, and substantia nigra, respectively. By contrast, there was no age-related decline of DAT in the thalamus.

Conclusions

[¹⁸F]FE-PE2I allowed reliable quantification of DAT, not only in the caudate and putamen but also in the substantia nigra. From the results, we demonstrated the age-related decline in the caudate and putamen as reported in previous studies, and additionally for those in the substantia nigra for the first time.     

In vivo quantitative proton MRSI study of brain development from childhood to adolescence

PURPOSE: To quantify regional variations in metabolite levels in the developing brain using quantitative proton MR spectroscopic imaging (MRSI). MATERIALS and METHODS: Fifteen healthy subjects three to 19 years old were examined by in vivo multislice proton MRSI. Concentrations of N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), and peak area ratios were determined in selected frontal and parietal gray and white matter regions, basal ganglia, and thalamus. RESULTS: In cortical gray matter regions, the ratio of NAA/Cho increased to a maximum at 10 years and decreased thereafter (P = 0.010). In contrast, in white matter, average ratios NAA/Cho increased linearly with age (P = 0.045). In individual brain regions, age-related changes in NAA/Cho were found in the putamen (P = 0.044). No significant age-related changes in NAA, Cho, Cr, or other metabolite ratios could be determined. CONCLUSION: Consistent with recent studies using other structural and functional neuroimaging techniques, our data suggest that small but significant changes occur in regional cerebral metabolism during childhood and adolescence. Non-linear age related changes of NAA/Cho in frontal and parietal areas, resembling previously reported age related changes in rates of glucose utilization and cortical volumes, may be associated with dendritic and synaptic development and regression. Linear age-related changes of NAA/Cho in white matter are also in agreement with age-related increases in white matter volumes, and may reflect progressive increases in axonal diameter and myelination.     

Localized brain proton NMR spectroscopy in young adult phenylketonuria patients

Localized proton magnetic resonance spectroscopy with short echo time (TE = 20 ms) was used to investigate biochemical changes in the cerebral white matter of 20 young adult patients (median 19 years) with phenylketonuria (PKU). Results were compared with those of a group of 12 age-matched healthy volunteers (median 25 years). Concentrations of Nacetyl-aspartate (NAA) and choline (Cho) relative to creatine (Cr) were unchanged. However, concentrations of inositol (Ins) relative to creatine were found to be significantly lower (P < 0.001) in the PKU patients (0.30 ± 0.09 versus 0.57 ± 0.17). Individual inositol concentrations did not correlate with age, diet, serum phenylalanine (Phe) levels or extent of pathological regions in the T,-weighted images. The lack of correlation with individual data suggests that the decreased inositol concentration could be related to a metabolic deficiency during fetal development. No signal from the phenyl ring protons of phenylalanine was detected in the PKU patients (phenylalanine serum concentration ? 1.27 mM), which suggests that concentration of phenylalanine may be lower in brain than in serum.     

Increased self-diffusion of brain water in normal aging

With magnetic resonance (MR) imaging, brain water self-diffusion was measured in 17 healthy volunteers 22–76 (mean, 44.6) years old. The calculated values for the apparent diffusion coefficients (ADCs) ranged from 0.58 × 10^?9 to 1.23 × 10^?9 m²/sec in cerebral white matter. A significant correlation was found between the ADC in white matter and age (r =.7069, P <.01). The calculated values for ADC in cortical gray matter ranged from 1.06 × 10^?9 to 1.72 × 10^?9 m²/sec no correlation was found between ADCs in gray matter and age. The increased ADC in white matter may be caused by an increase in the extracellular volume due to age-dependent neuronal degeneration or to changes in myelination. These findings have implications for future clinical investigations with diffusion MR imaging techniques in patients with neurologic diseases, and stress the importance of having an agematched group of healthy volunteers for comparison.     

Glucocorticoid treatment of brain tumor patients: changes of apparent diffusion coefficient values measured by MR diffusion imaging

Glucocorticoids (GCC) generally are administered to patients with brain tumors to relieve neurological symptoms by decreasing the water content in a peritumoral zone of edema. We hypothesized that diffusion imaging and apparent diffusion coefficient (ADC) values could detect subtle changes of water content in brain tumors and in peritumoral edema after GCC therapy. The study consisted of 13 patients with intra-axial brain tumor, and ADC was measured in the tumor, within peritumoral edema, and in normal white matter remote from the tumor before and after GCC therapy. ADC also was measured in normal white matter in four control patients with no intracranial disease who were treated with GCC for other indications. Conventional MR images showed no visually evident interval change in tumor size or the extent of peritumoral edema in any subject after GCC therapy, which nonetheless resulted in a decrease in mean ADC of 7.0% in tumors (P<0.05), 1.8% in peritumoral edema (P>0.05, not significant) and 5.8% in normal white matter (P<0.05). In patients with no intracranial disease, GCC therapy decreased mean ADC in white matter by 5.4% (P<0.05). ADC measurement can demonstrate subtle changes in the brain after GCC therapy that cannot be observed by conventional MR imaging. Measurement of ADC proved to be a sensitive means of assessing the effect of GCC therapy, even in the absence of visually discernible changes in conventional MR images.     

MRI of neuronal ceroid lipofuscinosis

We studied 30 patients with juvenile neuronal ceroid lipofuscinosis (JNCL). The patients (aged 6–25 years) and 43 age-matched healthy volunteers underwent MRI. After visual assessment, the signal intensity was measured on T2-weighted images in numerous locations. The thickness of the cortex and corpus callosum and the dimensions of the brain stem were measured. Mild to moderate cerebral atrophy was found in 14 of 30 patients, most of them over 14 years of age; 5 older patients had mild to moderate cerebellar atrophy. There was reduction in the size of the corpus callosum and brain stem. The thalamus, caudate nucleus and putamen appeared to give low signal in patients from the ages of 7, 11 and 11 years, respectively. In contrast, the signal intensity measured from the thalamus in these patients showed only a slight (insignificant) decrease compared with controls. The most significant alteration, an increase in measured signal intensity, was found in the white matter (P<0.0001), even in the youngest patients. The MRI findings correlated significantly with decreased intelligence, speech disturbances and motor problems. Although MRI findings in JNCL do not appear very specific and the visual changes develop relatively late, the absence of pathological MRI findings in the very early stage of the disease may play a part in differential diagnosis of the different types of NCL. Furthermore, the MRI findings may be used in assessing severity and prognosis, particularly in young patients.     

Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI

Conventional MRI (cMRI) has shown that brain abnormalities without clinical stroke can manifest in patients with sickle cell disease (SCD). We used quantitative MRI (qMRI) and psychometric testing to determine whether brain abnormalities can also be present in patients with SCD who appear normal on cMRI. Patients 4 years of age and older with no clinical evidence of stroke were stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice relaxation time (T1) of gray and white matter structures was measured by the precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive ability was assessed with a standard psychometric instrument (WISC-III or WISC-R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race-matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel T1 show that the proportion of voxels with T1 values intermediate between gray and white matter (ie, consistent with encephalomalacia) was 9% higher than controls in patients shown to be normal by cMRI (P < .05) and 15% higher than controls in patients shown to be abnormal by cMRI (P < .0005). The full scale intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by cMRI was significantly lower than both the patient siblings (P < .005) and the patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by cMRI scored lower than patients shown to be normal by cMRI, specifically on the subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment is thus significant, even in patients with SCD who were shown to be normal by cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that can be detected by qMRI. Because cognitive impairment can occur in children normal by cMRI, our findings imply that prophylactic therapy may be needed earlier in the course of SCD to mitigate neurologic damage.     

Estimation of the iron concentration in excised gray matter by means of proton relaxation measurements

To validate their correlation with tissue iron concentration, proton transverse relaxation measurements have been made at 2.35 T (100 MHz) in 25 samples of excised, frozen, but unfixed human gray matter tissue obtained from the globus pallidus, putamen, caudate, thalamus, and cortex of five postmortem brains free of neurological disease. The iron concentration was independently measured, using atomic absorption spectroscopy. The proton transverse relaxation measurements exploited the interecho time dependence of the apparent transverse relaxation rate, R_2app, obtained from a Carr-Purcell-Meiboom-Gill (CPMG) sequence. An empirical semilogarithmic relationship between R_2app and the interecho time provided a measure of the relaxation enhancement due to iron, namely, a slope p, which demonstrated a significant correlation (r = 0.78, P < 0.001) with tissue iron concentration. Moreover, a simple rate difference, δR_2app, determined between interecho time values of 6 and 60 ms, was also found to correlate significantly with iron concentration (r = 0.81, P < 0.001). Both of the foregoing correlations were better than that of R_2app itself. When the tissue samples were subdivided into brain structure groups, the intergroup differences in p reflected their known differences in iron accumulation and correlated with those of the mean group iron content, determined by atomic absorption spectrometry.     

Brain regional α-[<Superscript>11</Superscript>C]methyl-<Emphasis Type="SmallCaps">L</Emphasis>-tryptophan trapping,used as an index of 5-HT synthesis,in healthy adults: absence of an age effect

Purpose Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional α-[¹¹C]methyl-L-tryptophan (α-[¹¹C]MTrp) trapping rate constant (K*; μl·g⁻¹·min⁻¹), which, with certain assumptions, could be taken as a proxy of 5-HT synthesis. Methods Thirty-six healthy right-handed subjects had positron emission tomography (PET) scans following injection with α-[¹¹C]MTrp [18 males aged 46.6 ± 22.2 years (range 20–80 years) and 18 females aged 33.0 ± 15.5 years (range 20–80 years)]. The trapping rate constant, K*, was calculated with the graphical method for irreversible ligands using the sinus-venous input function. A priori selected volumes of interest (VOIs) were defined using an automatic algorithm. Results VOI analysis showed no correlation between age and brain regional K* values. As reported by others, significant age-related reductions of gray matter were observed in the thalamus and frontal and cingulate cortices; even with partial volume correction there was still no significant relationship between K* and age. Further exploratory SPM voxelwise correlation between age and α-[¹¹C]MTrp trapping, using p = 0.05 (uncorrected), as well as voxel-based morphometry, was in agreement with the VOI analysis. Conclusion The dissociation between age-related changes in brain anatomy and this index of serotonin synthesis suggests independent mechanisms underlying the normal aging process.     

Effects of Head Motion on the Evaluation of Age-related Brain Network Changes Using Resting State Functional MRI

Purpose:The estimation of functional connectivity (FC) measures using resting state functional MRI (fMRI) is often affected by head motion during functional imaging scans. Head motion is more common in the elderly than in young participants and could therefore affect the evaluation of age-related changes in brain networks. Thus, this study aimed to investigate the influence of head motion in FC estimation when evaluating age-related changes in brain networks.Methods:This study involved 132 healthy volunteers divided into 3 groups: elderly participants with high motion (OldHM, mean age (±SD) = 69.6 (±5.31), N = 44), elderly participants with low motion (OldLM, mean age (±SD) = 68.7 (±4.59), N = 43), and young adult participants with low motion (YugLM, mean age (±SD) = 27.6 (±5.26), N = 45). Head motion was quantified using the mean of the framewise displacement of resting state fMRI data. After preprocessing all resting state fMRI datasets, several resting state networks (RSNs) were extracted using independent component analysis (ICA). In addition, several network metrics were also calculated using network analysis. These FC measures were then compared among the 3 groups.Results:In ICA, the number of voxels with significant differences in RSNs was higher in YugLM vs. OldLM comparison than in YugLM vs. OldHM. In network analysis, all network metrics showed significant (P < 0.05) differences in comparisons involving low vs. high motion groups (OldHM vs. OldLM and OldHM vs. YugLM). However, there was no significant (P > 0.05) difference in the comparison involving the low motion groups (OldLM vs. YugLM).Conclusion:Our findings showed that head motion during functional imaging could significantly affect the evaluation of age-related brain network changes using resting state fMRI data.