Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis

BACKGROUND AND PURPOSE: A technique of segmenting total gray matter (GM) and total white matter (WM) in human brain is now available. We investigated the effects of age and sex on total fractional GM (%GM) and total fractional WM (%WM) volumes by using volumetric MR imaging in healthy adults. METHODS: Fifty-four healthy volunteers (22 men, 32 women) aged 20-86 years underwent dual-echo fast spin-echo MR imaging. Total GM, total WM, and intracranial space volumes were segmented by using MR image-based computerized semiautomated software. Volumes were normalized as a percentage of intracranial volume (%GM and %WM) to adjust for variations in head size. Age and sex effects were then assessed. RESULTS: Both %GM and %WM in the intracranial space were significantly less in older subjects (> or =50 years) than in younger subjects (<50 years) (P <.0001 and P =.02, respectively). Consistently, %GM decreased linearly with age, beginning in the youngest subjects. %WM decreased in a quadratic fashion, with a greater rate beginning only in adult midlife. Although larger GM volumes were observed in men before adjustments for cranium size, no significant differences in %GM or %WM were observed between the sexes. CONCLUSION: GM volume loss appears to be a constant, linear function of age throughout adult life, whereas WM volume loss seems to be delayed until middle adult life. Both appear to be independent of sex. Quantitative analysis of %GM and %WM volumes can improve our understanding of brain atrophy due to normal aging; this knowledge may be valuable in distinguishing atrophy of disease patterns from characteristics of the normal aging process.     

Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis.

PURPOSE: The purpose of this work was to determine the extent of disease and disease severity in the conventional MR normal-appearing gray matter (NAGM) and white matter (NAWM) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) utilizing quantitative magnetization transfer ratio (MTR) histogram analysis. METHOD: Twenty-seven patients with MS (16 RR, 11 SP) and 16 healthy control subjects were studied. MTR was calculated in the totally segmented GM and WM without T2 lesions in each group. RESULTS: Each of the RR and SP MS patient groups had significantly smaller MTR histogram mean values in NAGM and NAWM than the healthy subjects (p 相似文献   

Dirty-appearing white matter in multiple sclerosis: volumetric MR imaging and magnetization transfer ratio histogram analysis

BACKGROUND AND PURPOSE: In contrast to "normal-appearing" white matter (NAWM) in patients with multiple sclerosis (MS), there are subtle, abnormal and diffuse signal intensity changes often seen on T2-weighted MR images, which we have referred to as "dirty-appearing" white matter (DAWM). These areas of DAWM have slightly higher signal intensity than that of NAWM, but lower than that of lesion plaques. Our study was designed to determine the volumetric and magnetization transfer ratio (MTR) features of DAWM in patients with MS. METHODS: Dual-echo fast spin-echo MR imaging and magnetization transfer imaging were performed in 22 patients with relapsing-remitting MS. Slightly hyperintense DAWM areas were manually outlined on the basis of T2-weighted imaging findings. The volume and MTR of DAWM were calculated and compared with the volume and MTR of NAWM and T2 lesion plaques. RESULTS: The average volume of DAWM (18.3 mL) was greater than the average volume of T2 lesion plaques (11.0 mL, P =.04), and the mean MTR in DAWM (38.7%) differed significantly (P <.0001) from that in NAWM (40.7%) and plaques (33.3%). There was a modest negative correlation between either mean MTR (r = -0.60; P =.003) of DAWM or peak height (r = -0.50; P =.02) of DAWM with T2 lesion load. Neither DAWM volume nor total T2 abnormality (DAWM + plaques) volume correlates with the Expanded Disability Status Scale. CONCLUSION: The results of this study indicate that MTR is able to differentiate DAWM from lesion plaques and NAWM and that DAWM might be a different pathologic process of the disease. The notion and quantification of these subtle imaging findings of DAWM areas may improve our understanding of certain stages of disease progression and disease burden in patients with relapsing-remitting MS.     

Multiple sclerosis: magnetization transfer histogram analysis of segmented normal-appearing white matter

PURPOSE: To investigate and characterize the global distribution of magnetization transfer (MT) ratio values of normal-appearing white matter (NAWM) in patients with relapsing-remitting multiple sclerosis (MS) and test the hypothesis that the MT histogram for NAWM reflects disease progression. MATERIALS AND METHODS: Conventional and MT magnetic resonance (MR) images were obtained in 23 patients and 25 healthy volunteers. Clinical tests for comparison with the MT histogram parameters included the Extended Disability Status Scale and the ambulation index. Lesion load calculated with T2-weighted MR images and whole-brain and white matter volumes were measured. RESULTS: The location of the MT histogram peak and the mean MT ratio for NAWM were significantly lower in patients with MS than in control subjects. In longitudinal studies, the histogram peak location and mean MT ratio shifted in the direction of normal values as the duration of disease increased. A mean of 26.5% of the volume of new lesions identified on the later studies were demonstrated to have originated in NAWM corresponding to "lost" pixels on the histogram. CONCLUSION: MT histogram analysis of NAWM, including longitudinal analysis, may provide new prognostic information regarding lesion formation and increase understanding of the course of the disease.     

Whole brain imaging of HIV-infected patients: quantitative analysis of magnetization transfer ratio histogram and fractional brain volume

BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) histogram analysis and volumetric MR imaging are sensitive tools with which to quantify the tissue destructive effects in patients with white matter or neurodegenerative disease. Our purpose was to determine whether whole brain MTR and fractional brain parenchyma volume measurements are altered in HIV-1-infected patients who are neurologically symptomatic and in those who are asymptomatic. METHODS: We performed MR imaging and MTR studies of 15 neurologically symptomatic (seven patients) and asymptomatic (eight patients) HIV-1-seropositive patients and compared their findings with those of 10 seronegative normal control participants. MTR was computed on the basis of whole brain parenchyma segmented by using thin section dual echo MR images. RESULTS: The loss of brain tissue, indicated by fractional brain parenchyma volume, was more pronounced in neurologically symptomatic patients (P =.003) but not in asymptomatic patients (P =.23) when compared with control participants. As for whole brain MTR histogram analysis, both patient groups showed significant decrease in mean (P =.02) and median (P < or =.009) values, compared with normal control participants. There was a trend toward positive correlation (r > or = 0.56) between MTR histogram statistics and fractional brain parenchyma volume. CONCLUSION: Our results suggest that MTR histogram analysis is sensitive in detecting early involvement in neurologically asymptomatic patients with HIV and may, therefore, be used as a combined tool with volumetric measurement, which showed significant tissue loss only in symptomatic patients, to assess various stages of brain damage induced by HIV.     

A multicenter measurement of magnetization transfer ratio in normal white matter

To assess the importance of intercenter variations when measuring magnetization transfer ratio (MTR) in the brain, six European centers measured MTR in normal white matter. MTR ranged from 9 to 51 percent units (25 sequences). The effective flip angle of the saturating pulse divided by the pulse repetition time (ENRsat degrees/msec) was a good predictor of MTR (MTR = 3.25 ENRsat).     

Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: Gray matter may be affected by multiple sclerosis (MS), a white matter disease. Magnetization transfer ratio (MTR) is a sensitive and quantitative marker for structural abnormalities, and has been used frequently in the imaging of MS. In this study, we evaluated the amount of MTR of gray matter among patients with relapsing-remitting MS and healthy control subjects as well as the correlation between gray matter MTR abnormality and neurologic disability associated with relapsing-remitting MS. METHODS: We obtained fast spin-echo dual-echo and magnetization transfer (with and without MT saturation pulses) images from eighteen patients with relapsing-remitting MS and 18 age-matched healthy control subjects. Gray matter was segmented using a semiautomated system. Gray matter MTR histogram parameters, Kurtzke Expanded Disability Status Scale (EDSS), total T2 lesion volume, and gray matter volumes were obtained for statistical analysis. RESULTS: A significant difference was found in gray matter MTR between patients with relapsing-remitting MS and healthy subjects (mean and median). Gray matter MTR histogram normalized peak heights in patients inversely correlated with EDSS (r = -0.65, P =.01). There was also an inverse correlation between mean MTR of gray matter and total T2 lesion volume. CONCLUSION: The MTR of gray matter significantly differed between patients with relapsing-remitting MS and healthy control subjects, suggesting that MS is a more diffuse disease affecting the whole brain, and neuronal damage accumulates in step with T2 lesion volume. Our finding of the relationship between gray matter MTR and EDSS indicates that measurement of gray matter abnormality may be a potentially useful tool for assessing clinical disability in MS.     

Concentrations and magnetization transfer ratios of metabolites in gray and white matter.

The concentrations and magnetization transfer ratios (MTRs) in gray matter (GM) and white matter (WM) of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (Ins), and glutamate plus glutamine (Glx) were investigated using magnetic resonance spectroscopic imaging (MRSI). The macromolecule (MM) baseline was studied separately using a metabolite-nulling inversion. Three data sets were collected from a point-resolved spectroscopy (PRESS)-selected volume (TE/TR = 30/3000 ms) of human frontal lobe in vivo: one with MT pulses applied, one with an inversion pulse to null small metabolites, and one with no inversion or MT pulses. The MM signal, which was analyzed by integrating the metabolite-nulled spectrum between 0 and 3 ppm, was estimated to be 38% higher in GM than in WM. MM subtraction decreased the signal-to-noise ratio (SNR) and also decreased the reliability of LCModel quantification of most metabolites, but may have improved the accuracy of quantification of Glx. Glx and Cr were both found to correlate strongly with the GM volume fraction of the voxels. Cr showed the highest MTR, but the other metabolites also showed some attenuation of signal when the MT pulses were applied. The MTRs did not correlate with the GM volume fraction, which implies that the local environment of metabolites does not differ markedly between GM and WM.     

Lobar distribution of changes in gray matter and white matter in memory clinic patients: detected using magnetization transfer imaging

BACKGROUND AND PURPOSE: Previous studies have shown involvement of both gray matter (GM) and white matter (WM) in mild cognitive impairment (MCI) and Alzheimer disease (AD). In this study, we assessed the lobar distribution of the GM and WM pathology over the brain and the association of lobar distribution with global cognitive decline. MATERIALS AND METHODS: Fifty-five patients with AD, 19 patients with MCI, and 43 subjects with normal cognitive function participated in this study. GM and WM were segmented on dual fast spin-echo and fluid-attenuated inversion recovery MR images. A custom template representing anatomic areas was applied. Magnetization transfer imaging (MTI) peak height and mean magnetization transfer ratio (MTR) provided measures for structural brain damage. RESULTS: Both mean MTR and MTI peak height showed that patients with AD had more structural brain damage in the GM of all lobes compared with controls. Patients with MCI had lower GM peak height compared with controls for the temporal and frontal lobe. WM peak height was lower for all lobes investigated for patients with both AD and MCI. WM mean MTR was lower in the frontal, parietal, and temporal lobes for patients with AD compared with controls. Age and both temporal GM peak height and mean MTR were the only parameters that predicted cognition. CONCLUSION: This study shows that in addition to more focal GM MTI changes in the temporal and frontal lobes, widespread WM changes are present in the earliest stages of AD. This might point to an important role for WM pathology in the earliest stage of AD.     

Regional variations in normal brain shown by quantitative magnetization transfer imaging.

A quantitative magnetization transfer imaging (qMTI) study, based on a two-pool model of magnetization transfer, was performed on seven normal subjects to determine, on a regional basis, normal values for the pool sizes, exchange, and relaxation parameters that characterize the MT phenomenon. Regions were identified on high-resolution anatomical scans using a combination of manual and automatic methods. Only voxels identified as pure tissue at the resolution of the quantitative scans were considered for analysis. While no left/right differences were observed, significant differences were found among white-matter regions and gray-matter regions. These regional differences were compared with existing cytoarchitectural data. In addition, the pattern and magnitude of the regional differences observed in white matter was found to be different from that reported previously for an alternative putative MRI measure of myelination, the 10-50-ms T2 component described as myelin water.     

Inverse T(2) contrast at 1.5 Tesla between gray matter and white matter in the occipital lobe of normal adult human brain.

T(2) of cortical gray matter is generally assumed to be longer than that of white matter. It is shown here that this is not the case in the occipital lobe, but that this effect is often obscured at lower resolution and concealed in standard T(2)-weighted images. Using a high-resolution (1 x 1.3 x 2 mm(3)) segmented EPI Carr-Purcell-Meiboom-Gill sequence, T(2) relaxation times of the brain were measured at 1.5 T for eight healthy adult volunteers. The average T(2) values of cortical gray and white matter were found to be 88 +/- 2 and 84 +/- 3 msec in the frontal lobe, 84 +/- 2 and 83 +/- 3 msec in the parietal lobe, and 79 +/- 1 and 87 +/- 3 msec in the occipital lobe, respectively. This unexpected occipital T(2) contrast between gray and white matter is attributed to regional differences in iron concentration.     

Regional magnetization transfer ratio changes in mild cognitive impairment.

Reduction in temporal lobe volume is consistently found in dementia of Alzheimer's type (DAT). However, due to the lack of a consistent association between brain volume and cognitive decline in mild cognitive impairment (MCI), volumetric measures are not a reliable predictor for the progression of the disease. In our study, we hypothesized that changes in the magnetization transfer ratio (MTR) may reflect underlying brain pathology in the absence of quantifiable volumetric changes. Such a measure may be used as a predictor for abnormal cognitive decline in elderly subjects. The study was carried out on 15 normal elderly controls, 11 subjects with DAT, and 12 subjects with MCI. We used MTRs with magnetic resonance imaging (MRI) to detect tissue changes in the four lobes of each hemisphere, and compared that to the volumetric changes in the same regions. Our results indicate that the MTR of both temporal lobes is significantly reduced in subjects with MCI in the absence of significant volumetric changes. In comparison, DAT subjects have significantly reduced temporal lobe volumes and MTR. We conclude that changes in MTR have the potential to mark the progression of MCI to DAT, before volumetric changes are detected on conventional MRI scans.     

Diffusion-tensor MR imaging of gray and white matter development during normal human brain maturation

BACKGROUND AND PURPOSE: Conventional MR imaging findings of human brain development are thought to result from decreasing water content, increasing macromolecular concentration, and myelination. We use diffusion-tensor MR imaging to test theoretical models that incorporate hypotheses regarding how these maturational processes influence water diffusion in developing gray and white matter. METHODS: Experimental data were derived from diffusion-tensor imaging of 167 participants, ages 31 gestational weeks to 11 postnatal years. An isotropic diffusion model was applied to the gray matter of the basal ganglia and thalamus. A model that assumes changes in the magnitude of diffusion while maintaining cylindrically symmetric anisotropy was applied to the white matter of the corpus callosum and internal capsule. Deviations of the diffusion tensor from the ideal model predictions, due to measurement noise, were estimated by using Monte Carlo simulations. RESULTS: Developing gray matter of the basal ganglia and developing white matter of the internal capsule and corpus callosum largely conformed to theory, with only small departures from model predictions in older children. However, data from the thalamus substantially diverged from predicted values, with progressively larger deviations from the model with increasing participant age. CONCLUSION: Changes in water diffusion during maturation of central gray and white matter structures can largely be explained by theoretical models incorporating simple assumptions regarding the influence of brain water content and myelination, although deviations from theory increase as the brain matures. Diffusion-tensor MR imaging is a powerful method for studying the process of brain development, with both scientific and clinical applications.     

Highly diffusion-sensitized MRI of brain: dissociation of gray and white matter.

The brains of six healthy volunteers were scanned with a full tensor diffusion MRI technique to study the effect of a high b value on diffusion-weighted images (DWIs). The b values ranged from 500 to 5000 s/mm(2). Isotropic DWIs, trace apparent diffusion coefficient (ADC) maps, and fractional anisotropy (FA) maps were created for each b value. As the b value increased, ADC decreased in both the gray and white matter. Furthermore, ADC of the white matter became lower than that of the gray matter, and, as a result, the white matter became brighter than the gray matter in the isotropic DWIs. Quantitative analysis showed that these changes were due to nonmonoexponential diffusion signal decay of the brain tissue, which was more prominent in white matter than in gray matter. There was no significant change in relation to the b value in the FA maps. High b value appears to have a dissociating effect on gray and white matter in DWIs.     

Increased brain white matter diffusivity in normal adult aging: relationship to anisotropy and partial voluming.

Diffusion tensor imaging (DTI) was used to examine 1) age-related changes in genu, splenium, and centrum semiovale white matter diffusivity in 64 healthy men and women (age 23-85 years); 2) the relationship between diffusivity (trace) and fractional anisotropy (FA) across and within individuals; and 3) the role of macrostructural and microstructural partial voluming effects on the DTI metrics. Regional differences were greater in FA (approximately 43%) than in trace (approximately 16%). Depending on the region of interest, trace increased with age (r = 0.24 to 0.58) and FA decreased with age (r = -0.29 to -0.79). FA was inversely correlated with trace, even when controlling for age. Histogram analysis of trace and FA following systematic expansion and dilation of the white matter regions demonstrated greater susceptibility of FA than trace to error arising from macrostructural partial voluming, i.e., erroneous inclusion of primarily nonwhite-matter voxels. Three-phase ellipsoid shape analysis revealed that after morphometric erosion the spherical component remained greater in older than younger subjects in the splenium and centrum, suggesting that age-related reduction in FA arises from intravoxel increased interstitial fluid. Reducing the size of the white matter samples to control for macrostructural partial voluming attenuated but did not negate effects, indicating that observed changes in white matter with aging can reflect real microstructural alterations rather than sampling artifact. Morphological dilation of white matter regions of interest resulting in purposeful inclusion of non-white matter pixels significantly reduced mean FA, suggesting that reports of FA values below 0.25 in healthy adults may reflect partial voluming rather than actual changes in white matter coherence.