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.     

Diffusion-tensor MR imaging of the brain in human immunodeficiency virus-positive patients

BACKGROUND AND PURPOSE: There is early evidence that diffusion-tensor imaging (DTI) is useful in demonstrating subtle white matter alterations in different diseases of brain. We hypothesize that DTI in several brain regions in human immunodeficiency virus-positive (HIV+) patients is useful in the early detection of HIV-related brain injury. METHODS: MR imaging and DTI were performed in 60 HIV+ patients and in 30 controls. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC; mm/s(2)) maps were generated and coregistered on T2-weighted images. Regions of interest were placed in the splenium and genu of the callosum, the frontal white matter, and the hippocampus. HIV+ patients were divided into those whose CD4 count were <250 cells/mm(3) or >250 cells/mm(3). According to plasma viral loads, patients were divided into those whose viral loads were <50 copies/mL, 50-100,000 copies/mL, or >100,000 copies/mL. RESULTS: Statistically significant decrease of FA was found in the genu of the corpus callosum in HIV+ patients compared with controls. FA was reduced in the frontal white matter and hippocampi in HIV+ patients compared with controls. Differences, however, were not statistically significant. No statistically significant differences were found between the HIV+ groups for FA of the splenium or between these groups and the controls. ADC values were significantly increased in the genu of HIV+ patients when compared with controls and were also increased in other locations, but without statistical significance. CONCLUSION: As used in this study, DTI was not helpful in identifying patients with early HIV infection.     

MR imaging of heterotopic gray matter

Heterotopic gray matter nodules have long been recognized by pathologists at autopsies. A case of this cerebral congenital abnormality has been studied by CT and magnetic resonance.     

MR imaging of heterotopic gray matter

Magnetic resonance imaging is the current method of choice to diagnose heterotopic gray matter and associated cerebral malformations. We report a case of an epileptic child in whom heterotopic gray matter is present without any associated ventricular distortion.     

Segmentation of MR brain images into cerebrospinal fluid spaces, white and gray matter

An interactive computer method for quantifying CSF, white matter, and gray matter in magnetic resonance (MR) axial brain scans is presented. A stripping algorithm is used to remove the skull and scalp from each axial section. The images are then filtered to correct for radiofrequency inhomogeneity image artifacts. Late echo images are subtracted from or added to early echo images to enhance fluid/tissue and gray/white tissue contrast, respectively. Thresholds for fluid/tissue and gray/white separation are set interactively. A boundary pixel locking algorithm is used to handle ambiguities due to partial voluming between the fluid and tissue compartments. The MR brain scans from five healthy, young, normal men were obtained using a standard neuroanatomical reference technique. These data were processed and percentages computed for fluid, gray matter and white matter compartments. The gray/white ratios compare favorably with those determined in a published postmortem brain study.     

Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity

Diffusion magnetic resonance (MR) imaging is evolving into a potent tool in the examination of the central nervous system. Although it is often used for the detection of acute ischemia, evaluation of directionality in a diffusion measurement can be useful in white matter, which demonstrates strong diffusion anisotropy. Techniques such as diffusion-tensor imaging offer a glimpse into brain microstructure at a scale that is not easily accessible with other modalities, in some cases improving the detection and characterization of white matter abnormalities. Diffusion MR tractography offers an overall view of brain anatomy, including the degree of connectivity between different regions of the brain. However, optimal utilization of the wide range of data provided with directional diffusion MR measurements requires careful attention to acquisition and postprocessing. This article will review the principles of diffusion contrast and anisotropy, as well as clinical applications in psychiatric, developmental, neurodegenerative, neoplastic, demyelinating, and other types of disease.     

Diffusion-tensor MR imaging of the human brain with gradient- and spin-echo readout: technical note

Diffusion-tensor MR imaging of the brain is an objective method that can measure diffusion of water in tissue noninvasively. Five adult volunteers participated in this study that was performed to evaluate the potential of gradient- and spin-echo readout for diffusion-tensor imaging by comparing it with single-shot spin-echo echo-planar imaging. Gradient- and spin-echo readout provides comparable measures of water diffusion to single-shot spin-echo echo-planar readout with significantly less geometrical distortion at the expense of a longer imaging time.     

MR imaging of the brain: metabolic and toxic white matter diseases

Metabolic disorders of the brain are rare, complex and confusing. The diagnostic modality of choice nowadays is MRI. The high diagnostic sensitivity, however, is coupled with a lack of specificity and usually results in the depiction of similar appearing but clinically diverse white matter processes. For this reason it is essential to perform the MRI as early as possible during the course of the disease and to keep in close contact to the referring clinician to optimize image interpretation. Another precondition is to know the natural course of brain myelination and to know how this appears on the individual MR machine with different parameters. In some diseases like phenylketonuria MRI seems to be an excellent tool to monitor dietary treatment and patient compliance. In patients after radio- and / or chemotherapy MRI reveals the radiation induced leucencephalopathy and can usually differentiate between a recurrent malignancy.     

MR imaging of brain maturation in normal and developmentally handicapped children.

White matter myelination was assessed in the frontal, temporal, and occipital lobes and in the internal capsule in 91 neurodevelopmentally handicapped infants on T2-weighted images (spin echo 3,000/120 ms) and compared with myelination scores from 53 normal control subjects. Clinical diagnosis was birth asphyxia (34), seizures with delays of various causes (33), congenital infections (15), and intracerebral hemorrhages (9). Myelination in the total group of patients was generally delayed. However, we found distinct differences in myelin deposition between groups. Myelination of handicapped children with seizures or with intrauterine infections was retarded most severely at all ages. Children with intracerebral hemorrhages were almost never significantly different from normals in any part of the brain, whereas children with birth asphyxia had myelination scores in between. We conclude that magnetic resonance staging of developmental processes, such as myelination, in the infants' brain helps to recognize delays at an early age.     

Low choline concentrations in normal-appearing white matter of patients with multiple sclerosis and normal MR imaging brain scans

BACKGROUND AND PURPOSE: Spectroscopic studies (1H-MR spectroscopy) of normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) with MR imaging brain lesions have already been performed, but our intention was to investigate NAWM in MS patients who lack brain lesions to elucidate whether the same pathologic changes could be identified. MATERIALS AND METHODS: We checked 350 medical files of patients with MS who are registered in our institution. Fourteen patients (11 women and 3 men; mean age, 48.6 years; handicap score, Expanded Disability Status Scale [EDSS] 2.9; range, 1-6.5) with clinically definite MS and a normal MR imaging of the brain were included. 1H-MR spectroscopy was performed in 4 voxels (size approximately 17x17x17 mm3) using absolute quantification of metabolite concentrations. Fourteen healthy control subjects (11 women and 3 men; mean age, 43.3 years) were analyzed in the same way. RESULTS: Significant differences in absolute metabolite concentrations were observed, with the patients with MS showing a lower total concentration of N-acetyl compounds (tNA), including N-acetylaspartate and N-acetyl aspartylglutamate (13.5 mmol/L versus 14.6 mmol/L; P=.002) compared with the healthy control subjects. Unexpectedly, patients with MS presented significantly lower choline-containing compounds (Cho) compared with healthy control subjects (2.2 mmol/L versus 2.4 mmol/L; P<.001). The EDSS showed a positive correlation to myo-inositol concentrations (0.14 mmol/L per EDSS; r2=0.06) and a negative correlation to tNA concentrations (-0.41 mmol/L per EDSS; r2=0.22). CONCLUSION: The unexpected finding of lower Cho concentrations has not been reported previously. We suggest that patients with MS who lack lesions in the brain constitute a separate entity and may have increased protective or healing abilities.     

Differences between gray matter and white matter water diffusion in stroke: diffusion-tensor MR imaging in 12 patients

PURPOSE: To investigate differences in water diffusion between white matter and gray matter in acute to early subacute stroke with diffusion-tensor magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twelve patients with unilateral middle cerebral arterial infarcts were examined with diffusion tensor-encoded echo-planar MR imaging 17 hours to 5 days after stroke onset. Isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) images were computed. (D) values were measured in ischemic and contralateral gray matter and white matter by using A(sigma) images to differentiate white matter from gray matter. (D) images were compared with unidirectional and directionally averaged diffusion-weighted images. RESULTS: In all patients, (D) images showed two distinct levels of diffusion reduction in the infarct; more severe reduction occurred exclusively in white matter. (D) values were significantly less in infarcted white matter than in infarcted gray matter, whereas (D) values in the contralateral white matter and gray matter were not significantly different. Relative to the contralateral side, (D) values in the infarct were reduced by 46% in white matter and by 31% in gray matter (P <.001). Diffusion-weighted imaging caused underestimation of the magnitude and, in some cases, the spatial extent of the white matter diffusion abnormality. CONCLUSION: Isotropic diffusion is more reduced in white matter than in gray matter in acute to early subacute middle cerebral arterial stroke. Diffusion-tensor imaging may be more sensitive than diffusion-weighted imaging to white matter ischemia.     

应用扩散张量成像对正常儿童脑白质发育的初步研究

目的 应用扩散张量成像（DTI）分析不同年龄段、不同部位脑白质的各向异性，研究正常儿童脑白质的成熟规律。方法 将89例正常儿童（年龄2d至18岁）分为7组，〈6个月为第1组8例，6个月至1岁为第2组8例，1～3岁为第3组12例，3～5岁为第4组15例，5～8岁为第5组20例，8～12岁为第6组11例，12～18岁为第7组15例。分别行头部扩散张量成像，在各项异性分数（FA）图上测量不同脑区的各向异性，并对所测数据进行统计分析。结果 （1）不同部位FA值明显不同，胼胝体最高，灰质最低，且随组别数降低，FA值减低；（2）胼胝体、额、顶叶白质、半卵圆中心的FA值在第1、2组及第2、3组间差异有统计学意义，内囊前肢、枕叶放射的FA值在第2、3组，第3、4组及第4、5组间差异有统计学意义，F值均〉5．34，P〈0．05；（3）儿童脑白质各向异性随年龄增加而增加，FA值与年龄呈指数正相关，胼胝体、内囊、顶、枕、额叶白质及小脑中脚的相关系数均〉／0．5，P〈0．01。结论 扩散张量成像可反映活体脑白质细微的结构，可用于评价儿童脑发育情况。     

MR imaging of compact white matter pathways

A prominent decreased signal intensity can be seen in many of the heavily myelinated, compact fiber pathways of the brain on T2-weighted spin-echo MR images (TR = 2500 msec, TE = 80 msec). These areas include the anterior commissure, internal capsule, optic tract and radiations, fornix, mammillothalamic tract, superior frontooccipital fasciculus, cingulum, corpus callosum, uncinate fasciculus, and superior longitudinal fasciculus. All these pathways could be identified in normal subjects 3 years old and older when 1.5-T axial and coronal images of 50 adults and 17 children were reviewed. Correlation of the in vivo and postmortem MR appearance of two human brains with Perls and Luxol fast blue stains indicates that the short T2 reflects heavy myelination and fiber density, not iron deposition. This is in contrast to the short T2 signal seen in the subcortical U fibers and deep nuclei of the brain that result from iron deposition. These pathways also differ from areas of brain iron accumulation in that (1) they may appear as areas of short T1 on partial-saturation or inversion-recovery pulse sequences and (2) they can be seen with regularity in all patients over 3 years of age. It is important to distinguish between the effect of the myelin sheath and the effect of brain iron on the T2 relaxation values seen in the normal brain since both result in shortened T2 relaxation. The importance of the role of these fiber tracts in disease processes and in modifying the spread of vasogenic edema and tumor needs further investigation.     

Evaluation of normal brain development by prenatal MR imaging

PURPOSE: The aim of this study was to describe the normal pattern of development and maturation of the foetal brain with respect to gestational age as assessed with magnetic resonance imaging (MRI) and to provide an overview of the possibilities of the technique. MATERIALS AND METHODS: Foetal cerebral MRI was performed on 56 pregnant women between 19 and 37 weeks of gestation. Half-Fourier single-shot turbo spin-echo (HASTE), true fast imaging with steady precession (FISP), T1-weighted fast low angle shot (FLASH) two-dimensional (2D) and diffusion-weighted (DW) sequences with apparent diffusion coefficient (ADC) were obtained. Biometric parameters and developmental areas of the cerebral cortex were correlated to gestational age by using the Spearman rank correlation test. RESULT: We found a negative correlation between the germinal matrix/biparietal diameter ratio and gestational age and a positive correlation between the germinal and cortical matrix when expressed as external intraocular diameter ratio (R=0.452, p=0.02). The cortical mantle was correlated with biometric parameters, such as the biparietal diameter and the frontooccipital diameter, and with gestational age. The interhemispheric fissure, the parietooccipital fissure and the sylvian fissure were detectable by the 22nd week. In the grey matter, the mean ADC values varied from 1.76 x 10(-3) mm(2)/s (at week 19) to 0.89 x 10(-3) mm(2)/s (at week 37), whereas in the white matter, the values varied from 2.03 x 10(-3) mm(2)/s (at week 19) to 1.25 x 10(-3) mm(2)/s (at week 37). CONCLUSIONS: MRI provides a reliable valuation of brain maturation during pregnancy.     

Diffusion-weighted MR imaging in the brain in children: findings in the normal brain and in the brain with white matter diseases

PURPOSE: To establish quantitative standards for age-related changes in diffusion restriction of cerebral white matter in healthy children and to compare data with results in children with white matter diseases. MATERIALS AND METHODS: Diffusion-weighted magnetic resonance (MR) imaging was performed in 44 children (age range, 7 days to 7.5 years) without brain abnormalities and in 13 children with proved leukodystrophy. Apparent diffusion coefficient (ADC) and apparent anisotropy (AA) were measured in 11 regions of interest within white matter. Age-related changes were analyzed with regression analysis. RESULTS: During normal brain myelination, ADCs in different anatomic regions were high at birth (range, 1.04 x 10(-9) m(2)/sec +/- 0.05 [SD] to 1.64 x 10(-9) m(2)/sec +/- 0.09) and low after brain maturation (range, 0.75 x 10(-9) m(2)/sec +/- 0.02 to 0.92 x 10(-9) m(2)/sec +/- 0.02). AA was low at birth (range, 0.05 +/- 0.01 to 0.52 +/- 0.04) and high after brain maturation (range, 0.25 +/- 0.02 to 0.85 +/- 0.03). Age relationship could be expressed with monoexponential functions for all anatomic regions. Anisotropy preceded the myelination-related changes at MR imaging. ADC and AA in four children with Pelizaeus-Merzbacher disease were identical with results in healthy newborn children and showed no age dependency. In peroxisomal disorders, Krabbe disease, and mitochondriopathy, demyelination on T1- and T2-weighted MR images led to expected findings at diffusion-weighted MR imaging, with high ADC and low AA, whereas in Canavan disease and metachromatic leukodystrophy, the opposite findings were revealed, with low ADC within the demyelinated white matter. CONCLUSION: During early brain myelination, diffusion restriction in normal white matter increases. Anisotropy precedes myelination changes that are visible at MR imaging. Compared with T1- and T2-weighted MR imaging, diffusion-weighted MR imaging in white matter diseases reveals additional information.