Evaluation of myelination by means of the T2 value on magnetic resonance imaging

doi:10.1016/0387-7604(93)90083-K

Brain and Development

Volume 15, Issue 6, November–December 1993, Pages 433-438

https://doi.org/10.1016/0387-7604(93)90083-K Get rights and content

Abstract

The progress of myelination in the cerebrum was evaluated by visual inspection, and magnetic resonance (MR) imaging and the transverse relaxation time (T₂) was calculated from double echo images. Twenty-three pediatric cases, who did not show intracranial organic changes on MR examination, were included. The T₂ values in the corpus callosum (CC), frontal deep white matter (FWM), occipital deep white matter (OWM) and centrum semiovale (CS) were calculated, and the changes in these values with age were followed. During the first year of life, a rapid decrease in the T₂ value was seen, followed by a more gradual decrease. The T₂ value seemed to reach the adult level between 2 and 3 years of life in all areas examined. The T₂ values between 2 and 16 years in CC, FWM, OWM and CS were 59.7±3.6, 64.5±5.2, 69.8±4.8 and 66.3±3.3ms (mean±S.D.), respectively. The T₂ values in patients with clinically diagnosed Pelizaeus-Merzbacher disease (PMD) and late onset Krabbe disease were also calculated. In PMD, non-progressive prolongation of the T₂ value was observed in all areas. In late onset Krabbe disease, on the other hand, progressive prolongation of the T₂ values was mainly demonstrated in OWM and the posterior part of CS. These results suggest that the T₂ value in the cerebral white matter allows more objective judgement than visual inspection, and makes it possible to clarify the mechanism underlying abnormal myelination, i.e. progressive or not.

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Cited by (39)

Review of synthetic MRI in pediatric brains: Basic principle of MR quantification, its features, clinical applications, and limitations
2019, Journal of Neuroradiology
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However, precise visual evaluation is difficult, especially in the presence of developmental variability or if the observer lacks experience [41]. An objective assessment is required for accurate quantification of myelination [40,42]. Warntjes et al. [43] proposed a model in which each acquisition voxel is assumed to be composed of four partial volumes: myelin partial volume (VMY); cellular partial volume; free water partial volume; and excess parenchymal water partial volume (VEPW), where each partial volume has its own R1, R2, and PD [43].
Quantitative magnetic resonance imaging (MRI) with multislice, multi-echo, and multi-delay acquisition enables simultaneous quantification of R₁ and R₂ relaxation rates, proton density, and the B₁ field in a single acquisition, and requires only about 6 minutes for full-head coverage. Using dedicated SyMRI software, radiologists can generate any contrast-weighted image by manipulating the acquisition parameters, including repetition time, echo time, and inversion time. Moreover, automatic brain tissue segmentation, volumetry, and myelin measurement can also be performed. Using the SyMRI approach, a shorter scan time, an objective examination, and personalized MR imaging parameters can be obtained in daily clinical pediatric imaging. Here we summarize and review the use of SyMRI in imaging of the pediatric brain, including the basic principles of MR quantification along with its features, clinical applications, and limitations.
Multimodal magnetic resonance imaging assessment of white matter aging trajectories over the lifespan of healthy individuals
2012, Biological Psychiatry
Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers.
Healthy subjects (n = 171) 14–93 years of age were examined with transverse relaxation rate (R₂) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively).
Only R₂ reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R₂ < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R₂ and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor.
The R₂ and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.
Advanced Neonatal NeuroMRI
2012, Magnetic Resonance Imaging Clinics of North America
Citation Excerpt :
From MR imaging studies of normal postnatal brain development, several important time-dependent MR imaging signal changes, such as a shortening of T1 and T2 relaxation times of the gray and white matter,9–12 have been described previously. Most of the time-dependent changes are attributed to an increase in lipid concentration caused by the myelination process.13–17 Because the white matter appears as hyperintense on newborn T2-weighted images, the rapid shortening of T2 in the white matter results in “contrast inversion” between the white and gray matter during postnatal development (Fig. 3).
Atlas-based investigation of human brain tissue microstructural spatial heterogeneity and interplay between transverse relaxation time and radial diffusivity
2011, NeuroImage
Citation Excerpt :
Macroscopic volumetry derived by T1-weighted MRI can be used to investigate age related volume atrophy (Walhovd et al., 2005; Fjell et al., 2009; Ostby et al., 2009) and disease-driven volume atrophy (Ramasamy, et al., 2009; Hasan et al., 2009a) of various regions of the brain. Quantitative MRI tissue markers such as T2 relaxation time derived using multiple spin-echo maps (Ono et al., 1993; Whittall et al., 1997; Baratti et al., 1999) and diffusion tensor imaging (DTI) metrics (Pierpaoli et al., 1996; Basser, 1997) such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ||) and radial diffusivity (λ┴) are sensitive to tissue microstructural parameters such as intra-axonal and cellular integrity, water distribution and myelin content in the brain (Le Bihan et al., 2001; Beaulieu, 2002). Transverse relaxation time has been hypothesized to be a sensitive marker of myelination (Ono et al., 1993; Whittall et al., 1997), structural integrity (Georgiades et al., 2001; Bartzokis et al., 2004) and has also been shown to be affected by non-heme iron deposition (Haacke et al., 2005; Jara et al., 2006; Bartzokis et al., 2007; House et al., 2008; Mitsumori et al., 2009; Yao et al., 2009).
Microstructural metrics obtained using magnetic resonance imaging (MRI) such as transverse relaxation time and radial diffusivity have been used as in vivo markers of human brain tissue integrity. Considering the sensitivity of these parameters to some common biophysical contributors and their structural and spatial heterogeneity, we hypothesized that strong inter and intra-regional associations exist between these variables providing evidence to possible interplay between transverse relaxation time and radial diffusivity. To validate our hypothesis we obtained high resolution anatomical T1-weighted data and fused it with T2-relaxometry and diffusion tensor imaging (DTI) data on a cohort of healthy adults. The anatomical data were parcellated using FreeSurfer and then coaligned and fused with the T2 and DTI maps. Our data reveal some association between transverse relaxation and radial diffusivity that may help toward the interpretation and modeling of the biophysical contributors to the measured MRI metrics.
Development of T2-relaxation values in regional brain sites during adolescence
2011, Magnetic Resonance Imaging
Citation Excerpt :
T2-relaxation values increase with increase in free water content [11], and free water content changes with disease and normal aging processes [5,12]. The procedure has been used to evaluate age-related brain myelin changes in pediatrics [13], and in several pediatric and adult medical conditions, demonstrating abnormalities not readily visible on conventional MRI, including traumatic brain injury [14], neurodegenerative conditions [4,7,15], cerebral neoplasia [16], ischemia [17], and symptomatic lesional epilepsy [18]. However, current T2 relaxometry data have primarily evaluated very young infants or adult subjects, and those studies principally examined only limited brain areas.
Brain tissue changes accompany multiple neurodegenerative and developmental conditions in adolescents. Complex processes that occur in the developing brain with disease can be evaluated accurately only against normal aging processes. Normal developmental changes in different brain areas alter tissue water content, which can be assessed by magnetic resonance (MR) T2 relaxometry. We acquired proton-density (PD) and T2-weighted images from 31 subjects (mean age±S.D., 17.4±4.9 years; 18 male), using a 3.0-T MR imaging scanner. Voxel-by-voxel T2-relaxation values were calculated, and whole-brain T2-relaxation maps constructed and normalized to a common space template. We created a set of regions of interest (ROIs) over cortical gray and white matter, basal ganglia, amygdala, thalamic, hypothalamic, pontine and cerebellar sites, with sizes of ROIs varying from 12 to 243 mm³; regional T2-relaxation values were determined from these ROIs and normalized T2-relaxation maps. Correlations between R2 (1/T2) values in these sites and age were assessed with Pearson's correlation procedures, and gender differences in regional T2-relaxation values were evaluated with independent-samples t tests. Several brain regions, but not all, showed principally positive correlations between R2 values and age; negative correlations emerged in the cerebellar peduncles. No significant differences in T2-relaxation values emerged between males and females for those areas, except for the mid pons and left occipital white matter; males showed higher T2-relaxation values over females. The findings indicate that T2-relaxation values vary with development between brain structures, and emphasize the need to correct for such age-related effects during any determination of potential changes from control values.
Clinical applications of quantitative T2 determination: A complementary MRI tool for routine diagnosis of suspected myelination disorders
2008, European Journal of Paediatric Neurology
Citation Excerpt :
Thus, a monoexponential function could be used to deduce the T2 maps. Determination of T2 values in brain allowed more objective judgement than visual inspection, and made it possible to clarify whether the underlying abnormal myelination was progressive or not.9 However, in order to evaluate T2 values on patients for routine diagnostics it is prerequisite to know the range of T2 relaxation times on normal maturating brain at the corresponding age, which is unfortunately not yet available for routine use until now.
Though magnetic resonance imaging (MRI) plays an important role in studying pathological changes in central nervous system, a quantitative measure of contrast variance on MRI, allowing the detection of subtle signal variances in pathological processes, is not readily available for routine imaging. We report on the first experiences with evaluation of routine T2 relaxation time measurement as a diagnostic tool in routine imaging of suspected myelination disorders.
Twenty patients suffering from defined or suspected myelination disorders were examined by MRI. T2 relaxation time maps of the brain were derived from a triple spin echo sequence. T2 values were measured for each patient by regions of interest (ROI) analysis. As references age-dependent T2 prediction values in normal maturating brains were calculated by using a biexponentional function reported earlier. Deviations from these prediction values were used as an assisting tool both for detection of pathology and for monitoring of changes over time. These quantitative results were compared to conventional visual inspections by two independent neuroradiologists.
In 18 patients with single diagnostic MRI, the T2 measurements were more graduated or definite in 9/18 cases, confirmatory in 9/18 cases. In two patients with MRI follow up, the dynamic clinical course of the disease had no correlate in visual inspection of the images but was associated with the quantitative T2 values.
Quantitative T2 measurement is a promising tool for routine imaging as a complementary method in detecting and monitoring of suspected myelination disorders.

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Evaluation of myelination by means of the T2 value on magnetic resonance imaging

Abstract

Myelin in rat brain: changes in myelin composition during brain maturation

J Neurochem

Sequence of central nervous system myelination in human infancy. I. An autopsy study of myelination

J Neuropathol Exp Neurol

Developmental features of the neonatal brain: MR imaging. Part I. Gray-white matter differentiation and myelination

Radiology

MRI of normal brain maturation

AJNR

MR evaluation of early myelination patterns in normal and developmentally delayed infants

AJR

Evaluation of myelination by means of the T₂ value on magnetic resonance imaging