The bilateral cerebral vesicles that will form the cerebral hemispheres first appear at about 35 days of gestation as outpouchings of the telencephalon from the regions of the foramina of Monro. At the time of these outpouchings, the walls of the vesicles are uniformly thin and are connected in the midline by the lamina terminalis, a midline area derived from the roof plate that has shrunken due to apoptosis. The lamina terminalis does not grow as development proceeds; however, the cerebral vesicles exhibit marked expansion laterally, rostrally, ventrally, and caudally. As the vesicles expand, cellular layers develop within their walls, forming the germinal matrices from which the cells that form the cerebrum will eventually develop. The germinal matrices are initially composed only of a single region of proliferating cells (the ventricular zone), but as development proceeds, a more peripheral subventricular germinal zone develops, separated from the ventricular zone by a periventricular fiber-rich zone. These germinal zones are divided based upon their location, the type of neurons generated, and the ultimate destination of the neurons: (a) medial ganglionic eminence (located near the developing third ventricle, GABAergic neurons generated, including cortical interneurons, hippocampal interneurons, and globus pallidus interneurons); (b) lateral ganglionic eminence (located near the developing third ventricle, GABAergic neurons generated, mainly striatal projection neurons and olfactory interneurons, also some thalamic interneurons); (c) preoptic area (located near the
bottom of the developing third ventricle, GABAergic neurons generated, including cells to the preoptic area, amygdala, posterior globus pallidus, and cortex); (d) dorsal neocortical germinal zone (located in walls of developing lateral ventricles, glutamatergic neurons destined for the neocortex) (1,2,3,4,5,6,7). Neurons migrate from these germinal zones through the developing hemispheres to form the cerebral cortex, initially in an incomplete form that is often called the preplate. As the neurons migrate, they develop axonal connections with other cortical and subcortical (subplate) neurons. The axons form a prospective zone of white matter that is called the intermediate zone because it is in the region intermediate between the ventricular zone and the developing cortex. In addition to afferent and efferent axons, the intermediate zone contains migrating neurons and oligodendrocyte progenitor cells (8). Between the preplate and the intermediate zone is a transient area of loosely packed and loosely organized neurons that form temporary neuronal circuits, particularly with the thalamus (9); this zone is known as the subplate. The subplate is largest at the 30th postconceptional week (10). At that time, it is about four times thicker than the cortex, occupying up to 45% of the telencephalon, and is easily seen on fetal MRI as an area of T1 hypointensity and T2 hyperintensity between the intermediate zone and cortex (10,11,12). It gradually disappears after the 30th gestational week, as definitive cortical connections are established (10,11) but remains functional, in part, possibly for as much as the first half of the first postnatal year (10). Details of the development of the hemispheres are described in more detail in Chapter 5. For the purposes of the discussion to follow, it is sufficient to understand that the occipital pole begins to develop at about the 43rd gestational day and the temporal pole at approximately the 50th gestational day. During the early weeks of gestation, the surfaces of the cerebral hemispheres are smooth. The fetal sulci appear in an orderly sequence; the phylogenetically older sulci appear first, and the more recently acquired sulci appear later. The principal sulci and gyri form the characteristic pattern of the human cortex that can be identified in the full-term infant (Table 2-1). The primitive sylvian fissure, the earliest fetal sulcus, is usually present when the fetus is imaged in the fourth gestational month. The next sulci to appear are the calcarine, parieto-occipital, and cingulate sulci during the fifth month (by 20-22 weeks); the Rolandic (central), interparietal, and superior temporal sulci that appear toward the end of the sixth month (by 25 weeks); and the precentral, postcentral, superior frontal, and middle temporal sulci that appear during the seventh gestational month (24-28 weeks) (13) (Fig. 2-1 and Table 2-1). In the medial temporal lobe, the hippocampal sulci are variable and often asymmetrical; asymmetry is also often seen in the formation of the collateral sulcus (14). Because sulcal formation occurs so late in gestation, imaging studies of premature infants show sulci that are shallow and few in number. It is, therefore, important to know the postconceptional age of a child before assessing the sulcal pattern. Otherwise, a false diagnosis of lissencephaly may be made. In addition, as will be discussed in more detail later in the chapter, sulcation, myelination, and corpus callosum development are often delayed in prematurely born neonates compared to fetuses of the same postconceptual age.

van der Knaap et al. (20) have devised a method by which gyral development can be divided into five stages: (a) before 32 weeks, (b) 33 to 34 weeks, (c) 35 to 37 weeks, (d) 38 to 41 weeks, and (e) beyond 41 weeks. The gyral maturity is determined by measurements of the width of the gyri and depth of the sulci. The stage of gyral development is then assigned based upon the degree of gyral maturity in seven different regions of the brain. Battin et al. (21) and Ruoss et al. (22) have also developed systems of assessing sulcal development based on ratios of the width and depth of the sulci and gyri. Gyral development proceeds most rapidly in the area of the sensorimotor and visual pathways. These are also the areas in which myelination occurs earliest ((23) and following section), in which glucose uptake increases earliest (24), in which relative cerebral perfusion increases earliest (25), in which cortical microstructure matures most rapidly (26), and in which brain chemistry matures most rapidly (27). Gyral development takes place most slowly in the frontobasal, frontopolar, and anterior temporal regions, which are also the slowest regions to myelinate and to mature metabolically (24,25,27). It is important to evaluate the sulcal pattern of neonates and infants, as abnormal sulcation predicts abnormal functional development (28).

As mentioned earlier, the imaging modality being used determines which features of brain development can be evaluated. If the anterior fontanelle is large enough, ultrasound shows development of the gyri and sulci nearly as well as CT and MR but does not give information
about brain myelination. CT allows fairly good information about sulcal development but gives a poor assessment of myelin development and it exposes the baby to ionizing radiation; it is not recommended for brain imaging in the fetus, neonate, or infant unless other methods are unavailable. MR allows excellent assessment of myelination, sulcation, and chemical maturation and is the imaging technique of choice for evaluation of normal development in the neonate and infant.

Fetal MR imaging has been successfully utilized in a large number of centers for the past two decades (12,29,30,31,32,33,34,35). Studies have shown that the cerebral cortex and deep gray structures are relatively large before 20 weeks (Fig. 2-2) but that the cerebellum and cerebral white matter grow disproportionately during the last 20 weeks (36). Improvements in coil technology (particularly the use of multiarray-phased array coils), improved pulse sequences, and development of higher-field strength MRIs have allowed progressive improvement in the quality of the images. Studies (19,33,37,38,39) indicate that brain development follows a similar progression of sulcation in fetuses as in prematurely born infants; sulci are increasingly identified with increasing postconceptional age. However, it appears that sulcal development occurs earlier in utero than ex utero. In other words, sulci are seen slightly earlier in fetuses still in the uterus than in neonates of similar postconceptional ages that have been born prematurely (40). This may result from the fact that the subarachnoid spaces are considerably bigger in fetuses than in newborns of the same postconceptual age (40), allowing the sulci to be more easily seen. The reasons for this are not yet clear, nor are the precise differences in timing. Studies also show that the cerebrum and its components grow largely proportionally. For example, the volume of cortical gray matter, basal ganglia volumes, and ventricular volume parallel that of supratentorial volume, while supratentorial white matter volume grows more rapidly than overall supratentorial volume (41).

Prior to 20 weeks of gestation, the cerebral mantle is quite thin and the ventricles are relatively large (Fig. 2-2). Supratentorially, the T2 hypointensity of the germinal matrices lining the walls of the lateral ventricles is thicker than that of the cortex at 16 weeks (Fig. 2-2D); it is roughly equivalent in thickness to the cerebral white matter layer. The germinal matrix is thickest at the region of the caudate heads and should not be mistaken for a germinal matrix hemorrhage at this location. The more central ventricular zone and adjacent subventricular zone cannot be distinguished by in vivo imaging. Between the germinal zones and the cortex, MR also shows a layer of intermediate signal intensity, separated from the more peripheral cerebral cortex and more
central germinal matrix (Fig. 2-2C-E). Although previously believed to represent migrating glial cells, this layer has recently been identified as the intermediate zone or the developing fetal white matter (11). Projection and commissural axons are present, as are some late migrating neurons and many migrating astrocyte and oligodendrocyte precursors (42). Immediately peripheral to the intermediate zone and deep to the cerebral cortex is a region of T1 hypointensity/T2 hyperintensity (Fig. 2-2F), known as the subplate, a region composed of loosely spaced neurons where thalamocortical afferent axons, basal forebrain cholinergic afferent axons, and callosal and ipsilateral corticocortical axons accumulate for a variable period before entering the cortical plate to establish definitive thalamocortical and corticocortical synapses (10,43,44,45). These zones are most prominent in younger fetuses (<20 gestational weeks). Before 20 weeks, the sylvian fissures are
extremely shallow and no operculization can be identified. The basal ganglia can be identified and are intermediate in signal between the darker cortex and germinal zone and the lighter white matter (Fig. 2-2D). The cerebellum remains quite small at this age, barely bigger than the pons on axial images and smaller than the mesencephalic tectum on the midline sagittal image (Fig. 2-2A and B).

At 20 (Fig. 2-3) to 24 (Fig. 2-4) weeks of gestation, the cerebrum has grown considerably (especially the white matter; Fig. 2-3B-D), but it remains essentially agyric with the exception of the wide, vertically oriented sylvian fissures. The size of the brain is very small and the cerebral cortex is extremely thin, so thin imaging sections (≤3 mm) must be used for optimal evaluation. MR images show the cortex to be very hyperintense with respect to the underlying white matter on T1-weighted images and very hypointense compared to white matter on T2-weighted images (Figs. 2-3 and 2-4). The germinal matrix has not yet involuted and can still be seen as a stripe in the walls of the lateral ventricles that is isointense to the gray matter of the cortex on T1- and T2-weighted images (Fig. 2-2) and very hypointense on echo-planar T2 imaging; it is, however, thinner than in younger fetuses (18-20 weeks) and becomes thinner and discontinuous with further maturation (Fig. 2-4). At this age (23-24 weeks), the germinal matrices remain large and conspicuous as areas of relative
hyperintensity between the cerebral cortex and the white matter on T2-weighted imaging studies (12,46), but they seem to begin to disappear rapidly after 25 weeks. The lateral ventricles and the cisterns around the brain stem and cerebellum are visible and more prominent at this age than in the mature infant; they are relatively smaller at 23 to 24 weeks (Fig. 2-4) than at 18 to 20 weeks (Fig. 2-3). When imaging at 3T, the third and fourth ventricles are easily visualized at this age unless a lot of motion artifact is present; if difficulty is encountered, waiting a few minutes for the fetus to calm down usually results in good images. The globi pallidi typically appear hyperintense on T1-weighted images starting at about 20 weeks. This likely represents premyelination changes, such as the appearance of proteolipid protein in oligodendrocyte processes (47).

Between 24 and 30 weeks, the cerebral cortex shows development of shallow Rolandic (central), calcarine, pericallosal/callosomarginal, interparietal, and superior temporal sulci (Figs. 2-5 and 2-6); in some patients, the precentral, postcentral, superior frontal, and middle temporal sulci may be visualized. The subplate is still seen in the subcortical white matter as a layer of T1 hypointensity/T2 hyperintensity; it becomes difficult to see on imaging in the posterior frontal and




parietal lobes at about 28 weeks but remains visible in less mature areas such as the anterior frontal and temporal lobes for some time thereafter (12,46). Myelination is seen in some brain stem structures during this period, including the median longitudinal fasciculus (MLF; bright at 25 weeks on T1-weighted images, dark at 29 weeks on T2-weighted images), the lateral lemnisci (bright at 26 weeks on T1-weighted images, dark at 28 weeks on T2-weighted images), the medial lemnisci (bright at 27 weeks on T1-weighted images, dark at 30 weeks on T2-weighted images), and the superior and inferior cerebellar peduncles (bright at 28 weeks on T1-weighted images, dark at 29 weeks on T2-weighted images) (48). The basal ganglia and thalami are better seen at this age on MR imaging and have intensity similar to the cerebral cortex on both T1-and T2-weighted images, although not as hyperintense on T1-weighted images or as hypointense on T2-weighted images (Fig. 2-5I-L). The ventrolateral nucleus of the thalamus becomes hypointense compared with the remainder of the thalamus on T2-weighted images by about 25 weeks and hyperintense on T1-weighted images by 27 to 28 weeks, mostly due to its high cellularity and, possibly, to early myelination. The lateral ventricles, particularly the trigones and occipital horns, are less prominent at this age than at 22 to 23 weeks, probably secondary to both growth of the cerebral white matter and development of the calcarine sulci.

By 31 to 32 weeks, an increased number of gyri and shallow sulci become visible in the cerebral cortex of prematurely born neonates (Fig. 2-6). The sylvian fissures retain their immature appearance, although some development of the opercula can be detected. The cisterns around the brain stem and cerebellum remain large at this age, and the cerebrospinal fluid (CSF) spaces in the occipital region and in the interhemispheric fissure remain prominent, although the interhemispheric fissure is more variable in size. The cavum septi pellucidi and cavum vergae are prominent and will remain so throughout the first 40 postconceptual weeks (29,32). The dorsal brain stem (relatively hyperintense on T1-weighted images and hypointense on T2-weighted images) is contrasted by the unmyelinated ventral pons (Fig. 2-6E and I). The thalami and globi pallidi are contrasted by the unmyelinated (relatively hypointense on T1-weighted images and hyperintense on T2-weighted images) internal capsule (Fig. 2-6F and J). The signal intensity of the entire cerebral cortex is uniform at this age on both T1- and T2-weighted images. The subplate is poorly seen on T1-weighted images and is best identified in the anterior temporal lobes on T2-weighted images. The germinal matrix has involuted to a large degree. However, some curvilinear T2 hypointensity is seen extending along the lateral walls of the frontal horns of the lateral ventricles to the medial tip of the frontal lobes and into the olfactory sulci at this age (Fig. 2-6G and K); previously thought to be regions of residual germinal matrix (49), these areas turn out to be migrating GABAergic neurons that are present until about 6 postnatal months (50). The dorsal brain stem and superior and inferior cerebellar peduncles remain bright on T1-weighted images, but the middle cerebellar peduncles remain unmyelinated, isointense to the cerebral white matter. T2-weighted MR shows hypointensity in the dorsal brain stem (predominantly due to the MLF, medial and lateral lemnisci), superior and inferior cerebellar peduncles, nuclei of the inferior colliculi, far lateral putamen, and ventrolateral thalamic nucleus (51) (Fig. 2-6). The white matter of the centrum semiovale still appears completely unmyelinated.

At 34 to 36 weeks, the cerebral cortex has further thickened and more sulci have developed. Little change occurs in the signal intensity of the white matter between 32 and 36 postconceptional weeks (51). On T1-weighted MR, the posterior limb of the internal capsule remains hypointense as compared to the lentiform nucleus (Fig. 2-7C and D); some patients will show a small dot of hyperintensity in the posterior aspect of the posterior limb at 39 weeks (48). On T2-weighted images, the posterior limb of the internal capsule remains entirely hyperintense compared with surrounding structures (Fig. 2-7J). The sylvian fissures and, to a lesser extent, the CSF spaces in the posterior parietal area remain prominent (Fig. 2-7C-E, J, and K). Considerable variation in brain maturity can be seen at this age, some infants having a gyral pattern that resembles a term infant and others still appearing quite immature (29,32).

By 38 to 40 weeks, the brain has a nearly normal adult sulcal pattern (Fig. 2-8); the sulci are largely formed but are not as deep as they will become in the next several weeks. On T1-weighted MR studies, the dorsal brain stem, posterior portion of the posterior limb of the internal capsule, and the central portion of the corona radiata (the corticospinal tracts) are hyperintense compared to the rest of the brain. On T2-weighted images, the dorsal brain stem is hypointense and, at 39 to 40 weeks, a characteristic spot of hypointensity is present in the posterior limb of the internal capsule, lateral to the hypointense lateral thalamic nuclei. There are few differences between the CT images of a newborn term infant and those of older infants. The frontal white matter and parieto-occipital white matter remain relatively low in attenuation compared to the gray matter (Fig. 2-8A-E). This probably results from the known high water content of the newborn brain, related to the lack of myelination. The MR appearance of the newborn brain, on the other hand, is considerably different from that in older children, as discussed in the following section. The sylvian fissures may remain prominent in the immediate newborn period; the occipital CSF spaces may also remain somewhat large for several months. The cavum vergae and cavum septi pellucidi are usually present at birth; they disappear rapidly in the first few months after birth as the septal leaves fuse from back to front.

The cisterna magna and basilar cisterns are relatively large throughout infancy, as the cerebellum continues to grow considerably (compared to the cerebrum) during the first postnatal year. This enlargement is quite apparent on MR scans but less so on CT where only the axial plane is available and beam hardening artifact frequently obscures details in the basilar cistern area.

Childs et al. have proposed a scoring system for assessment of brain maturation in premature infants (52). The scoring system takes into account the degree of myelination, extent of sulcation, amount of involution of the germinal matrix of the lateral ventricles, and the character of the band of migrating cells (if present) in the white matter of the brain. This method shows considerable potential for determining whether the brains of neonates are developing properly. However, norms and standard deviations will need to be established for each weekly postconceptional age, and it must be determined whether these scores are sensitive and specific for predicting developmental abnormality.

Another way to assess brain maturation is size. Several authors have performed the service of measuring many structures of the developing fetal brain. A summary of these measurements is listed in Table 2-2. For more extensive lists of measurement, the book by Garel (29) and the paper by Parrazzini (31) are recommended.

From the perspective of T1 and T2 relaxation times, postnatal brain development consists primarily of changes in signal intensity associated with the process of myelination. A multiparametric imaging approach to assessing brain maturation showed that it correlated well with postmortem studies (53). Postmortem studies showed that myelination of the brain begins during the fifth fetal month with the myelination of the cranial nerves and continues throughout life. Perhaps the best way to think about the maturation of the brain is that myelination progresses more rapidly in functional systems that are utilized in early life than in those that are not utilized until the child is older. In the brain stem, the medial longitudinal fasciculus, lateral and medial lemnisci, and inferior and superior cerebellar peduncles, which transmit vestibular, acoustic, tactile, and proprioceptive sense, are myelinated at birth, whereas the middle cerebellar peduncles, which transmit motor impulses into the cerebellum, acquire myelin later and more slowly. Similarly, in the cerebrum, the geniculate and calcarine (optic), postcentral (somesthetic), and precentral (propriokinesthetic) regions acquire myelin early, whereas the posterior parietal, temporal, and frontal areas, which are association areas that integrate the sensory experience, acquire myelin later (23,54,55,56). On MRI, the sensory and motor pathways mature before association bundles. The spinothalamic tract is the most advanced in maturation, followed by the optic radiations, the middle portion of the corticospinal tract, and the fornix. Most projection bundles (except the anterior limb of the internal capsule) thus mature earlier than limbic, commissural, and association bundles. Within the limbic and commissural bundles, the fornix tends to mature earlier than the cingulum, while the splenium and genu of the corpus callosum seem to mature before the callosal body. The arcuate and superior longitudinal fasciculi, the anterior limb of the internal capsule, and the external capsule all mature late (53). Yakovlev and Lecours (56), staining the brain with the Weigert stain for myelin, showed that myelination proceeds rapidly within the brain up to about of 2 years of age. The process slows markedly after 2 years, although fibers to and from the association areas of the brain in the anterior frontal and anterior temporal lobes continue to myelinate well into the third and fourth decades of life.

In general, changes in white matter maturation are seen best on T1-weighted images during the first 6 to 8 months of life and on T2-weighted images between the ages of 6 and 18 months. This generalization mostly holds true as our imaging protocols evolve and our protocols become less purely based on relaxation times. Maturation of both the brain stem and cerebellum seem to be more sensitively assessed on T2-weighted images (57,58,59). We obtain both T1- and T2-weighted axial sequences for imaging patients in these age groups, using parameters described in Chapter 1 (3D spoiled gradient echo sequence for T1-weighted images and fairly heavily T2-weighted images with long repetition and echo times). Other imaging sequences that give heavily T1-weighted and T2-weighted images will work, as well. For example, fast spin-echo T2-weighted sequences will show changes of myelination, although myelination appears slightly more advanced on fast spin-echo than on conventional spin-echo images (60). Although visually apparent signal changes of the white matter seem to be largely complete by about the age of 2 years, measurements of relaxivity have shown that T1 shortening of white matter and gray matter continues into adolescence, probably secondary to continued myelination and consequent diminution of brain water (61). The inability to qualitatively detect this continuing change by conventional MR imaging probably reflects the fact that the relaxation rates of gray and white matter change proportionately; thus, no relative change is appreciated.

As maturation in the centrum semiovale progresses, nearly all subjects have persistent areas of high signal intensity in the white matter lateral to the bodies of the lateral ventricles and, more prominently, dorsal and superior to the ventricular trigones on T2-weighted images (Fig. 2-17A-C). The areas may be homogeneous or they may be patchy (and made more so by dilated perivascular spaces that are common in this region [Fig. 2-17D-F]). They are more difficult to identify on the first echo of the long TR sequence than on the second and usually appear isointense to surrounding white matter on a proton density image; they may be visible on FLAIR images, depending upon the exact imaging parameters and machine. The primary cause of this high signal intensity is probably the known delayed myelination of the fiber tracts involving the association areas of the posterior and inferior parietal and posterior temporal cortex. As noted above, large perivascular spaces probably contribute to the high signal intensity, particularly in the peritrigonal area (see subsequent paragraph in this section). Yakovlev and Lecours called these regions the “terminal zones” because some of the axons in these regions do not stain for myelin until the fourth decade (56). These areas of persistent high signal intensity are seen throughout the first decade and, in some patients, into the second decade of life.

It is important to differentiate the terminal zones from white matter injury resulting from prematurity (see Chapter 4), hydrocephalus (see Chapter 8), and metabolic disorders (see Chapter 3); all can be associated with areas of T2 hyperintensity in the peritrigonal region. In general, the white matter injury of prematurity is more sharply defined and is situated more inferiorly, lateral to the trigones and near the optic radiations. Injured white matter is of very high intensity and is typically bright on FLAIR images and on “proton density” (long TR [>2 seconds] short echo time [TE] [<60 ms]) sequences. More importantly, white matter injury is commonly associated with loss of brain tissue, typically resulting in irregularity of the ventricular wall; abnormally deep cortical sulci, with the cortex sometimes extending down to the ventricular surface; and thinning of the posterior body or splenium of the corpus callosum (see examples of white matter injury of prematurity in Chapter 4). The difficult differentiation between normal areas of peritrigonal high signal intensity and white matter injury of prematurity is aided by identification of a layer of myelinated white matter between the trigone of the ventricle and the terminal zones in normal patients (Fig. 2-17C) (65). When the peritrigonal high signal is due to periventricular leukomalacia, this layer of normally myelinated white matter is absent. Differentiation from hydrocephalus is made easier when a shunt or third ventriculostomy (see Chapter 8) can be detected on the MR study (or when ventricles are still enlarged from unshunted hydrocephalus). White matter disease due to metabolic disorders is typically much more extensive than peritrigonal; details are described in Chapter 3.

Just as sulcation develops in an orderly manner, white matter signal changes associated with maturation and myelination of axons appear as shortening of T1 and T2 relaxation times in an orderly and predictable manner (23). These should be assessed on all brain MRIs of infants and young children (Table 2-3). As the white matter matures, T1 shortening occurs, resulting in increasing hyperintensity of the white matter on T1 images, and is followed by T2 shortening, which results in decreasing signal intensity (23,68); these changes vary little with field strength or specifics of the sequence (conventional spin echo, fast spin echo, inversion recovery, spoiled gradient echo, etc.) as long as the sequence is related to T1 and T2 relaxation. During the first 6 months of life, T1-weighted images are most useful for assessing normal brain maturation. On T1-weighted images, high signal intensity should appear in the anterior limbs of the internal capsules and should extend distally from deep cerebellar white matter into the cerebellar folia, by 3 months of age. The splenium of the corpus callosum should be of moderately high signal intensity by the fourth month, and the genu of the corpus callosum should be of high signal intensity by age 6 months. An essentially adult pattern is seen by approximately 8 months of age with the exception that some of the most subcortical white matter fibers (particularly in the anterior frontal and anterior temporal lobes) have not acquired high signal intensity. After age 6 months, T2-weighted images are more useful in the assessment of normal brain maturation. On T2-weighted images, the splenium of the corpus callosum should be of low signal intensity by 6 months of age, the genu of the corpus callosum by 8 months of age, and the anterior limb of the internal capsule by 11 months of age. The deep frontal white matter should be of low signal intensity by age 14 months. With the exception of the subcortical white matter, the entire brain should have an adult appearance by 18 months, and the subcortical white matter should be mature by about 30 months.

Many different approaches have been used to grade brain maturation according to the changes in T1 and T2 relaxation. Some authors (68,69,70,71) have been largely descriptive. Others (23,72) have tried to quantify myelination and create milestones of normal myelination by which delayed myelination can be identified using quantitative diffusion techniques (73,74,75,76) or magnetization transfer (77), but these techniques, which are valuable for research, are not practical in everyday practice. Dietrich et al. (78) approached the subject of normal brain maturation
by dividing the appearance of the brain on T2-weighted spin-echo images into three patterns: (a) infantile (birth to 6 months), (b) isointense (8-12 months), and (c) early adult (10 months onward). In the infantile pattern, the cerebral white matter is hyperintense relative to gray matter, whereas the adult pattern shows hypointense white matter. The appearance of the isointense and early adult patterns is delayed in patients with developmental delay. A similar, but more complex, staging system, dividing brain maturation into five stages, has been proposed by Staudt et al. (79,80) Bird et al. (81) determined that the gray and white matter should be isointense by age 4 months on T1-weighted images and by 9 to 10 months on T2-weighted images. They considered the age at which gray and white matter are isointense as a critical factor in evaluating patients for developmental delay. Some authors have analyzed the images in terms of patterns and attempted to assess degree of, and delay in, maturation on the basis of the pattern (57,58,82,83,84). We choose to assess maturation through the use of the normal milestones described above, as it is a rapid and reliable method that does not require any postprocessing of the imaging data. Indeed, any of the methods described above are easy to use and reliable.

A number of studies (85,86) have postulated the existence of a window of time during which delayed myelination can be detected by MR. This window seems to be between the ages of 4 months and 2 years. Delayed myelination can be detected in children older than 24 months only when it is severe.