J. Anat. (2004) 204, pp465–474
Cerebral cortex three-dimensional profiling in human
fetuses by magnetic resonance imaging
Blackwell Publishing, Ltd.
Andrea Sbarbati,1 Francesca Pizzini,2 Paolo F. Fabene,1 Elena Nicolato,1 Pasquina Marzola,1
Laura Calderan,1 Alessandro Simonati,3 Laura Longo,4 Antonio Osculati5 and Alberto Beltramello2
1
Department of Morphological–Biomedical Sciences, Section of Anatomy and Histology, and
Department of Neurological and Visual Sciences, Section of Neurology, University of Verona, Italy
2
Service of Neuroradiology, Verona City Hospital, Italy
4
Natural Science Museum, Verona, Italy
5
Department of Medicine and Public Health, University of Insubria, Italy
3
Abstract
Seven human fetuses of crown /rump length corresponding to gestational ages ranging from the 12th to the 16th
week were studied using a paradigm based on three-dimensional reconstruction of the brain obtained by magnetic
resonance imaging (MRI). The aim of the study was to evaluate brain morphology in situ and to describe developmental dynamics during an important period of fetal morphogenesis. Three-dimensional MRI showed the increasing degree of maturation of the brains; fronto-occipital distance, bitemporal distance and occipital angle were
examined in all the fetuses. The data were interpreted by correlation with the internal structure as visualized using
high-spatial-resolution MRI, acquired using a 4.7-T field intensity magnet with a gradient power of 20 G cm−1. The
spatial resolution was sufficient for a detailed detection of five layers, and the contrast was optimized using
sequences with different degrees of T1 and T2 weighting. Using the latter, it was possible to visualize the subplate
and marginal zones. The cortical thickness was mapped on to the hemispheric surface, describing the thickness
gradient from the insular cortex to the periphery of the hemispheres. The study demonstrates the utility of MRI
for studying brain development. The method provides a quantitative profiling of the brain, which allows the
calculation of important morphological parameters, and it provides informative regarding transient features of the
developing brain.
Key words development; fetal; neuroimaging; neuronal migration; neuroradiology; subplate zone.
Introduction
Two- or three-dimensional (2D or 3D) ultrasound is the
standard imaging technique used for prenatal diagnosis
of suspected fetal abnormalities, but studies have also
shown the utility of magnetic resonance imaging (MRI)
for the assessment of fetal organs (McCarthy et al. 1985;
Mintz et al. 1987; Schierlitz et al. 2001). This approach
has proved useful in volumetric analysis of important
Correspondence
Professor Andrea Sbarbati, Dipartimento di Scienze MorfologicoBiomediche, Sezione di Anatomia ed Istologia, Strada le Grazie 8,
37134 Verona, Italy. T: +39 45 8027155; F: +39 45 8027163;
E: andrea.sbarbati@univr.it
Accepted for publication 25 March 2004
© Anatomical Society of Great Britain and Ireland 2004
structures like the germinal matrix and lateral ventricles
(Kinoshita et al. 2001). However, 3D MRI studies on
large populations are still lacking and as a consequence
it is difficult to assess the normal pattern of a developing
brain. There are large ongoing projects devoted to MRI
analysis of fetal tissues (Cohen, 2002), but developmental data should be obtained from different collections
of fetuses, to avoid bias due to racial differences or
preservation methods. Sectional MRI data provide
information on neuronal migration processes, revealing a layered appearance of the cortex and germinal
matrix (Kostovic et al. 2002). In the developing brain,
seven transient layers are present in the cerebral cortex
(i.e. ventricular, periventricular, subventricular, intermediate, subplate zones, cortical plate and marginal
zone) and good correlation has been found between
histology and MRI data on T1-weighted (T1W) sequences
466 3D MRI of fetal brain, A. Sbarbati et al.
at 2.0 T (Kostovic et al. 2002). Five laminar compartments of varying MRI signal intensity have been
detected. However, detailed visualization of some
layers composing the developing cortex has not yet
been achieved. In particular, specific methods for
detection of subplate and marginal zones are lacking.
High-field-intensity MRI permits a better signal-tonoise ratio with respect to standard MRI using clinical
magnets, and could generate better imaging of the
thin cerebral layers. Such data could include 3D images,
providing a more complete description of the developmental process.
In the present work, we studied a series of human
fetuses ranging from the 12th to the 16th week of
gestational age (GA). During this period important
maturational events take place in the developing
brain (Chi et al. 1977). We used a paradigm based on
3D reconstruction of the brain obtained by MRI at
different field intensities. The data were interpreted by
comparison with the internal structure obtained by 4.7T MRI and with histological specimens. The major aim
of the study was to evaluate brain morphology in
situ, avoiding artefacts due to removal from the cranial
cavity, and to describe developmental dynamics during
an important period of fetal morphogenesis. A further
aim was to relate the 3D morphology of the brain
to internal structures, optimizing MRI pulse sequences
for visualization of transient layers present during development, such as the subplate and the marginal zone.
Materials and methods
Seven human fetuses of 65, 85, 100, 105, 110, 116 and
125 mm crown–rump length (CRL), corresponding to GAs
ranging from the 12th to the 16th week, were studied.
The fetuses were selected from Medical Faculty and
Natural Science Museum (Verona, Italy) collections for
their good state of preservation. Some of the fetuses
had been used in previous MRI studies (Sbarbati et al.
1998). The cadavers were fixed by immersion in 20%
formalin, for routine examination, and conserved in this
solution. They were removed from this solution only
for the time of the scan.
Magnetic resonance images at 1.5 T were acquired
using a Symphony system (Siemens). Entire fetuses
were positioned within a knee coil for a better signalto-noise ratio. Multiplanar reconstruction (MPR) T1W
sagittal localizer and fast spin echo (SE) MPR T1W
images were acquired. The acquisition parameters
were: repetition time (TR) = 1900 ms; echo time (TE) =
4.09 ms; slab thickness = 72 mm; matrix size and fieldof-view (FOV) were adjusted to obtained a voxel size
of 0.6 × 0.4 × 0.5 mm3. The total imaging time was
20–25 min.
Data were processed on a Sun Advantage window
4.0 workstation. A 3D reconstruction was made of the
fetal brains. Subsequently, the 3D brains were visually
analysed in the conventional anatomical views (superior,
inferior, anterior and posterior). Images in views
other than the axial, coronal and sagittal were also
taken into consideration. Fronto-occipital distance
and bitemporal distance were calculated on the 3D
reconstruction, using brains orientated in the axial
and coronal planes, respectively. The fronto-occipital
distance was the linear distance between the anterior
extremity of the frontal pole and the posterior extremity
of the occipital pole. The bitemporal distance was the
linear distance between the most protruding points
of each temporal pole. The interobserver variability of
the measurements was less than 1%. For each fetus,
the fronto-occipital/bitemporal ratio was calculated.
Statistical analysis was carried out using Pearson’s test.
The occipital angle was calculated on a lateral projection
using two lines tangential to the inferior and superior
borders of the occipital lobe.
For MRI at 4.7 T, the specimens were removed from
formalin, sealed in a polyethylene container and examined using a Biospec Tomograph (Bruker, Karlsruhe,
Germany) equipped with a horizontal magnet (Oxford
Ltd, Oxford, UK) having a 33-cm bore with a gradient
power of 20 G cm−1, and a Silicon Graphics O2 computer. Proton MRI was performed with all the fetuses
positioned in a 72-mm internal diameter birdcage coil.
Then, 2D and 3D images were acquired. Two-dimensional
images were obtained in different planes at high
space resolution and using SE sequences. Moderately
T2-weighted (T2W) images were acquired with the
following parameters: TR = 2000 ms; TE = 60 ms; number
of averages (NEX) = 8; FOV = 6 × 6 cm2; slice thickness =
1 mm, matrix size = 256 × 256 corresponding to an
in-plane resolution of 0.234 × 0.234 mm2. Strongly
T2W images were acquired with: TR = 3000 ms;
TE = 80 ms; NEX = 16; FOV = 6 × 6 cm2; slice thickness =
1 mm; matrix size = 512 × 512 corresponding to an inplane resolution of 0.117 × 0.117 mm2. T1W SE images
were acquired with TR = 800 ms; TE = 25 ms; NEX = 4;
FOV = 6 × 6 cm2; slice thickness = 1 mm and matrix
size = 512 × 512.
© Anatomical Society of Great Britain and Ireland 2004
3D MRI of fetal brain, A. Sbarbati et al. 467
Three-dimensional images were acquired using a spoiled
gradient-echo sequence with the following parameters:
TR = 80 ms; TE = 6 ms; FOV = 12 × 6 cm2, slab thickness =
6 cm; matrix size = 256 × 128 × 128 corresponding to a
space resolution of 0.469 × 0.469 × 0.469 mm3.
MRI data were analysed by comparison with histological sections obtained from ten paraffin-embedded,
Nissl- or haematoxylin–eosin-stained fetuses of corresponding gestational age from the collection of
the Department of Neurological and Visual Sciences,
Section of Neurology, University of Verona.
The thickness of the cortex was calculated in both
the hemispheres of each fetus using a sectional MRI
data set. We analysed 146 axial slices encompassing
the whole brain, out of the 256 slices acquired. In each
slice, the thickness of the cortex was evaluated at 12
points chosen at regular intervals according to a systematized protocol using Paravision (Bruker) software.
In total, 1752 points were evaluated in each cerebral
hemisphere. The measurements of the thickness of the
cortex were projected on to the telencephalic lateral
surface of a 3D anatomical image of the same brain
and then displayed in pseudo-colour.
Fig. 1 (A) Parasagittal 4.7-T MR image
( T1W) of a representative fetus (CRL
116 mm). The wide space (b) separating
the telencephalic vesicles (d) from the
skull wall is visible. The ganglionic
eminence (c) appears as a high-intensity
crescent on the floor of the lateral
ventricle (a). (B) MRI of fetal brain (T1W,
transverse section at the level of the line
shown in A). The medial wall of the
hemispheres is the thinnest and shows
the fronto-parietal incisure (arrows).
(C) Fronto-occipital and bitemporal
distances in the examined fetuses.
(D) Occipital angle of the examined
fetuses.
© Anatomical Society of Great Britain and Ireland 2004
Results
Three-dimensional morphology of the hemispheres
High-spatial-resolution (4.7 T) MRI showed that a
wide space, in which developing meninges were visible,
separates the developing brain from the cranial
wall (Fig. 1). Considering that formalin fixation modifies
anatomical volumes, the exact dimension of this space
was difficult to calculate. However, visual inspection
showed that it was widest at the supero-lateral surface
of the brain. In the 3D reconstruction, all the examined
brains appeared lissencephalic. The longitudinal
cerebral fissure separated the telencephalic vesicles,
and the lateral cerebral sulcus (sylvian fissure) was visible
on their lateral surface (Fig. 2). The brains showed a
similar surface morphology even though their degree of
maturation was variable. All the parameters measured
(i.e. fronto-occipital distance, bitemporal distance and
occipital angle, Fig. 1C,D) were significantly correlated
to CRL (correlation coefficient R = 0.965, 0.915 and
− 0.902, respectively; P < 0.005). The plot in Fig. 1(C) shows
that, in the interval of gestational age considered,
both parameters show a linear increase, although with
468 3D MRI of fetal brain, A. Sbarbati et al.
Fig. 2 Three-dimensional reconstruction of a series of fetal
brains (MRI 1.5T). (A) Superior view. (B) Lateral view. The
fronto-occipital distance of the brains has been normalized
at the same value for all the fetuses. In Figs 2–4, the CRL is
reported for each fetus to allow comparison of their
morphological evolution. In B, the arrow indicates the
parieto-occipital fossa. The dotted line surrounds the
fronto-parietal prelobe, which appears as a single structure.
The region between the dotted line and the arrow belongs to
the fronto-parietal prelobe. The occipital angle is also shown.
different rates. The elongation of the fronto-occipital
distance exceeded that of the bitemporal distance. As
a consequence, the fronto-occipital/bitemporal ratio
progressively increased with gestational age (from 1.1
to 1.2, 1.2, 1.2, 1.2, 1.3 and 1.4).
In 65–105 mm fetuses, the longitudinal cerebral
fissure (Fig. 2) was relatively wide and shaped like an
hourglass, due to the presence of a minimal interhemispheric distance around its median segment. Two
incisures (i.e. fronto-parietal and parieto-occipital) were
visible at the medial border of the hemispheres (Fig. 1B).
In 110–125 mm fetuses, the longitudinal fissure appeared
more regular and narrower. The two incisures remained
visible but were less deep. The presence of these incisures
was confirmed in high-resolution sectional images, in
which they appeared as two notches on the medial wall
of the telencephalic vesicle (Fig. 1B).
In 65–105 mm fetuses, it was impossible to distinguish a clear separation between the frontal and
parietal lobes: for descriptive purposes, we identified a
single structural unit that could be termed the frontoparietal prelobe (Fig. 2). This crescent-shaped structure
surrounding the lateral cerebral sulcus displayed a
smooth regular surface. Its anterior extremity was
conical with a rather pointed apex. The extremities of
the two hemispheres were convergent (Fig. 3). In 110–
125 mm fetuses, the frontal poles had rounded extremities that, in a frontal view, showed approximately
parallel axes.
Sectional MRI (Figs 4 and 5) showed that the wall is
thicker in areas surrounding the ganglionic eminence and
progressively thinner distally (i.e. near the longitudinal
cerebral fissure and at the apex of the frontal pole).
In all the fetuses, the parietal lobe appeared as
a slightly convex area with a smooth surface. On the
lateral surface of the brain (Fig. 2) a depressed area was
visible between the developing parietal and occipital
regions, in correspondence with the dorsal–posterior
border of the lateral sulcus (parieto-occipital fossa,
Fig. 2B). Owing to the presence of the lateral sulcus
and of the parieto-occipital fossa, the developing telencephalon appeared divisible into two main components that could be identified as the fronto-parietal
and temporo-occipital prelobes (Fig. 2B).
In 65–105 mm fetuses, the temporal pole appeared
as a curved tube, with a medial concavity and a thin
rostral extremity (Figs 2 and 3). The axes of the poles
were rostrally convergent. In 110–125 mm fetuses, the
temporal poles progressively enlarged and their rostral
extremities showed a rounded shape. The axes of the
poles were caudally convergent.
In the 65–100 mm fetuses in our series, the occipital
lobe was poorly developed, appearing as a posterior
extension of the temporal lobe (Fig. 4). In fetuses of
105–125 mm CRL, it showed a round shape and a smooth
regular surface. Its growth was the main reason for
the greater length of the antero-posterior axis compared
with the bitemporal axis.
Sectional MRI showed that the occipital cortex was
thin, in particular at the distal end of the pole and in
areas near the inferior surface of the brain.
© Anatomical Society of Great Britain and Ireland 2004
3D MRI of fetal brain, A. Sbarbati et al. 469
Fig. 3 Three-dimensional
reconstruction of a series of fetal brains
(MRI 1.5T). (A) Anterior view. (B)
Inferior view.
The lateral cerebral sulcus was visible in all the fetuses
(Fig. 2). Comparing fetuses at different degrees of maturity,
a clear difference was noted in the morphology of the
lateral sulcus. In 65–100 mm fetuses, the sulcus appeared
as a light depression of the lateral surface limited by a
curved border, and the opercula were not yet formed.
© Anatomical Society of Great Britain and Ireland 2004
The parieto-occipital fossa reached the medial
border of the hemisphere, separating the parietal from
the occipital lobes. In some fetuses the borders of the
developing opercula formed an angle of about 30°,
opening ventrally. Sectional images showed that at the
level of the future insular cortex there was a thickening
470 3D MRI of fetal brain, A. Sbarbati et al.
Fig. 4 (A) Three-dimensional
reconstruction of a series of fetal brains,
posterior view (MRI 1.5T). (B) Sectioned
3D reconstruction of a series of fetuses,
anterior view (MRI 1.5T). The coronal
section of the brain shows the
decreasing thickness of the cortex,
starting from the ganglionic eminence.
of the lateral wall of the hemisphere. This latter structure
can be subdivided into a medial and a lateral portion.
The medial portion showed a high intensity signal, thus
corresponding to the germinal matrix. The lateral
portion showed an intensity similar to that of the
developing cortex and was composed of basal nuclei
(Figs 4B, 5 and 6).
In 105–110 mm fetuses, the development of the
lateral sulcus was characterized by an expansion of the
opercula. The future insular cortex displayed a square
© Anatomical Society of Great Britain and Ireland 2004
3D MRI of fetal brain, A. Sbarbati et al. 471
Fig. 5 Correlation of the 3D
morphology with internal structures
(fetus 125 mm CRL). Using a sectional
data set (A) the thickness of the cortex
has been projected on to the
telencephalic lateral surface and is
displayed in pseudo-colour (B).
shape with four margins (i.e. anterior, dorsal, posterior
and inferior). The surface corresponding to the developing insular cortex showed a regular surface with a
slight central elevation.
In the fetus of 125 mm CRL, the lateral sulcus appeared
as a deep depression and the developing insular cortex
was triangular in shape and delimited by a superior–
anterior and an inferior–posterior margin. The two
margins formed a ventrally opening angle of about 18°.
Correlation of the 3D morphology with internal
structures
Comparing sectional data with the 3D reconstruction,
it was possible to project the thickness of the developing brain structures on to the telencephalic lateral
surface (Fig. 5). The maps showed that an area of thick
cerebral cortex surrounds the projection of the ganglionic eminence on the surface. Thinner areas were found
at the apex of the frontal lobe and in the temporal
occipital lobe. Areas of intermediate thickness were
found between the dorsal ending of the lateral sulcus
and the longitudinal fissure.
Fig. 6 (A) MRI (4.7T) of fetal brain ( T2W, transverse section,
CRL 85 mm). The asterisk indicates the ganglionic eminence.
Cortical areas marked by squares are enlarged in B and C. a,
liquor; b, marginal zone; c, cortical plate; d, subplate zone; e,
intermediate (fetal white matter), subventricular
periventricular zones; f, ventricular zone. ( D) High-resolution
T2W MRI of the fetal cortex (left panel) in comparison with a
low-magnification histological section (right panel,
haematoxylin–eosin staining). 1, ventricular zone; 2,
periventricular zone; 3, subventricular zone; 4, intermediate
zone; 5, subplate zone; 6, cortical plate; 7, marginal zone.
Interpretation of the layers was made in accordance with
Kostovic et al. (2002). A, ×3.4; B and C, ×13.6; D, ×34.
© Anatomical Society of Great Britain and Ireland 2004
Optimization of sequence for analysis of the
developing cortex
In our paradigm, a quite high spatial resolution was
obtained using a 4.7-T field intensity magnet with a
gradient power of 20 G cm−1. At these conditions, the
spatial resolution was sufficient for detailed visualization of the marginal and subplate zones. The contrast
was optimized using sequences with different degrees
of T2 weighting. In particular, for the marginal and
472 3D MRI of fetal brain, A. Sbarbati et al.
subplate zones, a moderately T2W pulse sequence
appeared capable of providing considerable detail with
respect to the adjacent layers (Fig. 6). Strongly T2W
sequences resulted in images of lesser quality and did
not seem adequate for detection of marginal zones, due
to the strong intensity of the signal emitted by cerebrospinal fluid. Using the proposed moderately T2W sequence, the signal emitted by the liquor was reduced and
the thickness of the marginal layer was quite evident.
Layers in the developing cortex; T1W images
Using T1W images, the more cellular layers generated
a more intense signal (Fig. 1). As a consequence, the
ventricular zone and the germinal matrix of the ganglionic eminence, both characterized by a cellular pattern,
appeared clearly in the images. The subventricular zone
appeared to be of intermediate intensity. Strips of lowintensity material were visible in some areas, probably
due to bundles of axons. The subplate zone emitted a
signal of low intensity. The cortical plate, characterized
by a cellular pattern, appeared clearly in T1W images. The
marginal zone emitted a signal of low intensity.
Layers in the developing cortex; optimized T2W
images
Using the proposed T2W pulse sequence a detailed
analysis of the developing cortex was achieved (Fig. 6).
The ventricular zone and the germinal matrix of the
ganglionic eminence, both characterized by a cellular
pattern, appeared dark in images. The subventricular
zone appeared of intermediate intensity. Strips of lowintensity material were visible in some areas, probably
due to bundles of axons. The subplate zone emitted
a signal of strong intensity (Fig. 6C, layer marked d ).
The cortical plate, characterized by a cellular pattern,
appeared dark in images (Fig. 6C, layer marked c). The
marginal zone emitted a signal of strong intensity
(Fig. 6C, layer marked b). The intense emitted signal makes
it possible to detect small irregularities in the layer.
Discussion
Advantages and methodological limitations of 3D MRI
analysis
The development of the brain is a complex event, the
spatial organization of which is difficult to study using
conventional anatomical methods, and difficult to
explain in simple mechanical terms (Sidman & Rakic, 1982).
In fetuses, the brain parenchyma is a delicate, almost
gelatinous structure and its removal from the cranial
cavity may cause deformation, hampering the quantitative evaluation of important parameters relevant
to the stage of maturation. In particular, the dissection
of immature human fetal specimens may be difficult
because the partially myelinated brain does not fix
well, even after preservation in formaldehyde for several
years, due to its high water content (Kier & Truwit,
1996).
The present study demonstrates the utility of MRI
in the study of brain development. The 3D reconstruction obtained is quite similar to those provided by
necropsy but with an absence of mechanical artefacts.
The method also provides a quantitative profiling of
the brain, allowing the calculation of important
morphological parameters. In addition, 3D MRI reconstruction appears to provide important informative
regarding transient features of the developing brain.
The data clearly demonstrate some transient features
such as the parieto-occipital fossa or the incisures
visible between the lateral and medial walls of the
hemispheres.
However, caution is necessary in examination of the
aldehyde-fixed brain, considering the changes induced
in volumes and conformation. In addition, it is important to avoid overestimation of data obtained from
collection material, the normality of which is not always
evident.
A study based on gross photographs of fixed brain by
Chi et al. (1977) reported difficulty in distinguishing
between an early gyral depression and an artefactual
tear or fold. In situ MRI studies could be useful to
minimize this kind of artefact. In their study Chi et al.
(1977) did not show photographs, only very schematic
drawings; however, our data seem to confirm almost
entirely their classical description. The only differences
concern description of the development of the lateral
sulcus. Chi et al. (1977) state that the superior border of
the insula can be designated the circular sulcus, and the
inferior border the proper sylvian fissure. According to
their description the circular sulcus extends rostrally
first, then curves around in a circular pattern and is
joined by the posterior end of the sylvian fissure. In our
specimens, this progression is not visible, and in 100 –
125 mm fetuses the inferior border appears more
evident than the superior border.
© Anatomical Society of Great Britain and Ireland 2004
3D MRI of fetal brain, A. Sbarbati et al. 473
Mapping of sectional parameters on 3D reconstruction
We correlated 3D MRI morphology with parameters
obtained by sectional analysis, mapping cortical thickness on to the hemispheric surface and thereby clearly
showing the thickness gradient from the insular cortex
to the periphery of the hemispheres.
It is likely that this approach, together with improved
MRI visualization of the cortex, could allow mapping
of features such as the thickness of single layers, thus
providing new data on the evolution of the neuronal
migratory pathway.
Visualization of layers in the developing cortex
Aldehyde fixation changes the relaxation characteristics of the tissue, and therefore the sequences usually
employed for in vivo study of the brain must be reconsidered in studies on necropsy material. To obtain a
complete visualization of the developing cortex in the
age window taken into consideration, we propose using
two pulse sequences. As has been amply demonstrated,
the cell-rich layers (i.e. germinal matrix, ventricular
layer and cortical plate) emit an intense signal with T1W
pulse sequence. Water-rich subplate and marginal
zones emit an intense signal with T2W sequence. This
sequence also provides good visualization of the
subventricular layer. The signal originating from several
cellular layers is markedly reduced in T2W images,
whereas it is strong in T1W images.
In the present study, the results obtained by this
approach confirm and extend previous demonstrations
of the layered appearance of the fetal cerebral wall
(Girard & Raybaud, 1992; Brisse et al. 1997). In particular, we achieved a detailed visualization of the
subplate zone. This transient structure is the 5th layer of
the developing cortex. In both primates and humans,
it has been shown that thalamocortical afferents
accumulate in the subplate zone before entering the
cortical plate. The transient subplate zone is still well
developed in the newborn frontal cortex (Kostovic
et al. 1989). At histology, this zone is characterized by
a strongly hydrophilic matrix that is rich in acid mucopolysaccharides. At histochemistry, the subplate zone is
stained by Alcian blue (Kostovic et al. 2002). By contrast,
adjacent zones (i.e. intermediate zone/fetal white
matter and cortical plate) are Alcian negative. Structurally,
the subplate zone contains a large extracellular space
through which neurons and growth cones migrate. In
© Anatomical Society of Great Britain and Ireland 2004
a detailed study of the developing human cerebrum,
Kostovic et al. (2002) found that changes in the MRI
lamination pattern of the human fetal cerebral wall
are predominantly caused by changes in the subplate
zone. Histochemical staining of the extracellular matrix
enabled selective visualization of the subplate zone
and correlation with an increase in MRI signal intensity
in the subplate zone and ingrowth and accumulation
of thalamocortical and corticocortical afferents and
their subsequent relocation to the cortical plate. The
authors concluded that dynamic changes in the MRI
appearance of the subplate zone and histochemical
staining of its extracellular matrix can be used as indirect
parameters for an assessment of normal vs. disturbed
unfolding of crucial histogenetic events that are involved
in prenatal shaping of the human cerebral cortex. However, in the paper by Kostovic et al. (2002), the subplate
zone appeared as a layer of low MRI signal intensity at
all the gestational ages studied. Our work expands the
results of Kostovic et al. (2002), demonstrating that,
using a 4.7-T magnet (with a smaller bore and a higher
signal-to-noise ratio with respect to clinical 2-T instruments), it is possible to obtain higher spatial resolution
(117 vs. 406 µm) reducing partial volume artefacts in a
structure with seven layers and a total thickness in large
areas inferior to 3 mm. In addition, we demonstrate that
the signal intensity of the subplate zone is dependent
on the pulse sequence used, with T2W images proving
more effective in visualizing the structure.
Final considerations
The present results demonstrate that MRI technology
allows brain profiling in human fetuses from the 12th
to the 16th week of gestational age. In the same
specimens, high-field-intensity MRI provides a detailed
analysis of the layered cerebral cortex. If large virtual
collections of developing brains were available, this
would facilitate comparisons between data from
different countries and vertebrate species. Such data
could be useful in understanding neuronal migration
disorders (Barkovich, 1995; Barkovich et al. 1996).
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