DOI: 10.1148/rg.251045085
RadioGraphics 2005;25:53-65
© RSNA, 2005
Diffusion-Tensor MR Imaging and Fiber Tractography: A New Method of Describing Aberrant Fiber Connections in Developmental CNS Anomalies1
Seung-Koo Lee, MD,
Dong Ik Kim, MD,
Jinna Kim, MD,
Dong Joon Kim, MD,
Heung Dong Kim, MD,
Dong Seok Kim, MD and
Susumu Mori, PhD
1 From the Departments of Radiology (S.K.L., D.I.K., J.K., D.J.K.), Pediatrics (H.D.K.), and Neurosurgery (D.S.K.), Yonsei University College of Medicine, 134 Shinchondong, Seodaemungu, Seoul 120-752, Korea; and the Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Md (S.M.). Recipient of a Certificate of Merit award for an education exhibit at the 2003 RSNA Scientific Assembly. Received April 21, 2004; revision requested May 21 and received July 7; accepted July 8. All authors have no financial relationships to disclose. Address correspondence to S.K.L. (e-mail: slee@yumc.yonsei.ac.kr).
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Abstract
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Congenital anomalies of the central nervous system (CNS) often demonstrate aberrant white matter connections, which may be better characterized with diffusion-tensor imaging (DTI) and fiber tractography (FT) than with conventional magnetic resonance (MR) imaging. DTI-FT demonstrates abnormal hemispheric fiber connections in callosal agenesis or acquired disease of the corpus callosum. Decreased anisotropy of white matter adjacent to the malformed cortex and an aberrant course of major fiber pathways due to dysplastic white matter are common findings in cortical dysplasia. Increased anisotropy of dysplastic gray matter in heterotopia supports the hypothesis that developing neurons migrate from the ependyma to the cortex with a radial growth pattern. In periventricular leukomalacia, DTI-FT demonstrates an intact corticospinal tract and decreased thalamocortical sensory connections, which are responsible for the spasticity of cerebral palsy owing to impairment of inhibitory function. Joubert syndrome comprises malformation of the cerebellar vermis and an aberrant connection between the cerebellum and the cerebral cortex via an elongated and abnormally shaped superior cerebellar peduncle, which are well visualized with DTI-FT. In developmental CNS disease, DTI-FT demonstrates additional findings beyond those seen with conventional MR imaging. Future studies will focus on determining the significance of the aberrant fiber connections and their relationships to the clinical manifestations of CNS anomalies.
© RSNA, 2005
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Introduction
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Diffusion-tensor magnetic resonance (MR) imaging (DTI) and fiber tractography (FT) are new methods that can demonstrate the orientation and integrity of white matter fibers in vivo (1–5); however, their clinical application is still under investigation. Previous studies include an evaluation of axonal damage caused by a chronic infarct or motor neuron disease (6), a direct insult to axonal fibers such as multiple sclerosis (7,8), or acute disseminated encephalomyelitis (9).
Developmental central nervous system (CNS) diseases, both congenital and postnatal, can be a spotlighted field of DTI due to the potential for generating a fiber pathway and aberrant connections in the case of a blockage of normal white matter formation.
In this review, the authors examine developmental CNS anomalies with DTI and FT and investigate their clinical usefulness in describing the aberrant fiber connections to provide a better understanding of the pathogenetic mechanisms of congenital diseases. Specific topics discussed are the imaging protocol, abnormalities of the corpus callosum, malformations of cortical development, cerebral palsy, posterior fossa malformations, and technical considerations and conclusions.
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Imaging Protocol
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A short acquisition time and instant processing are essential for the clinical feasibility of a certain procedure. The authors applied single-shot spin-echo echo-planar imaging (EPI) and parallel imaging techniques to achieve motion-free and higher signal-to-noise ratio (SNR) DTI. The total imaging time for DTI and FT was 7–9 minutes according to the section numbers, which was added to the routine MR imaging examinations. Informed consent was received from all patients or the participant’s parents or legal guardian, and all procedures were performed with the approval of the institutional review board for clinical studies.
Acquisition of MR Images
All studies were performed on a 1.5-T Gyroscan Intera system (Philips Medical Systems, Best, the Netherlands) by using a six-channel sensitivity encoding (SENSE) head coil. The diffusion-weighted imaging was performed by using single-shot spin-echo echo-planar imaging with a navigator echo phase correction (motion correction) and a SENSE factor of 2. This study used a data matrix of 96 acquisitions, which was reconstructed to 128 over a field of view of 220 mm. The imaging sections were positioned to make the section perpendicular to the anterior commissure–posterior commissure (AC-PC) line. The section thickness was 2.3 mm without a gap (45–55 sections). Other imaging parameters were as follows: echo time = 70 msec, repetition time = 6,599–8,280 msec, number of acquisitions = two, b = 600 sec/mm2.
Data Processing
The data were processed on a Windows 2000 (Microsoft, Redmond, Wash) personal computer equipped with Philips Research Image-processing Development Environment (PRIDE) software (Philips Medical Systems), which is based on the Fiber Assignment by Continuous Tracking (FACT) method (10). Anisotropy was calculated by using orientation-independent fractional anisotropy (FA), and diffusion-tensor MR imaging–based color maps were created from the FA values and the three vector elements. The vector maps were assigned to red (x element, left-right), green (y, anterior-posterior), and blue (z, superior-inferior) with a proportional intensity scale according to the FA. Three-dimensional FT was then achieved by connecting voxel to voxel with the FACT algorithm. The threshold values for the termination of the fiber tracking were less than 0.3 for FA and greater than 45° for the trajectory angles between the ellipsoids.
Anatomic Landmarks and ROI Locations for Major White Matter Fibers
For tracking of the white matter fibers, the region of interest (ROI) method was applied. Experienced neuroradiologists (S.K.L., D.I.K.) with knowledge of the fiber pathways placed the single or multiple ROIs on the color maps. The plane of the ROI was varied according to the running direction of the white matter fibers (eg, corticospinal tract on the axial views, corpus callosum on the sagittal views) (Fig 1).
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Figure 1a. ROIs for generating FT images of the major white matter fiber tracts. (a) FT image of the corticospinal tract (left) is generated from the fibers connecting two ROIs in the longitudinal pontine fibers and the posterior limb of the internal capsule (right). (b) FT images of the corpus callosum (left and bottom right) are generated from a single ROI at the precise anatomic locations on the sagittal color map (top right). (c) FT image of longitudinal fiber bundles connecting anteroposteriorly (green fibers) (left) is generated from ROIs on coronal color maps (right). The superior longitudinal fasciculus (slf) is connected to the arcuate fasciculus (af); these fiber tracts are generated from a single ROI. Fiber tracts of other longitudinal fibers like the cingulum (c) and inferior longitudinal fasciculus (ilf) are also generated from coronal images. (d) FT image of the middle cerebellar peduncles (left) is generated from single ROIs on the coronal view (right). These fiber tracts form a midline crossing by means of the red transverse pontine fibers (thick arrow), and some extend to cortical connections superiorly (thin arrows). (e) FT images of the superior (yellow) and inferior (blue) cerebellar peduncles (left and bottom right) are generated from single ROIs on axial color maps (top right). RAO = right anterior oblique.
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Figure 1b. ROIs for generating FT images of the major white matter fiber tracts. (a) FT image of the corticospinal tract (left) is generated from the fibers connecting two ROIs in the longitudinal pontine fibers and the posterior limb of the internal capsule (right). (b) FT images of the corpus callosum (left and bottom right) are generated from a single ROI at the precise anatomic locations on the sagittal color map (top right). (c) FT image of longitudinal fiber bundles connecting anteroposteriorly (green fibers) (left) is generated from ROIs on coronal color maps (right). The superior longitudinal fasciculus (slf) is connected to the arcuate fasciculus (af); these fiber tracts are generated from a single ROI. Fiber tracts of other longitudinal fibers like the cingulum (c) and inferior longitudinal fasciculus (ilf) are also generated from coronal images. (d) FT image of the middle cerebellar peduncles (left) is generated from single ROIs on the coronal view (right). These fiber tracts form a midline crossing by means of the red transverse pontine fibers (thick arrow), and some extend to cortical connections superiorly (thin arrows). (e) FT images of the superior (yellow) and inferior (blue) cerebellar peduncles (left and bottom right) are generated from single ROIs on axial color maps (top right). RAO = right anterior oblique.
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Figure 1c. ROIs for generating FT images of the major white matter fiber tracts. (a) FT image of the corticospinal tract (left) is generated from the fibers connecting two ROIs in the longitudinal pontine fibers and the posterior limb of the internal capsule (right). (b) FT images of the corpus callosum (left and bottom right) are generated from a single ROI at the precise anatomic locations on the sagittal color map (top right). (c) FT image of longitudinal fiber bundles connecting anteroposteriorly (green fibers) (left) is generated from ROIs on coronal color maps (right). The superior longitudinal fasciculus (slf) is connected to the arcuate fasciculus (af); these fiber tracts are generated from a single ROI. Fiber tracts of other longitudinal fibers like the cingulum (c) and inferior longitudinal fasciculus (ilf) are also generated from coronal images. (d) FT image of the middle cerebellar peduncles (left) is generated from single ROIs on the coronal view (right). These fiber tracts form a midline crossing by means of the red transverse pontine fibers (thick arrow), and some extend to cortical connections superiorly (thin arrows). (e) FT images of the superior (yellow) and inferior (blue) cerebellar peduncles (left and bottom right) are generated from single ROIs on axial color maps (top right). RAO = right anterior oblique.
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Figure 1d. ROIs for generating FT images of the major white matter fiber tracts. (a) FT image of the corticospinal tract (left) is generated from the fibers connecting two ROIs in the longitudinal pontine fibers and the posterior limb of the internal capsule (right). (b) FT images of the corpus callosum (left and bottom right) are generated from a single ROI at the precise anatomic locations on the sagittal color map (top right). (c) FT image of longitudinal fiber bundles connecting anteroposteriorly (green fibers) (left) is generated from ROIs on coronal color maps (right). The superior longitudinal fasciculus (slf) is connected to the arcuate fasciculus (af); these fiber tracts are generated from a single ROI. Fiber tracts of other longitudinal fibers like the cingulum (c) and inferior longitudinal fasciculus (ilf) are also generated from coronal images. (d) FT image of the middle cerebellar peduncles (left) is generated from single ROIs on the coronal view (right). These fiber tracts form a midline crossing by means of the red transverse pontine fibers (thick arrow), and some extend to cortical connections superiorly (thin arrows). (e) FT images of the superior (yellow) and inferior (blue) cerebellar peduncles (left and bottom right) are generated from single ROIs on axial color maps (top right). RAO = right anterior oblique.
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Figure 1e. ROIs for generating FT images of the major white matter fiber tracts. (a) FT image of the corticospinal tract (left) is generated from the fibers connecting two ROIs in the longitudinal pontine fibers and the posterior limb of the internal capsule (right). (b) FT images of the corpus callosum (left and bottom right) are generated from a single ROI at the precise anatomic locations on the sagittal color map (top right). (c) FT image of longitudinal fiber bundles connecting anteroposteriorly (green fibers) (left) is generated from ROIs on coronal color maps (right). The superior longitudinal fasciculus (slf) is connected to the arcuate fasciculus (af); these fiber tracts are generated from a single ROI. Fiber tracts of other longitudinal fibers like the cingulum (c) and inferior longitudinal fasciculus (ilf) are also generated from coronal images. (d) FT image of the middle cerebellar peduncles (left) is generated from single ROIs on the coronal view (right). These fiber tracts form a midline crossing by means of the red transverse pontine fibers (thick arrow), and some extend to cortical connections superiorly (thin arrows). (e) FT images of the superior (yellow) and inferior (blue) cerebellar peduncles (left and bottom right) are generated from single ROIs on axial color maps (top right). RAO = right anterior oblique.
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Abnormalities of the Corpus Callosum
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Normal Development of the Corpus Callosum
Between 8 and 20 weeks gestation, the corpus callosum is formed by development of the callosal precursors and the fibers from the hemispheric cortex (11). These callosal precursors secrete the chemoattractant axonin-1 to guide the developing axons across the midline (12). Therefore, each region of the hemispheric fibers is connected to the contralateral side through the corpus callosum.
Complete Agenesis of the Corpus Callosum
Agenesis of the corpus callosum (ACC) is characterized by typical MR imaging findings such as a "cartwheel configuration" of the interhemispheric sulcal markings, absence of the cingulate gyrus, and colpocephalic features of the lateral ventricles. At DTI-FT, fibers from the hemispheric cortex fail to cross the midline and form a thick bundle running anteroposteriorly (ie, the Probst bundle) (Fig 2).
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Figure 2a. Prenatally diagnosed ACC in a newborn girl. (a) Midline sagittal MR image shows absence of the corpus callosum and cingulate gyrus and a radial configuration of the sulcal markings (arrows). (b) FT image shows a thickened bundle of anteroposteriorly running fibers (green and blue fibers), which is the Probst bundle. Note the normal corticospinal tract (yellow fibers).
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Figure 2b. Prenatally diagnosed ACC in a newborn girl. (a) Midline sagittal MR image shows absence of the corpus callosum and cingulate gyrus and a radial configuration of the sulcal markings (arrows). (b) FT image shows a thickened bundle of anteroposteriorly running fibers (green and blue fibers), which is the Probst bundle. Note the normal corticospinal tract (yellow fibers).
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In some cases, ACC is an incidental finding and the patient is asymptomatic. Normal motor fibers and major interconnecting fibers in the brainstem are demonstrated in such cases. Previous reports describe a thickened anterior commissure in ACC (13), although the thickness varies on a patient-by-patient basis. In the case of complex anomalies, the DTI findings vary according to the extent of the affected structures.
Partial Agenesis of the Corpus Callosum
The corpus callosum develops from the genu portion followed by the body, the splenium, and lastly the rostrum. Therefore, the posterior part or rostrum is hypoplastic in the case of partial ACC. A high FA value and strong fiber connection through the remaining portion of the corpus callosum are demonstrated in partial ACC (14). The white matter fibers from the parieto-occipital lobe form a back-to-front bundle and enter into the remaining genu portion. Fibers from the frontal lobe also join the connection through a partially formed corpus callosum, forming an H-shaped configuration of hemispheric fibers on axial views (Fig 3).
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Figure 3a. Partial ACC in a 9-year-old boy with seizure disorder. (a) Axial inversion-recovery image shows partial ACC with a remaining genu portion (*) and colpocephalic configuration of the lateral ventricles (arrows). (b) FT image shows anteroposteriorly running Probst bundles (green fibers) (arrowheads). These converge into the small remaining genu portion (arrow), which connects fibers from not only the frontal lobe but also from other regions of the brain. Compare this appearance with the normal configuration of the corpus callosum and the midline crossing fibers shown in Figure 1b.
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Figure 3b. Partial ACC in a 9-year-old boy with seizure disorder. (a) Axial inversion-recovery image shows partial ACC with a remaining genu portion (*) and colpocephalic configuration of the lateral ventricles (arrows). (b) FT image shows anteroposteriorly running Probst bundles (green fibers) (arrowheads). These converge into the small remaining genu portion (arrow), which connects fibers from not only the frontal lobe but also from other regions of the brain. Compare this appearance with the normal configuration of the corpus callosum and the midline crossing fibers shown in Figure 1b.
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Familial Spastic Paraplegia with a Thin Corpus Callosum
Hereditary spastic paraplegia (HSP) is a heterogeneous group of neurodegenerative diseases, and a subtype of complicated HSP has been reported in Japan and Korea (15). HSP manifests as a progressive spastic gait in the second decade, and dementia, muscle rigidity, and cerebellar ataxia can occur in combination. At MR imaging, thin-ning of the corpus callosum is demonstrated, par-ticularly of the anterior part, which suggests progressive atrophy after the complete formation of the corpus callosum.
At DTI and FT, the decreased fibers through the anterior part of the corpus callosum are demonstrated with intact splenial fibers (Fig 4). Patients with HSP and a thin corpus callosum usually show upper motor neuron signs. However, the gross morphology of the corticospinal tract is within the normal limits at FT.
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Figure 4a. Hereditary spastic paraplegia in an 18-year-old woman with a progressive spastic gait disturbance that began at the age of 12 years. (a) Sagittal T1-weighted MR image shows thinning of the genu and anterior body of the corpus callosum (arrows). (b) FT image shows loss of the callosal fibers through the genu and anterior body (arrows), whereas the fibers through the rostrum, splenium, and posterior body are normal. Note that the corticospinal tract is normal (arrowheads) even though the patient has spastic motor dysfunction.
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Figure 4b. Hereditary spastic paraplegia in an 18-year-old woman with a progressive spastic gait disturbance that began at the age of 12 years. (a) Sagittal T1-weighted MR image shows thinning of the genu and anterior body of the corpus callosum (arrows). (b) FT image shows loss of the callosal fibers through the genu and anterior body (arrows), whereas the fibers through the rostrum, splenium, and posterior body are normal. Note that the corticospinal tract is normal (arrowheads) even though the patient has spastic motor dysfunction.
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Malformations of Cortical Development
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Normal Development of the Cortex
In the developing brain, neuronal migration occurs from the ependymal portion to the cortex by means of a radial growth pattern with the guidance of the radial glial fiber system (16). In a premature brain, a highly anisotropic cortical ribbon appears, which reflects the directivity of neuronal migration (17).
Cortical Dysplasia
DTI has a powerful ability to demonstrate the integrity of the white matter and allows detection of abnormalities of the brain tissue in an earlier stage than conventional T2- or T1-weighted imaging. Although DTI can be used to assess gray matter abnormalities like cortical infarction (18) or malformations of cortical development (19), evaluation of the gray matter with DTI is not of great value because of the low FA of the gray matter and a partial volume effect by cerebrospinal fluid in the sulcus. Furthermore, some Eddy current artifacts may ruin the exact measurement of the FA at the surface of the brain. Instead, DTI and FT can be used to evaluate the integrity of the white matter adjacent to the dysplastic cortex. DTI and FT allow perfect visualization of decreased FA around the corticomedullary junction and fiber connection between deep white matter and dysplastic cortex in comparison with the normal contralateral side (Fig 5). In the case of severely dysplastic white matter, an aberrant course of the underlying white matter tract can be detected with DTI-FT (Fig 6).
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Figure 5a. Cortical dysplasia in a 10-year-old girl with long-standing intractable seizure disorder. (a) Axial T2-weighted MR image shows slightly increased signal intensity in the white matter of the left temporo-occipital lobe with blurring of corticomedullary differentiation (arrows). (b) Interictal axial single photon emission computed tomographic (SPECT) scan shows decreased perfusion in the abnormal area (arrows). (c) Ictal axial SPECT scan shows increased perfusion in the same area (arrowheads). (d) Axial FT image, generated from an ROI in the posterior part of the corona radiata and the inferior longitudinal fasciculus, shows decreased fiber connections around the subcortex of the affected temporo-occipital lobe (arrowheads) compared with the branching pattern of the normal contralateral occipital cortex.
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Figure 5b. Cortical dysplasia in a 10-year-old girl with long-standing intractable seizure disorder. (a) Axial T2-weighted MR image shows slightly increased signal intensity in the white matter of the left temporo-occipital lobe with blurring of corticomedullary differentiation (arrows). (b) Interictal axial single photon emission computed tomographic (SPECT) scan shows decreased perfusion in the abnormal area (arrows). (c) Ictal axial SPECT scan shows increased perfusion in the same area (arrowheads). (d) Axial FT image, generated from an ROI in the posterior part of the corona radiata and the inferior longitudinal fasciculus, shows decreased fiber connections around the subcortex of the affected temporo-occipital lobe (arrowheads) compared with the branching pattern of the normal contralateral occipital cortex.
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Figure 5c. Cortical dysplasia in a 10-year-old girl with long-standing intractable seizure disorder. (a) Axial T2-weighted MR image shows slightly increased signal intensity in the white matter of the left temporo-occipital lobe with blurring of corticomedullary differentiation (arrows). (b) Interictal axial single photon emission computed tomographic (SPECT) scan shows decreased perfusion in the abnormal area (arrows). (c) Ictal axial SPECT scan shows increased perfusion in the same area (arrowheads). (d) Axial FT image, generated from an ROI in the posterior part of the corona radiata and the inferior longitudinal fasciculus, shows decreased fiber connections around the subcortex of the affected temporo-occipital lobe (arrowheads) compared with the branching pattern of the normal contralateral occipital cortex.
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Figure 5d. Cortical dysplasia in a 10-year-old girl with long-standing intractable seizure disorder. (a) Axial T2-weighted MR image shows slightly increased signal intensity in the white matter of the left temporo-occipital lobe with blurring of corticomedullary differentiation (arrows). (b) Interictal axial single photon emission computed tomographic (SPECT) scan shows decreased perfusion in the abnormal area (arrows). (c) Ictal axial SPECT scan shows increased perfusion in the same area (arrowheads). (d) Axial FT image, generated from an ROI in the posterior part of the corona radiata and the inferior longitudinal fasciculus, shows decreased fiber connections around the subcortex of the affected temporo-occipital lobe (arrowheads) compared with the branching pattern of the normal contralateral occipital cortex.
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Figure 6a. Cortical dysplasia in a 22-year-old woman with motor seizure disorder of the left hand. (a) Axial T2-weighted MR images show a thickened and dysplastic cortex (left) with signal intensity changes in the underlying white matter (right). (b) Axial FA map shows decreased anisotropy in the affected white matter (arrows); the gray matter change could not be adequately evaluated. (c) Axial functional MR images of the brain show that the region activated by movement of the left hand (bottom) is displaced inferiorly and laterally in comparison with the region activated by movement of the normal contralateral side (top). (d) FT image shows a curved course of the corticospinal tract along the inferior margin of the dysplastic white matter, an appearance that matches the findings on the functional MR images.
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Figure 6b. Cortical dysplasia in a 22-year-old woman with motor seizure disorder of the left hand. (a) Axial T2-weighted MR images show a thickened and dysplastic cortex (left) with signal intensity changes in the underlying white matter (right). (b) Axial FA map shows decreased anisotropy in the affected white matter (arrows); the gray matter change could not be adequately evaluated. (c) Axial functional MR images of the brain show that the region activated by movement of the left hand (bottom) is displaced inferiorly and laterally in comparison with the region activated by movement of the normal contralateral side (top). (d) FT image shows a curved course of the corticospinal tract along the inferior margin of the dysplastic white matter, an appearance that matches the findings on the functional MR images.
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Figure 6c. Cortical dysplasia in a 22-year-old woman with motor seizure disorder of the left hand. (a) Axial T2-weighted MR images show a thickened and dysplastic cortex (left) with signal intensity changes in the underlying white matter (right). (b) Axial FA map shows decreased anisotropy in the affected white matter (arrows); the gray matter change could not be adequately evaluated. (c) Axial functional MR images of the brain show that the region activated by movement of the left hand (bottom) is displaced inferiorly and laterally in comparison with the region activated by movement of the normal contralateral side (top). (d) FT image shows a curved course of the corticospinal tract along the inferior margin of the dysplastic white matter, an appearance that matches the findings on the functional MR images.
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Figure 6d. Cortical dysplasia in a 22-year-old woman with motor seizure disorder of the left hand. (a) Axial T2-weighted MR images show a thickened and dysplastic cortex (left) with signal intensity changes in the underlying white matter (right). (b) Axial FA map shows decreased anisotropy in the affected white matter (arrows); the gray matter change could not be adequately evaluated. (c) Axial functional MR images of the brain show that the region activated by movement of the left hand (bottom) is displaced inferiorly and laterally in comparison with the region activated by movement of the normal contralateral side (top). (d) FT image shows a curved course of the corticospinal tract along the inferior margin of the dysplastic white matter, an appearance that matches the findings on the functional MR images.
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Heterotopia
In the case of heterotopic gray matter in the white matter, the arrested neurons exist in the white matter bundles and might have some degree of directivity like the normal white matter tracts and show increased anisotropy. Gray matter in the white matter, that is, nodular or band heterotopia, showed a higher anisotropic value compared to the normal cortex with statistical significance (0.28 ± 0.07 vs 0.18 ± 0.02, P = .0003) (Fig 7). Subependymal gray matter showed slightly lower FA values without statistical significance (0.16 ± 0.01, P = .0859). In the case of band heterotopia, failure of connection between deep white matter and the cortex was clearly demonstrated at FT (Fig 7).
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Figure 7a. Heterotopia in an 18-month-old girl with delayed development. (a) Axial T2-weighted MR image shows thick band heterotopia, the so-called double cortex. (b) Axial FA map shows that heterotopic gray matter has high anisotropy, a finding suggestive of its radial orientation and of arrested neuronal migration. (c) FT image shows failure of the normal connection between the deep white matter and the cortex and absence of cortico-cortical connections (arrows). cc = corpus callosum, cst = corticospinal tract. (d) FT image obtained in a normal child shows normal subcortical U-fibers (arrows) and fiber connectivity between the deep white matter and the cortex. cc = corpus callosum, cst = corticospinal tract.
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Figure 7b. Heterotopia in an 18-month-old girl with delayed development. (a) Axial T2-weighted MR image shows thick band heterotopia, the so-called double cortex. (b) Axial FA map shows that heterotopic gray matter has high anisotropy, a finding suggestive of its radial orientation and of arrested neuronal migration. (c) FT image shows failure of the normal connection between the deep white matter and the cortex and absence of cortico-cortical connections (arrows). cc = corpus callosum, cst = corticospinal tract. (d) FT image obtained in a normal child shows normal subcortical U-fibers (arrows) and fiber connectivity between the deep white matter and the cortex. cc = corpus callosum, cst = corticospinal tract.
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Figure 7c. Heterotopia in an 18-month-old girl with delayed development. (a) Axial T2-weighted MR image shows thick band heterotopia, the so-called double cortex. (b) Axial FA map shows that heterotopic gray matter has high anisotropy, a finding suggestive of its radial orientation and of arrested neuronal migration. (c) FT image shows failure of the normal connection between the deep white matter and the cortex and absence of cortico-cortical connections (arrows). cc = corpus callosum, cst = corticospinal tract. (d) FT image obtained in a normal child shows normal subcortical U-fibers (arrows) and fiber connectivity between the deep white matter and the cortex. cc = corpus callosum, cst = corticospinal tract.
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Figure 7d. Heterotopia in an 18-month-old girl with delayed development. (a) Axial T2-weighted MR image shows thick band heterotopia, the so-called double cortex. (b) Axial FA map shows that heterotopic gray matter has high anisotropy, a finding suggestive of its radial orientation and of arrested neuronal migration. (c) FT image shows failure of the normal connection between the deep white matter and the cortex and absence of cortico-cortical connections (arrows). cc = corpus callosum, cst = corticospinal tract. (d) FT image obtained in a normal child shows normal subcortical U-fibers (arrows) and fiber connectivity between the deep white matter and the cortex. cc = corpus callosum, cst = corticospinal tract.
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This study suggests that increased anisotropy of the heterotopic gray matter results from the histologic nature and embryogenetic mechanism, that is, gray matter tissue in white matter bundles and a radial growth pattern of neuronal migration. The partial volume effect by the surrounding white matter also plays a role in the increasing anisotropy in the case of nodular heterotopia.
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Cerebral Palsy
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Cerebral palsy is a nonprogressive disorder with various motor dysfunctions with a diverse cause. The most common cause of childhood cerebral palsy is hypoxic brain injury and periventricular leukomalacia (PVL) in premature births (20). Before the era of DTI, an impairment of the corticospinal tract was believed to be responsible for the motor dysfunction. A recent study by Hoon et al (21) reported that sensory fibers were the problem in PVL, and they showed a normal descending corticospinal tract at DTI and FT. The results were well correlated by a previous study of cerebral palsy with SPECT, which demonstrated thalamic hypoperfusion in PVL and suggested that the spasticity of cerebral palsy may be associated with a dysfunction of the inhibitory stimuli from the thalamus (20).
In PVL, with either spastic quadriplegia or diplegia, severe atrophy of the periventricular fibers is demonstrated at DTI and FT due to previous germinal matrix hemorrhage. The corticospinal tract is usually normal, and sensory fibers are decreased in comparison with those of age-matched control subjects (Fig 8). The connecting fibers between the thalamus and parietal cortex, the posterior thalamic radiations, are also absent (Fig 8). Thinning of the corpus callosum due to volume loss of periventricular white matter (PVWM) can be observed. The severity of spasticity (diplegic vs quadriplegic) is not well correlated with the degree of PVWM volume loss, and this requires further investigation. In hemiplegic cerebral palsy, the motor dysfunction is well correlated with the DTI and FT findings. The atrophied lesional side corticospinal tract is clearly depicted at FT (Fig 9).
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Figure 8a. Cerebral palsy in a 6-year-old boy with spastic quadriplegia and periventricular leukomalacia. (a) Axial T2-weighted MR image shows loss of periventricular white matter and dilatation of the lateral ventricle, findings typical of periventricular leukomalacia. (b) Lateral FT image shows thinning of sensory fiber tracts (sf) and absence of posterior thalamic radiations. All fibers to and from the thalamus were generated from the left thalamus (th) (pink area). The corticospinal tract is normal. (c) Lateral FT image obtained in a normal child shows the fibers connected to the thalamus (th). Note the abundant fiber bundles from the thalamus to the parieto-occipital lobe, posterior thalamic radiations (ptr), and sensory fibers (sf) in comparison with the findings in periventricular leukomalacia seen in b.
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Figure 8b. Cerebral palsy in a 6-year-old boy with spastic quadriplegia and periventricular leukomalacia. (a) Axial T2-weighted MR image shows loss of periventricular white matter and dilatation of the lateral ventricle, findings typical of periventricular leukomalacia. (b) Lateral FT image shows thinning of sensory fiber tracts (sf) and absence of posterior thalamic radiations. All fibers to and from the thalamus were generated from the left thalamus (th) (pink area). The corticospinal tract is normal. (c) Lateral FT image obtained in a normal child shows the fibers connected to the thalamus (th). Note the abundant fiber bundles from the thalamus to the parieto-occipital lobe, posterior thalamic radiations (ptr), and sensory fibers (sf) in comparison with the findings in periventricular leukomalacia seen in b.
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Figure 8c. Cerebral palsy in a 6-year-old boy with spastic quadriplegia and periventricular leukomalacia. (a) Axial T2-weighted MR image shows loss of periventricular white matter and dilatation of the lateral ventricle, findings typical of periventricular leukomalacia. (b) Lateral FT image shows thinning of sensory fiber tracts (sf) and absence of posterior thalamic radiations. All fibers to and from the thalamus were generated from the left thalamus (th) (pink area). The corticospinal tract is normal. (c) Lateral FT image obtained in a normal child shows the fibers connected to the thalamus (th). Note the abundant fiber bundles from the thalamus to the parieto-occipital lobe, posterior thalamic radiations (ptr), and sensory fibers (sf) in comparison with the findings in periventricular leukomalacia seen in b.
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Figure 9a. Cerebral palsy in a 20-month-old girl with spastic hemiplegia. (a) Axial T2-weighted MR image obtained at the level of the basal ganglia shows changes of cerebromalacia in the left internal capsule, thalamus, and putamen. (b) Axial magnified MR image of the mid pons shows no abnormalities. (c) Axial color-coded vector map shows decreased volume of the left corticospinal tract as a faint blue area on the left side of the pons (arrow). (d) Axial color-coded vector map obtained in an age-matched control subject shows a symmetrical configuration of the corticospinal tract (cst) and other major fibers passing through the pons. mcp = middle cerebellar peduncle, ml = medial lemniscus, tpf = transverse pontine fibers. (e) FT image shows volume loss of the left corticospinal tract.
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Figure 9b. Cerebral palsy in a 20-month-old girl with spastic hemiplegia. (a) Axial T2-weighted MR image obtained at the level of the basal ganglia shows changes of cerebromalacia in the left internal capsule, thalamus, and putamen. (b) Axial magnified MR image of the mid pons shows no abnormalities. (c) Axial color-coded vector map shows decreased volume of the left corticospinal tract as a faint blue area on the left side of the pons (arrow). (d) Axial color-coded vector map obtained in an age-matched control subject shows a symmetrical configuration of the corticospinal tract (cst) and other major fibers passing through the pons. mcp = middle cerebellar peduncle, ml = medial lemniscus, tpf = transverse pontine fibers. (e) FT image shows volume loss of the left corticospinal tract.
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Figure 9c. Cerebral palsy in a 20-month-old girl with spastic hemiplegia. (a) Axial T2-weighted MR image obtained at the level of the basal ganglia shows changes of cerebromalacia in the left internal capsule, thalamus, and putamen. (b) Axial magnified MR image of the mid pons shows no abnormalities. (c) Axial color-coded vector map shows decreased volume of the left corticospinal tract as a faint blue area on the left side of the pons (arrow). (d) Axial color-coded vector map obtained in an age-matched control subject shows a symmetrical configuration of the corticospinal tract (cst) and other major fibers passing through the pons. mcp = middle cerebellar peduncle, ml = medial lemniscus, tpf = transverse pontine fibers. (e) FT image shows volume loss of the left corticospinal tract.
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Figure 9d. Cerebral palsy in a 20-month-old girl with spastic hemiplegia. (a) Axial T2-weighted MR image obtained at the level of the basal ganglia shows changes of cerebromalacia in the left internal capsule, thalamus, and putamen. (b) Axial magnified MR image of the mid pons shows no abnormalities. (c) Axial color-coded vector map shows decreased volume of the left corticospinal tract as a faint blue area on the left side of the pons (arrow). (d) Axial color-coded vector map obtained in an age-matched control subject shows a symmetrical configuration of the corticospinal tract (cst) and other major fibers passing through the pons. mcp = middle cerebellar peduncle, ml = medial lemniscus, tpf = transverse pontine fibers. (e) FT image shows volume loss of the left corticospinal tract.
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Figure 9e. Cerebral palsy in a 20-month-old girl with spastic hemiplegia. (a) Axial T2-weighted MR image obtained at the level of the basal ganglia shows changes of cerebromalacia in the left internal capsule, thalamus, and putamen. (b) Axial magnified MR image of the mid pons shows no abnormalities. (c) Axial color-coded vector map shows decreased volume of the left corticospinal tract as a faint blue area on the left side of the pons (arrow). (d) Axial color-coded vector map obtained in an age-matched control subject shows a symmetrical configuration of the corticospinal tract (cst) and other major fibers passing through the pons. mcp = middle cerebellar peduncle, ml = medial lemniscus, tpf = transverse pontine fibers. (e) FT image shows volume loss of the left corticospinal tract.
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Posterior Fossa Malformations
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Posterior fossa malformations such as Arnold-Chiari syndrome or Dandy-Walker malformation did not show remarkable findings at DTI and FT. Joubert syndrome is a subtype of posterior fossa malformation and consists of vermian hypoplasia and derangement of the cerebellar-brainstem connections or cerebellocortical connections. At MR imaging, the typical "molar tooth appearance" of the superior cerebellar peduncle (SCP) is diagnostic, and partial or complete absence of the vermis is demonstrated. At DTI and FT, a thickened and elongated SCP with a horizontal configuration can be seen.
Three patients with Joubert syndrome underwent DTI and FT examination, and all of them showed a thickened SCP and a connection to the pre-motor and motor cortex. In age-matched control subjects, a visual inspection showed that the SCP was smaller than in Joubert syndrome and there were few fibers to the cortex (Fig 10). This suggests that there is some modified connection from the cerebellum to the cerebral cortex in Joubert syndrome.
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Figure 10a. Joubert syndrome in an 18-month-old boy with delayed development and hypotonia. (a) Axial T2-weighted MR image shows a "molar tooth" appearance of the SCP (arrows) and vermian hypoplasia, which are the typical findings of Joubert syndrome. (b) Axial FA (left) and color vector (right) maps show high anisotropy and an anteroposterior direction (green area) of the SCP with thickening (arrowheads). (c) FT image shows an elongated SCP (arrowheads) with a strong connection from the cerebellum to both the sensory and motor cortices (arrow). cst = corticospinal tract. (d) FT image obtained in a normal age-matched control subject shows normal volume of the SCP and normal cortical connections compared with those in Joubert syndrome seen in c. cst = corticospinal tract.
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Figure 10b. Joubert syndrome in an 18-month-old boy with delayed development and hypotonia. (a) Axial T2-weighted MR image shows a "molar tooth" appearance of the SCP (arrows) and vermian hypoplasia, which are the typical findings of Joubert syndrome. (b) Axial FA (left) and color vector (right) maps show high anisotropy and an anteroposterior direction (green area) of the SCP with thickening (arrowheads). (c) FT image shows an elongated SCP (arrowheads) with a strong connection from the cerebellum to both the sensory and motor cortices (arrow). cst = corticospinal tract. (d) FT image obtained in a normal age-matched control subject shows normal volume of the SCP and normal cortical connections compared with those in Joubert syndrome seen in c. cst = corticospinal tract.
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Figure 10c. Joubert syndrome in an 18-month-old boy with delayed development and hypotonia. (a) Axial T2-weighted MR image shows a "molar tooth" appearance of the SCP (arrows) and vermian hypoplasia, which are the typical findings of Joubert syndrome. (b) Axial FA (left) and color vector (right) maps show high anisotropy and an anteroposterior direction (green area) of the SCP with thickening (arrowheads). (c) FT image shows an elongated SCP (arrowheads) with a strong connection from the cerebellum to both the sensory and motor cortices (arrow). cst = corticospinal tract. (d) FT image obtained in a normal age-matched control subject shows normal volume of the SCP and normal cortical connections compared with those in Joubert syndrome seen in c. cst = corticospinal tract.
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Figure 10d. Joubert syndrome in an 18-month-old boy with delayed development and hypotonia. (a) Axial T2-weighted MR image shows a "molar tooth" appearance of the SCP (arrows) and vermian hypoplasia, which are the typical findings of Joubert syndrome. (b) Axial FA (left) and color vector (right) maps show high anisotropy and an anteroposterior direction (green area) of the SCP with thickening (arrowheads). (c) FT image shows an elongated SCP (arrowheads) with a strong connection from the cerebellum to both the sensory and motor cortices (arrow). cst = corticospinal tract. (d) FT image obtained in a normal age-matched control subject shows normal volume of the SCP and normal cortical connections compared with those in Joubert syndrome seen in c. cst = corticospinal tract.
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There have been many reports on the shape of the brainstem and SCP (22). However, a detailed description of the fiber itself was impossible with conventional imaging. DTI and FT are the only methods that can demonstrate such aberrant fiber connections in the diseased state and provide a better understanding of a malformed brain.
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Technical Considerations and Conclusions
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This study applied the DTI procedure by using single-shot spin-echo echo-planar imaging (EPI) and sensitivity encoding (SENSE). Since its introduction to the clinical field by Pruessmann et al (23), SENSE has provided a fast imaging time and reduced susceptibility and motion artifacts. The total imaging time was 7–9 minutes with two-signal averaging, which was tolerable for all patients. The DTI processing time was less than 5 minutes. The major fiber tracts were generated within a few seconds, and the radiologists or neurologists easily performed all procedures. The 10-minute DTI and fiber tracking protocol used in this study is a simple procedure and can be added to a routine sequence; that is, it is no longer a research tool but is a strong clinical modality that demonstrates white matter disease. Furthermore, pediatric patients may have more potential to form a modified fiber connection, particularly in the case of congenital diseases, which is a challenging field of DTI-FT for a future clinical study.
Some problems with DTI-FT need to be considered. First, DTI-FT is a powerful anatomic imaging tool that can demonstrate the gross fiber architecture but not the functional or synaptic connection. With a clinical 1.5-T imaging unit or even with a high-field-strength system, the spatial resolution of DTI-FT is approximately 1–2 mm. In that voxel, there must be plenty of synaptic connections and crossing fibers. However, these could not be detected in the voxels. Therefore, major fiber bundles such as the corticospinal tract or corpus callosum can be the real fiber pathways at DTI-FT, relaying fibers like the cerebello-thalamo-cortical circuits, which cannot be depicted with DTI-FT; this is a limitation of DTI-FT.
Second, the fiber tracking technique is quite operator dependent, and the operator should have a detailed knowledge of the neuroanatomy. The standard ROI location and placement of the adequate threshold value for fiber tracking are essential for achieving an objective and uniform fiber tracking result. Another important consideration in FT is setting the threshold values of FA and trajectory angles for termination of tracking. For example, we applied different values for FA and trajectory angles between ellipsoids in generating the corticospinal tract; for example, from 0.2 to 0.3 for FA and from 0.75 to 0.85 for angles (0 = full deflection, 1 = no deflection) (Fig 11). High threshold values for FA demonstrated fewer fibers and only a straight corticospinal tract from the precentral gyrus to the brainstem, whereas a low threshold for FA demonstrated more fiber connections to the lateral aspect of the precentral gyrus and contralateral hemisphere through the corpus callosum. A large threshold for deflection angle demonstrated more fibers to distant areas.
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Figure 11. Effects of different threshold values for termination of fiber tracking. FT images show that lowering the FA threshold and increasing the trajectory angle (right) can generate more fibers and contralateral connections than increasing the FA threshold and lowering the trajectory angle (left). Note the fiber connections to the lateral aspect of the precentral gyrus (arrowheads) and the contralateral connections through the corpus callosum (small arrows) and pons (large arrow).
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With our results, we can postulate that the operator can generate more fibers by intention or ignore intact tracts according to the threshold setting for fiber tracking termination. This is quite important, because modified or aberrant fiber connections do occur in diseased conditions, and the modified fiber tracts can be exaggerated or underestimated by using various threshold values. Therefore, the results of this study should be repeatedly reproduced in the future by other scientists using fiber tracking techniques other than those described herein.
Third, DTI-FT still depends on a qualitative visual analysis by the radiologist and requires further development of the quantification and standardization methods. Nevertheless, the ability of DTI-FT in demonstrating the white matter architecture is unparalleled by any other imaging modality, and further active clinical applications are required.
In conclusion, this study obtained additional or unique findings in CNS developmental disease by using DTI-FT in comparison with those obtained by using conventional MR imaging. Future studies will be focused on determining the meaning of the aberrant fiber connections and their relationship with the clinical manifestations of the CNS anomalies.
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Footnotes
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Abbreviations: ACC = agenesis of the corpus callosum,
CNS = central nervous system,
DTI = diffusion-tensor imaging,
FA = fractional anisotropy,
FT = fiber tractography,
ROI = region of interest,
SCP = superior cerebellar peduncle
See the commentary by Yousem
following this article.
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References
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Abstract
Introduction
