CLINICAL REPORT PEDIATRICS Diffusion Imaging of the Congenitally Thickened Corpus Callosum

SUMMARY: This report presents 4 subjects with congenital segmental callosal thickening, an uncommon malformation studied with MR imaging and DTI. Medical records were reviewed for genetic testing and neurodevelopmental status. Three subjects had profound developmental delay; 3 had seizures. MR imaging showed segmental thickening of the rostral and/or midcallosal body. Associated anomalies included polymicrogyria in 1 patient and optic hypoplasia in 1. DTI showed that the segmental thickening was due to anomalous longitudinal supracallosal fibers visually separable from the paired cingulum in 3 patients; in 1 patient, the cingulum was poorly formed. Genetic testing was negative for Fragile X syndrome. Microarray DNA analysis showed 3 copy losses (2q27.3, 3p21.31, 7q21.11) and 1 copy gain (8p11.23) in 1 patient, while testing in the other subject was negative for losses or gains. Potential explanations for the anomalous fibers include heterotopic cingulum, an enlarged indusium griseum, and aberrant callosal fibers. ABBREVIATIONS: FA fractional anisotropy; IG indusium griseum; M-CMTC marmorata telangiectatica congenita syndrome; NF neurofibromatosis Conventional MR imaging is useful in the characterization of congenital anomalies of the corpus callosum, which are typically classified according to the pattern and extent of callosal hypoplasia. Diffusion imaging and diffusion tractography provide information about the composition of the normal corpus callosum by delineating the topography and the link between callosal microstructure and function. In callosal hypogenesis, diffusion imaging depicts aberrant heterotopic callosal fibers and provides insight into the topographic orientation of the Probst bundles in callosal agenesis. In contrast to callosal agenesis, which is a relatively common brain malformation, congenital anomalies in which all or a portion of the corpus callosum is thickened are uncommon and limited to a case report by MR imaging and a series by prenatal sonography. There are few reports of DTI of the thickened corpus callosum. This report presents 4 patients with segmental thickening of the rostral and/or midcallosal body in which DTI showed that the thickening was due to anomalous longitudinal midline fibers. The associated neurocognitive deficits suggest that the anomalous longitudinal fibers may be indicative of a more widespread disorder of axonal development, which may escape detection with conventional MR imaging. MATERIALS AND METHODS This study was approved by the institutional review board. Given the retrospective nature, informed parental consent was not obtained. During a 10-year period, 4 subjects were identified with focal or diffuse thickening of the corpus callosum by conventional MR imaging, who also underwent DTI and diffusion tractography. Conventional MR imaging included multiplanar T1, T2 FLAIR, and T2 fast spin-echo sequences at 1.5T or 3T. The corpus callosum was defined as thickened on the midsagittal T1 image when the thickness of the callosal body exceeded the thickness of the splenium and genu; the callosal thickness was measured by using electronic calipers on the MR imaging operator console. DTI was performed by using single-shot echo-planar imaging with the following parameters: TR/TE, 7000 –9000/84 –102 ms; 128 128 matrix; 2-mm voxel size; 2-mm section thickness; no gap. Diffusion gradients were applied in 30 noncollinear directions with b 1000 s/mm. There were 2–3 acquisitions covering the whole head. Scanning time for DTI ranged from 12 to 15 minutes. Eddy current correction, image registration, and motion correction were performed on the MR imaging operator console before transfer of diffusion data to a proprietary workstation (Extended WorkSpace; Philips Healthcare, Best, the Netherlands). A pediatric neuroradiologist, with 20 years of experience and extensive experience with diffusion tractography, manually placed Received April 17, 2012; accepted after revision June 5. From the Department of Radiology, Children’s Medical Center Dallas–University of Texas Southwestern Medical Center at Dallas, Dallas, Texas. Please address correspondence to Nancy K. Rollins, MD, Department of Radiology, Children’s Medical Center Dallas–University of Texas Southwestern Medical Center at Dallas, 1935 Medical District Dr, Dallas, Texas 75235; e-mail: nancy.rollins@ childrens.com Indicates open access to non-subscribers at www.ajnr.org http://dx.doi.org/10.3174/ajnr.A3245 660 Rollins Mar 2013 www.ajnr.org regions of interest on the directionally encoded color maps, encompassing the corpus callosum and supracallosal fibers so that the resultant 3D renderings included the entire corpus callosum and the cingulum, which form the outer limbic arch. Diffusion tractography was performed by using fiber association by continuous tractography, in which tracts were seeded from all voxels in the corpus callosum and supracallosal fibers had FA 0.15 and a turning angle of 70°. Because the diffusion image data had not been acquired by using high-angular-resolution diffusion and given the insensitivity of DTI to intravoxel crossing fibers, fibers were not further segmented according to projections to specific areas of the brain. FIG 1. A 2-year-old boy with pervasive developmental delay.A, Midsagittal T1 image showsmarked thickening of themidcallosal body (14.2 mm) with subjective shortening of the callosal length. B, Midsagittal directionally encoded color map. The arrow indicates longitudinal supracallosal fibers, which account for the callosal thickening. Longitudinal fibers are not normally seen in the midline; like association fibers, the normal cingulum does not cross themidline. C, Coronal color map. The largemidline longitudinal fibers are separate from the paired cingulum (arrows). D, Top-down projection of the supracallosal fibers on diffusion tractography. E, Axial top-down tractography from a healthy subject for comparison. The cingulum is seen as parasagittal rather than midline. Demographics and anomalies associated with thickened corpus callosum Case Age/Sex Indication for MRI Maximum Callosal Thickness Fornices Cingulum Associated Abnormalities 1 25 mo/Male Seizures, DD 14.2 mm Thickened Formed bilaterally None 2 20 mo/Female Seizures, mild DD 8.7 mm Atrophic right Incompletely formed left Acquired right MTS 3 18 mo/Male Seizures, DD 9.9 mm Normal Formed bilaterally PMG, PGH 4 12 yr/Male Autism, DD, decreased vision, seizures 9.2 mm Normal Hypoplastic Optic pathway hypoplasia Note:—DD indicates developmental delay; PMG, polymicrogyria; PGH, periventricular gray matter heterotopia; MTS, mesial temporal sclerosis. AJNR Am J Neuroradiol 34:660–65 Mar 2013 www.ajnr.org 661 CASE STUDIES Patient 1 was a 2-year-old boy with pervasive developmental delay, hypotonia, and generalized seizures since infancy, born full-term after an uncomplicated delivery to nonconsanguineous parents. There were no dysmorphic features, and head circumference was normal. Genetic testing limited to Fragile X syndrome was normal (Table). MR imaging showed that the corpus callosum was shortened in an anteroposterior dimension; the midcallosal body measured 14.2 mm in the region of maximum thickness (Fig 1) and had normal signal intensity on both T1 and T2 images. The fornices were thickened; there were no malformations of cortical development. The directionally encoded color maps and diffusion tractography showed that the corpus callosum was bordered superiorly by longitudinal green fibers. The cingulum was fully formed and visually separable from the anomalous supracallosal fibers. The second subject was a 20-monthold girl initially referred at 11 months of age for new-onset febrile seizures and persistent lethargy. The patient had been born full-term after an uncomplicated pregnancy and was initially developmentally and physically normal, though developmental milestones were lagging at 20 months of age. Genetic analysis was not done. Assessed on the midsagittal T1 image, the corpus callosum was subjectively shortened; the rostral body measured 8.2 mm (Fig 2) with normal signal intensity on all sequences. There was restricted diffusion within the right mesial temporal lobe but no visible malformations of cortical development. Subsequent MR imaging at 20 months of age showed a stable appearance to the corpus callosum. There was interval development of right mesial temporal sclerosis with atrophy of the right fornix. The directionally encoded color map showed longitudinal midline supracallosal fibers in the thickened portion of the corpus callosum, which, by diffusion tractography, were separate from the cingulum. The third subject was an 18-month-old boy referred for pervasive developmental delay, failure to thrive and recurrent aspiration. The patient had mild hemifacial microsomia, a malformed left thumb, and bilateral cryptorchidism. Findings of DNA microarray analysis by using comparative genomic hybridization were normal. MR imaging at 3T showed that the callosal body measured 9.2 mm and was thicker than the splenium and genu (Fig 3) with normal signal intensity. There was bilateral peri-Sylvian and bifrontal polymicrogyria along with multifocal periventricular gray matter heterotopias. Diffusion imaging showed a triangle-shaped longitudinal midline supracallosal fiber bundle visually separate from the supracallosal portions of the cingulum, which appeared to fuse with the prefrontal segments of the