Variability of homotopic and heterotopic callosal connectivity in partial agenesis of the corpus callosum: a 3T diffusion tensor imaging and Q-ball tractography study

Abstract

Background and purpose: Little is known about the anatomic connectivity of callosal axons in individuals with partial agenesis of the corpus callosum (pAgCC). We used tractography based on both diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) to investigate interhemispheric white matter connectivity in pAgCC.

Materials and methods: DTI and HARDI were performed at 3T on 6 individuals with pAgCC and 8 control subjects. For HARDI analysis, a Q-ball reconstruction method capable of visualizing multiple intravoxel fiber orientations was used. In both DTI and HARDI, whole-brain 3D fiber tractography was performed by using deterministic streamline algorithms. Callosal fibers were then segmented to identify separately connections between homologous cortical regions (homotopic fibers) and nonhomologous regions (heterotopic fibers) by using manually drawn regions of interest.

Results: In control individuals, we observed densely connected homotopic fibers. However, in individuals with pAgCC, we identified not only homotopic connections but also heterotopic connections in 4 of 6 subjects. Furthermore, the observed homotopic connections in pAgCC did not necessarily correlate with the position or size of the residual callosum. The nature of homotopic and heterotopic connectivity varied considerably among subjects with pAgCC, and HARDI recovered more callosal fibers than DTI.

Conclusion: Individuals with pAgCC demonstrate a remarkable diversity of callosal connectivity, including a number of heterotopic tracts that are absent in healthy subjects. The patterns of their callosal connections cannot be predicted from the appearance of their callosal fragments on conventional MR imaging. More tracts and more extensive fibers within tracts are recovered with HARDI than with DTI.

Figures

Fig 1.

Callosal tract segmentation procedure, shown for a control subject (A−F) and for pAgCC subject 5 (G−L). A region of interest is first placed over the entire callosum, and tracts are colored according to their direction with the standard red-blue-green convention used for DTI color maps (A and G). Individual tracts are then segmented by using 2 additional regions of interest defining lobar regions in each hemisphere. For the control subject, homotopic anterior (B) and posterior (C) frontal, parietal (D), and occipitotemporal (E) tracts are segmented. For the subject with pAgCC, homotopic anterior frontal (H) and occipitotemporal (I) tracts and bilateral heterotopic frontal occipitotemporal (J and K) tracts are isolated. In K, an exclusion region of interest (pink) is used to eliminate homotopic occipitotemporal connections. All segmented tracts are then displayed together (F and L). All 3D tracts are shown projected onto axial sections.

Fig 2.

T1-weighted anatomic images and DTI tractography of 6 subjects with pAgCC (top panels) and 2 representative controls (bottom panel). Axial (left) and midline sagittal (middle) T1 sections are shown for each subject. Callosal fragments are identified with yellow arrows, whereas heterotopic fibers visible on T1-weighted images are denoted by red arrows. Midline sagittal DTI color maps are shown with segmented callosal fibers (right). For subjects with pAgCC, connectivity ranged from anterior frontal connections (subject 3) to only posterior frontal and occipitotemporal connections (subject 4). One individual (subject 5) displayed a discontinuous set of homotopic callosal connections, with anterior frontal and occipitotemporal connectivity without any posterior frontal or parietal connections. Control subjects (not shown) displayed similar callosal morphology and tractography results. Tracts are segmented and colored according to their cortical projections: homotopic anterior frontal, blue; homotopic posterior frontal, orange; homotopic parietal, pink; homotopic occipitotemporal, green; heterotopic left anterior-right posterior, yellow; heterotopic right anterior-left posterior, red.

Fig 3.

Q-ball tractography of subjects with pAgCC. All homotopic and heterotopic segmented tracts are shown on both axial (top) and midline sagittal (bottom) projections, with the subject number indicated in the upper left corner of the axial images. Fibers are colored as in Fig 2, with pink and purple fibers for subject 6 representing anterior frontal-temporal heterotopic connections.

Fig 4.

Q-ball tractography of heterotopic callosal connections. Isolated heterotopic connections are displayed for subjects 3–6. Fibers are shown projected on an axial section (left). A magnified view of the callosal fragment is also shown in the midsagittal plane (right) to demonstrate that all heterotopic connections are well isolated from other homotopic fibers.

Fig 5.

Comparison of DTI and QBI tractography. For a control subject (top) and a subject with pAgCC (subject 5, bottom), segmented tracts are shown by using DTI tractography performed on a DTI acquisition at b = 1000 s/mm2 (A and D) and on a HARDI acquisition at b = 3000 s/mm2 (B and E). QBI tractography is shown for the same HARDI acquisition at b = 3000 s/mm2 (C and F). QBI tractography yields more extensive fibers, including more lateral frontal fibers and denser temporal fibers in the control subject and an additional heterotopic fiber in the subject with pAgCC (red in F) not recovered by DTI tractography.