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Review
. 2021 Jun 1;39(16):1775-1785.
doi: 10.1200/JCO.20.02315. Epub 2021 Apr 22.

Brain Imaging in Pediatric Cancer Survivors: Correlates of Cognitive Impairment

Shelli R Kesler  1 , Charlotte Sleurs  2   3 , Brenna C McDonald  4 , Sabine Deprez  3   5 , Ellen van der Plas  6 , Brian J Nieman  7   8   9
Affiliations
Review

Brain Imaging in Pediatric Cancer Survivors: Correlates of Cognitive Impairment

Shelli R Kesler et al. J Clin Oncol. .
No abstract available

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Figures

FIG 1.
FIG 1.
Neuroimaging findings in childhood cancer survivors. Both childhood cancer and its treatment have the potential to introduce toxicities in the brain. Neuroimaging in survivorship represents the net effect of these cancer- and treatment-related injuries, as well as the brain's intrinsic repair processes in the context of ongoing development. Key findings highlighted in the text are depicted under the macrostructure, microstructure, neuronal activity, and vasculature and metabolism headings. Up (↑) and down (↓) arrows indicate reported increases or decreases, respectively, in the corresponding metric. Where both arrows are indicated (↓↑), both decreases and increases have been reported, either because of regional variations or because of different literature reports. The dash (–) indicates reports of no change in outcome. Regional alterations measured by neuroimaging have broader implications for the whole brain network, which may be assessed through connectome measures, and for cognition and behavior, and can significantly impact quality of life in childhood cancer survivors. AFD, apparent fiber density; CBF, cerebral blood flow; ctx area, cortical area; ctx thk, cortical thickness; dMRI, diffusion MRI; FA, fractional anisotropy; FDG, fluorodeoxyglucose; fMRI, functional MRI; GM, gray matter; MD, mean diffusivity; MEG, magnetoencephalography; MK, mean kurtosis; MTR, magnetization transfer ratio; MWF, myelin water fraction; ODI, orientation dispersion index; osc freq, oscillatory frequency; PET, positron emission tomography; RD, radial diffusivity; rs conn, resting-state connectivity; sMRI, structural MRI; WM, white matter.
FIG 2.
FIG 2.
Anatomical MRI and image processing for assessment of brain structure in childhood cancer survivors. Based on anatomical scans, typically T1-weighted or a combination of T1- and T2-weighted MRI scans, morphometric analyses can be performed to assess global and regional changes in brain structure, including volumes, areas, thicknesses, etc. In the middle, voxel-based morphometry is depicted, in which the anatomical images are processed to produce tissue type images in which the intensity of a voxel represents the relative proportion of each tissue type in that voxel. These can be statistically compared between groups (eg, childhood cancer survivor v control). At right, surface-based morphometry is illustrated for quantification of the cortex, including characterization of its folding. Measures include cortical thickness, gyrification, and sulcus depth. CSF, cerebrospinal fluid; GM, gray matter; WM, white matter.
FIG 3.
FIG 3.
Diffusion MRI and modeling to estimate WM microstructure changes in childhood cancer survivors. (A) Diffusion of water in WM is affected by myelin and axons. Modeling of this effect allows parameter maps to be generated, which are sensitive to different microstructural changes. Imaging parameter maps sensitive to white matter microstructural alterations in childhood cancer survivors and discussed in this review are depicted. At right, alternative MRI contrasts known to be sensitive to myelin content are also depicted. (B) Advanced diffusion-weighted imaging techniques allow characterization of WM architecture using the diffusion of water molecules, which is highly directional (anisotropic) in healthy WM (i) because of axonal membranes and myelin sheaths. Axonal loss (ii) or demyelination (iii) results in less anisotropic diffusion and therefore changes in diffusion imaging parameter maps and related structural brain connectivity. Sample results are shown at bottom and include: (iv) brain regions showing significantly decreased FA in ALL survivors who received CSI compared with healthy controls (reprinted with permission [2013] American Society of Clinical Oncology. All rights reserved.); (v) decreased AFD in the corpus callosum in childhood sarcoma survivors who received systemic chemotherapy compared with healthy controls (reprinted with permission from Human Brain Mapping); and (vi) structural connectome organization change in young survivors of ALL who received CNS-directed chemotherapy (reprinted with permission from Brain Connectivity). AFD, apparent fiber density; ALL, acute lymphoblastic leukemia; CSI, craniospinal irradiation; FA, fractional anisotropy; MD, mean diffusivity; MK, mean kurtosis; MR, magnetic resonance; MT, magnetization transfer imaging; MWF, myelin water fraction; ODI, orientation dispersion index; RD, radial diffusivity; WM, white matter.
FIG 4.
FIG 4.
Sample preclinical neuroimaging results in models of childhood cancer survivorship. At left, a murine functional connectome derived from resting-state fMRI is depicted. The connectome models the brain as a network of nodes (regions) with joining edges (connections). Relative size of the spheres (ie, nodes) indicates the number of edges (gray lines) passing through them. At right, a color fiber map is used for visualization of murine DTI data, in which colors indicate virtual white matter streamline direction (red: right-left; blue: inferior-superior; green: anterior-posterior). DTI, diffusion tensor imaging; fMRI, functional MRI.
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References

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