Abnormal microstructure of the atrophic thalamus in preterm survivors with periventricular leukomalacia

Abstract

Background and purpose: The neuroanatomic substrate of cognitive deficits in long-term survivors of prematurity with PVL is poorly understood. The thalamus is critically involved in cognition via extensive interconnections with the cerebral cortex. We hypothesized that the thalamus is atrophic (reduced in volume) in childhood survivors of prematurity with neuroimaging evidence of PVL and that the atrophy is associated with selective microstructural abnormalities within its subdivisions.

Materials and methods: We performed quantitative volumetric and DTI measurements of the thalamus in 17 children with neuroimaging evidence of PVL (mean postconceptional age, 5.6 ± 4.0 years) who were born prematurely and compared these with 74 term control children (5.7 ± 3.4 years).

Results: The major findings were the following: 1) a significant reduction in the overall volume of the thalamus in patients with PVL compared with controls (P < .0001), which also correlated with the severity of PVL (P = .001); 2) significantly decreased FA (P = .003) and increased λ(⊥) (P = .02) in the thalamus overall and increased axial, radial, and mean diffusivities in the pulvinar (P < .03), suggesting injury to afferent and efferent myelinated axons; and 3) a positive correlation of pulvinar abnormalities with those of the parieto-occipital white matter in periventricular leukomalacia, suggesting that the pulvinar abnormalities reflect secondary effects of damaged interconnections between the pulvinar and parieto-occipital cortices in the cognitive visual network.

Conclusions: There are volumetric and microstructural abnormalities of the thalamus in preterm children with PVL, very likely reflecting neuronal loss and myelinated axonal injury. The selective microstructural damage in the pulvinar very likely contributes to abnormal cognitive visual processing known to occur in such survivors.

Fig 1.

Thalamic subdivision small and large region-of-interest anatomic locations. A, The small circular regions of interest are fixed at a diameter of 4 mm. Region-of-interest placements in the anterior, lateral, medial, and posterior (pulvinar) nuclei of the thalamus are shown on the FA (1) and ADC (2) maps. B, Large region-of-interest subdivisions are shown on the same FA and ADC maps.

Fig 2.

Range of severity of PVL and whole thalamic regions of interest. Rows: A, Severe PVL. B, Mild PVL. C, Healthy control. Columns: 1) T2-weighted. 2) FLAIR. 3) FA. 4) ADC. The T2 and FLAIR images for the patients with PVL show periventricular hyperintensity. The severity of PVL in each case is evident from the degree of periventricular white matter volume loss compared with the control. The contours for acquiring the DTI metrics are shown on the FA and ADC images for the whole thalamus.