Quantitative differentiation between healthy and disordered brain matter in patients with neurofibromatosis type I using diffusion tensor imaging

Abstract

Background and purpose: Hyperintensities on T2-weighted images are seen in the brains of most patients with neurofibromatosis type I (NF-1), but the origin of these unidentified bright objects (UBOs) remains obscure. In the current study, we examined the diffusion characteristics of brain tissue in children with NF-1 to test the hypothesis that a microstructural abnormality is present in NF-1.

Materials and methods: Diffusion tensor imaging (DTI) was performed in 50 children with NF-1 and 8 controls. Circular regions of interest were manually placed in 7 standardized locations in both hemispheres, including UBO sites. Apparent diffusion coefficients (ADC), fractional anisotropy (FA), and axial anisotropy (A(m)) were used to differentiate quantitatively between healthy and disordered brain matter. Differences in eigenvalues (lambda(1), lambda(2), lambda(3)) were determined to examine parenchymal integrity.

Results: We found higher ADC values for UBOs than for normal-appearing sites (P < .01) and higher ADC values for normal-appearing sites than for controls (P < .04 in 5 of 7 regions). In most regions, we found no differences in FA or A(m). Eigenvalues lambda(2) and lambda(3) were higher at UBO sites than in normal-appearing sites (P < .04).

Conclusion: With ADC, it was possible to differentiate quantitatively between normal- and abnormal-appearing brain matter in NF-1 and also between normal-appearing brain matter in NF-1 and healthy brain matter in controls, indicating subtle pathologic damage disrupting the tissue microstructure in the NF-1 brain. Higher diffusivity for lambda(1), lambda(2), and lambda(3) indicates that this disturbance of microstructure is caused by accumulation of fluid or vacuolation.

Fig 1.

Region-of-interest placement. Transverse b = 0 s/mm² images of a healthy control (multi-repetition single-shot echo-planar sequence; section thickness of 3 mm with no gap; 25 gradient directions; b = 1000 s/mm²; TR/TE = 15,000/82.1 ms; 1 average; FOV of 240 × 240 mm²; matrix of 128 × 128; voxel size of 1.8 × 1.8 × 3.0 mm³). Circular regions of interest are placed in the CWM (A), the CP and HI (B), the TH (C), the GP (D), and FWM and POWM (E).

Fig 2.

DTIs of the globus pallidus. Transverse DTIs (multi-repetition single-shot echo-planar sequence; section thickness of 3 mm with no gap; 25 gradient directions; b = 1000 s/mm²; TR/TE = 15,000/82.1 ms; 1 average; FOV of 240 × 240 mm²; matrix of 128 × 128; voxel size of 1.8 × 1.8 × 3.0 mm³). Girl with NF-1 (13 years of age) with a unilateral UBO in the GP. Arrow indicates an area of high intensity on the b = 0 s/mm² image and high values on the ADC, λ₂ (lambda 2), and λ₃ (lambda 3) maps.

Fig 3.

Mean ADC values. The cohort is divided in 3 groups: NF-1 regions with UBOs (UBO), NF-1 regions with normal-appearing brain matter (NAS), and controls. Mean ADC values for UBOs are higher than those for NAS in all regions (except POWM and FWM where no UBOs were found). Mean ADC values for NAS are significantly higher than those of controls in all regions, except CP. For convenience, the results of the HI area are presented in the same figure as the results of the other regions of interest. HI hyperintensities are presented as UBOs and normal-appearing HI areas as NAS. Significant differences between UBO and NAS are indicated by ★ and between NAS and controls by ⧫.

Fig 4.

FA values. Mean FA values ± SD for UBO, normal-appearing sites (NAS), and controls are plotted for the 7 regions of interest. Few significant differences are found between UBO and NAS, indicated by ★.

Fig 5.

A_m values. Mean A_m values ± SD for UBO, normal-appearing sites (NAS), and controls per regions of interest. Significant differences between UBO and NAS are indicated by ★ and between NAS and controls by ⧫.

Fig 6.

Eigenvalues per region. For UBO, normal-appearing sites (NAS), and controls, mean values for the 3 eigenvalues are plotted for each region. In all regions where UBOs are found, λ₁, λ₂, and λ₃ are higher for UBOs than for NAS and higher for NAS compared with controls. Significant differences between UBO and NAS are indicated by ★ and between NAS and controls by ⧫.