Selecting the best index for following the temporal evolution of apparent diffusion coefficient and diffusion anisotropy after hypoxic-ischemic white matter injury in neonates

Abstract

Background and purpose: Diffusion-weighted (DW) MR imaging is a useful technique for detecting ischemia. In adults and neonates, however, temporal changes on DW images after ischemia complicate interpretation. Our purpose was to investigate the temporal evolution of the apparent diffusion coefficient (ADC), diffusion-tensor (DT) imaging components, and anisotropy in neonatal brain after hypoxic-ischemic white matter injury and to determine which anisotropy index is preferable.

Methods: DT images were obtained with single-shot echo-planar imaging, by using pulsed field gradients in six directions. Sixteen volunteers and 10 term neonates with normal MR images were evaluated to obtain reference values. Among the anisotropy indexes of fractional anisotropy (FA), relative anisotropy (RA), volume ratio (VR), linear (CI) and planar (Cp) diffusion, and axial anisotropy (Am), simulations were performed to select the most appropriate indexes for clinical practice. The ADC, DT imaging components, and anisotropy were evaluated as a function of time after onset of symptoms in 11 neonates with hypoxic ischemia.

Results: In neonates, changes in lesions were characterized by a large decrease (40%) in all eigenvalues, with a stronger decrease in the direction perpendicular to the fibers, resulting in increased anisotropy indexes. The temporal evolution of the relative change in ADC did not show a significant trend (P >.05). The relative change in anisotropy decreased linearly with time (P <.05), with the strongest trend in anisotropy index Am.

Conclusion: In clinical practice, anisotropy indexes FA, RA and Am appear to be useful. Am is the best index to monitor anisotropy changes. DT imaging provides information about diffusion parallel and perpendicular to white matter fibers, which helps the interpretation of physiologic changes after hypoxic-ischemic injury.

Fig 1.

Definition of the regions of interest in the adult brain. 1 indicates corpus callosum; 2, white matter.

Fig 2.

Eigenvalue space plots as defined by Bahn (33), plotted for anisotropy index FA. FA is high (bright) for both λ₃/λ₁ and λ₂/λ₁ close to zero, which corresponds to a cigar-shaped diffusion ellipse. But FA is still relatively large for λ₂/λ₁ close to 1, the pancake-shaped diffusion ellipse.

Fig 3.

A–D, Average ADC, eigenvalues, and anisotropy indexes in frontal white matter (WM) and in the corpus callosum (CC), measured in 16 adult volunteers (A and B) and in 10 full-term neonates with normal MR images (C and D).

Fig 4.

A–C, Eigenvalue space plots, as introduced by Bahn (33) (explained in Fig 2), for FA, RA, and A_m. In the middle row, the corresponding anisotropy maps are shown for a neonate with lesions (arrow) in the frontal white matter and occipital white matter. Note the increased anisotropy corresponding to the low ADC area. In the bottom row, T2-weighted image, IR image, and ADC map in the same neonate are shown.

Fig 5.

A–D, Results of simulations of the effect of random noise on ADC and eigenvalues (A and C) and anisotropy (B and D) for the adult case (A and B) and neonate case (C and D). Open symbols indicate the input values (Table 2); filled symbols, the values after noise was added. The error bars show the standard deviation of the simulated results.

Fig 6.

Relative change in FA, RA, and A_m as a function of a change in one of the eigenvalues λ₁, λ₂, and λ₃. The change is defined as a factor times the original value; the factor is displayed on the x-axis. The relative change is shown for three input settings, corresponding to adult white matter (top row), neonatal white matter (middle row), and a case close to isotropic (bottom row). The gray area is the area in which the function is valid, that is where λ₁ > λ₂ > λ₃.

Fig 7.

Average absolute values for the ADC (top image), the three eigenvalues λ₁, λ₂, and λ₃ (middle row), and the three anisotropy indexes FA, RA, and A_m (bottom row) as a function of time after the onset of symptoms for neonates with a white matter lesion.

Fig 8.

A–C, Time evolution of the relative change (Change equation) in ADC values (A), the three eigenvalues (B), and the anisotropy indexes FA, RA, and A_m (C) after hypoxic-ischemic brain injury in neonates. Trend lines are shown only if the trend was significant (P < .05).