Response to Letter to the Editor: Diffusion of the Corpus Callosum in Young Infants

Diffusion of the Corpus Callosum in Young Infants

We would like to thank you for the opportunity to respond to the queries raised in Dr. Groenendaal’s letter. We would also like to thank Dr. Groenendaal for his interest in our paper and for taking the time to express his concerns.

We agree with Dr. Groenendaal that the presence of restricted diffusion in the splenium of the corpus callosum (SOCC) in neonates with perinatal asphyxia should not be deemed as a normal finding. In the conclusion section of our paper, we emphasized that although the presence of “restricted diffusion” in the SOCC may be normal when the MRI is performed on a 3T system, correlation with clinical presentation (the presence of perinatal asphyxia in this current context) and stage of brain maturation is extremely important. It is definitely not our intention to suggest that restricted diffusion within the SOCC in all young infants with MRI brain performed on a 3T system are normal. It is also not surprising that our observation differs from that of Alderliesten et al[1] as only infants with hypoxic-ischemic injuries were included in their study and hence, the observed restricted diffusion in the corpus callosum is undoubtedly pathological. In contrast, our recruited patients have no known medical conditions, which may result in restricted diffusion within the SOCC.

We also agree that quantitative measurement of apparent diffusion coefficient (ADC) value is the gold standard to ascertain if the perceived “restricted diffusion” truly represents the presence of a pathological condition. This is however, challenging especially within the neonatal and early infantile periods as the corpus callosum is thin and flat, rendering the placement of region of interest (ROI) for quantitative ADC measurement highly challenging. Definition of a normal ADC value is also often challenging in the pediatric population, especially in the first 2 years of life as the measured ADC value is highly dependent upon the stage of myelination and/or brain maturation.[2] [3] The ADC cut-off value provided by Dr. Groenendaal (0.969 × 10–3 mm²/s) was used to predict outcomes in patients with perinatal asphyxia. Therefore, this cut-off value may not be useful to differentiate normal from pathological “restricted diffusion” within the SOCC. Furthermore, the intent of our study is to highlight the potential pitfall of relative “restricted diffusion” within the SOCC in young infants imaged on a 3T system and not to establish the normal range of quantitative ADC measurements in our patient cohort. Hence, quantitative ADC measurements were not performed.

With regards to the indications for MRI scans, approximately 22% of our patients were healthy control population from a previous prospective study. The rest of the patients were scanned for various clinical indications, such as suspected structural abnormalities on antenatal scans, suspected congenital infections and developmental delay. Although not all of our recruited patients were healthy infants, they were carefully selected. Patients with conditions which may result in restricted diffusion in the SOCC (including hypoxic-ischemic injury) were excluded. As not all of our patients were healthy infants, this was also included as one of the limitations to our study.

As mentioned by Dr. Groenendaal in his letter, diffusion weighted imaging is very much dependent upon the imaging parameters used. We acknowledged this fact and hence have included the details of our imaging protocols in Table 2 of our previous paper.

• References

• 1 Alderliesten T, de Vries LS, Khalil Y. , et al. Therapeutic hypothermia modifies perinatal asphyxia-induced changes of the corpus callosum and outcome in neonates. PLoS ONE 2015; 10: e0123230 . doi:10.1371/journal.pone.0123230
• 2 Zhang L, Thomas KM, Davidson MC, Casey BJ, Heier LA, Uluğ AM. MR quantitation of volume and diffusion changes in the developing brain. AJNR Am J Neuroradiol 2005; 26: 45-49
• 3 Morriss MC, Zimmerman RA, Bilaniuk LT, Hunter JV, Haselgrove JC. Changes in brain water diffusion during childhood. Neuroradiology 1999; 41: 929-934