Malek Makki

After birth, neonates with dextrotransposition of the great artery (d-TGA) require cardiopulmonary bypass (CPB) surgery within the first week of life. Despite improving perioperative intensive care management with lowering overall mortality rate, morbidity remains high, especially regarding the neurodevelopmental outcome in psychomotor and cognitive abilities during long-term follow-up. Impairment of the central nervous system has been determined as the characteristic pattern of brain injury in neonates with severe forms of d-TGA. To date the etiology of these impairments is not fully understood. Our aim was to use DTI to assess acute acquired brain injury and delayed brain maturation following CPB surgery. We selected the corpus callosum because it is formed between 12 and 16 weeks of gestation, right after heart structures complete formation, and at the beginning of blood circulation.

The diffusion changes are tightly linked to the degree of cohesiveness and cylindrical packing of axonal fibers and reduced extra-axonal space, due to the natural thickness of myelin as the white matter matures over time. Increases of diffusion components and decrease of anisotropy values observed in postsurgical compared to presurgical DTI may be explained by either abnormal axonal pruning, axonal swelling, lack/disruption of myelin sheaths, smaller degree of neurofibrils organization (i.e., microtubules and neurofilaments), demyelination issues, fewer oligodendrocytes, or a combination of these processes.  Whether these processes are due to CPB surgery procedures or are ongoing phenomena that start at the fetal level cannot be determined without either a follow-up exam or fetal DTI.  A better knowledge of the timing of brain abnormalities will enable  better counseling of parents and medical caretakers. Possible findings of our research project may have important clinical and research implications. Advanced cerebral MRI can quantify brain development and injury at a time when intervention for brain protection may be possible. Early detection of abnormal brain maturation and injury is important for the design of

preventive, protective, and rehabilitative  strategies in the management of children with congenital heart disease.

Fetal heart formation is completed around 12 weeks of gestation, and the white matter maturation of the corpus callosum develops between 12 and 16 weeks of gestation; the corpus callosum grows in size and volume in this period. Thus, as a result of our study, it has been suggested to measure the volume of the genu and splenium and to correlate these with DTI metrics.

This ongoing study requires more patients and healthy controls to confirm our findings in a larger cohort. In the acquisition part, the first idea is to perform a longitudinal study (follow-up at 1 year old, 2 years old, etc.). In the processing part, we will also expand the current study by segmenting the corpus callosum into 5 regions (genu, rostrum, body, isthmus, splenium) to test the  hypothesis that white matter delay observed in the genu might be in another segment of the body. We will quantify the volume of each area (3D T1WI), correlate the results with diffusion parameters, and discriminate the demyelination process from dysmyelination.

Diffusion measurements of the 5 substructures have been achieved, and we will submit our paper to Pediatric Research. When the volume study is completed we aim to submit a paper to AJNR.

Read this article at AJNR.org . . .