Assessment of brain development in children with developmental delay using amide proton transfer weighted (APTw) MRI
Xiaolu Tang1, Hong Zhang1, Xuna Zhao2,3, Jinyuan Zhou2, and Yun Peng1

1Imaging Center, Beijing Children’s Hospital, Capital Medical University, Beijing, China, People's Republic of, 2Neurosection, Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 3Philips Healthcare, Beijing, China, People's Republic of

Synopsis

Amide proton transfer weighted (APTw) imaging is a novel molecular MRI technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides in myelination process. However it is not well known to brain developments in children with developmental delay using APTw MRI. The aim of our work is to explore the brain development in children with developmental delay (DD) using APTw MRI. The final conclusion shows that APTw MRI is a promising technique to assess children with DD at a molecular level.

INTRODUCTION

Molecular MR imaging technique is one of hot spot of biomedical research. Conventional magnetization transfer (MT) imaging is sensitive to a semi-solid macromolecular phase in tissue. The changes of MTR values is parallel with myelination (1) and more sensitive to measuring myelination (2). Amide proton transfer weighted (APTw) MRI as a novel molecular MRI technique that can noninvasively detect endogenous mobile proteins and peptides (3,4) have been widely employed to study brain tumor, stroke, and so on. However it is not well known to brain developments in children with developmental delay using APTw MRI.

PURPOSE

The aim of our work is to explore the brain development in children with developmental delay (DD) using APTw MRI.

METHODS

Pediatric neurologists evaluated the children with DD according to Gessell test (The scores lowered 75). There was no any specific etiology. 18 cases (age range: 3 to 35 months) were recruited; 2 cases were severe retardation, 3 cases were moderate retardation and 13 cases were mild retardation in clinical diagnosis; 14 cases were no abnormal signals and 4 cases were slight delayed myelination in imaging diagnosis. 18 normal cases (age range: 3 to 35 months) were adopted, who had no neurological or mental illness. All DD and normal subjects were imaged on a 3Tesla Philips MR system. APTw MR imaging data were acquired at multiple frequency offsets: from -6 to 6 ppm. The saturation time and power were 800 ms and 2 μT respectively. Three transverse slices of the head, including pons, basal ganglia and centrum semiovale (CS) were acquired for APTw imaging. 10 ROIs were measured: pons, middle cerebellar peduncle (MCP), genu of corpus callosum (GOCC), splenium of corpus callosum (SOCC), frontal white matter (FWM), occipital white matter (OWM), head of caudate nucleus (HOCN), putamen, thalamus and CS.

RESULTS AND DISCUSSIONS

Compared to normal controls, the z-spectra and MTRasym spectra of abnormal group show slightly higher levels in Pons, MCP, GOCC, SOCC, FWM, OWM and CS, but no clearly differences are exhibited in HOCN, putamen and thalamus. Figure 1 (a) and (b) respectively shows z-spectra and MTRasym spectra for children with DD and normal controls in FWM. Figure 1(a) shows that the z-spectra is symmetric, and in the positive and negative 3~6 ppm region the calulated values of children with DD is slightly higher than that of normal controls. As showed in Figure 1(b), in the 2~5 ppm region the MTRasym spectra of children with DD present a visibly higher values compared to normal subjects. Especially, this differences become even more obvious around 2~3.5 ppm, which are corresponding to the exchangeable amide proton range in the spectra. Figure 2 shows the T2-weighted, MTR, and APTw MR images of a 15-month-old children with DD and a 15-month-old normal child. Compared to the normal subject, slightly higher APTw intensities in the CS, FWM, OWM (white arrows) are visualized in children with DD. The facts that the changes of z-spectra, MTRasym spectra and APTw MR images in children with DD may mainly be associated with the delayed myelination progress in the brain development, reflecting the differences of the semi-solid and mobile macromolecular phases in tissue between children with DD and normal children. There were no obvious differences of z-spectra and MTRasym spectra observed in HOCN, putamen and thalamus for DD and normal controls, which probably due to gray matter nucleis.

CONCLUSION

The slightly increased APTw effects shown in z-spectra and MTRasym of chidren with DD indicates that the myelination deveolpment of children in DD could be delayed compared to normal subjects. APTw MRI is a novel and promising technique to assess children with DD at a molecular level.

Acknowledgements

Thank my all teammates, they made great contributions to the work.

References

(1) Engelbrecht et al. Neuroimage. 1998;19:1923. (2) Nossin-Manor et al. Neuroimage. 2013;64:505. (3) Zhou et al. MRM. 2003;50:1120. (4) Zhou et al. Nat Med. 2003;9:1085.

Figures

Figure 1 Contrast of z-spectra (a) and MTRasym spectra (b) between children with DD and normal controls in FWM. Z-spectra of children with DD is slightly high in the positive and negative 3~6 ppm region. MTRasym spectra of children with DD is even obviously high around 2~3.5 ppm region.

Figure 2 Comparison of T2-weighted, MTR, and APTw MR images of a 15-month-old children with DD and a 15-month-old normal child. Slightly higher APTw intensities in the CS, FWM,OWM (white arrows) are visualized in the children with DD than normal control.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
3698