Amide proton transfer imaging of neonatal brain development and brain injury: a preliminary study
Yang Zheng1, Xiaoming WANG1, Xuna Zhao2, and Jinyuan Zhou3

1Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China, People's Republic of, 2Philips Healthcare, Beijing, China, Beijing, China, People's Republic of, 3Division of MR Research, Department of Radiology, Johns Hopkins University, Maryland, USA, Baltimore, MD, United States


Yang Zheng M.D. Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang 110004,PR China E-mail address: Tel.: +86 13889830846


The neonatal brain is under a continuous developmental process and brain maturity varies during different developmental phases. The maturation of the developing brain primarily involves myelinization and neuroglial cell proliferation. During brain development and maturation, brain injury caused by a variety of factors may damage the relative balance of the internal brain environment; this results in changes in the internal brain environment. The brain development process of neonates is manifested as neuroglial cell proliferation and myelinization. Neuroglial cell proliferation is defined as an increase of cell density accompanied by the synthesis of proteins for myelinization. To evaluate neonatal brain development and injury at the internal environmental level with the application of amide proton transfer (APT) imaging by measuring the APT values of several part of the brain.


A total of 51 neonatal patients who underwent MR examination were enrolled in the study. Among them, there were 38 newborns with no abnormalities and 13 cases with brain injury who underwent conventional MR examination. All neonates underwent scanning with a pencil beam and second-order shimming, transmitted by body coils and received by an eight-channel sensitivity-encoding (SENSE) coil using a Philips 3.0T MRI (Achieva 3.0T TX; Philips Healthcare Systems, Best, The Netherlands). The traditional MRI scanning modes were T1WI, T2WI, DWI. The sequences and parameters for traditional MRI were as follows: fast field echo (FFE) sequence for T1WI: TR 200 ms; TE 2.3 ms; Flip angle, 75°; FOV, 180 × 161 × 89 mm; matrix 224 × 162; slice thickness, 5 mm; scan time, 42.8 s; turbo spin echo (TSE) sequence for T2WI; TR 4.6 ms: TE 200 ms; FOV, 180 × 155 × 74 mm; matrix, 224 × 162; slice thickness, 5 mm; scan time, 36.8 s.After obtaining informed consent and permission of clinicians, routine MR was followed by additional APT scan. APT imaging is single slice scanning, performed at the basal ganglia level in all neonates, and in the case group, with increased localization at the level of lesion, and with the contralateral relatively normal area as self-control. APT raw data were imported to the interactive data analysis language program (IDL; Research Systems, Inc., Boulder, CO, USA) for analysis, measurement, and reconstruction of pseudo-color images. After the raw data were analyzed automatically by the software, the acquired APT images were comparatively analyzed by two senior diagnostic radiologists. The traditional MRI images (T1WI, T2WI) was used as references when choosing ROIs, but we chose ROIs on the original acquired M0: deep white matter in both frontal lobes, both basal ganglia, and deep white matter in both occipital lobes (Figure 1). Each ROI was carefully drawn and measured three times; thus, the results were averaged to provide the APT value of this ROI. The APT value of the acquisition region was used to reflect the signal intensity of the ROI. In APT pseudo-color images, the signals were displayed as red-to-blue in a descending sequence; the APT values were displayed similarly. The APT values of bilateral frontal subcortical white matter, basal ganglia and occipital subcortical white matter were measured for all neonates, as well as the APT values of the lesion and contralateral areas. Several statistical methods were used for statistical analysis.


In the control group, bilateral frontal subcortical white matter, basal ganglia and occipital subcortical white matter had no significant difference in APT value (P > 0.05). Between the different parts of the brain, APT values were significantly different (P < 0.05), and were associated with gestational age linear positive correlation. In the case group, there were significant differences in APT values between the lesion side and contralateral area, being significantly lower in lesion side than the contralateral side (P < 0.05). In the case group, the APT values of different parts of the brain were lower than the control group with the same gestational age (P < 0.05).


From changes in the protein and pH level in the neonatal brain, APT imaging can help understand neonatal brain development and evaluate brain injury.


Amide proton transfer (APT) imaging is a noninvasive imaging method of MR, and it is capable of detecting mobile cellular proteins and peptides and monitoring pH effects.


This study was supported by National Natural Science Foundation of China (NO. 30570541, 30770632, 81271631). Acknowledge the NIH grant P41 EB015909.


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The traditional MRI image (a) was referenced for the ROIs (T1WI was used as a reference in this case), and deep white matter in both frontal lobes, both basal ganglia, and deep white matter in both occipital lobes were selected; the ROIs were marked accordingly in (b).

Distribution of APT of the deep white matter in the occipital lobe (a), deep white matter in the frontal lobe (b), and basal ganglia (c) by gestational age (days) in the control group.

Distribution and comparison of APT values between the lesion region and the contralateral region in the case group.

Comparison of brain APT values between the case group and the control group (P < 0.05 vs. sham controls)

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