Apparent diffusion coefficient values of the normal foetal brain developing

PURPOSE The non-invasiveness and sensitivity of diffusion weighted techniques (DWI) in detecting microstructural changes in cerebral tissues due to pathologies, suggest exploiting apparent diffusion coefficient (ADC) measurement in prenatal diagnostics. One of the limitations of the foetal DWI is the quality of the images, since fast sequences are applied to avoid movements of the fetus, avoiding signal averages. In this work we have addressed the problem by using denoising methods recently developed 1,2 . We calculated ADC values in different brain areas of healthy fetuses as a function of the gestational age (GA). METHOD AND MATERIALS Diffusion-weighted imaging (DWI) was performed in 35 normal pregnancies at 1.5T (Siemens Avanto, Erlangen, Germany), without mother-foetal sedation. The GA range was 19-38 weeks. The MRI protocol included a DW-Spin Echo EPI with TR/TE=4000/79; bandwidth=1628 Hz/px; matrix=192x192; FOV 379mm 2 . In-plane resolution=2x2mm 2 , slice-thickness=4mm, NSA=2, with b-values equal to 50,200,700 s/mm² along the three (x, y, z) orthogonal axes. Eight regions of interest (ROIs) were manually placed in the Frontal White Matter (FWM), Occipital WM (OWM), Thalamus (TH), Basal Ganglia (BG) Cerebellum (CH), Pons, lateral ventricle Cerebral Spinal Fluid (CSF) and amniotic fluid. All DWIs were denoised by dwidenoise tool 1 and corrected for Gibbs-ringing artifacts 2 . ADC was measured in each ROI through a fitting procedure developed in MATLAB and the goodness of fit was evaluated with the root mean squared error (RMSE). The Kruskal- Wallis test was used to calculate the differences in ADC measured at the II and III trimester and Spearman’s test was used to evaluate the correlation between ADC values and GA. Signal-to-noise ratio (SNR) of DWI with and without denoising correction at each b value was also obtained to evaluate the reliability of estimated ADC values. RESULTS SNR and the quality of DW-images considerably increased after noise and artifacts correction (Fig. 1), while the goodness-of-fit changed negligibly (RMSEraw=0.07, RMSEcorr=0.06). In partial agreement with literature 3-5 ADC values of CH and Pons show significant negative correlations with GA (R =-0.87, -0.80, respectively, all p<0.0001), while a positive correlation was found between ADC and GA in FWM (R=0.56, p<0.01), in disagreement with literature 3-5 . However, the behavior of ADC vs GA in FWM increases in parallel to GA increases during the second trimester and it decreases with GA increase in the third trimester of gestation. No significant correlation was found between ADC and GA in TH, OWM, CH, BG and CSF. ADC mean values of CH, Pons, FWM and TH are significantly different between second and third trimester (Table 1). DISCUSSION/CONCLUSION The routine of image correction provided a reasonable and fast method for improving the quality of DWI-images and providing a reliable identification of ROIs . ADC results are in agreement with the normal progression of myelination that occurs from central to peripheral brain and from dorsal to ventral within a region 6 . Regional differences in foetal ADC values and their evolution with GA reflect microstructural and physiological changes due to brain maturation. Our preliminary data may provide a comparison base for the evaluation of parenchymal CNS abnormalities in prenatal MRI diagnosis. References 1. J. Veraart, E. Fieremans, and D.S. Novikov Diffusion MRI noise mapping using random matrix theory. Magn. Res. Med. 2016; 76(5):1582-93. 2. Kellner E, Dhital B, Kiselev VG and Reisert M. Gibbs‐ringing artifact removal based on local subvoxel‐shifts. Magnetic resonance in medicine 2016; 76(5):1574-1581. 3. M.M. Schneider et al. Normative apparent diffusion coefficient values in the developing foetal brain. Am. J. Neuroradiol. 2009; 30(9):1799-1803. 4. R. Han et al. Assessment of apparent diffusion coefficient of normal foetal brain development from gestational age week up to term age: a preliminary study. Foetal diagn. Ther. 2014;37(2):102-107. 5. G. Yaniv et al. Region-specific changes in brain diffusivity in foetal isolated mild ventriculomegaly. Eur Radiol 2016; 26:840-848. 6. J. A. Matsumoto, ‎C. M. Gaskin, ‎D. Kreitel, B. Li. MRI Atlas of pediatric brain maturation and anatomy. Oxford University Press, 2017