Article Figures & Data
Figures
- FIG 1.
ROI placement is demonstrated in a female fetus (postmortem MR imaging performed 68 hours after medically indicated termination of pregnancy due to corpus callosum agenesis with cortical malformations at 28 + 0 GA) on T2R-based maps provided by MRF (A and C) and Synthetic MR imaging (B and D). A and B, ROI drawings of the medulla oblongata. C and D, ROI drawings of the midbrain.
- FIG 2.
The flow diagram indicates how the study sample was derived. Overall, 29 postmortem fetal MR data sets were acquired between January 2021 and March 2023. Only axial postmortem fetal MR data acquired at >15 + 0 (weeks + days) GA were included (n = 26). Cases in which no axial imaging data were available (n = 1) and those data that were acquired <15 + 0 GA (n = 2) were excluded from this study.
- FIG 3.
Demonstration of the relationships between Synthetic MR imaging and MRF-based T1R (A and C) and T2R (B and D) metrics (determined in the medulla oblongata [A and B] and the midbrain [C and D]) and the individual developmental stages at the time of postmortem fetal imaging.
- FIG 4.
Correlation between histology and MR imaging (medulla oblongata: level of the inferior olivary nucleus) at different developmental stages (24 + 1 [A, B, and C] [termination of pregnancy due to congenital disorder of glycosylation syndrome] versus 32 + 1 [D, E, and F] [termination of pregnancy due to Coffin-Siris syndrome]) based on immunohistochemical detection of MBP (A and D), SyMRI (B and E), and MRF-derived (C and F) quantitative T1R-mapping (ie, color-coded voxels according to the respective T1R metrics [as indicated by the color scale in B, C, E, and F]). The MBP-based histology specimens (A [magnification: ×2.1] and D [magnification: ×1.3]) reveal considerable myelination (brown staining) (magnification [×100] [right upper image elements in A and D of myelin deposited within the inferior cerebellar peduncle [asterisks in A and D]) in the dorsal/tegmental brainstem (inferior cerebellar peduncle [double arrows in D] and medial longitudinal fascicle [arrows in D]) and the medial lemniscus (dotted arrows in D) at 32 + 1, while myelin is relatively scarce at 24 + 1. Quantitative SyMRI (B and E) and MRF-based (C and F) imaging demonstrates myelin-related relaxation time shortening (bluish color-coding) in the dorsal medulla oblongata (arrows in E and F) (foremost induced by myelin deposited within the inferior cerebellar peduncles) at 32 + 1, which is absent at 24 + 1. These MR-based findings are in good agreement with histology and underline the high sensitivity of quantitative imaging for early stages of myelin development.
- FIG 5.
Comparison between histology (postmortem at 30 + 0 GA) (termination of pregnancy due to agenesis of the corpus callosum and suspected Coffin-Siris syndrome) and nearly age-matched postmortem MR imaging in another case (MR imaging at 31 + 2 GA) (termination of pregnancy due to tubulinopathy). Klüver-Barrera staining (A and C) and immunohistochemical detection of MBP (B and D) of the medulla oblongata (level of the inferior olivary nucleus) (A and B) and the midpons (C and D) are shown. T2 BLADE (reference MR image) (E) and SyMRI (F) versus MRF-based (G) quantitative T1R-mapping (ie, color-coded voxels according to the respective T1R metrics as indicated by the color scale in F and G) is demonstrated. While Klüver-Barrera staining of the medulla oblongata (A) and the pons (C) does not reveal myelinated tissue (myelin would appear as a bluish staining), MBP-based histology already depicts myelination (brown staining) of the medial lemniscus (asterisks) (longest diameter: 1.6 mm), the lateral lemniscus (arrowheads) (longest diameter: 0.7 mm), the medial longitudinal fascicle (arrows in B and D) (longest diameter: 0.8 mm), and the inferior cerebellar peduncles (dashed arrows), which is accompanied by a subtle brownish background staining within the dorsal or tegmental areas, respectively. As opposed to other myelin-staining methods (eg, Klüver-Barrera), MBP-based histology is considered more sensitive to early stages of myelination.27 Quantitative SyMRI (F) and MRF-based (G) imaging already demonstrates relaxation time shortening (bluish color-coding) in the dorsal/tegmental brainstem at the pontomedullary junction (arrows in F and G), which is in good agreement with MBP-based myelin staining and underlines its sensitivity for “premyelination” states.24
Tables
Region ICC Medulla oblongata (T1R) 0.805 (95% CI, 0.595–0.913) Medulla oblongata (T2R) 0.661 (95% CI, 0.351–0.841) Midbrain (T1R) 0.920 (95% CI, 0.821–0.965) Midbrain (T2R) 0.779 (95% CI, 0.547–0.900)
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