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Diagnostic Specificity of Cerebral Magnetic Resonance Imaging for Punctate White Matter Lesion Assessment in a Preterm Sheep Fetus Model

  • Maternal Fetal Medicine/Biology: Original Article
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Abstract

Recent studies, using magnetic resonance imaging (MRI) to assess white matter injury in preterm brains, increasingly recognize punctate white matter lesions (PWML) as the primary lesion type. There are some papers showing the relationship between the size and number of PWML and the prognosis of infants. However, the histopathological features are still unknown. In this study, we experimentally induced periventricular leukomalacia (PVL) in a sheep fetus model, aiming to find whether MRI can visualize necrotic foci (small incipient lesions of PVL) as PWML. Three antenatal insults were employed to induce PVL in preterm fetuses at gestational day 101–117: (i) hypoxia under intrauterine inflammation, (ii) restriction of artificial placental blood flow, and (iii) restriction of artificial placental blood flow after exposure to intrauterine inflammation. MRI was performed 3–5 days after the insults, and standard histological studies of the PVL validated its findings. Of the 89 necrotic foci detected in histological samples from nine fetuses with PVL, 78 were visualized as PWML. Four of the lesions detected as abnormal findings on MRI could not be histologically detected as corresponding abnormal findings. The diagnostic sensitivity and positive predictive values of histologic focal necrosis visualized as PWML were 0.92 and 0.95, respectively. The four lesions were excluded from these analyses. These data suggest that MRI can visualize PVL necrotic foci as PWML 3–5 days after the injury induction. PWML can spontaneously become obscure with time after birth, so their accurate diagnosis in the acute phase can prevent overlooking mild PVL.

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Acknowledgments

The authors gratefully thank the staff in our laboratory for their technical assistance.

Funding

This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan (Grant Number 24591597).

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Authors and Affiliations

  1. Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan

    Masae Kobayashi, Shimpei Watanabe, Tadashi Matsuda, Hideyuki Ikeda, Tatsuro Nawa, Shinichi Sato, Haruo Usuda & Takushi Hanita

  2. Department of Veterinary Pathology, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan

    Yoshiyasu Kobayashi

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  1. Masae Kobayashi
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  2. Shimpei Watanabe
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  3. Tadashi Matsuda
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  4. Hideyuki Ikeda
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  5. Tatsuro Nawa
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  9. Yoshiyasu Kobayashi
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Contributions

The authors’ responsibilities were as follows: M.K., S.W., and T.M. developed the study design; S.W. conducted most research activities; H.I., T.N., S.S., H.U., T.H., and Y.K. contributed to samples and data collection, and discussion of the data information. M.K. and S.W. wrote the first draft of the manuscript; all authors read and approved the final manuscript.

Corresponding author

Correspondence to Shimpei Watanabe.

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The authors declare that they have no conflicts of interest.

Ethics Approval

All experimental procedures conformed to “Regulations for Animal Experiments and Related Activities at Tohoku University” and were reviewed by the Institutional Laboratory Animal Care and Use Committee of Tohoku University, and finally approved by the President of the University.

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Kobayashi, M., Watanabe, S., Matsuda, T. et al. Diagnostic Specificity of Cerebral Magnetic Resonance Imaging for Punctate White Matter Lesion Assessment in a Preterm Sheep Fetus Model. Reprod. Sci. 28, 1175–1184 (2021). https://doi.org/10.1007/s43032-020-00401-5

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  • DOI: https://doi.org/10.1007/s43032-020-00401-5

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