Neuroradiology DOI 10.1007/s00234-015-1487-7
Low-grade intraventricular hemorrhage disrupts cerebellar white matter in preterm infants: evidence from diffusion tensor imaging Takashi Morita & Masafumi Morimoto & Kei Yamada & Tatsuji Hasegawa & Shigemi Morioka & Satoshi Kidowaki & Masaharu Moroto & Satoshi Yamashita & Hiroshi Maeda & Tomohiro Chiyonobu & Sachiko Tokuda & Hajime Hosoi
Received: 23 August 2014 / Accepted: 5 January 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Introduction Recent diffusion tensor imaging (DTI) studies have demonstrated that leakage of hemosiderin into cerebrospinal fluid (CSF), which is caused by high-grade intraventricular hemorrhage (IVH), can affect cerebellar development in preterm born infants. However, a direct effect of low-grade IVH on cerebellar development is unknown. Thus, we evaluated the cerebellar and cerebral white matter (WM) of preterm infants with low-grade IVH. Methods Using DTI tractography performed at termequivalent age, we analyzed 42 infants who were born less than 30 weeks gestational age (GA) at birth (22 with lowgrade IVH, 20 without). These infants were divided into two birth groups depending on GA, and we then compared the presence and absence of IVH which was diagnosed by cerebral ultrasound (CUS) within 10 days after birth or conventional magnetic resonance imaging (MRI) at term-equivalent age in each group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at the superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP), motor tract, and sensory tract were measured. Results In the SCP, preterm born infants with IVH had lower FA values compared with infants without IVH. In particular, younger preterm birth with IVH had lower FA values in the SCP and motor tract and higher ADC values in the MCP. T. Morita : M. Morimoto (*) : T. Hasegawa : S. Morioka : S. Kidowaki : M. Moroto : S. Yamashita : H. Maeda : T. Chiyonobu : S. Tokuda : H. Hosoi Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan e-mail: [email protected]
K. Yamada Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Conclusion Low-grade IVH impaired cerebellar and cerebral WM, especially in the SCP. Moreover, younger preterm infants exhibited greater disruptions to cerebellar WM and the motor tract than infants of older preterm birth. Keywords Intraventricular hemorrhage (IVH) . Hemosiderin . Superior cerebellar peduncle (SCP) . Fractional anisotropy (FA) . Apparent diffusion coefficient (ADC)
Introduction Current neonatal and perinatal intensive care has led to decrease in the mortality rates of preterm infants [1, 2]. However, preterm birth is associated with neurodevelopmental disability, cognitive deficits, and attention deficit/hyperactivity disorder [3, 4]. Intraventricular hemorrhage (IVH) is the most common pattern of brain injury in preterm infants  and is related to development of neurodevelopmental disabilities such as cerebral palsy (CP) and cognitive and motor abnormalities [6, 7]. Preterm birth is also associated with underdeveloped cerebellum, for example cerebellar volume reduction . Studies have shown that IVH leads to underdeveloped cerebellum, reporting reduced cerebellum volumes visualized with cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) [9, 10]. Moreover, cerebellar volume reduction has been associated with adverse effects on neuropsychological outcomes in preterm infants [11, 12]. Cerebellar development accelerates from 20 to 40 weeks gestational age (GA), with particularly rapid changes in the cerebellar cortex [13, 14]. During this period, IVH can lead to the leakage of hemosiderin into cerebrospinal fluid (CSF) where it is subsequently
deposited on the cerebellar surface disturbing the structure of cerebellar cortex . As mentioned above, IVH affects cerebellar development. Moreover, high-grade IVH was reported to be associated with poor neurodevelopmental outcome [15, 16]. However, the influence of low-grade IVH on neurodevelopmental outcome in preterm infants is less clear , although a few studies have described significant neurodevelopmental disabilities including cerebral palsy, visual impairment , and mental dysfunction  in preterm infants with low-grade IVH compared with preterm infants without low-grade IVH. There is evidence that low-grade IVH can affect cerebellar development using volumetric analysis . However, using diffusion tensor imaging (DTI) analysis, Tam et al. further refined this finding and reported that high-grade IVH, but not low-grade IVH, can alter the microstructure of the middle cerebellar peduncle (MCP) and deep cerebellar nuclei in preterm infants . In the present study, we further examined the effect of low-grade IVH on cerebral and cerebellar microstructure using DTI tractography.
Methods This study was approved by the Kyoto Prefectural University of Medicine Research Ethics Committee, and written informed consent was obtained from the parents of each patient. Patients MRI was performed on 394 infants who were admitted to the neonatal intensive care unit (NICU) at our university hospital, between January 2004 and December 2010 for clinical diagnosis purposes before discharge. Brain MRI scans here are routinely performed at term-equivalent age for most premature infants who are born at less than 30 weeks gestation age. We first performed quantitative DTI assessment with blinding to the conventional MR findings and clinical details. Exclusion criteria were as follows: (1) preterm infants with a GA above 30 weeks at birth, (2) brain abnormalities such as PVL, (3) IVH grades III–IV (classified according to Papile et al. ) on CUS, (4) clinical evidence of congenital malformation or syndrome, and (5) no detection for fiber tracking because of motion artifact. Inclusion criteria were scanning MR at term-equivalent age (range, 37–43 weeks corrected GA). Three hundred and fifty-two infants were excluded from the study, and a remaining 42 infants (24 were male, 18 were female) met our criteria. GA was determined from the date of the mother’s last menstrual period and according to antenatal ultrasound scans. The 42 preterm infants were first assessed for the presence and absence of IVH (IVH and no IVH groups).
Next, the infants were further divided into two birth GA groups: group