Alexandra Wong1, Thomas Chavez2, Jodie Votava-Smith2, David Miller2, Hollie Lai2, Sylvia delCastillo2, Lisa Paquette3, and Ashok Panigrahy2
1New York Medical College, Valhalla, NY, United States, 2Los Angeles, CA, United States, 3University of Southern California, Los Angeles, CA, United States
Synopsis
Children with congenital heart disease (CHD)
demonstrate problems with multi-domain cognitive control of unknown etiology.
Cingo-opercular and cerebellar brain networks are known to be critical in
multi-domain cognitive control including language function. Little is known
about the comparative structural growth trajectories of the cerebellum and
operculum in CHD patients. To our knowledge, the literature only describes
fetal opercular measurements by ultrasound.1 And, data from the
neonatal period is scant, gathered from children suffering from “temporary
neurologic dysfunction” or from cadaveric specimens.2,3 The fetal
cerebellum has been described on MRI mostly in terms of its volume4,5
or area,6 although a few have used linear measurements as the basis
of their fetal cerebellar growth illustration.7,8,9Purpose
The aim of this study
is to use simple, commonly available measurements to compare the longitudinal
trajectory of opercular and cerebellar structural growth by MRI in fetuses and
neonates with CHD to control cases without CHD.
Methods
Patients with CHD were
prospectively enrolled from January 2011 to June 2015, and underwent
serial fetal (1.5T) and postnatal pre and post-operative (3T) MRI
imaging. Comparable cross sectional imaging was performed in the non-CHD
patients both in the fetal and neonatal period. Like fetal single shot
fast spin echo and neonatal T2 images were used for manual linear cross
sectional measurement (Figure 2). Multivariate (MV) analysis was used for adjustments
and curve fitting.
Results
Sixty-two expectant mothers
were prospectively enrolled, with 11 CHD fetuses and 51 non-CHD fetuses. A
total of 80 scans were performed, including 35 serial scans (9 in the
non-CHD group) in the same patient. MV analysis, adjusting for gestational
age, demonstrated altered brain trajectories in selected cerebellar and
opercular measurements in the CHD patients compared to the non-CHD group
(Table 1). The slopes of the trajectory measurement for both the opercular
and cerebellar structures were similar suggesting synchronous aberrant
development in the CHD patients (Figure 1).
Discussion
Brain maturation in fetuses
and neonates with CHD is known to be delayed and often disarrayed. There were no comparisons for fetal
opercular normative growth; therefore, this study provides the first
description of such in normal fetuses contrasted to fetuses with CHD. Additionally,
this is the first study to localize maldevelopment of CHD fetuses and
neonates in two brain regions very important for language, and probably
additional higher order cognitive orchestration is important. The potential for this abnormality to be
an imaging biomarker for patient risk stratification to qualify for
rehabilitation services is possible. Additionally, examination of clinical
variables during the perinatal and perioperative period may identify
modifiable aspects of care to be protective of a vulnerable developing
brain.
Conclusion
Synchronous altered early
structural development of the cerebellum and the operculum are present in
patients with CHD and can be readily identified. These results suggest
that cingulo-opercular and cerebellar cognitive control brain networks are
at risk in patients with CHD. Further correlative longitudinal functional
connectivity studies and behavior outcomes studies are warranted in
patients with CHD.
Acknowledgements
The Children's Heart Foundation, Children's Hospital Los Angeles CTSI, SC CTSI (which is part of the Clinical and Translational Science Awards (CTSA) a national network funded through the National Center for Advancing Translational Sciences (NCATS) at the NIH (Grant Number UL1TR000130))References
1. Quarello E, Stirnemann J,
Ville Y, Guibaud L. Assessment of fetal Sylvian fissure opercularization
between 22 and 32 weeks: a subjective approach. Ultrasound Obstet Gyencol. 2008; 32:44–49.
2. Chen C, Zimmerman RA, Faro
S, Parrish B, Wang Z, Bilaniuk LT, Chou T. MR of the cerebral
operculum: topographic identification and measurement of interopercular
distance in healthy infants and children. AJNR Am J Neuroradiol. 1995; 16:1677-1687.
3. Naidich TP, Kang E,
Fatterpekar GM, Delman BN, Gultekin SH, Wolfe D, Ortiz O, Yousry I, Weismann
M, Yousry TA. The insula: anatomic study and MR imaging display at 1.5T. AJNR Am J Neuroradiol. 2004;
25:222-232.
4. Liu F, Zhang Z, Lin X, Teng
G, Meng H, Yu Y, Fang F, Zang F, Li Z, Liu S. Development of the human
fetal cerebellum in the second trimester: a post mortem magnetic resonance
imaging evaluation. J Anatomy.
2011; 219:582-288.
5. Hatab M, Kamourieh SW,
Twickler DM. MR volume of the fetal cerebellum in relation to growth. J Magn Reson Im. 2008; 28:840-845.
6. Ber R, Bar-Yosef O, Hoffmann
C, Shashar D, Achiron R, Katorza E. Normal fetal posterior foass in MR
imaging: new biometric data and possible clinical significance. AJNR Am J Neuroradiol. 2015;
36:795-802.
7. Tilea B, Alberti C,
Adamsbaum C, Armoogum P, Oury JF, Cabrol D, Sebag G, Kalifa G, Garel C.
Cerebral biometry in fetal magnetic resonance imaging: new reference data.
Ultrasound Obstet Gyencol. 2009;
33:173-181.
8. Garel C. Fetal cerebral
biometry: normal parenchymal findings and ventricular size. Eur Radiol. 2005; 15:809-813.
9. Sanzo-Cortes M,
Egana-Ugrinovic G, Zupan R, Figueras F, Gratacos E. Brainstem and
cerebellar differences and their association with neurobehavior in term
small-for-gestational-age fetuses assessed by fetal MRI. Am J Obstet Gynecol. 2014; 210:425.e1-e8.
.