Neurophysiologic Profiling of At-Risk Low and Very Low Birth-Weight Infants Using Magnetic Resonance Imaging

Abstract

Low birth-weight (LBW) and very low birth-weight (VLBW) newborns have increased risks of brain injuries, growth failure, motor difficulties, developmental coordination disorders or delay, and adult-onset vascular diseases. However, relatively little is known of the neurobiologic underpinnings. To clarify the pathophysiologic vulnerabilities of such neonates, we applied several advanced techniques for assessing brain physiology, namely T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI) and phase-contrast (PC) MRI. This enabled quantification of oxygen extraction fraction (OEF), global cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO₂). A total of 50 neonates (LBW-VLBW, 41; term controls, 9) participated in this study. LBW-VLBW neonates were further stratified as those with (LBW-VLBW-a, 24) and without (LBW-VLBW-n, 17) structural MRI (sMRI) abnormalities. TRUST and PC MRI studies were undertaken to determine OEF, CBF, and CMRO₂. Ultimately, CMRO₂ proved significantly lower (p = 0.01) in LBW-VLBW (vs term) neonates, both LBW-VLBW-a and LBW-VLBW-n subsets showing significantly greater physiologic deficits than term controls (p = 0.03 and p = 0.04, respectively). CMRO₂ and CBF in LBW-VLBW-a and LBW-VLBW-n subsets did not differ significantly (p > 0.05), although OEF showed a tendency to diverge (p = 0.15). However, OEF values in the LBW-VLBW-n subset differed significantly from those of term controls (p = 0.02). Compared with brain volume or body weight, these physiologic parameters yield higher area-under-the-curve (AUC) values for distinguishing neonates of the LBW-VLBW-a subset. The latter displayed distinct cerebral metabolic and hemodynamic, whereas changes were marginal in the LBW-VLBW-n subset (i.e., higher OEF and lower CBF and CMRO₂) by comparison. Physiologic imaging may therefore be useful in identifying LBW-VLBW newborns at high risk of irreversible brain damage.

Keywords: CBF; CMRO2; OEF; PC MRI; TRUST MRI; low birth weight (LBW); very low birth weight (VLBW).

FIGURE 1

T2-relaxation-under-spin-tagging (TRUST) MRI for quantifying venous oxygenation (Yv) in superior sagittal sinus (SSS). (A) Raw images of control and labeled scans; (B) Various images (i.e., control-labeled) as function of T2-weighting [effective echo times (eTEs) of 0, 40, 80, and 160 ms; black arrow at SSS); and (C) Blood signals in SSS of TRUST MRI fitted to monoexponential function of eTE to yield blood T₂, in turn converted to Yv via calibration plot.

FIGURE 2

Cerebral blood flow determination via phase-contrast (PC) MRI. (A) Slice positions overlaid on angiogram image (each red bar indicating imaging slice of one PC MRI scan), performing four PC MRI scans in each subject to assess internal carotid arteries (left, LICA; right, RICA) and vertebral arteries (left, LVA; right, RVA), respectively; and (B) Corresponding PC MRI images (delayed).

FIGURE 3

T1-, T2-, and diffusion-weighted imaging (T1WI, T2WI, and DWI) studies of low birth-weight/very low birth-weight (LBW–VLBW) and term neonates: (A–C) 35⁺¹ week-old male newborn (birth weight, 2,000 g) with subarachnoid hemorrhages of posterior cranial fossa (LBW–VLBW-a subset); (D–F) 35⁺¹ week-old female newborn (birth weight, 2,200 g) with white matter damage and periventricular leukomalacia (LBW–VLBW-a subset), showing multiple increased signal intensities on T1WI and DWI, decreased signal intensity on T2WI, and cystic lesions of centrum semiovale bilaterally; (G–I) 34⁺⁵ week-old male newborn (birth weight, 1,625 g) with no MRI abnormalities (LBW–VLBW-n subset); and (J–L) maps indicating 42⁺³ week-old male term newborn (birth weight, 3,400 g) with no MRI abnormalities.

FIGURE 4

Box plots of corrected birth weight, OEF, cerebral metabolic rate of oxygen (CMRO₂), cerebral blood flow (CBF), and brain volume, comparing low birth-weight/very low birth-weight (LBW-VLBW) and term newborns, LBW-VLBW-a and LBW-VLBW-n subsets, LBW-VLBW-a subset and term newborns, and LBW-VLBW-n subset and term newborns: (A,K,P) Corrected birth weights of LBW-VLBW newborns (+/-MRI abnormalities) exceeded by those of term newborns; (C,D,M,N,R,S) Corrected CMRO₂ and CBF rates differed significantly in LBW-VLBW and term neonates (p < 0.001, p = 0.007), LBW-VLBW-a subset and term neonates (p = 0.001, p = 0.011), and LBW-VLBW-n subset and term neonates (p < 0.001, p = 0.021); (Q) Corrected OEF differed significantly in LBW-VLBW-n subset and term neonates (p < 0.001); (F–J) Corrected values similar (p > 0.05) in LBW-VLBW-a and LBW-VLBW-n subsets; and (B,E,L,O,T) Other values devoid of significant differences (p > 0.05), all data expressed as mean ± standard deviation.

FIGURE 5

Receiver operating characteristic (ROC) curves for five models [birth weight, oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO₂), cerebral blood flow (CBF), and brain volume] in identifying LBW-VLBW newborns with abnormal structural MRIs (LBW-VLBW-a subset). (A) Fair utility of OEF, CMRO₂, and CBF in distinguishing members of LBW-VLBW-a subset from LBW-VLBW and term newborns and (B) Fair utility of OEF only in distinguishing members of LBW-VLBW-a subset from LBW-VLBW neonates. Higher area-under-the-curve (AUC) values for physiologic parameters, compared with morphologic indices of brain weight and volume.