Hemodynamic and Metabolic Assessment of Neonates With Punctate White Matter Lesions Using Phase-Contrast MRI and T2-Relaxation-Under-Spin-Tagging (TRUST) MRI

Abstract

The brain's hemodynamic and metabolism of punctate white matter lesions (PWML) is poorly understood due to a scarcity of non-invasive imaging techniques. The aim of this study was to apply new MRI techniques to quantify cerebral metabolic rate of oxygen (CMRO2), global cerebral blood flow (CBF), oxygen saturation fractions in venous blood (Yv) and oxygen extraction fraction (OEF) in neonates with PWML, for better understanding of the pathophysiology of PWML. Fifty-one newborns were recruited continuously, including 23 neonatal patients with PWML and 28 normal control neonates. Phase-contrast (PC) MRI and T2-Relaxation-Under-Spin-Tagging (TRUST) MRI were performed for the measurement of CBF and Yv. OEF and CMRO2 were calculated from the CBF and Yv values. The total maturation score (TMS) was assessed for each neonate on standard T1, 2-weighted images to evaluate cerebral maturation. The CMRO2, CBF, Yv, and OEF values were compared between groups, and their associations with age and TMS were evaluated. Significant differences between PWML group and control group were found in CMRO2 (P = 0.020), CBF (P = 0.027), Yv (P = 0.012), OEF (P = 0.018). After age/maturation is accounted for, Yv and OEF showed significant dependence on the groups (P < 0.05). Newborns with PWML had lower OEF and higher Yv. CMRO2, CBF and brain volume were correlated with age (P < 0.001) and TMS (P < 0.05). It is feasible to use non-invasive MRI methods to measure cerebral oxygen supply and consumption in neonates with PWML. Newborns with PWML have lower oxygen consumption. Yv and OEF may be helpful for the diagnosis of PWML. The positive correlation between CBF and TMS, and between CMRO2 and TMS suggested that as myelination progresses, the blood supply and oxygen metabolism in the brain increase to meet the escalating energy demand.

Characterization of MRI techniques to assess neonatal brain oxygenation and blood flow

“…Our data demonstrated an 18% overestimation of neonatal blood flow in PC MRI scans acquired at 0.4 and 0.5 mm resolutions compared with that acquired at 0.3 mm resolution. Several previous studies have reported CBF measurements in neonates using PC MRI with low imaging resolutions, such as 1 mm, 0.6 mm, and 0.5 mm . Therefore, our results suggest that interpreting literature values of CBF acquired with low PC resolutions should be done with an abundance of caution regarding overestimation.…”

“…When combined, they provide an assessment of the brain's oxygen consumption, specifically the cerebral metabolic rate of oxygen (CMRO 2 ) . These biomarkers have significant implications in brain development and pathological conditions in neonates, such as hypoxic ischemic encephalopathy, hydrocephalus, congenital heart disease, and punctate white matter injury . Although several studies have demonstrated proof of principle of these measurements with MRI, the techniques and imaging parameters used were diverse and, more importantly, there has not been a systematic effort at sequence characterization.…”

“…We examined two sequences relevant to the brain's oxygen homeostasis, T 2 ‐relaxation‐under‐spin‐tagging (TRUST) MRI for the assessment of OEF and phase‐contrast (PC) MRI for CBF measurement. The study focused on these two methods because they are among the most commonly used sequences for oxygenation and blood flow measurements, respectively, and both have shown some promises in neonatal applications . For both sequences, we characterized the dependence of the results on imaging resolution, given the considerably smaller size of the neonatal brain.…”

“…1 These biomarkers have significant implications in brain development 2,3 and pathological conditions in neonates, such as hypoxic ischemic encephalopathy, [4][5][6][7][8] hydrocephalus, 9 congenital heart disease, 10 and punctate white matter injury. 11 Although several studies have demonstrated proof of principle of these measurements with MRI, 7,10,12 the techniques and imaging parameters used were diverse and, more importantly, there has not been a systematic effort at sequence characterization. Despite recent advances in neonatal-specific head coils, 13,14 optimization of pulse sequences for physiological imaging, which often has high signal variability and low signal-to-noise ratio (SNR), is particularly important in neonatal MRI because of the small brain size and high susceptibility to motion in this special population.…”

“…It is pragmatically challenging to conduct technical studies in neonates. To date, most neonatal studies have been performed on neonatal patients who had clinical indications for MRI, 7,8,10,11,15,16 and the research sequences were conducted as add-ons to clinical sequences. This is because it is difficult to recruit normal neonates who would otherwise not undergo MRI to participate in MRI research studies.…”