Tai-Wei Wu

MRI detection of brown adipose tissue with low fat content in newborns with hypothermia.

PURPOSE To report the observation of brown adipose tissue (BAT) with low fat content in neonates with hypoxic-ischemic encephalopathy (HIE) after they have undergone hypothermia therapy. MATERIALS AND METHODS The local ethics committee approved the imaging study. Ten HIE neonates (3 males, 7 females, age range: 2-3days) were studied on a 3-T MRI system using a low-flip-angle (3°) six-echo proton-density-weighted chemical-shift-encoded water-fat pulse sequence. Fat-signal fraction (FF) measurements of supraclavicular and interscapular (nape) BAT and adjacent subcutaneous white adipose tissues (WAT) were compared to those from five non-HIE neonates, two recruited for the present investigation and three from a previous study. RESULTS In HIE neonates, the FF range for the supraclavicular, interscapular, and subcutaneous regions was 10.3%-29.9%, 28.0%-57.9%, and 62.6%-88.0%, respectively. In non-HIE neonates, the values were 23.7%-42.2% (p=0.01), 45.4%-59.5% (p=0.06), and 67.8%-86.3% (p=0.38), respectively. On an individual basis, supraclavicular BAT FF was consistently the lowest, interscapular BAT values were higher, and subcutaneous WAT values were the highest (p<0.01). CONCLUSION We speculate that hypothermia therapy in HIE neonates likely promotes BAT-mediated non-shivering thermogenesis, which subsequently leads to a depletion of the tissues intracellular fat stores. We believe that this is consequently reflected in lower FF values, particularly in the supraclavicular BAT depot, in contrast to non-HIE neonates.

The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study

Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy (1H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand.

Transitional Hemodynamics in Preterm Neonates: Clinical Relevance.

BACKGROUND Each newborn enters this world facing tremendous respiratory, hemodynamic and neuroendocrine challenges while going through drastic physiological changes during the process of adaption from fetal to postnatal life. Even though the vast majority of term infants transition smoothly without apparent consequences, this task becomes increasingly arduous for the extremely preterm infant. METHODS & RESULTS This article reviews the physiology and pathophysiology of cardiovascular adaptation of the very preterm neonate. In particular it describes the physiology of fetal circulation, summarizes the hemodynamic changes occurring during preterm births and discusses the impact of the most frequently seen clinical scenarios that place additional burden on the premature infant during immediate transition. Finally an emphasis is placed on discussing common clinical dilemmas and practical aspects of developmental hemodynamics such as neonatal hypotension and patent ductus arteriosus; clinical presentations the neonatologist encounters on a daily basis. CONCLUSION The review provides a physiology-based view on the hemodynamics of the immediate postnatal transitional period.

Hemodynamic reference for neonates of different age and weight: a pilot study with electrical cardiometry

Objective:Electrical cardiometry (EC) is an impedance-based monitor that provides noninvasive, real-time hemodynamic assessment. However, the reference values for neonates have not been established.Study Design:EC (Aesculon) was applied to hemodynamically stable preterm and term infants. Hemodynamic variables included cardiac output (CO), cardiac index (CI), stroke volume (SV) and heart rate (HR). Their gestational age (GA), weight and body surface area (BSA) were recorded.Results:A total of 280 neonates were studied. Their GA ranged from 265/7 to 414/7 weeks, weight 800 to 4420 g and BSA 0.07 to 0.26 m2. CO was positively correlated to GA, weight and BSA (r=0.681, 0.822, 0.830, respectively; all P<0.001). Using regression analysis, CO was most significantly correlated to BSA. Mean CI was 2.55±0.37 l min−1 per m2.Conclusion:Hemodynamic reference by EC is notably distinct among neonates of diverse maturity. CO is most closely correlated to BSA.

Incidence and outcomes of acute kidney injury in extremely-low-birth-weight infants

Background Acute kidney injury (AKI) is a common event in the neonatal intensive care unit (NICU), especially in extremely-low-birth-weight (ELBW) infants. This cohort study investigated the incidence of and risk factors for AKI in ELBW infants and their overall survival at the postmenstrual age (PMA) of 36 weeks. Methods All ELBW infants admitted to our NICU between January 2010 and December 2013 were enrolled. Those who died prior to 72 hours of life, had congenital renal abnormality, or had only one datum of the serum creatinine (SCr) level after the first 24 hours of life were excluded. The criteria used for the diagnosis of AKI was set according to the modified neonatal KDIGO AKI definition. Results AKI occurred in 56% of 276 infants. Specifically, stage 1, stage 2, and stage 3 AKI occurred in 30%, 17%, and 9% of ELBW infants, respectively. High-frequency ventilation support (adjusted odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.78–6.67, p< 0.001), the presence of patent ductus arteriosus (adjusted OR: 4.3, 95% CI: 2.25–8.07, p < 0.001), lower gestational age (adjusted OR for gestational age: 0.7, 95% CI: 0.58–0.83, < 0.001), and inotropic agent use (adjusted OR: 2.6, 95% CI: 1.31–5.21, p = 0.006) were independently associated with AKI. Maternal pre-eclampsia was a protective factor (adjusted OR: 0.4, 95% CI: 0.14–0.97, p = 0.044). Infants with AKI had higher mortality before the PMA of 36 weeks with an adjusted hazard ratio (HR) of 5.34 (95% CI: 1.21–23.53, p = 0.027). Additionally, infants with stage 3 AKI had a highest HR of 10.60, 95% CI: 2.09–53.67, p = 0.004). Conclusion AKI was a very common event (56%) in ELBW infants and was associated with a lower GA, high-frequency ventilation support, the presence of PDA, and inotropic agent use. AKI reduced survival of ELBW infants before the PMA of 36 weeks.

Arterial spin-labeling perfusion imaging of children with subdural hemorrhage: Perfusion abnormalities in abusive head trauma

BACKGROUND AND PURPOSE Perfusion abnormalities have not been well described in children with subdural hemorrhage (SDH). We investigated whether patients with abusive head trauma (AHT+) had more perfusion abnormalities than those without (AHT-). MATERIALS AND METHODS We reviewed the perfusion MR studies of 12 infants with SDH and 21 controls. The perfusion images were obtained using a pseudo-continuous arterial spin-labeling sequence with volumetric fast spin-echo readout. An MR perfusion scoring system (0-6 points) was devised to facilitate appraisal of the extent of abnormalities. An asymmetry index (AI) was calculated for each region of perfusion abnormality. Comparison of perfusion scores across the AHT+, AHT-, and control groups was performed. The AIs of the hypoperfused lesions and hyperperfused lesions in patients were separately compared with those of the controls. The neurological outcomes of the patients were associated with imaging abnormalities. RESULTS Perfusion abnormalities were found in five (83%) of six AHT+ patients and in one (17%) of six AHT- patients. The AHT+ group recorded a significantly higher perfusion score than did both the AHT- group and the controls. Four patients with hypoperfused lesions exhibited significantly lower AI (P=.002) than did the controls, and three patients with hyperperfused lesions had significantly higher AI (P=.006) than did the controls. Of the four patients with hypoperfused lesions, two expired and one experienced hemiparesis. CONCLUSIONS Patients with AHT have higher perfusion abnormality scores than patients with other causes of SDH and controls. Moreover, hypoperfusion may suggest a poor clinical outcome.

Changes in cardiac output and cerebral oxygenation during prone and supine sleep positioning in healthy term infants

Objective To investigate the changes in systemic and cerebral haemodynamics between supine and prone sleep in healthy term infants during the early postnatal period. Design/methods Healthy term infants without congenital anomalies, patent ductus arteriosus and/or small for gestational age status were enrolled. Infants were placed in supine (SP1), prone (PP) and back in supine (SP2) position for 15 min each while asleep. Cardiac output (CO) and stroke volume (SV) were assessed by electrical velocimetry (EV) and echocardiography (echo), and cerebral regional oxygen saturation (CrSO2) in the frontal lobes was monitored by near-infrared spectroscopy. Heart rate (HR) and SpO2 were continuously monitored by conventional monitoring. Results In 34 healthy term infants (mean age 3.7±1.2 days; 16 females), 66 sets of serial CO measurements (34 EV and 32 echo) in three sleep positions were obtained. Mean COEV and COecho were 182±57 (SP1), 170±50 (PP) and 177±54 (SP2), and 193±48 (SP1), 174±40 (PP) and 192±50 (SP2) mL/kg/min, respectively. Mean SVEV and SVecho were 1.46±0.47 (SP1), 1.36±0.38 (PP) and 1.37±0.39 (SP2), and 1.54±40 (SP1), 1.38±0.38 (PP) and 1.51±0.41 (SP2) mL/kg, respectively. Repeated measures analysis of variance revealed a decrease in CO and SV during prone positions by both EV and echo, while HR, SpO2 and CrSO2 did not change. Thirty-eight per cent of the CO measurements decreased≥10% during prone positioning. Conclusions In healthy term infants, CO decreases in prone position due to a decrease in SV and not HR. CO recovers when placed back in supine. However, frontal lobe CrSO2 does not change in the different positions.

Hemodynamic Changes During Rewarming Phase of Whole-Body Hypothermia Therapy in Neonates with Hypoxic-Ischemic Encephalopathy

Objective To delineate the systemic and cerebral hemodynamic response to incremental increases in core temperature during the rewarming phase of therapeutic hypothermia in neonatal hypoxic‐ischemic encephalopathy (HIE). Study design Continuous hemodynamic data, including heart rate (HR), mean arterial blood pressure (MBP), cardiac output by electrical velocimetry (COEV), arterial oxygen saturation, and renal (RrSO2) and cerebral (CrSO2) regional tissue oxygen saturation, were collected from 4 hours before the start of rewarming to 1 hour after the completion of rewarming. Serial echocardiography and transcranial Doppler were performed at 3 hours and 1 hour before the start of rewarming (T‐3 and T‐1; “baseline”) and at 2, 4, and 7 hours after the start of rewarming (T+2, T+4, and T+7; “rewarming”) to determine Cardiac output by echocardiography (COecho), stroke volume, fractional shortening, and middle cerebral artery (MCA) flow velocity indices. Repeated‐measures analysis of variance was used for statistical analysis. Results Twenty infants with HIE were enrolled (mean gestational age, 38.8 ± 2 weeks; mean birth weight, 3346 ± 695 g). During rewarming, HR, COecho, and COEV increased from baseline to T+7, and MBP decreased. Despite an increase in fractional shortening, stroke volume remained unchanged. RrSO2 increased, and renal fractional oxygen extraction (FOE) decreased. MCA peak systolic flow velocity increased. There were no changes in CrSO2 or cerebral FOE. Conclusions In neonates with HIE, CO significantly increases throughout rewarming. This is due to an increase in HR rather than stroke volume and is associated with an increase in renal blood flow. The lack of change in cerebral tissue oxygen saturation and extraction, in conjunction with an increase in MCA peak systolic velocity, suggests that cerebral flow metabolism coupling remained intact during rewarming.

Cerebral Lactate Concentration in Neonatal Hypoxic-Ischemic Encephalopathy: In Relation to Time, Characteristic of Injury, and Serum Lactate Concentration

Background Cerebral lactate concentration can remain detectable in neonatal hypoxic-ischemic encephalopathy (HIE) after hemodynamic stability. The temporal resolution of regional cerebral lactate concentration in relation to the severity or area of injury is unclear. Furthermore, the interplay between serum and cerebral lactate in neonatal HIE has not been well defined. The study aims to describe cerebral lactate concentration in neonatal HIE in relation to time, injury, and serum lactate. Design/methods Fifty-two newborns with HIE undergoing therapeutic hypothermia (TH) were enrolled. Magnetic resonance imaging and spectroscopy (MRI + MR spectroscopy) were performed during and after TH at 54.6 ± 15.0 and 156 ± 57.6 h of life, respectively. Severity and predominant pattern of injury was scored radiographically. Single-voxel 1H MR spectra were acquired using short-echo (35 ms) PRESS sequence localized to the basal ganglia (BG), thalamus (Thal), gray matter (GM), and white matter. Cerebral lactate concentration was quantified by LCModel software. Serum and cerebral lactate concentrations were plotted based on age at time of measurement. Multiple comparisons of regional cerebral lactate concentration based on severity and predominant pattern of injury were performed. Spearman’s Rho was computed to determine correlation between serum lactate and cerebral lactate concentration at the respective regions of interest. Results Overall, serum lactate concentration decreased over time. Cerebral lactate concentration remained low for less severe injury and decreased over time for more severe injury. Cerebral lactate remained detectable even after TH. During TH, there was a significant higher concentration of cerebral lactate at the areas of injury and also when injury was more severe. However, these differences were no longer observed after TH. There was a weak correlation between serum lactate and cerebral lactate concentration at the BG (rs = 0.3, p = 0.04) and Thal (rs = 0.35, p = 0.02). However, in infants with moderate–severe brain injury, a very strong correlation exists between serum lactate and cerebral lactate concentration at the BG (rs = 0.7, p = 0.03), Thal (rs = 0.9 p = 0.001), and GM (rs = 0.6, p = 0.04) regions. Conclusion Cerebral lactate is most significantly different between regions and severity of injury during TH. There is a moderate correlation between serum and cerebral lactate concentration measured in the deep gray nuclei during TH. Differences in injury and altered regional cerebral metabolism may account for these differences.