Preliminary observations of a system for determination of phototherapy exposure over a neonate body shape.

While it is possible to determine the irradiance and spectral content for a given neonatal phototherapy device at various locations over a neonate's surface, this does not allow estimation of the total rate of energy delivery within a specific spectral range over the neonate's exposed body surface. A series of 192 blue wavelength enhanced silicon photodiodes was distributed over the surface of a commercially available newborn body shape and connected to a specially designed interface circuit. Placement of photosensors over the surface of the baby shape was determined with consideration of the surface area of twelve specific anatomical areas where each was allocated 16 individual photodiodes. Calibration of detection channels for specific wavelength intervals was undertaken using a Bentham dmc150 spectroradiometer system and also a separate hand held spectroradiometer. This made it possible to estimate the effective integrated dose rate in Watts for specific wavelength intervals such as 460 nm to 490 nm as identified by the American Academy of Pediatrics for phototherapy lamp devices. This allowed identification of dose rate contributions from specific anatomical areas. Initial observations are reported for a range of phototherapy lamp systems and the findings are discussed in terms of their predicted relative clinical effectiveness. Options are also discussed in relation to the future development of the reported measurement system.

Use of a hand-held spectroradiometer for the measurement of neonatal phototherapy lamp outputs.

The measurement capability of a hand-held spectroradiometer for validation of phototherapy light treatment for neonates is described. This function is compared with that of a double grating monochromator system with photomultiplier detector, where parameters evaluated included wavelength accuracy and accuracy of irradiance within set wavelength intervals - 460 nm to 490 nm and 400 nm to 550 nm. Measurements carried out in a clinical setting revealed that the hand-held spectroradiometer provided an acceptable level of accuracy for determining output characteristics of the phototherapy devices investigated. It was observed that measurement errors were more significant for studies involving direct contact with light emitting surfaces. It was identified that the spectral resolution of the MSC15 device could act to degrade the accuracy of the device where narrow spectrum peaks occurred around the limits of specific identified bandwidths - such as at 460 nm and 490 nm. This was identified not to be an issue with typical light emitting diode phototherapy systems, where the spectral outputs do not contain narrow spectral components. The device lends itself also to use by clinical staff in the clinical environment to verify the output of phototherapy lamps. The availability of such hand-held spectroradiometer devices represents an advance on the use of output meters suppled by equipment manufacturers.

Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study.

BACKGROUND: In neonatal encephalopathy, the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance (MR) spectroscopy (MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after neonatal encephalopathy. METHODS: We did a prospective multicentre cohort study across eight neonatal intensive care units in the UK and USA, recruiting term and near-term neonates who received therapeutic hypothermia for neonatal encephalopathy. We excluded infants with life-threatening congenital malformations, syndromic disorders, neurometabolic diseases, or any alternative diagnoses for encephalopathy that were apparent within 6 h of birth. We obtained T1-weighted, T2-weighted, and diffusion-weighted MRI and thalamic proton MRS 4-14 days after birth. Clinical neurodevelopmental tests were done 18-24 months later. The primary outcome was the association between MR biomarkers and an adverse neurodevelopmental outcome, defined as death or moderate or severe disability, measured using a multivariable prognostic model. We used receiver operating characteristic (ROC) curves to examine the prognostic accuracy of the individual biomarkers. This trial is registered with ClinicalTrials.gov, number NCT01309711. FINDINGS: Between Jan 29, 2013, and June 25, 2016, we recruited 223 infants who all underwent MRI and MRS at a median age of 7 days (IQR 5-10), with 190 (85%) followed up for neurological examination at a median age of 23 months (20-25). Of those followed up, 31 (16%) had moderate or severe disability, including one death. Multiple logistic regression analysis could not be done because thalamic N-acetylaspartate (NAA) concentration alone accurately predicted an adverse neurodevelopmental outcome (area under the curve [AUC] of 0·99 [95% CI 0·94-1·00]; sensitivity 100% [74-100]; specificity 97% [90-100]; n=82); the models would not converge when any additional variable was examined. The AUC (95% CI) of clinical examination at 6 h (n=190) and at discharge (n=167) were 0·72 (0·65-0·78) and 0·60 (0·53-0·68), respectively, and the AUC of abnormal amplitude integrated EEG at 6 h (n=169) was 0·73 (0·65-0·79). On conventional MRI (n=190), cortical injury had an AUC of 0·67 (0·60-0·73), basal ganglia or thalamic injury had an AUC of 0·81 (0·75-0·87), and abnormal signal in the posterior limb of internal capsule (PLIC) had an AUC of 0·82 (0·76-0·87). Fractional anisotropy of PLIC (n=65) had an AUC of 0·82 (0·76-0·87). MRS metabolite peak-area ratios (n=160) of NAA-creatine (<1·29) had an AUC of 0·79 (0·72-0·85), of NAA-choline had an AUC of 0·74 (0·66-0·80), and of lactate-NAA (>0·22) had an AUC of 0·94 (0·89-0·97). INTERPRETATION: Thalamic proton MRS measures acquired soon after birth in neonatal encephalopathy had the highest accuracy to predict neurdevelopment 2 years later. These methods could be applied to increase the power of neuroprotection trials while reducing their duration. FUNDING: National Institute for Health Research UK.