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Background

  1. Top of page
  2. Background
  3. MRIcNI
  4. Conclusion
  5. Acknowledgements
  6. References

Preterm birth and neurodevelopmental delay

‘Brain injury in premature infants is of enormous public health importance because of the large number of such infants who survive with serious neurodevelopmental disability.’[1] In 2009, 6.2% of all births in Australia were low birthweight (LBW, <2.5 kg), 1% were very LBW (VLBW, <1.5 kg) and 8.2% were preterm (<37 weeks gestation).[2] While survival rates of VLBW infants have improved, this has been accompanied by an increase in the number of those survivors who have long-term neurological deficits.[3] Preterm birth and LBW are associated with higher rates of cerebral palsy, intellectual disability and sensory impairment than in babies born at term.[4] As magnetic resonance imaging (MRI) is increasingly applied in this field, it is becoming apparent that a higher proportion of this patient group suffers from a broader spectrum of subtle structural abnormalities that underlie the neurodevelopmental disabilities of educational and behavioural problems; this broader focus includes minor neuromotor dysfunction, specific learning disability and language, visual-perceptual and attention deficits.[4]

Pathology in brief

Periventricular white matter injury (PWMI) (Fig. 1) is the most common form of brain injury in the very preterm infant and, therefore, the leading cause of chronic neurological morbidity in preterm infants.[5] PWMI includes both diffuse myelination disturbances and focal cystic necrotic lesions (periventricular leukomalacia (PVL)).[5] The incidence of PVL appears to be declining, while focal or diffuse non-cystic injury is now the predominant lesion.[1, 5] In terms of clinicopathological correlation, it appears that cystic PVL accounts for the small group of infants who show spastic diplegia, while non-cystic PVL is linked to those who display more subtle deficits including cognitive deficits.[1] Neuronal/axonal disease and deficits in volumetric development are likely to contribute to the spectrum of cognitive, attentional, behavioural, educational and socialisation problems that have been observed.[1]

figure

Figure 1. Axial T2-weighted MRI at two levels of a 2-month-old showing widespread intraventricular and periventricular haemorrhage and cystic periventricular leukomalacia.

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Imaging of preterm infants

While ultrasound (US) is effective for detecting severe white matter lesions in preterm infants, particularly where cystic porencephalic lesions are present, MRI can detect less severe damage.[6] MRI is more sensitive for detecting the diffuse, non-cystic form of PVL than US.[7, 8] MRI demonstrates the site and extent of abnormalities more precisely and shows maturational processes in detail.[9-11] Infants with diffuse white matter injury have been shown to be at risk for motor and cognitive impairment, as well as behavioural problems.[12] Horsch et al. reported 18% of infants born before 27 weeks gestation had moderate to severe white matter abnormalities on brain MRI at term.[13]

Indications for neonatal MRI

Van Wezel-Meijler et al.[14, 15] have proposed the following widely accepted indications for brain MRI in the neonate:

  • Prematurity, <30 weeks' gestational age
  • Hypoxic-ischaemic encephalopathy stage 2 or 3 in (near) full-term neonates
  • US diagnosis of significant parenchymal brain injury, such as inhomogeneous periventricular echodensities, cystic PVL, periventricular haemorrhagic infarction, arterial infarction
  • US diagnosis of severe post-haemorrhage ventricular dilatation
  • Traumatic delivery
  • Clinical or US suspicion of abnormalities in the posterior fossa
  • Clinical or US suspicion of abnormalities at the brain's convexity
  • Severe and/or symptomatic hypoglycaemia
  • (Suspected) metabolic disease
  • Clinical or US suspicion of brain inflammation (meningitis, encephalitis, brain abscess)
  • Congenital malformations with possible involvement of the brain
  • Neurological signs of encephalopathy, such as seizures, abnormal consciousness and/or asymmetry, not sufficiently explained by US findings

In addition to conventional (T1 and T2 weighted) MRI, more advanced techniques such as diffusion tensor imaging, connectivity, tractography, volumetric analysis, surface-based morphometry, steady-state functional MRI (fMRI) and connectomics are also being applied, albeit some only in a research setting, to the field of prematurity and neurodevelopmental disability[16] (Fig. 2).

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Figure 2. A research application. Axial, sagittal and coronal views of neonatal white matter tracts in the brain using diffusion MRI tractography on T1 structural images. The colours of the white matter tracts indicate their orientation (red, left–right; blue, inferior–superior; green, anterior–posterior).

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Safety and quality issues with MRI in the neonate

MRI is a relatively safe technique, is non-invasive and does not involve radiation. However, the necessity of transporting vulnerable patients out of the neonatal intensive care unit (NICU) to the radiology department to obtain an MRI scan carries a risk. Safety guidelines regarding physical properties of MRI in this population have been published.[17, 18] Newborn infants are prone to hypothermia, may be haemodynamically unstable, may require respiratory support and/or intravenous infusions and are vulnerable to noise and other adverse effects of handling and transport. Due to their small head size, the use of standard MR head coils can result in suboptimal picture quality and so adult knee coils may be used. These risks or limitations can be significantly reduced with the use of the MRI-compatible neonatal incubator (MRIcNI) (Fig. 3), and the use of smaller dedicated head and body coils yields high image quality.[19-22] MRIcNIs have made it possible to carry out safely the MR examination on younger, smaller infants, and those that are unstable.[19]

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Figure 3. MRI-compatible neonatal incubator (Lammers Medical Technology Nomag Incubator) – image provided by Imaging Solutions Pty Ltd, Australian distributor.

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MRIcNI

  1. Top of page
  2. Background
  3. MRIcNI
  4. Conclusion
  5. Acknowledgements
  6. References

Background

Safety and efficacy of the MRIcNI in clinical practice has been reported. Bluml et al.[22] demonstrated the feasibility and safety of use of an MRIcNI in 13 newborns, and further found that the diagnostic quality of images obtained was superior to those taken with standard MRI equipment. Rona et al.[19] found that the implementation of their MRIcNI resulted in being able to safely carry out MR examinations on younger, smaller and more unstable infants, with improved image quality and decreased mean imaging time. They routinely sedated all infants regardless of use of MRIcNI but found that a repeated dose was never necessary when they used their MRIcNI. Whitby et al.[20] conducted a study involving seven neonates scanned using an MRIcNI in combination with a fast imaging protocol. None of the neonates were sedated or anaesthetised. They found all of the neonates remained stable throughout scanning, and image quality was graded as good or excellent in all cases. Erberich et al.[21] described the safe use of an MRIcNI for obtaining high resolution images of the neonatal brain and fMRI with superior signal-to-noise ratio. The authors highlighted the potential for contribution to non-invasive studies of human brain development.

The MRI-compatible incubator

An MRIcNI (Nomag IC, Lammers Medical Technology, Lubeck, Germany, Fig. 4), with dedicated head and body coils for use with both 1.5T and 3T MRI machines, has been purchased by the University of Queensland in conjunction with the Royal Brisbane and Women's Hospital and the Royal Children's Hospital. This was the first Australian purchase of a device of this type.

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Figure 4. The MRI-compatible neonatal incubator (Lammers Medical Technology Nomag Incubator) – image provided by Imaging Solutions Pty Ltd.

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The MRIcNI is suitable for patients with a weight up to approximately 4500 g and a head circumference up to approximately 40 cm. It has an MRI-compatible chassis with an independent power and gas supply, pulse oximetry and provision for an MRI-compatible ventilator, infusion pumps and suction device. The unit sits on a trolley, which facilitates intra- and inter-hospital transportation of the infant. The incubator has hand ports so that the infant can be positioned correctly prior to imaging by medical staff. Custom-made head and body coils are used. With the use of an MRIcNI, the infant may be transported to the MRI scanner while intubated and ventilated by an MRI-compatible ventilator and connected to infusion pumps. Vital signs including heart rate, pulse and oxygen saturation can be monitored. In addition, the air temperature and humidity levels of the incubator can be set, and these are automatically maintained.

Use of the MRIcNI

The MRIcNI at our institution is used for clinically indicated MRI scans of neonates and, in addition, is currently being used in a research study. Over 50 babies have been scanned for clinical indications using the MRIcNI, which has replaced the use of evacuated bean bags and wrappings to assist in keeping the infant immobilised and warm. The MRIcNI is currently used to obtain high-quality images in a randomised clinical trial to determine whether massage in preterm infants leads to structural (MR tractography) or functional (fMRI, dense array electroencephalography) alterations in brain development.

This institution obtained a head coil compatible with the 1.5T MRI scanner, and head, abdominal and spine coils for use in the 3T MRI scanner. All neonates referred for MRI as part of clinical care are scanned using the MRIcNI. Primarily, this involves referrals for MRI brain for premature or term neonates but has also included babies with spina bifida referred for spine MRI and abdominal MRI for abdominal and renal indications.

Logistics of transfer

Transfer into the MRIcNI is performed in the NICU by NICU staff. Neonates receiving enteral feeds are usually fed in the NICU prior to transfer into the MRIcNI. The baby is placed in the pre-warmed MRIcNI and connected to the oxygen saturation monitor, infusion pumps and ventilator if required, in NICU prior to transfer to the Radiology Department. If the body coil is to be used, this replaces the mattress before the infant is placed in the MRIcNI. Neonatal earmuffs and a light swaddling blanket are applied at this stage (clinical protocols describing this process in more detail are available from the authors on request). This process provides for a minimum of interference once the baby is settled into the MRIcNI in NICU. After arrival at the MR unit the appropriate head coil is inserted from a dedicated opening port at the head of the incubator. The MRIcNI is then lifted from the trolley onto the MR bed. Scanning is performed while the infant is in the MRIcNI and continuously connected to the saturation monitor and ventilator and IV pumps.

Our experience and user tips

We have found the MRIcNI to provide a safe, thermo-stable environment for scanning neonates, have achieved satisfactory image quality and have been able to avoid sedation in the vast majority of cases. In over 3 years of usage of the MRIcNI, there have been no associated patient adverse events.

Several practical issues have arisen when using the MRIcNI:

  • At least 30 to 45 min pre-warming is needed for the unit to reach the appropriate temperature setting required for babies, in particular the higher temperature setting required for preterm babies.
  • The patient monitor interface on the MRIcNI includes cot temperature, pulse rate and oximetry readings, but they can be difficult to read from the MRI control room due to the screen size of the monitor, which is relatively small for viewing from a distance. We recommend that staff remain in the scan room throughout the procedure to monitor the well-being of the baby if they cannot clearly visualise the monitor interface from the control room. This need occurs infrequently.
  • The MRI-compatible ventilator (Pneupac babyPAC, Smith Medical International Ltd, Luton, UK) is connected with a portable non-magnetic compressed gas cylinders during the transfer between the NICU and the MRI scan room, before switching to the gas supply in the MRI scan room. The current MRI-compatible ventilator is not designed to provide humidified or preheated gas and developments would be beneficial for longer-term ventilation of babies. There have been some difficulties in sourcing a gas supplier to refill the portable MRI-compatible air and oxygen cylinders because of their special status outside the usual medical gas cylinder refilling program.
  • We have relied on the use of extensions of infusion lines from non-MRI-compatible infusion pumps, which are located outside the MRI scan room. We have recently purchased purpose-designed MRI-compatible infusion pumps (IRadimed, Winter Park, FL, USA), which eliminate the need for infusion line extensions.

Conclusion

  1. Top of page
  2. Background
  3. MRIcNI
  4. Conclusion
  5. Acknowledgements
  6. References

The MRIcNI has improved the safety of MRI for neonates and has contributed to better image quality. It is a significant resource for research in preterms, LBW and term babies with brain injury. It is providing better access to imaging for younger, smaller and sicker infants in the clinical setting. In the future this device will allow for more advanced imaging techniques to be applied to this vulnerable population. It will facilitate translational research that is essential in the task of determining how to improve neurodevelopmental outcomes in this vulnerable high-risk population.

Acknowledgements

  1. Top of page
  2. Background
  3. MRIcNI
  4. Conclusion
  5. Acknowledgements
  6. References

We acknowledge the assistance of Mr Ray Buckley and his staff, and Ms Karen Hose and the NICU staff at the Royal Brisbane and Women's Hospital for their assistance. Thanks to A/Prof Stephen Rose and Kerstin Pannek for the MR tractography images of study babies, and Imaging Solutions Pty Ltd for images of the incubator.

Funding for the incubator was provided by a University of Queensland Major Equipment and Infrastructure grant, Royal Brisbane and Women's Hospital, Royal Children's Hospital and Royal Children's Hospital Foundation, Brisbane.

References

  1. Top of page
  2. Background
  3. MRIcNI
  4. Conclusion
  5. Acknowledgements
  6. References
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