1st Supervisor: Enrico De Vita, King’s College London
2nd Supervisor: Jo Hajnal, King’s College London
Aim of the PhD Project:
Ultrahigh field (UHF) MRI (>=7T) offers increased sensitivity and research has shown significant potential improvements in data quality for a number of applications in adults. However few studies scanned children at 7T so far, with the youngest subjects being 5 years old[1]. The highest field at which neonates have been scanned is 4.7T[2].
We aim to pioneer the investigation of brain development in normal and ex-preterm infants with UHF 7T MRI, pushing spatial resolution limits and exploring novel high field contrast to visualise their small developing structures.
This is a highly technical challenge that will involve electromagnetic modelling of babies in the scanner to determine how to examine them safely; this will be followed by novel MRI acquisition development to optimize imaging of the immature neonatal brain and participation in the first studies of babies at UHF.
This project is ideally suited for a physicist or engineer with a strong interest in tackling the challenges of innovative biomedical technology and applications and the willingness to engage with a highly multidisciplinary team. The application area of developmental neuroscience may add motivation.
Project Description:
MRI is extremely valuable in studying normal and abnormal brain development in neonates. The developing Human Connectome Project (dHCP), led jointly by King’s, Imperial and Oxford University, aims to map early life development by acquiring MRI anatomical and functional data from fetuses and neonates. Ongoing analysis of dHCP data is hoped to provide new insights into structural and functional development (see Figure). However there remain key unknowns relating to the effects of prematurity and perinatal trauma on brain development that existing MRI approaches are unlikely to resolve.
One challenge of imaging neonates, is achieving sufficient spatial resolution to visualise small brain structures, maintaining reasonable acquisition times and acceptable noise levels. The dHCP uses a clinical 3T MRI scanner technology primarily designed for imaging adults combined with bespoke neonatal brain receiver coils and purpose designed patient handling[3]. However, even the dedicated acquisition protocol providing anatomical resolution of 0.8mm isotropic is still only just able to resolve key structures and for example is not able to differentiate cortical layers.
MR sensitivity increases approximately with field strength. If the associated technical challenges can be adequately addressed, the extra sensitivity provided by UHF-MRI can be traded for enhanced resolution, image quality, or acquisition speed.
With more than 60 systems worldwide (Feb 2017) UHF-MRI is providing important advances in biomedical research. For instance 7T MRI can provide information not visible at lower fields on focal brain lesions in epileptic subjects and in multiple sclerosis[4,5]; ultra high resolution brain imaging is also revealing astonishing anatomical details particularly with enhanced T2* contrast that makes UHF particularly well suited for studying deep nuclei characterised by high iron content[6,7].
We will explore for the first time the benefits of UHF-MRI for enhancing the available image data quality for neonatal subjects. The objective is a closer look at their brain during a period of exuberant development, when it is both different from adult brain (with different MRI properties) and is changing fast. We aim to produce a 7T protocol that exceeds the dHCP neonatal protocol in sensitivity and resolution, and use this to explore critical facets of brain development and damage, such as patterns of deep grey nuclei damage in hypoxic ischemic injury and subtle vascular changes associated with prematurity[8].
The project will evolve through 3 phases:
1. Establishing Safety
Since neonatal imaging has never been attempted at 7T the first task will be to demonstrate that safe operation can be assured. The key risk that must be addressed is subject heating during MR imaging, quantified by the specific absorption rate (SAR) of radiofrequency energy; this is intrinsically higher at higher fields and currently limits the use of some MR sequences used routinely at 1.5T and 3T.
We will build on our previous work at lower fields[9] to do EM modelling of whole body SAR and thermal heating for neonates of different sizes and in different positions, within dedicated RF coils available for the 7T system. This will involve realistic digital human phantoms and models of actual RF coils. Validation will be through experiments on phantoms. Once a safe operating regime can be demonstrated, ethical approval to study neonates will be sought.
2. Sequence optimisation
The MRI properties of the neonatal brain are distinct from more mature brains. High water content and incomplete myelination are responsible for a reverse grey-white matter contrast and longer MR relaxation times.
We will start by numerical analysis[10] to predict signal properties in potential imaging sequences using known T1/T2 values for neonates extrapolated to 7T from lower field.
Building on our dHCP experience, following an initial focus on anatomy, functional sequences and diffusion sequences for microstructural imaging will be optimised. MR spectroscopy (MRS) will also be investigated as this is another area where UHF presents clear advantages in terms of spectral resolution and SNR compared to lower field strengths.
3. In-vivo studies
Once ethical approval is in place, actual neonatal relaxation times will be mapped and candidate sequences appropriately adjusted. In an initial pilot study, acquisition protocols will be further optimized. A systematic study of the neonatal brain comparing term born subjects with ex pre-term infants at 7T will then be designed and conducted. This data will be placed alongside reference data collected at 3T on age matched subjects as part of the developing Human Connectome Project and a comparative analysis performed.
Literature:
1. Harris AD, Singer HS, Horska A, et al., GABA and glutamate in children with primary complex motor stereotypies: an 1 H-MRS study at 7T. American Journal of Neuroradiology 2016;37(3):552-7.
2. De Vita E, Bainbridge A, Cheong JLY, et al., Magnetic Resonance Imaging of Neonatal Encephalopathy at 4.7T. Pediatrics 2006;118(6):e1812-21.
3. Hughes EJ, Winchman T, Padormo F, et al. A dedicated neonatal brain imaging system. Magn. Reson. Med. 2017; 78(2):794-804.
4. Harrison DM, Oh J, Roy S, et al. Thalamic lesions in multiple sclerosis by 7T MRI: clinical implications and relationship to cortical pathology. Multiple Sclerosis. 2015;21(9):1139-1150.
5. De Ciantis A, Barba C, Tassi L, et al., 7T MRI in focal epilepsy with unrevealing conventional field strength imaging. Epilepsia 2016; 57:445–454.
6. Stucht D, Danishad KA, Schulze P, et al., Highest Resolution In Vivo Human Brain MRI Using Prospective Motion Correction. PLoS ONE 2015; 10(7): e0133921.
7. Cho ZH, Min HK, Oh SH, et al., Direct visualization of deep brain stimulation targets in Parkinson disease with the use of 7-tesla magnetic resonance imaging. J Neurosurg. 2010; 113(3):639-47.
8. Malamateniou, C., Counsell, S. J., Allsop, et al., The effect of preterm birth on neonatal cerebral vasculature studied with magnetic resonance angiography at 3 Tesla. NeuroImage 2006, 32(3), 1050–1059.
9. Malik SJ, Beqiri A, Price AN, et al., Specific absorption rate in neonates undergoing magnetic resonance procedures at 1.5 T and 3 T. NMR Biomed. 2015;28:344–352.
10. Teixeira RPAG, Malik SJ, Hajnal JV, Joint System Relaxometry (JSR) and Cramer-Rao Lower Bound Optimization of Sequence Parameters: A Framework for Enhanced Precision of DESPOT T1 and T2 Estimation. Magn. Reson. Med. 2017; doi: 10.1002/mrm.26670.
