Biometric assessments of the posterior fossa by fetal MRI: A systematic review.

BACKGROUND: Posterior fossa abnormalities (PFAs) are commonly identified within routine screening and are a frequent indication for fetal magnetic resonance imaging (MRI). Although biometric measurements of the posterior fossa (PF) are established on fetal ultrasound and MRI, qualitative visual assessments are predominantly used to differentiate PFAs. OBJECTIVES: This systematic review aimed to assess 2-dimensional (2D) biometric measurements currently in use for assessing the PF on fetal MRI to delineate different PFAs. METHODS: The protocol was registered (PROSPERO ID CRD42019142162). Eligible studies included T2-weighted MRI PF measurements in fetuses with and without PFAs, including measurements of the PF, or other brain areas relevant to PFAs. RESULTS: 59 studies were included - 6859 fetuses had 62 2D PF and related measurements. These included linear, area and angular measurements, representing measures of PF size, cerebellum/vermis, brainstem, and supratentorial measurements. 11 measurements were used in 10 or more studies and at least 1200 fetuses. These dimensions were used to characterise normal for gestational age, diagnose a range of pathologies, and predict outcome. CONCLUSION: A selection of validated 2D biometric measurements of the PF on fetal MRI may be useful for identification of PFA in different clinical settings. Consistent use of these measures, both clinically and for research, is recommended.

Longitudinal development in the preterm thalamus and posterior white matter: MRI correlations between diffusion weighted imaging and T2 relaxometry.

Infants born prematurely are at increased risk of adverse neurodevelopmental outcome. The measurement of white matter tissue composition and structure can help predict functional performance. Specifically, measurements of myelination and indicators of myelination status in the preterm brain could be predictive of later neurological outcome. Quantitative imaging of myelin could thus serve to develop biomarkers for prognosis or therapeutic intervention; however, accurate estimation of myelin content is difficult. This work combines diffusion MRI and multi-component T2 relaxation measurements in a group of 37 infants born very preterm and scanned between 27 and 58 weeks equivalent gestational age. Seven infants have longitudinal data at two time points that we analyze in detail. Our aim is to show that measurement of the myelin water fraction is achievable using widely available pulse sequences and state-of-the-art algorithmic modeling of the MR imaging procedure and that a multi-component fitting routine to multi-shell diffusion weighted data can show differences in neurite density and local spatial arrangement in grey and white matter. Inference on the myelin water fraction allows us to demonstrate that the change in diffusion properties of the preterm thalamus is not solely due to myelination (that increase in myelin content accounts for about a third of the observed changes) whilst the decrease in the posterior white matter T2 has no significant component that is due to myelin water content. This work applies multi-modal advanced quantitative neuroimaging to investigate changing tissue properties in the longitudinal setting. Hum Brain Mapp 37:2479-2492, 2016. © 2016 Wiley Periodicals, Inc.

Longitudinal measurement of the developing grey matter in preterm subjects using multi-modal MRI.

Preterm birth is a major public health concern, with the severity and occurrence of adverse outcome increasing with earlier delivery. Being born preterm disrupts a time of rapid brain development: in addition to volumetric growth, the cortex folds, myelination is occurring and there are changes on the cellular level. These neurological events have been imaged non-invasively using diffusion-weighted (DW) MRI. In this population, there has been a focus on examining diffusion in the white matter, but the grey matter is also critically important for neurological health. We acquired multi-shell high-resolution diffusion data on 12 infants born at ≤ 28 weeks of gestational age at two time-points: once when stable after birth, and again at term-equivalent age. We used the Neurite Orientation Dispersion and Density Imaging model (NODDI) (Zhang et al., 2012) to analyse the changes in the cerebral cortex and the thalamus, both grey matter regions. We showed region-dependent changes in NODDI parameters over the preterm period, highlighting underlying changes specific to the microstructure. This work is the first time that NODDI parameters have been evaluated in both the cortical and the thalamic grey matter as a function of age in preterm infants, offering a unique insight into neuro-development in this at-risk population.

Preterm birth affects the developmental synergy between cortical folding and cortical connectivity observed on multimodal MRI.

The survival rates of infants born prematurely have improved as a result of advances in neonatal care, although there remains an increased risk of subsequent disability. Accurate measurement of the shape and appearance of the very preterm brain at term-equivalent age may guide the development of predictive biomarkers of neurological outcome. We demonstrate in 92 preterm infants (born at an average gestational age of 27.0±2.7weeks) scanned at term equivalent age (scanned at 40.4±1.74weeks) that the cortical sulcation ratio varies spatially over the cortical surface at term equivalent age and correlates significantly with gestational age at birth (r=0.49,p<0.0001). In the underlying white matter, fractional anisotropy of local white matter regions correlated significantly with gestational age at birth at term equivalent age (for the genu of the corpus callosum r=0.26,p=0.02 and for the splenium r=0.52,p<0.001) and in addition the fractional anisotropy in these local regions varies according to location. Finally, we demonstrate that connectivity measurements from tractography correlate significantly and specifically with the sulcation ratio of the overlying cortical surface at term equivalent age in a subgroup of 20 infants (r={0.67,0.61,0.86}, p={0.004,0.01,0.00002}) for tract systems emanating from the left and right corticospinal tracts and the corpus callosum respectively). Combined, these results suggest a close relationship between the cortical surface phenotype and underlying white matter structure assessed by diffusion weighted MRI. The spatial surface pattern may allow inference on the connectivity and developmental trajectory of the underlying white matter complementary to diffusion imaging and this result may guide the development of biomarkers of functional outcome.

White matter NAA/Cho and Cho/Cr ratios at MR spectroscopy are predictive of motor outcome in preterm infants.

PURPOSE: To determine (a) whether diffuse white matter injury of prematurity is associated with an increased choline (Cho)-to-creatine (Cr) ratio and a reduced N-acetylaspartate (NAA)-to-Cho ratio and whether these measures can be used as biomarkers of outcome and (b) if changes in peak area metabolite ratios at magnetic resonance (MR) spectroscopy are associated with changes in T2 and fractional anisotropy (FA) at MR imaging. MATERIALS AND METHODS: The local ethics committee approved this study, and informed parental consent was obtained for each infant. At term-equivalent age, 43 infants born at less than 32 weeks gestation underwent conventional and quantitative diffusion-tensor and T2-weighted MR imaging. Single-voxel point-resolved proton (hydrogen 1) MR spectroscopy was performed from a 2-cm(3) voxel centered in the posterior periventricular white matter. Outcome was evaluated by using Bayley scales at a corrected age of 1 year. Associations were investigated with Pearson product moment or Spearman rank order correlation. Differences in ratios in infants with and infants without impairment were tested by using t tests. RESULTS: NAA/Cho and Cho/Cr ratios correlated with the scaled gross motor score and the composite motor score, independent of gestational age (P < .05). FA at diffusion-tensor MR imaging and T2 at MR imaging correlated with the NAA/Cho ratio (P < .05 for both) but not with the Cho/Cr ratio. Infants with motor scores of less than 85 (impaired) had an increased Cho/Cr ratio (P < .03) and a reduced NAA/Cho ratio (P < .01) compared to those without impairment. A combination of increased Cho/Cr ratio and decreased NAA/Cho ratio predicted impaired motor outcome at a corrected age of 1 year with a sensitivity of 0.80 (95% confidence interval [CI]: 0.57, 0.94) and a specificity of 0.80 (95% CI: 0.66, 0.88). CONCLUSION: The combination of Cho/Cr and NAA/Cho ratios measured in the posterior periventricular white matter at term-equivalent age is predictive of motor outcome at 1 year in infants born at less than 32 weeks gestation.

AdaPT: An adaptive preterm segmentation algorithm for neonatal brain MRI.

Advances in neonatal care have improved the survival of infants born prematurely although these infants remain at increased risk of adverse neurodevelopmental outcome. The measurement of white matter structure and features of the cortical surface can help define biomarkers that predict this risk. The measurement of these structures relies upon accurate automated segmentation routines, but these are often confounded by neonatal-specific imaging difficulties including poor contrast, low resolution, partial volume effects and the presence of significant natural and pathological anatomical variability. In this work we develop and evaluate an adaptive preterm multi-modal maximum a posteriori expectation-maximisation segmentation algorithm (AdaPT) incorporating an iterative relaxation strategy that adapts the tissue proportion priors toward the subject data. Also incorporated are intensity non-uniformity correction, a spatial homogeneity term in the form of a Markov random field and furthermore, the proposed method explicitly models the partial volume effect specifically mitigating the neonatal specific grey and white matter contrast inversion. Spatial priors are iteratively relaxed, enabling the segmentation of images with high anatomical disparity from a normal population. Experiments performed on a clinical cohort of 92 infants are validated against manual segmentation of normal and pathological cortical grey matter, cerebellum and ventricular volumes. Dice overlap scores increase significantly when compared to a widely-used maximum likelihood expectation maximisation algorithm for pathological cortical grey matter, cerebellum and ventricular volumes. Adaptive maximum a posteriori expectation maximisation is shown to be a useful tool for accurate and robust neonatal brain segmentation.

Regional neonatal brain absolute thermometry by 1H MRS.

Therapeutic hypothermia is standard care for infants with moderate to severe encephalopathy. (1) H MRS thermometry (MRSt) measures regional brain absolute temperature using the temperature-dependent water chemical shift. This study evaluates the clinical feasibility of MRSt in human neonates, and correlates white matter (WM) and thalamus (Thal) MRSt with conventional rectal temperature (Trectal ) measurement. Fifty-six infants born at term underwent perinatal MRSt for suspected hypoxic-ischaemic brain injury and 33 infants born preterm had MRSt at a term-equivalent age; 56 of the 89 had Trectal measured after MRSt of either a Thal or posterior WM voxel, or both. MRSt used point-resolved spectroscopy (no water suppression; TR = 1370 ms; TE = 288 ms; 1.5 × 1.5 × 1.5 cm(3) Thal and 1.1 × 1.3 × 1.4 cm(3) WM voxels). Time domain data were phase and frequency corrected before summation and motion-corrupted data were excluded from further analysis using simple criteria [preprocessing + quality assurance (QA)]. Two published water temperature-dependence calibrations [both using cerebral creatine (Cr), choline (Cho) and N-acetylaspartate (Naa) as independent reference peaks] were compared. The temperature measurements derived from Cr, Cho and Naa were combined to give a single amplitude-weighted combination temperature (TAWC ). WM and Thal TAWC correlated linearly with Trectal (Thal slope, 0.82 ± 0.04, R(2) = 0.85, p < 0.05; WM slope, 0.95 ± 0.04, R(2) = 0.78, p < 0.05). Preprocessing + QA improved the correlation between WM TAWC and Trectal (R(2) increased from 0.27 to 0.78, p < 0.001). Both calibration datasets showed specific inconsistencies between the temperatures calculated using Cr, Cho and Naa reference peaks when applied to this neonatal dataset. Neonatal MRSt is clinically feasible. Preprocessing + QA improved MRSt reliability in WM. The consideration of MRSt calibration internal biases is necessary before combining MRSt temperatures from multiple reference peaks to obtain TAWC.

Clinical value of cortical bursting in preterm infants with intraventricular haemorrhage.

BACKGROUND: In healthy preterm infants, cortical burst rate and temporal dynamics predict important measures such as brain growth. We hypothesised that in preterm infants with germinal matrix-intraventricular haemorrhage (GM-IVH), cortical bursting could provide prognostic information. AIMS: We determined how cortical bursting was influenced by the injury, and whether this was related to developmental outcome. STUDY DESIGN: Single-centre retrospective cohort study at University College London Hospitals, UK. SUBJECTS: 33 infants with GM-IVH ≥ grade II (median gestational age: 25 weeks). OUTCOME MEASURES: We identified 47 EEGs acquired between 24 and 40 weeks corrected gestational age as part of routine clinical care. In a subset of 33 EEGs from 25 infants with asymmetric injury, we used the least-affected hemisphere as an internal comparison. We tested whether cortical burst rate predicted survival without severe impairment (median 2 years follow-up). RESULTS: In asymmetric injury, cortical burst rate was lower over the worst- than least-affected hemisphere, and bursts over the worst-affected hemisphere were less likely to immediately follow bursts over the least-affected hemisphere than vice versa. Overall, burst rate was lower in cases of GM-IVH with parenchymal involvement, relative to milder structural injury grades. Higher burst rate modestly predicted survival without severe language (AUC 0.673) or motor impairment (AUC 0.667), which was partly mediated by structural injury grade. CONCLUSIONS: Cortical bursting can index the functional injury after GM-IVH: perturbed burst initiation (rate) and propagation (inter-hemispheric dynamics) likely reflect associated grey matter and white matter damage. Higher cortical burst rate is reassuring for a positive outcome.

TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult.

In the current study, we explored the role of TNF cluster cytokines on the lipopolysaccharide (LPS)-mediated, synergistic increase in brain injury after hypoxic ischemic insult in postnatal day 7 mice. Pretreatment with moderate doses of LPS (0.3 µg/g) resulted in particularly pronounced synergistic injury within 12 h. Systemic application of LPS alone resulted in a strong upregulation of inflammation-associated cytokines TNFα, LTß, interleukin (IL) 1ß, IL6, chemokines, such as CXCL1, and adhesion molecules E-Selectin, P-Selectin and intercellular adhesion molecule-1 (ICAM1), as well as a trend toward increased LTα levels in day 7 mouse forebrain. In addition, it was also associated with strong activation of brain blood vessel endothelia and local microglial cells. Here, deletion of the entire TNF gene cluster, removing TNFα, LTß and LTα completely abolished endotoxin-mediated increase in the volume of cerebral infarct. Interestingly, the same deletion also prevented endothelial and microglial activation following application of LPS alone, suggesting the involvement of these cell types in bringing about the LPS-mediated sensitization to neonatal brain injury.

Distribution of pH changes in mouse neonatal hypoxic-ischaemic insult.

We assessed the distribution in brain pH after neonatal hypoxic-ischaemic insult and its correlation with local injury. Postnatal day 7 mice were injected with neutral red and underwent left carotid occlusion and exposure to 8% oxygen. Images captured from the cut surface of snap-frozen brain were used to calculate the pH from the blue-green absorbance ratios. Carotid occlusion alone had no effect, but combined with hypoxia caused rapid, biphasic pH decline, with the first plateau at 15-30 min, and the second at 60-90 min. The ipsilateral dorsal cortex, hippocampus, striatum and thalamus were most affected. Contralateral pH initially showed only 30% of the ipsilateral decline, becoming more acidotic with increasing duration. Systemic blood analysis revealed, compared with hypoxia alone, that combined insult caused a 63% decrease in blood glucose (1.3 ± 0.2 mM), a 2-fold increase in circulating lactate (17.7 ± 2.9 mM), a reduction in CO(2) to 1.9 ± 0.1 kPa and a drop in pH (7.26 ± 0.06). Re-oxygenation resulted in the normalisation of systemic changes, as well as a global alkaline rebound in brain pH at 4-6 h. A topographic comparison of brain injury showed only a partial correlation with pH changes, with the severest injury occurring in the ipsilateral hippocampus and sparing acidic parts of the contralateral cortex.

Prognostic value of neonatal EEG following therapeutic hypothermia in survivors of hypoxic-ischemic encephalopathy.

OBJECTIVE: Early prediction of neurological deficits following neonatal hypoxic-ischemic encephalopathy (HIE) may help to target support. Neonatal animal models suggest that recovery following hypoxia-ischemia depends upon cortical bursting. To test whether this holds in human neonates, we correlated the magnitude of cortical bursting during recovery (≥postnatal day 3) with neurodevelopmental outcomes. METHODS: We identified 41 surviving infants who received therapeutic hypothermia for HIE (classification at hospital discharge: 19 mild, 18 moderate, 4 severe) and had 9-channel electroencephalography (EEG) recordings as part of their routine care. We correlated burst power with Bayley-III cognitive, motor and language scores at median 24 months. To examine whether EEG offered additional prognostic information, we controlled for structural MRI findings. RESULTS: Higher power of central and occipital cortical bursts predicted worse cognitive and language outcomes, and higher power of central cortical bursts predicted worse motor outcome, all independently of structural MRI findings. CONCLUSIONS: Clinical EEG after postnatal day 3 may provide additional prognostic information by indexing persistent active mechanisms that either support recovery or exacerbate brain damage, especially in infants with less severe encephalopathy. SIGNIFICANCE: These findings could allow for the effect of clinical interventions in the neonatal period to be studied instantaneously in the future.

Super-resolution Reconstruction MRI Application in Fetal Neck Masses and Congenital High Airway Obstruction Syndrome.

OBJECTIVE: Reliable airway patency diagnosis in fetal tracheolaryngeal obstruction is crucial to select and plan ex utero intrapartum treatment (EXIT) surgery. We compared the clinical utility of magnetic resonance imaging (MRI) super-resolution reconstruction (SRR) of the trachea, which can mitigate unpredictable fetal motion effects, with standard 2-dimensional (2D) MRI for airway patency diagnosis and assessment of fetal neck mass anatomy. STUDY DESIGN: A single-center case series of 7 consecutive singleton pregnancies with complex upper airway obstruction (2013-2019). SETTING: A tertiary fetal medicine unit performing EXIT surgery. METHODS: MRI SRR of the trachea was performed involving rigid motion correction of acquired 2D MRI slices combined with robust outlier detection to reconstruct an isotropic high-resolution volume. SRR, 2D MRI, and paired data were blindly assessed by 3 radiologists in 3 experimental rounds. RESULTS: Airway patency was correctly diagnosed in 4 of 7 cases (57%) with 2D MRI as compared with 2 of 7 cases (29%) with SRR alone or paired 2D MRI and SRR. Radiologists were more confident (P = .026) in airway patency diagnosis when using 2D MRI than SRR. Anatomic clarity was higher with SRR (P = .027) or paired data (P = .041) in comparison with 2D MRI alone. Radiologists detected further anatomic details by using paired images versus 2D MRI alone (P < .001). Cognitive load, as assessed by the NASA Task Load Index, was increased with paired or SRR data in comparison with 2D MRI. CONCLUSION: The addition of SRR to 2D MRI does not increase fetal airway patency diagnostic accuracy but does provide improved anatomic information, which may benefit surgical planning of EXIT procedures.

Pressure passivity of cerebral mitochondrial metabolism is associated with poor outcome following perinatal hypoxic ischemic brain injury.

Hypoxic ischemic encephalopathy (HIE) leads to significant morbidity and mortality. Impaired autoregulation after hypoxia-ischaemia has been suggested to contribute further to injury. Thalamic lactate/N-Acetylasperate (Lac/NAA) peak area ratio of > 0.3 on proton (1H) magnetic resonance spectroscopy (MRS) is associated with poor neurodevelopment outcome following HIE. Cytochrome-c-oxidase (CCO) plays a central role in mitochondrial oxidative metabolism and ATP synthesis. Using a novel broadband NIRS system, we investigated the impact of pressure passivity of cerebral metabolism (CCO), oxygenation (haemoglobin difference (HbD)) and cerebral blood volume (total haemoglobin (HbT)) in 23 term infants following HIE during therapeutic hypothermia (HT). Sixty-minute epochs of data from each infant were studied using wavelet analysis at a mean age of 48 h. Wavelet semblance (a measure of phase difference) was calculated to compare reactivity between mean arterial blood pressure (MABP) with oxCCO, HbD and HbT. OxCCO-MABP semblance correlated with thalamic Lac/NAA ( r = 0.48, p = 0.02). OxCCO-MABP semblance also differed between groups of infants with mild to moderate and severe injury measured using brain MRI score ( p = 0.04), thalamic Lac/NAA ( p = 0.04) and neurodevelopmental outcome at one year ( p = 0.04). Pressure passive changes in cerebral metabolism were associated with injury severity indicated by thalamic Lac/NAA, MRI scores and neurodevelopmental assessment at one year of age.

Oxygen dependency of mitochondrial metabolism indicates outcome of newborn brain injury.

There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneous decreases in peripheral oxygen saturation (desaturations) were recorded between 6 and 81 h after birth. We observed differences in the cerebral metabolic responses to these episodes that were related to the predicted outcome of the injury, as determined by subsequent magnetic resonance spectroscopy derived lactate/N-acetyl-aspartate. We demonstrated that a strong relationship between cerebral metabolism (broadband NIRS-measured cytochrome-c-oxidase (CCO)) and cerebral oxygenation was associated with unfavourable outcome; this is likely to be due to a lower cerebral metabolic rate and mitochondrial dysfunction in severe encephalopathy. Specifically, a decrease in the brain tissue oxidation state of CCO greater than 0.06 µM per 1 µM brain haemoglobin oxygenation drop was able to predict the outcome with 64% sensitivity and 79% specificity (receiver operating characteristic area under the curve = 0.73). With further work on the implementation of this methodology, broadband NIRS has the potential to provide an early, cotside, non-invasive, clinically relevant metabolic marker of perinatal hypoxic-ischaemic injury.

Proton magnetic resonance spectroscopy lactate/N-acetylaspartate within 2 weeks of birth accurately predicts 2-year motor, cognitive and language outcomes in neonatal encephalopathy after therapeutic hypothermia.

OBJECTIVE: Brain proton (1H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) 1H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score. SUBJECTS AND METHODS: 55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d-42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and 1H MRS at 3T on day 2-14 (median day 5). MRIs were scored. Bayley III was assessed at 24 (22-26) months. RESULTS: 16 babies died (1 inborn, 15 outborn); 20, 19 and 21 babies had poor motor, cognitive and language outcomes. Using a threshold of 0.39, sensitivity and specificity of BGT Lac/NAA for 2-year motor outcome was 100% and 97%, cognition 90% and 97% and language 81% and 97%, respectively. Sensitivity and specificity for motor outcome of mean diffusivity (threshold 0.001 mm2/s) up to day 9 was 72% and 100% and fractional anisotropy (threshold 0.198) was 39% and 94%, respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3). CONCLUSION: BGT Lac/NAA on 1H MRS at 3T within 14 days accurately predicts 2-year motor, cognitive and language outcome and may be a marker directing decisions for therapies after cooling.

Cortical folding of the preterm brain: a longitudinal analysis of extremely preterm born neonates using spectral matching.

INTRODUCTION: Infants born extremely preterm (<28 weeks of gestation) are at risk of significant neurodevelopmental sequelae. In these infants birth coincides with a period of rapid brain growth and development, when the brain is also vulnerable to a range of insults. Mapping these changes is crucial for identifying potential biomarkers to predict early impairment. METHODS: In this study we use surface-based spectral matching techniques to find an intrasubject longitudinal surface correspondence between the white-grey matter boundary at 30 and 40 weeks equivalent gestational age in nine extremely preterm born infants. RESULTS: Using the resulting surface correspondence, we identified regions that undergo more cortical folding of the white-grey matter boundary during the preterm period by looking at changes in well-known curvature measures. We performed Hotelling T(2) statistics to evaluate the significance of our findings. DISCUSSION: The prefrontal and temporal lobes exhibit most development during the preterm period, especially in the left hemisphere. Such correspondences are a promising result as longitudinal measurements of change in cortical folding could provide insightful information about the mechanical properties of the underlying tissue and may be useful in inferring changes during growth and development in this vulnerable period.

Erratum: Cortical folding of the preterm brain: a longitudinal analysis of extremely preterm born neonates using spectral matching.

[This corrects the article DOI: 10.1002/brb3.488.].

Longitudinal measurement of the developing thalamus in the preterm brain using multi-modal MRI.

Preterm birth is a significant public health concern. For infants born very preterm (≤ 32 weeks completed gestation), there is a high instance of developmental disability. Due to the heterogeneity of patient outcomes, it is important to investigate early markers of future ability to provide effective and targeted intervention. As a neuronal relay centre, the thalamus is critical for effective cognitive function and, thus, development of white matter connections between the thalamus and cortex is vital. By non-invasively examining the state of the thalamus we can monitor development in the preterm period. To track the development we develop a novel registration technique to combine data from multiple modalities, in order to derive the transformation from a preterm scan, to a scan of the same infant at term-equivalent age. By measuring the changes in diffusion parameters over this period on a per-voxel basis, we hope to provide unique insight into neurodevelopment.