Optimized T1- and T2-weighted volumetric brain imaging as a diagnostic tool in very preterm neonates.

BACKGROUND: T1- and T2-W MR sequences used for obtaining diagnostic information and morphometric measurements in the neonatal brain are frequently acquired using different imaging protocols. Optimizing one protocol for obtaining both kinds of information is valuable. OBJECTIVE: To determine whether high-resolution T1- and T2-W volumetric sequences optimized for preterm brain imaging could provide both diagnostic and morphometric value. MATERIALS AND METHODS: Thirty preterm neonates born between 24 and 32 weeks' gestational age were scanned during the first 2 weeks after birth. T1- and T2-W high-resolution sequences were optimized in terms of signal-to-noise ratio, contrast-to-noise ratio and scan time and compared to conventional spin-echo-based sequences. RESULTS: No differences were found between conventional and high-resolution T1-W sequences for diagnostic confidence, image quality and motion artifacts. A preference for conventional over high-resolution T2-W sequences for image quality was observed. High-resolution T1 images provided better delineation of thalamic myelination and the superior temporal sulcus. No differences were found for detection of myelination and sulcation using conventional and high-resolution T2-W images. CONCLUSION: High-resolution T1- and T2-W volumetric sequences can be used in clinical MRI in the very preterm brain to provide both diagnostic and morphometric information

T2 Mapping from Super-Resolution-Reconstructed Clinical Fast Spin Echo Magnetic Resonance Acquisitions

Relaxometry studies in preterm and at-term newborns have provided insight into brain microstructure, thus opening new avenues for studying normal brain development and supporting diagnosis in equivocal neurological situations. However, such quantitative techniques require long acquisition times and therefore cannot be straightforwardly translated to in utero brain developmental studies. In clinical fetal brain magnetic resonance imaging routine, 2D low-resolution T2-weighted fast spin echo sequences are used to minimize the effects of unpredictable fetal motion during acquisition. As super-resolution techniques make it possible to reconstruct a 3D high-resolution volume of the fetal brain from clinical low-resolution images, their combination with quantitative acquisition schemes could provide fast and accurate T2 measurements. In this context, the present work demonstrates the feasibility of using super-resolution reconstruction from conventional T2-weighted fast spin echo sequences for 3D isotropic T2 mapping. A quantitative magnetic resonance phantom was imaged using a clinical T2-weighted fast spin echo sequence at variable echo time to allow for super-resolution reconstruction at every echo time and subsequent T2 mapping of samples whose relaxometric properties are close to those of fetal brain tissue. We demonstrate that this approach is highly repeatable, accurate and robust when using six echo times (total acquisition time under 9 minutes) as compared to gold-standard single-echo spin echo sequences (several hours for one single 2D slice)

Neuroepigenetics of preterm white matter injury

Introduction: Preterm birth is increasing worldwide and is a major cause of neonatal death. Survivors are at increased risk of neurodisability, cognitive, social and psychiatric disorders in later life. Alterations to the white matter can be assessed using diffusion tensor imaging (DTI) MRI and are associated with poor neurodevelopmental outcome. The pathogenesis of white matter injury is multifactorial and several clinical risk and resilience factors have been identified. DNA methylation (DNAm) is an epigenetic process which links stressful early life experience to later life disease and is associated with normal brain development, neuronal processes and neurological disease. Several studies have shown DNAm is altered by the perinatal environment, however its role in preterm white mater injury is yet to be investigated. Aims: 1. To examine the relationship between preterm birth and white matter integrity 2. To investigate the effect of neuroprotective treatments and deleterious clinical states on white matter integrity in preterm infants 3. To assess the best DTI method of quantifying white matter integrity in a neonatal population 4. To investigate the effect of preterm birth on DNA methylation and 5. To determine the clinical and imaging factors that contribute to the variance in DNA Methylation caused by preterm birth Methods: DTI data was acquired from preterm infants (< 32 weeks’ gestation or < 1500 grams at birth) at term equivalent age (TEA) and term controls (> 37 weeks’ gestation at birth). Region-of-interests (ROI) and tract-averaged methods of DTI analysis were performed to obtain measurements of fractional anisotropy (FA) and mean diffusivity (MD) in the genu of corpus callosum, posterior limb of internal capsule and centrum semiovale. Clinical data was collected for all infants and the effect of prematurity, neuroprotective agents and clinical risk factors on white matter integrity were analysed. 8 major white matter tracts were segmented using probabilistic neighbourhood tractography (PNT), a tract-averaged technique which also allowed the calculation of tract shape. The two DTI techniques were compared to evaluate agreement between results. DNA was collected from preterm infants and term controls at TEA, and a genome-wide analysis of DNAm was performed. DTI parameters from probabilistic neighborhood tractography (PNT) methodology and clinical risk and resilience factors were used to inform a principal components analysis to investigate the contribution of white matter integrity and clinical variables to variance in DNAm. Results: FA and MD were significantly affected by preterm birth on ROI analysis. In addition, DTI parameters were affected by clinical factors that included antenatal magnesium sulphate, histological chorioamnionitis and bronchopulmonary dysplasia. Evaluation of DTI methodology revealed good accuracy in repeated ROI measurements but limited agreement with tract-averaged values. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants, compared with controls. 10 of these genes have a documented association with neural function or neurological disease. Differences detected in the array were validated with pyrosequencing which captured additional differentially methylated CpGs. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 principal components (PC); corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Conclusions: Preterm birth is associated with alterations in white matter integrity which is modifiable by clinical risk factors and neuroprotective agents. ROI analysis may not provide sufficient representation of white matter tracts in their entirety. Prematurity is related to alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for future work and contributed to the understanding of the pathogenesis of preterm brain injury

From micro‐ to macro‐structures in multiple sclerosis: what is the added value of diffusion imaging

Diffusion imaging has been instrumental in understanding damage to the central nervous system as a result of its sensitivity to microstructural changes. Clinical applications of diffusion imaging have grown exponentially over the past couple of decades in many neurological and neurodegenerative diseases, such as multiple sclerosis (MS). For several reasons, MS has been extensively researched using advanced neuroimaging techniques, which makes it an ‘example disease’ to illustrate the potential of diffusion imaging for clinical applications. In addition, MS pathology is characterized by several key processes competing with each other, such as inflammation, demyelination, remyelination, gliosis and axonal loss, enabling the specificity of diffusion to be challenged. In this review, we describe how diffusion imaging can be exploited to investigate micro‐, meso‐ and macro‐scale properties of the brain structure and discuss how they are affected by different pathological substrates. Conclusions from the literature are that larger studies are needed to confirm the exciting results from initial investigations before current trends in diffusion imaging can be translated to the neurology clinic. Also, for a comprehensive understanding of pathological processes, it is essential to take a multiple‐level approach, in which information at the micro‐, meso‐ and macroscopic scales is fully integrated