Real-time motion and main magnetic field correction in MR spectroscopy using an EPI volumetric navigator

In population groups where subjects do not lie still during Magnetic Resonance Spectroscopy (MRS) scans, real-time volume of interest (VOI), frequency, and main magnetic field (B0) shim correction may be necessary. This work demonstrates firstly that head movement causes significant B0 disruption in both single voxel spectroscopy and spectroscopic imaging

Real-time motion and magnetic field correction for GABA editing using EPI volumetric navigated MEGA-SPECIAL sequence: Reproducibility and Gender effects

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter and is of great interest to the magnetic resonance spectroscopy (MRS) community due to its role in several neurological diseases and disorders. Since GABA acquisition without macromolecule contamination requires long scan times and strongly depends on magnetic field (B0) stability, it is highly susceptible to motion and B0 inhomogeneity. In this work, a pair of three-dimensional (3D) echo planar imaging (EPI) volumetric navigators (vNav) with different echo times, were inserted in MEGA-SPECIAL to perform prospective correction for changes in the subject's head position and orientation, as well as changes in B0. The navigators do not increase acquisition time and have negligible effect on the GABA signal. The motion estimates are obtained by registering the first of the pairs of successive vNav volume images to the first volume image. The 3D field maps are calculated through complex division of the pair of vNav contrasts and are used for estimating zero- and first-order shim changes in the volume of interest (VOI). The efficacy of the vNav MEGA-SPECIAL sequence was demonstrated in-vitro and in vivo. Without motion and shim correction, spectral distortions and increases in spectral fitting error, linewidth and GABA concentration relative to creatine were observed in the presence of motion. The navigated sequence yielded high spectral quality despite significant subject motion. Using the volumetric navigated MEGA-SPECIAL sequence, the reproducibility of GABA measurements over a 40 minute period was investigated in two regions, the anterior cingulate (ACC) and medial parietal (PAR) cortices, and compared for different analysis packages, namely LCModel, jMRUI and GANNET. LCModel analysis yielded the most reproducible results, followed by jMRUI and GANNET. GABA levels in ACC were unchanged over time, while GABA levels in PAR were significantly lower for the second measurement. In ACC, GABA levels did not differ between males and females. In contrast, males had higher GABA levels in PAR. This gender difference was, however, only present in the first acquisition. Only in males did GABA levels in PAR decrease over time. These results demonstrate that gender differences are regional, and that GABA levels may fluctuate differently in different regions and sexes

Neurobiology, not artifacts: Challenges and guidelines for imaging the high risk infant

The search for the brain-basis of atypical development in human infants is challenging because the process of imaging and the generation of the MR signal itself relies on assumptions that reflect biophysical properties of the brain tissue. These assumptions are not inviolate, have been questioned by recent empirical evidence from high risk infant-sibling studies, and to date remain largely underexamined at the between-group level. In particular, I consider recent work showing that infants at High vs. Low familial risk (HR vs. LR, respectively) for developing Autism Spectrum Disorders (ASD) have atypical patterns of head movements during an MR scan that are functionally important—they are linked to future learning trajectories in toddlerhood. Addressing head movement issues in neuroimaging analyses in infant research as well as understanding the causes of these movements from a developmental perspective requires acknowledging the complexity of this endeavor. For example, head movement signatures in infants can interact with experimental task conditions (such as listening to language compared to sleeping), autism risk, and age. How can new knowledge about newborns' individual, subject-specific behavioral differences which may impact MR signal acquisition and statistical inference ignite critical thinking for the field of infant brain imaging across the spectrum of typical and atypical development? Early behavioral differences between HR and LR infant cohorts that are often examples of “artifactual” confounds in MR work provide insight into nascent neurobiological differences, including biophysical tissue properties and hemodynamic response variability, in these and related populations at risk for atypical development. Are these neurobiological drivers of atypical development? This work identifies important knowledge gaps and suggests guidelines at the leading edge of baby imaging science to transform our understanding of atypical brain development in humans. The precise study of the neurobiological underpinnings of atypical development in humans calls for approaches including quantitative MRI (qMRI) pulse sequences, multi-modal imaging (including DTI, MRS, as well as MEG), and infant-specific HRF shapes when modeling BOLD signal

Investigation of Neonatal Pulmonary Structure and Function via Proton and Hyperpolarized Gas Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a modality that utilizes the phenomenon of nuclear magnetic resonance (NMR) to yield tomographic images of the body. Proton (1H) MRI has historically been successful in soft tissues but has suffered in the lung due to a variety of technical challenges, such as the low proton-density, rapid T2* relaxation time of the lung parenchymal tissue, and inherent physiological motion in the chest. Recent developments in radial ultrashort echo time (UTE) MRI have in part overcome these issues. In addition, there has been much progress in techniques for hyperpolarization of noble gases (3He and 129Xe) out of thermal equilibrium via spin exchange optical pumping, which can greatly enhance the gas NMR signal such that it is detectable within the airspaces of the lung on MRI. The lung is a unique organ due to its complex structural and functional dynamics, and its early development through the neonatal (newborn) period is not yet well understood in normal or abnormal conditions. Pulmonary morbidities are relatively common in infants and are present in a majority of patients admitted to the neonatal intensive care unit, often stemming from preterm birth and/or congenital defects. Current clinical lung imaging in these patients is typically limited to chest x-ray radiography, which does not provide tomographic information and so has lowered sensitivity. More rarely, x-ray computed tomography (CT) is used but exposes infants to ionizing radiation and typically requires sedation, both of which pose increased risks to pediatric patients. Thus the opportunity is ripe for application of novel pulmonary MRI techniques to the infant population. However, MR imaging of very small pulmonary structure and microstructure requires fundamental changes in the imaging theory of both 1H UTE MRI and hyperpolarized gas diffusion MRI. Furthermore, such young patients are often non-compliant, yielding a need for new and innovative techniques for monitoring respiratory and bulk motion. This dissertation describes methodology development and provides experimental results in both 1H UTE MRI and hyperpolarized 3He and 129Xe gas diffusion MRI, with investigation into the structure and function of infant lungs at both the macrostructural and microstructural level. In particular, anisotropically restricted gas diffusion within infant alveolar microstructure is investigated as a measurement of airspace size and geometry. Additionally, the phenomenon of respiratory and bulk motion-tracking via modulation of the k-space center\u27s magnitude and phase is explored and applied via UTE MRI in various neonatal pulmonary conditions to extract imaging-based metrics of diagnostic value. Further, the proton-density regime of pulmonary UTE MRI is validated in translational applications. These techniques are applied in infants with various pulmonary conditions, including patients diagnosed with bronchopulmonary dysplasia, congenital diaphragmatic hernia, esophageal atresia/tracheoesophageal fistula, tracheomalacia, and no suspected lung disease. In addition, explanted lung specimens from both infants with and without lung disease are examined. Development and implementation of these techniques involves a strong understanding of the physics-based theory of NMR, hyperpolarization, and MR imaging, in addition to foundations in hardware, software, and image analysis techniques. This thesis first outlines the theory and background of NMR, MRI, and pulmonary physiology and development (Part I), then proceeds into the theory, equipment, and imaging experiments for hyperpolarized gas diffusion MRI in infant lung airspaces (Part II), and finally details the theory, data processing methods, and applications of pulmonary UTE MRI in infant patients (Part III). The potential for clinical translation of the neonatal pulmonary MRI methods presented in this dissertation is very high, with the foundations of these techniques firmly rooted in the laws of physics

Studying neuroanatomy using MRI

The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging, and disease. Developments in MRI acquisition, image processing, and data modelling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro- and mesoscopic structure and inferring microstructural properties; we also describe key artefacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, though methods need to improve and caution is required in its interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works

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: (i) sensitivity and specificity of basal ganglia and thalamus (BGT) 1H MRS Lac/NAA for prediction of Bayley III outcomes at 2-years using optimized metabolite fitting (Tarquin) with threonine and total NAA; (ii) prediction of motor outcome with diffusion-weighted MRI; iii) BGT Lac/NAA correlation with the NICHD MRI score. MATERIALS AND METHODS: 55 (16 inborn, 39 outborn) NE infants at 39w+5d (35w+5d-42w+0d) admitted between February 2012 and August 2014 to UCH 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: Sixteen 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 (MD; threshold 0.001 mm2 /s) up to day 9 was 72% and 39% and fractional anisotropy (FA; threshold 0.198) was 100%, and 94% respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3). CONCLUSIONS: 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

MR Imaging of the Preterm Brain: safer better faster stronger

__Abstract__ Human brain development and maturation consist of complex processes that span from the first trimester of pregnancy to adult life. These processes include: 1) neuronal proliferation, characterized by generation of neurons in the dorsal subventricular zone and ventral germinative epithelium of the ganglionic eminence; 2) migration, where neurons move from these zones to specific sites where they will reside for life; 3) organization, in which neurons differentiate to subplate neurons, align, orientate and connect through their axons and dendrites. Glial cells differentiate into astrocytes, oligodendrocytes and microglia, and 4) myelination, where oligodendrocytes produce myelin that will be deposited around axons. Preterm infants are born in this critical period, in which the brain is particularly vulnerable to exogenous and endogenous events. Perinatal hypoxia-ischemia, hyperoxia, infection and hypocarbia can result in fluctuations in cerebral blood flow, inflammation, increased excitotoxicity and oxidative stress, all of which can affect normal brain ontogenesis and cause irreversible injury. In general, the two most commonly recognized variants of preterm brain injury are: periventricular white matter (WM) injury and hemorrhage in the germinal matrix and lateral ventricle. These injury patterns will be discussed separately in the following sections

Characterisation of Longitudinal Brain Morphology, Neurometabolism and Prenatal to Neonatal Brain Growth in Patients with Congenital Heart Disease

Congenital heart disease (CHD) affect 8 in 1000 newborns (Liu et al. 2019). The consequences of CHD vary greatly, depending on the specific type of CHD. While advancements in surgical techniques and patient care have led to a high survival rate for severe types of CHD, patients are still at risk of impaired neurodevelopment (ND). Early ND impairment can manifest in various domains, including motor, cognitive or language development (Latal 2016). As a result, one area of CHD research is dedicated to studying the brain development of these patients. This thesis focuses on the longitudinal description of brain development during the late fetal and neonatal period. First, we explored whether deformation-based morphometry (DBM) could be a suitable tool to study CHD patients from fetal to neonatal time period by applying this method to a healthy control cohort. Next, we analysed longitudinally collected data from two studies, primarily focusing on quantifying brain development and searching for associations with ND outcomes in CHD patients. In the first study we explored how DBM could be applied to fetal and neonatal MRI data to observe asymmetry changes during this period. By using DBM, we were able to reveal temporal changes of asymmetry patterns. However, the results may greatly depend on the various combinations of analysis tools and their parameters used. In the second study, where we compared brain development in CHD patients to healthy controls, we therefore relied on volume and surface measurements to quantify growth. Here, we could show that the total brain volume growth trajectory for CHD patients was reduced compared to healthy controls. Finally, we investigated neurometabolite ratios in CHD patients and their association to ND outcome. While we found that a specific neurometabolite ratio (NAA/Cho; N-acetylaspartate to choline-containing compounds) was reduced in the CHD cohort compared to healthy controls, we could not find any association with ND outcome measured at one year of age. In conclusion, the work presented in this thesis uses various methods to study brain development in a longitudinal manner. The findings provide further evidence that brain 4 development in CHD patients is altered while its association with ND outcome requires further investigation

CHARACTERIZATION OF BRAIN TISSUE MICROSTRUCTURES WITH DIFFUSION MRI

Diffusion MRI is a useful medical imaging tool for noninvasive mapping of the neuroanatomy and brain connectivity. In this dissertation, we worked on developing diffusion MRI techniques to probe brain tissue microstructures from various perspectives. Spatial resolution of the diffusion MRI is the key to obtain accurate microstructural information. In Chapter 2 and 3, we focused on developing high-resolution in vivo diffusion MRI techniques, such as 3D fast imaging sequence and a localized imaging approach using selective excitation RF pulses. We demonstrated the power of the superior resolution in delineating complex microstructures in the live mouse brain. With the high resolution diffusion MRI data, we were able to map the intra-hippocampal connectivity in the mouse brain, which showed remarkable similarity with tracer studies (Chapter 4). Using the localized fast imaging technique, we were the first to achieve in utero diffusion MRI of embryonic mouse brain, which revealed the microstructures in the developing brains and the changes after inflammatory injury (Chapter 5). The second half of the dissertation explores the restricted water diffusion at varying diffusion times and microstructure scales, using the oscillating gradient spin-echo (OGSE) diffusion MRI. We showed in the live normal mouse brains that unique tissue contrasts can be obtained at different oscillating frequency. We demonstrated in a neonatal mouse model of hypoxia-ischemia, that in the edema brain tissues, diffusion MRI signal changed much faster with oscillating frequency compared to the normal tissue, indicating significant changes in cell size associated with cytotoxic edema (Chapter 6). In the mild injury mice, OGSE showed exquisite sensitivity in detecting subtle injury in the hippocampus, which may relate to microstructural changes in smaller scales, such as the subcellular organelles (Chapter 7). Finally, we addressed the technical issues of OGSE diffusion MRI, and proposed a new hybrid OGSE sequence with orthogonally placed pulsed and oscillating gradients to suppress the perfusion related pseudo-diffusion (Chapter 8). In conclusion, we developed in vivo high-resolution diffusion techniques, and time-dependent diffusion measurements to characterize brain tissue microstructures in the normal and diseased mouse brains. The knowledge gained from this dissertation study may advance our understanding on microstructural basis of diffusion MRI