Longitudinal assessment of early-life white matter development with quantitative relaxometry in nonhuman primates.

Alterations in white matter (WM) development are associated with many neuropsychiatric and neurodevelopmental disorders. Most MRI studies examining WM development employ diffusion tensor imaging (DTI), which relies on estimating diffusion patterns of water molecules as a reflection of WM microstructure. Quantitative relaxometry, an alternative method for characterizing WM microstructural changes, is based on molecular interactions associated with the magnetic relaxation of protons. In a longitudinal study of 34 infant non-human primates (NHP) (Macaca mulatta) across the first year of life, we implement a novel, high-resolution, T1-weighted MPnRAGE sequence to examine WM trajectories of the longitudinal relaxation rate (qR1) in relation to DTI metrics and gestational age at scan. To the best of our knowledge, this is the first study to assess developmental WM trajectories in NHPs using quantitative relaxometry and the first to directly compare DTI and relaxometry metrics during infancy. We demonstrate that qR1 exhibits robust logarithmic growth, unfolding in a posterior-anterior and medial-lateral fashion, similar to DTI metrics. On a within-subject level, DTI metrics and qR1 are highly correlated, but are largely unrelated on a between-subject level. Unlike DTI metrics, gestational age at birth (time in utero) is a strong predictor of early postnatal qR1 levels. Whereas individual differences in DTI metrics are maintained across the first year of life, this is not the case for qR1. These results point to the similarities and differences in using quantitative relaxometry and DTI in developmental studies, providing a basis for future studies to characterize the unique processes that these measures reflect at the cellular and molecular level.

Using quantitative MRI to study brain responses to immune challenge with interferon-α.

Inflammatory processes in the Central Nervous System (CNS) have been proposed to mediate the association between peripheral inflammation and the development of psychiatric disorders, but we currently lack sensitive measures of CNS inflammation for human studies in vivo. Here we used quantitative MRI (qMRI) to explore the in vivo central response to a peripheral immune challenge in healthy humans, and we assessed whether changes in quantitative relaxometry MRI parameters were associated with changes in peripheral inflammation. Quantitative relaxation times (T1 & T2) and Proton Density (PD) were measured in n â€‹= â€‹6 healthy males (mean age â€‹= â€‹30.5 â€‹± â€‹6.8 years) in two MRI assessments collected before and 24 â€‹hours after a subcutaneous injection of the proinflammatory cytokine and immune activator, interferon-alpha (IFN-α). Serum levels of immune markers and markers of blood-brain barrier integrity (S100B) were also measured before and after the injection. Region of interest and histogram-based analyses (optimized for the small sample size) showed a statistically significant increase of both T1 (t(5) â€‹= â€‹3.78, p â€‹= 0.013) and PD (t(5) â€‹= â€‹2.91, p â€‹= â€‹0.033) parameters in the bilateral hippocampus after IFN-α administration. T1 peak values in bilateral hippocampus were positively correlated with serum Tumour Necrosis Factor-alpha levels at 24 â€‹h after the injection, when this cytokine peaked (Spearman's rho â€‹= â€‹0.67, p â€‹= â€‹0.018) and negatively correlated with S100B levels (Spearman's rho â€‹= â€‹-0.826, p â€‹= â€‹0.001). Our data suggest that peripheral administration of IFN-α produces acute changes in brain qMRI which might indicate a brain immune response. This is supported by the association of such changes with low-grade peripheral inflammation.

Quantitative rotating frame relaxometry methods in MRI.

Macromolecular degeneration and biochemical changes in tissue can be quantified using rotating frame relaxometry in MRI. It has been shown in several studies that the rotating frame longitudinal relaxation rate constant (R1ρ ) and the rotating frame transverse relaxation rate constant (R2ρ ) are sensitive biomarkers of phenomena at the cellular level. In this comprehensive review, existing MRI methods for probing the biophysical mechanisms that affect the rotating frame relaxation rates of the tissue (i.e. R1ρ and R2ρ ) are presented. Long acquisition times and high radiofrequency (RF) energy deposition into tissue during the process of spin-locking in rotating frame relaxometry are the major barriers to the establishment of these relaxation contrasts at high magnetic fields. Therefore, clinical applications of R1ρ and R2ρ MRI using on- or off-resonance RF excitation methods remain challenging. Accordingly, this review describes the theoretical and experimental approaches to the design of hard RF pulse cluster- and adiabatic RF pulse-based excitation schemes for accurate and precise measurements of R1ρ and R2ρ . The merits and drawbacks of different MRI acquisition strategies for quantitative relaxation rate measurement in the rotating frame regime are reviewed. In addition, this review summarizes current clinical applications of rotating frame MRI sequences. Copyright © 2016 John Wiley & Sons, Ltd.

Individual feature maps: a patient-specific analysis tool with applications in temporal lobe epilepsy.

PURPOSE: MRI-based diagnosis of temporal lobe epilepsy (TLE) can be challenging when pathology is not visually evident due to low image contrast or small lesion size. Computer-assisted analyses are able to detect lesions common in a specific patient population, but most techniques do not address clinically relevant individual pathologies resulting from the heterogeneous etiology of the disease. We propose a novel method to supplement the radiological inspection of TLE patients (n = 15) providing patient-specific quantitative assessment. METHOD: Regions of interest are defined across the brain and volume, relaxometry, and diffusion features are extracted from them. Statistical comparisons between individual patients and a healthy control group (n = 17) are performed on these features, identifying and visualizing significant differences through individual feature maps. Four maps are created per patient showing differences in intensity, asymmetry, and volume. RESULTS: Detailed reports were generated per patient. Abnormal hippocampal intensity and volume differences were detected in all patients diagnosed with mesial temporal sclerosis (MTS). Abnormal intensities in the temporal cortex were identified in patients with no MTS. A laterality score correctly distinguished left from right TLE in 12 out of 15 patients. CONCLUSION: The proposed focus on subject-specific quantitative changes has the potential of improving the assessment of TLE patients using MRI techniques, possibly even redefining current imaging protocols for TLE.

Quantitative relaxometry and diffusion MRI for lateralization in MTS and non-MTS temporal lobe epilepsy.

We developed novel methodology for investigating the use of quantitative relaxometry (T1 and T2) and diffusion tensor imaging (DTI) for lateralization in temporal lobe epilepsy. Patients with mesial temporal sclerosis confirmed by pathology (N=8) and non-MTS unilateral temporal lobe epilepsy (N=6) were compared against healthy controls (N=19) using voxel-based analysis restricted to the anterior temporal lobes, and laterality indices for each MRI metric (T1, T2, fractional anisotropy (FA), mean diffusivity, axial and radial diffusivities) were computed based on the proportion of significant voxels on each side. The diffusivity metrics were the most lateralizing MRI metrics in MTS and non-MTS subsets, with significant differences also seen with FA, T1 and T2. Patient-specific multi-modal laterality indices were also computed and were shown to clearly separate the left-onset and right-onset patients. Marked differences between left-onset and right-onset patients were also observed, with left-onset patients exhibiting stronger laterality indices. Finally, neocortical abnormalities were found to be more common in the non-MTS patients. These preliminary results on a small sample size support the further investigation of quantitative MRI and multi-modal image analysis in clinical determination of seizure onset. The presence of more neocortical abnormalities in the non-MTS group suggests a role in seizure onset or propagation and motivates the investigation of more sensitive histopathological analysis to detect and delineate potentially subtle neocortical pathology.