Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer's disease pathology and neurodegeneration along the Alzheimer's disease continuum.

Introduction: White matter (WM) degeneration is a critical component of early Alzheimer's disease (AD) pathophysiology. Diffusion-weighted imaging (DWI) models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator MRI (MAP-MRI), have the potential to identify early neurodegenerative WM changes associated with AD. Methods: We imaged 213 (198 cognitively unimpaired) aging adults with DWI and used tract-based spatial statistics to compare 15 DWI metrics of WM microstructure to 9 cerebrospinal fluid (CSF) markers of AD pathology and neurodegeneration treated as continuous variables. Results: We found widespread WM injury in AD, as indexed by robust associations between DWI metrics and CSF biomarkers. MAP-MRI had more spatially diffuse relationships with Aß42/40 and pTau, compared with NODDI and DTI. Discussion: Our results suggest that WM degeneration may be more pervasive in AD than is commonly appreciated and that innovative DWI models such as MAP-MRI may provide clinically viable biomarkers of AD-related neurodegeneration in the earliest stages of AD progression.

Motion-corrected 4D-Flow MRI for neurovascular applications.

Neurovascular 4D-Flow MRI has emerged as a powerful tool for comprehensive cerebrovascular hemodynamic characterization. Clinical studies in at risk populations such as aging adults indicate hemodynamic markers can be confounded by motion-induced bias. This study develops and characterizes a high fidelity 3D self-navigation approach for retrospective rigid motion correction of neurovascular 4D-Flow data. A 3D radial trajectory with pseudorandom ordering was combined with a multi-resolution low rank regularization approach to enable high spatiotemporal resolution self-navigators from extremely undersampled data. Phantom and volunteer experiments were performed at 3.0T to evaluate the ability to correct for different amounts of induced motions. In addition, the approach was applied to clinical-research exams from ongoing aging studies to characterize performance in the clinical setting. Simulations, phantom and volunteer experiments with motion correction produced images with increased vessel conspicuity, reduced image blurring, and decreased variability in quantitative measures. Clinical exams revealed significant changes in hemodynamic parameters including blood flow rates, flow pulsatility index, and lumen areas after motion correction in probed cerebral arteries (Flow: P<0.001 Lt ICA, P=0.002 Rt ICA, P=0.004 Lt MCA, P=0.004 Rt MCA; Area: P<0.001 Lt ICA, P<0.001 Rt ICA, P=0.004 Lt MCA, P=0.004 Rt MCA; flow pulsatility index: P=0.042 Rt ICA, P=0.002 Lt MCA). Motion induced bias can lead to significant overestimation of hemodynamic markers in cerebral arteries. The proposed method reduces measurement bias from rigid motion in neurovascular 4D-Flow MRI in challenging populations such as aging adults.

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.

Spatiotemporal dynamics of nonhuman primate white matter development during the first year of life.

White matter (WM) development early in life is a critical component of brain development that facilitates the coordinated function of neuronal pathways. Additionally, alterations in WM have been implicated in various neurodevelopmental disorders, including psychiatric disorders. Because of the need to understand WM development in the weeks immediately following birth, we characterized changes in WM microstructure throughout the postnatal macaque brain during the first year of life. This is a period in primates during which genetic, developmental, and environmental factors may have long-lasting impacts on WM microstructure. Studies in nonhuman primates (NHPs) are particularly valuable as a model for understanding human brain development because of their evolutionary relatedness to humans. Here, 34 rhesus monkeys (23 females, 11 males) were imaged longitudinally at 3, 7, 13, 25, and 53 weeks of age with T1-weighted (MPnRAGE) and diffusion tensor imaging (DTI). With linear mixed-effects (LME) modeling, we demonstrated robust logarithmic growth in FA, MD, and RD trajectories extracted from 18 WM tracts across the brain. Estimated rate of change curves for FA, MD, and RD exhibited an initial 10-week period of exceedingly rapid WM development, followed by a precipitous decline in growth rates. K-means clustering of raw DTI trajectories and rank ordering of LME model parameters revealed distinct posterior-to-anterior and medial-to-lateral gradients in WM maturation. Finally, we found that individual differences in WM microstructure assessed at 3 weeks of age were significantly related to those at 1 year of age. This study provides a quantitative characterization of very early WM growth in NHPs and lays the foundation for future work focused on the impact of alterations in early WM developmental trajectories in relation to human psychopathology.

Volumetric late gadolinium-enhanced myocardial imaging with retrospective inversion time selection.

PURPOSE: To develop and validate a novel free-breathing 3D radial late gadolinium-enhanced magnetic resonance imaging technique (3D LGE-MRI) with isotropic resolution and retrospective inversion time (TI) selection for myocardial viability imaging. MATERIALS AND METHODS: The 3D radial LGE-MRI method featuring an interleaved and bit-reversed radial k-space trajectory was evaluated in 12 subjects that also had clinical breath-hold Cartesian 2D LGE-MRI. The 3D LGE-MRI acquisition requires a predicted TI and a user-controlled data acquisition window that determines the sampling width around the predicted TI. Sliding window reconstructions with update rates of 1× the repetition time (TR) allow for a user selectable TI to obtain the maximum nulling of the myocardium. The retrospective nature of the acquisition allows the user to choose from a range of possible TI times centered on the expected TI. Those projections most corrupted by respiratory motion, as determined by a respiratory bellows signal, were resampled according to the diminishing variance algorithm. The quality of the left ventricular myocardial nulling on the 3D LGE-MRI and 2D LGE-MRI was assessed using a 4-point Likert scale by two experienced radiologists. Comparison of image quality scores for the two methods was performed using generalized estimating equations. RESULTS: All 3D LGE-MRI cases produced similar nulling of myocardial signal as the 2D LGE-MRI. The image quality of myocardial nulling was not significantly different between the two acquisitions (mean nulling of 3.4 for 2D vs. 3.1 for 3D, and P = 0.0645). The average absolute deviation from mean scores was also not determined to be statistically significant (1.8 for 2D and 0.4 for 3D and P = 0.1673). Total acquisition time was ∼9 minutes for 3D LGE-MRI with voxel sizes ranging from 1.6(3) to 2.0(3) mm(3) . Conversely, the total imaging time was twice as long for the 2D DCE-MRI (>17 minutes) with an eight times larger voxel size of 1.4 × 2.2 × 7.0 mm. CONCLUSION: The 3D LGE-MRI technique demonstrated in this study is a promising alternative for the assessment of myocardial viability in patients who have difficulty sustaining breath-holds for the clinical standard 2D LGE-MRI.

Improved waveform fidelity using local HYPR reconstruction (HYPR LR).

The recently introduced HYPR (HighlY constrained backPRojection) method allows reconstruction of serial images from highly undersampled data. In HYPR, individual timeframes are obtained via unfiltered backprojections of normalized sinograms using anatomical constraints provided by a composite image. Here we develop the idea of constraining the backprojected data further to a series of local regions of interest in order to decrease the corruption of local information by distant signals. HYPR LR (local reconstruction) permits the use of a longer temporal window in the formation of the composite image, resulting in increased signal-to-noise ratio and quantitative reconstruction accuracy. Unlike HYPR, the new HYPR LR method can be applied to images acquired with arbitrary k-space trajectories. It is suitable for a broad range of medical imaging applications involving serial changes in image sequence, offering exciting new opportunities in the future.