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Brainstem tissue microstructural properties change across the adult lifespan. However, studies elucidating the biological processes that govern brainstem maturation and degeneration in-vivo are lacking. In the present work, conducted on a large cohort of 140 cognitively unimpaired subjects spanning a wide age range of 21 to 94 years, we implemented a multi-parameter approach to characterize the sex- and age differences. In addition, we examined regional correlations between myelin water fraction (MWF), a direct measure of myelin content, and diffusion tensor imaging indices, and transverse and longitudinal relaxation rates to evaluate whether these metrics provide information complementary to MWF. We observed region-dependent differences in myelin content and axonal density with age and found that both exhibit an inverted U-shape association with age in several brainstem substructures. We emphasize that the microstructural differences captured by our distinct MRI metrics, along with their weak associations with MWF, strongly indicate the potential of using these outcome measures in a multi-parametric approach. Furthermore, our results support the gain-predicts-loss hypothesis of tissue maturation and degeneration in the brainstem. Indeed, our results indicate that myelination follows a temporally symmetric time course across the adult life span, while axons appear to degenerate significantly more rapidly than they mature.

Adequate cerebral blood flow (CBF) is essential to a healthy central nervous system (CNS). Previous work suggests that CBF differs between men and women, and declines with age and certain pathologies, but a highly controlled systematic study across a wide age range, and incorporating white matter (WM) regions, has not been undertaken. Here, we investigate age- and sex-related differences in CBF in gray matter (GM) and WM regions in a cohort (N = 80) of cognitively unimpaired individuals over a wide age range. In agreement with literature, we find that GM regions exhibited lower CBF with age. In contrast, WM regions exhibited higher CBF with age in various cerebral regions. We attribute this new finding to increased oligodendrocyte metabolism to maintain myelin homeostasis in the setting of increased myelin turnover with age. Further, consistent with prior studies, we found that CBF was higher in women than in men in all brain structures investigated. Our work provides new insights into the effects of age and sex on CBF. In addition, our results provide reference CBF values for the standard ASL protocol recommended by the ISMRM Perfusion Study Group and the European ASL in Dementia consortium. Thus, these results provide a foundation for further investigations of CNS perfusion in a variety of settings, including aging, cerebrovascular diseases, and dementias.

The relationship between regional brain myelination and aging has been the subject of intense study, with magnetic resonance imaging perhaps the most effective modality for elucidating this. However, most of these studies have used nonspecific methods to probe myelin content, including diffusion tensor imaging, magnetization transfer ratio, and relaxation times. In the present study, we used the BMC-mcDESPOT analysis, a direct and specific method for imaging of myelin water fraction (MWF), a surrogate of myelin content. We investigated age-related differences in MWF in several brain regions in a large cohort of cognitively unimpaired participants, spanning a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by decreases at older ages. We also observed that these age-related differences vary across different brain regions, as expected. Our results provide evidence for nonlinear associations between age and myelin in a large sample of well-characterized adults, using a direct myelin content imaging method.

Purpose To extend the null signal method (NSM) for B1 mapping to 3 T magnetic resonance imaging (MRI). Background The NSM operates in the steady state regime and exploits the linearity of the spoiled gradient recalled echo (SPGR) signal around the 180° flip angle (FA). Using linear regression, B1 maps are derived from three SPGR images acquired at different FAs with a short repetition time. While the conventional NSM allows accurate mapping of B1 for moderate B1 variation, we observed that this method fails for the larger B1 variations typical of high-field MRI. Methods We analyzed the effect of the FA range of the acquired SPGR images on B1 determination using the NSM for 3 T MRI through extensive numerical and in vivo analyses. B1 maps derived from the extended angle-range NSM (EA-NSM) were calculated and compared to those derived from the conventional, more restricted angle range, NSM, and to those derived from the reference, but much more time-consuming, double angle method (DAM). Furthermore, we investigated the compatibility of EA-NSM B1 mapping and the half-scan and SENSE reconstruction methods for accelerating acquisition time. Results Our results show that the use of the conventional FA range leads to substantial inaccuracies in B1 determination. Both numerical and in vivo analyses demonstrate that expanding the FA range of the acquired SPGR images substantially improves the accuracy of B1 maps. Furthermore, B1 maps derived from EA-NSM were demonstrated to be quantitatively comparable to those derived from the lengthy DAM protocol. We also found that B1 maps derived from SPGR images using the EA-NSM and imaging acceleration methods were comparable to those derived from images acquired without acceleration. Finally, the use of half scanning combined with SENSE reconstruction permits whole-brain B1 mapping in ~1 min. Conclusions The EA-NSM permits accurate, fast, and practical B1 mapping in a 3 T clinical setting.

BackgroundMyelin loss and cerebral blood flow (CBF) decline are central features of several neurodegenerative diseases. Myelin maintenance through oligodendrocyte metabolism is an energy-demanding process, so that myelin homeostasis is particularly sensitive to hypoxia, hypoperfusion or ischaemia. However, in spite of its central importance, little is known about the association between blood supply and myelin integrity.ObjectiveTo assess associations between cortical and subcortical CBF, and subcortical myelin content, in critical brain white matter regions.Materials and methodsMRI was performed on a cohort of 67 cognitively unimpaired adults. Using advanced MRI methodology, we measured whole-brain longitudinal and transverse relaxation rates (R1 and R2), sensitive but non-specific markers of myelin content, and myelin water fraction (MWF), a direct surrogate of myelin content, as well as regional CBF, from each of these participants.ResultsAll quantitative relaxometry metrics were positively associated with CBF in all brain regions evaluated. These associations between MWF or R1 and CBF, and, to a lesser extent, between R2 and CBF, were statistically significant in most brain regions examined, indicating that lower regional cortical or subcortical CBF corresponds to a decrease in local subcortical myelin content. Finally, all relaxometry metrics exhibited a quadratic, inverted U-shaped, association with age; this is attributed to the development of myelination from young to middle age, followed by progressive loss of myelin in later years.ConclusionsIn this first study examining the association between local blood supply and myelin integrity, we found that myelin content declines with CBF across a wide age range of cognitively normal subjects.

Changes in longitudinal relaxation time (T(1)) and proton density (PD) are sensitive indicators of microstructural alterations associated with various central nervous system diseases as well as brain maturation and aging. In this work, we introduce a new approach for rapid and accurate high-resolution (HR) or ultra HR (UHR) mapping of T(1) and apparent PD (APD) of the brain with correction of radiofrequency field, B(1), inhomogeneities. The four-angle method (FAM) uses four spoiled-gradient recalled-echo (SPGR) images acquired at different flip angles (FA) and short repetition times (TRs). The first two SPGR images are acquired at low-spatial resolution and used to accurately map the active B(1)(+) field with the recently introduced steady-state double angle method (SS-DAM). The estimated B(1)(+) map is used in conjunction with the two other SPGR images, acquired at HR or UHR, to map T(1) and APD. The method is evaluated with numerical, phantom, and in-vivo imaging measurements. Furthermore, we investigated imaging acceleration methods to further shorten the acquisition time. Our results indicate that FAM provides an accurate method for simultaneous HR or UHR mapping of T(1) and APD in human brain in clinical high-field MRI. Derived parameter maps without B(1)(+)correction suffer from large inaccuracies, but that this issue is well-corrected through use of the SS-DAM. Furthermore, the use of the SPGR imaging, with short TR and phased-array coil acquisition permits substantial imaging acceleration and enables robust HR or UHR T(1) and APD mapping in a clinically acceptable time frame with whole brain coverage obtained in less than 2 min or 5 min. The method exhibits high reproducibility and benefits from the use of the conventional SPGR sequence, available in all preclinical and clinical MRI machines, and very simple modelling addressing a critical outstanding issue in neuroimaging.

Background Cerebral blood flow (CBF) is an emerging biomarker for normal aging and neurodegenerative diseases. Arterial spin labeling (ASL) perfusion MRI permits noninvasive quantification of CBF. However, high-quality mapping of CBF from ASL imaging is challenging, largely due to noise. New method We demonstrate the ability of the recently introduced nonlocal estimation of multispectral magnitudes (NESMA) filter to greatly improve determination of CBF estimates from ASL imaging data. We evaluated the results of NESMA-ASL for CBF mapping from data obtained on human brain ( n = 10) across a wide age range (21–74 years) using a standard clinical protocol. Results were compared to those obtained from unfiltered images or filtered images using conventional and advanced filters. Quantitative analyses for different spatial image resolutions and signal-to-noise ratios, SNRs, were also conducted. Results Our results demonstrate the potential of NESMA-ASL to permit high-quality high-resolution CBF mapping. NESMA-ASL substantially reduces random variation in derived CBF estimates while preserving edges and small structures, with minimal bias and dispersion in derived CBF estimates. Comparison with existing methods NESMA-ASL outperforms all evaluated filters in terms of noise reduction and detail preservation. Further, unlike other filters, NESMA-ASL is straightforward to implement requiring only one user-defined parameter, which is relatively insensitive to SNR or local image structure. Conclusions In-vivo estimation of CBF in the human brain from ASL imaging data was markedly improved through use of the NESMA-ASL filter. The use of NESMA-ASL may contribute significantly to the goal of high-quality high-resolution CBF mapping within a clinically feasible acquisition time.