Putative MRI markers of iron in deep gray matter have demonstrated age related changes during discrete periods of healthy childhood or adulthood, but few studies have included subjects across the lifespan. This study reports both transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) of four primary deep gray matter regions (thalamus, putamen, caudate, and globus pallidus) in 498 healthy individuals aged 5–90 years. In the caudate, putamen, and globus pallidus, increases of QSM and R2* were steepest during childhood continuing gradually throughout adulthood, except caudate susceptibility which reached a plateau in the late 30s. The thalamus had a unique profile with steeper changes of R2* (reflecting additive effects of myelin and iron) than QSM during childhood, both reaching a plateau in the mid‐30s to early 40s and decreasing thereafter. There were no hemispheric or sex differences for any region. Notably, both R2* and QSM values showed more inter‐subject variability with increasing age from 5 to 90 years, potentially reflecting a common starting point in iron/myelination during childhood that diverges as a result of lifestyle and genetic factors that accumulate with age.

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Purpose: Quantitative susceptibility mapping (QSM) has been employed for both iron evaluation and segmentation of deep gray matter (DGM), but QSM sequences are not typically used in standard brain volumetric studies, which use T1-weighted magnetization-prepared rapid acquisition with gradient echo (MPRAGE) with short TE. Here, QSM produced directly from standard MPRAGE phase (QSM MPRAGE ) is evaluated for segmentation and quantification of highly iron-rich DGM regions. Methods: Simulations were used to explore quality and possible limitations. In addition, QSM from a standard multi-echo gradient-echo (QSM GRE ) was compared to QSM MPRAGE in 40 healthy adults at 3T. DGM structures with weak contrast on MPRAGE magnitude were evaluated for improving segmentation with QSM MPRAGE , with focus on the iron-rich globus pallidus (GP). Furthermore, susceptibility quantification was assessed on six DGM nuclei and compared to standard QSM GRE . Results: Limited by TE and signal-to-noise ratio, only iron-rich regions like GP and dentate nucleus produced adequate contrast on QSM MPRAGE , confining applications to such regions. QSM MPRAGE improved GP segmentation with mean Dice scores raised by 9.0%, and mean volumetric differences reduced by 9.7%. Simulations suggested that phase contrast-to-noise ratio (CNR) should be above 3.0 to attain segmentation improvement. For quantification purposes, higher CNR is required, and typical QSM MPRAGE provided comparable estimates to QSM GRE in large iron-rich DGM nuclei. Conclusion: Despite the short TE of standard MPRAGE, QSM MPRAGE can improve GP segmentation over the use of MPRAGE magnitude alone and roughly quantify high-iron regions in DGM. Thus, reconstructing QSM MPRAGE can be a useful addition to volumetric studies that rarely include standard QSM GRE . K E Y W O R D Sdeep gray matter, globus pallidus, MPRAGE, QSM, segmentation | 1487 NAJI et Al.

Iron concentration in the human brain plays a crucial role in several neurodegenerative diseases and can be monitored noninvasively using quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping from multiecho T2*‐weighted images. Large population studies enable better understanding of pathologies and can benefit from pooling multisite data. However, reproducibility may be compromised between sites and studies using different hardware and sequence protocols. This work investigates QSM and R2* reproducibility at 3 T using locally optimized sequences from three centers and two vendors, and investigates possible reduction of cross‐site variability through postprocessing approaches. Twenty‐four healthy subjects traveled between three sites and were scanned twice at each site. Scan‐rescan measurements from seven deep gray matter regions were used for assessing within‐site and cross‐site reproducibility using intraclass correlation coefficient (ICC) and within‐subject standard deviation (SDw) measures. In addition, multiple QSM and R2* postprocessing options were investigated with the aim to minimize cross‐site sequence‐related variations, including: mask generation approach, echo‐timing selection, harmonizing spatial resolution, field map estimation, susceptibility inversion method, and linear field correction for magnitude images. The same‐subject cross‐site region of interest measurements for QSM and R2* were highly correlated (R2 ≥ 0.94) and reproducible (mean ICC of 0.89 and 0.82 for QSM and R2*, respectively). The mean cross‐site SDw was 4.16 parts per billion (ppb) for QSM and 1.27 s−1 for R2*. For within‐site measurements of QSM and R2*, the mean ICC was 0.97 and 0.87 and mean SDw was 2.36 ppb and 0.97 s−1, respectively. The precision level is regionally dependent and is reduced in the frontal lobe, near brain edges, and in white matter regions. Cross‐site QSM variability (mean SDw) was reduced up to 46% through postprocessing approaches, such as masking out less reliable regions, matching available echo timings and spatial resolution, avoiding the use of the nonconsistent magnitude contrast between scans in field estimation, and minimizing streaking artifacts.

PurposeSusceptibility maps reconstructed from thin slabs may suffer underestimation due to background‐field removal imperfections near slab boundaries and the increased difficulty of solving a 3D‐inversion problem with reduced support, particularly in the direction of the main magnetic field. Reliable QSM reconstruction from thin slabs would enable focal acquisitions in a much‐reduced scan time.MethodsThis work proposes using additional rapid low‐resolution data of extended spatial coverage to improve background‐field estimation and regularize the inversion‐to‐susceptibility process for high resolution, thin slab data. The new method was tested using simulated and in‐vivo brain data of high resolution (0.33 × 0.33 × 0.33 mm3 and 0.54 × 0.54 × 0.65 mm3, respectively) at 3T, and compared to the standard large volume approach.ResultsUsing the proposed method, in‐vivo high‐resolution QSM at 3T was obtained from slabs of width as small as 10.4 mm, aided by a lower‐resolution dataset of 24 times coarser voxels. Simulations showed that the proposed method produced more consistent measurements from slabs of at least eight slices. Reducing the mean ROI error to 5% required the low‐resolution data to cover ˜60 mm in the direction of the main field, have at least 2‐mm isotropic resolution that is not coarser than the high‐resolution data by more than four‐fold in any direction.ConclusionApplying the proposed method enabled focal QSM acquisitions at sub‐millimeter resolution within reasonable acquisition time.