Locus coeruleus integrity is related to an exploitation-based decision-making bias in older adulthood.

Optimal decision-making balances exploration for new information against exploitation of known rewards, a process mediated by the locus coeruleus and its norepinephrine projections. We predicted that an exploitation-bias that emerges in older adulthood would be associated with lower microstructural integrity of the locus coeruleus. Leveraging in vivo histological methods from quantitative MRI-magnetic transfer saturation-we provide evidence that older age is associated with lower locus coeruleus integrity. Critically, we demonstrate that an exploitation bias in older adulthood, assessed with a foraging task, is sensitive and specific to lower locus coeruleus integrity. Because the locus coeruleus is uniquely vulnerable to Alzheimer's disease pathology, our findings suggest that aging, and a presymptomatic trajectory of Alzheimer's related decline, may fundamentally alter decision-making abilities in later life.

Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.

Decreased long-range temporal correlations in the resting-state functional magnetic resonance imaging blood-oxygen-level-dependent signal reflect motor sequence learning up to 2 weeks following training.

Decreased long-range temporal correlations (LRTC) in brain signals can be used to measure cognitive effort during task execution. Here, we examined how learning a motor sequence affects long-range temporal memory within resting-state functional magnetic resonance imaging signal. Using the Hurst exponent (HE), we estimated voxel-wise LRTC and assessed changes over 5 consecutive days of training, followed by a retention scan 12 days later. The experimental group learned a complex visuomotor sequence while a complementary control group performed tightly matched movements. An interaction analysis revealed that HE decreases were specific to the complex sequence and occurred in well-known motor sequence learning associated regions including left supplementary motor area, left premotor cortex, left M1, left pars opercularis, bilateral thalamus, and right striatum. Five regions exhibited moderate to strong negative correlations with overall behavioral performance improvements. Following learning, HE values returned to pretraining levels in some regions, whereas in others, they remained decreased even 2 weeks after training. Our study presents new evidence of HE's possible relevance for functional plasticity during the resting-state and suggests that a cortical subset of sequence-specific regions may continue to represent a functional signature of learning reflected in decreased long-range temporal dependence after a period of inactivity.

Fast magnetization transfer saturation imaging of the brain using MP2RAGE T1 mapping.

PURPOSE: Magnetization transfer saturation (MTsat) mapping is commonly used to examine the macromolecular content of brain tissue. This study compared variable flip angle (VFA) T1 mapping against compressed-sensing MP2RAGE (csMP2RAGE) T1 mapping for accelerating MTsat imaging. METHODS: VFA, MP2RAGE, and csMP2RAGE were compared against inversion-recovery T1 in an aqueous phantom at 3 T. The same 1-mm VFA, MP2RAGE, and csMP2RAGE protocols were acquired in 4 healthy subjects to compare T1 and MTsat. Bloch-McConnell simulations were used to investigate differences between the phantom and in vivo T1 results. Ten healthy controls were imaged twice with the csMP2RAGE MTsat protocol to quantify repeatability. RESULTS: The MP2RAGE and csMP2RAGE protocols were 13.7% and 32.4% faster than the VFA protocol, respectively. At these scan times, all approaches provided strong repeatability and accurate T1 times (< 5% difference) in the phantom, but T1 accuracy was more impacted by T2 for VFA than for MP2RAGE. In vivo, VFA estimated longer T1 times than MP2RAGE and csMP2RAGE. Simulations suggest that the differences in the T1 measured using VFA, MP2RAGE, and inversion recovery could be explained by the magnetization-transfer effects. In the test-retest experiment, we found that the csMP2RAGE has a minimum detectable change of 2.3% for T1 mapping and 7.8% for MTsat imaging. CONCLUSIONS: We demonstrated that MP2RAGE can be used in place of VFA T1 mapping in an MTsat protocol. Furthermore, a shorter scan time and high repeatability can be achieved using the csMP2RAGE sequence.

Loss of age-related laminar differentiation of intracortical myelin in bipolar disorder.

Age-related changes of intracortical myelin in bipolar disorder (BD) have been observed to deviate from the quadratic age curve observed in healthy controls (HC), but it is unclear if this holds at varying cortical depths. From BD (n = 44; age range = 17.6-45.5 years) and HC (n = 60; age range = 17.1-45.8 years) participants, we collected 3T T1-weighted (T1w) images with strong intracortical contrast. Signal values were sampled from 3 equivolume cortical depths. Linear mixed models were used to compare age-related changes in the T1w signal between depths and between groups at each depth. In HC, the age-related changes were significantly different between the superficial one-fourth depth and the deeper depths in the right ventral somatosensory (t = -4.63; FDRp = 0.00025), left dorsomedial somatosensory (t = -3.16; FDRp = 0.028), left rostral ventral premotor (t = -3.16; FDRp = 0.028), and right ventral inferior parietal cortex (t = -3.29; FDRp = 0.028). BD participants exhibited no differences in the age-related T1w signal between depths. Illness duration was negatively correlated with the T1w signal at the one-fourth depth in the right anterior cingulate cortex (rACC; rho = -0.50; FDRp = 0.029). Physiological age-related and depth-specific variation in the T1w signal were not observed in BD. The T1w signal in the rACC may reflect lifetime disease burden in the disorder.

The possible influence of third-order shim coils on gradient-magnet interactions: an inter-field and inter-site study.

OBJECTIVE: To assess the possible influence of third-order shim coils on the behavior of the gradient field and in gradient-magnet interactions at 7 T and above. MATERIALS AND METHODS: Gradient impulse response function measurements were performed at 5 sites spanning field strengths from 7 to 11.7 T, all of them sharing the same exact whole-body gradient coil design. Mechanical fixation and boundary conditions of the gradient coil were altered in several ways at one site to study the impact of mechanical coupling with the magnet on the field perturbations. Vibrations, power deposition in the He bath, and field dynamics were characterized at 11.7 T with the third-order shim coils connected and disconnected inside the Faraday cage. RESULTS: For the same whole-body gradient coil design, all measurements differed greatly based on the third-order shim coil configuration (connected or not). Vibrations and gradient transfer function peaks could be affected by a factor of 2 or more, depending on the resonances. Disconnecting the third-order shim coils at 11.7 T also suppressed almost completely power deposition peaks at some frequencies. DISCUSSION: Third-order shim coil configurations can have major impact in gradient-magnet interactions with consequences on potential hardware damage, magnet heating, and image quality going beyond EPI acquisitions.

High-resolution diffusion-weighted imaging at 7 Tesla: Single-shot readout trajectories and their impact on signal-to-noise ratio, spatial resolution and accuracy.

Diffusion MRI (dMRI) is a valuable imaging technique to study the connectivity and microstructure of the brain in vivo. However, the resolution of dMRI is limited by the low signal-to-noise ratio (SNR) of this technique. Various multi-shot acquisition strategies have been developed to achieve sub-millimeter resolution, but they require long scan times which can be restricting for patient scans. Alternatively, the SNR of single-shot acquisitions can be increased by using a spiral readout trajectory to minimize the sequence echo time. Imaging at ultra-high fields (UHF) could further increase the SNR of single-shot dMRI; however, the shorter T2* of brain tissue and the greater field non-uniformities at UHFs will degrade image quality, causing image blurring, distortions, and signal loss. In this study, we investigated the trade-off between the SNR and resolution of different k-space trajectories, including echo planar imaging (EPI), partial Fourier EPI, and spiral trajectories, over a range of dMRI resolutions at 7T. The effective resolution, spatial specificity and sharpening effect were measured from the point spread function (PSF) of the simulated diffusion sequences for a nominal resolution range of 0.6-1.8 mm. In-vivo partial brain scans at a nominal resolution of 1.5 mm isotropic were acquired using the three readout trajectories to validate the simulation results. Field probes were used to measure dynamic magnetic fields offline up to the 3rd order of spherical harmonics. Image reconstruction was performed using static ΔB0 field maps and the measured trajectories to correct image distortions and artifacts, leaving T2* effects as the primary source of blurring. The effective resolution was examined in fractional anisotropy (FA) maps calculated from a multi-shell dataset with b-values of 300, 1000, and 2000 s/mm2 in 5, 16, and 48 directions, respectively. In-vivo scans at nominal resolutions of 1, 1.2, and 1.5 mm were acquired and the SNR of the different trajectories calculated using the multiple replica method to investigate the SNR. Finally, in-vivo whole brain scans with an effective resolution of 1.5 mm isotropic were acquired to explore the SNR and efficiency of different trajectories at a matching effective resolution. FA and intra-cellular volume fraction (ICVF) maps calculated using neurite orientation dispersion and density imaging (NODDI) were used for the comparison. The simulations and in vivo imaging results showed that for matching nominal resolutions, EPI trajectories had the highest specificity and effective resolution with maximum image sharpening effect. However, spirals have a significantly higher SNR, in particular at higher resolutions and even when the effective image resolutions are matched. Overall, this work shows that the higher SNR of single-shot spiral trajectories at 7T allows us to achieve higher effective resolutions compared to EPI and PF-EPI to map the microstructure and connectivity of small brain structures.

Characterization of an automated method to segment the human locus coeruleus.

Following the development of magnetic resonance imaging (MRI) methods to assay the integrity of catecholamine nuclei, including the locus coeruleus (LC), there has been an effort to develop automated methods that can accurately segment this small structure in an automated manner to promote its widespread use and overcome limitations of manual segmentation. Here we characterize an automated LC segmentation approach (referred to as the funnel-tip [FT] method) in healthy individuals and individuals with LC degeneration in the context of Alzheimer's disease (AD, confirmed with tau-PET imaging using [18F]MK6240). The first sample included n = 190 individuals across the AD spectrum from cognitively normal to moderate AD. LC signal assayed with FT segmentation showed excellent agreement with manual segmentation (intraclass correlation coefficient [ICC] = 0.91). Compared to other methods, the FT method showed numerically higher correlation to AD status (defined by presence of tau: Cohen's d = 0.64) and AD severity (Braak stage: Pearson R = -.35, cognitive function: R = .25). In a separate sample of n = 12 control participants, the FT method showed excellent scan-rescan reliability (ICC = 0.82). In another sample of n = 30 control participants, we found that the structure of the LC defined by FT segmentation approximated its expected shape as a contiguous line: <5% of LC voxels strayed >1 voxel (0.69 mm) from this line. The FT LC segmentation shows high agreement with manual segmentation and captures LC degeneration in AD. This practical method may facilitate larger research studies of the human LC-norepinephrine system and has potential to support future use of neuromelanin-sensitive MRI as a clinical biomarker.

Modeling venous bias in resting state functional MRI metrics.

Resting-state (rs) functional magnetic resonance imaging (fMRI) is used to detect low-frequency fluctuations in the blood oxygen-level dependent (BOLD) signal across brain regions. Correlations between temporal BOLD signal fluctuations are commonly used to infer functional connectivity. However, because BOLD is based on the dilution of deoxyhemoglobin, it is sensitive to veins of all sizes, and its amplitude is biased by draining veins. These biases affect local BOLD signal location and amplitude, and may also influence BOLD-derived connectivity measures, but the magnitude of this venous bias and its relation to vein size and proximity is unknown. Here, veins were identified using high-resolution quantitative susceptibility maps and utilized in a biophysical model to investigate systematic venous biases on common local rsfMRI-derived measures. Specifically, we studied the impact of vein diameter and distance to veins on the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), Hurst exponent (HE), regional homogeneity (ReHo), and eigenvector centrality values in the grey matter. Values were higher across all distances in smaller veins, and decreased with increasing vein diameter. Additionally, rsfMRI values associated with larger veins decrease with increasing distance from the veins. ALFF and ReHo were the most biased by veins, while HE and fALFF exhibited the smallest bias. Across all metrics, the amplitude of the bias was limited in voxel-wise data, confirming that venous structure is not the dominant source of contrast in these rsfMRI metrics. Finally, the models presented can be used to correct this venous bias in rsfMRI metrics.

High spatial overlap but diverging age-related trajectories of cortical magnetic resonance imaging markers aiming to represent intracortical myelin and microstructure.

Statistical effects of cortical metrics derived from standard T1- and T2-weighted magnetic resonance imaging (MRI) images, such as gray-white matter contrast (GWC), boundary sharpness coefficient (BSC), T1-weighted/T2-weighted ratio (T1w/T2w), and cortical thickness (CT), are often interpreted as representing or being influenced by intracortical myelin content with little empirical evidence to justify these interpretations. We first examined spatial correspondence with more biologically specific microstructural measures, and second compared between-marker age-related trends with the underlying hypothesis that different measures primarily driven by similar changes in myelo- and microstructural underpinnings should be highly related. Cortical MRI markers were derived from MRI images of 127 healthy subjects, aged 18-81, using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Their gross spatial distributions were compared with gene expression-derived cell-type densities, histology-derived cytoarchitecture, and quantitative R1 maps acquired on a subset of participants. We then compared between-marker age-related trends in their shape, direction, and spatial distribution of the linear age effect. The gross anatomical distributions of cortical MRI markers were, in general, more related to myelin and glial cells than neuronal indicators. Comparing MRI markers, our results revealed generally high overlap in spatial distribution (i.e., group means), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers can be different from microstructural changes that affect these markers in aging.

Optimization of acquisition parameters for cortical inhomogeneous magnetization transfer (ihMT) imaging using a rapid gradient echo readout.

PURPOSE: Imaging biomarkers with increased myelin specificity are needed to better understand the complex progression of neurological disorders. Inhomogeneous magnetization transfer (ihMT) imaging is an emergent technique that has a high degree of specificity for myelin content but suffers from low signal to-noise ratio (SNR). This study used simulations to determine optimal sequence parameters for ihMT imaging for use in high-resolution cortical mapping. METHODS: MT-weighted cortical image intensity and ihMT SNR were simulated using modified Bloch equations for a range of sequence parameters. The acquisition time was limited to 4.5 min/volume. A custom MT-weighted RAGE sequence with center-out k-space encoding was used to enhance SNR at 3 T. Pulsed MT imaging was studied over a range of saturation parameters, and the impact of the turbo factor on the effective ihMT resolution was investigated. 1 mm isotropic ihMTsat maps were generated in 25 healthy adults. RESULTS: Greater SNR was observed for larger number of bursts consisting of 6-8 saturation pulses each, combined with a high readout turbo factor. However, that protocol suffered from a point spread function that was more than twice the nominal resolution. For high-resolution cortical imaging, we selected a protocol with a higher effective resolution at the cost of a lower SNR. We present the first group-average ihMTsat whole-brain map at 1 mm isotropic resolution. CONCLUSION: This study presents the impact of saturation and excitation parameters on ihMTsat SNR and resolution. We demonstrate the feasibility of high-resolution cortical myelin imaging using ihMTsat in less than 20 min.

Normative Values of Neuromelanin-Sensitive MRI Signal in Older Adults Obtained Using a Turbo Spin Echo Sequence.

BACKGROUND: The integrity and function of catecholamine neurotransmitter systems can be assessed using neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker. PURPOSE: To support future application of NM-MRI as a clinical biomarker by defining the normative range of NM-MRI signal and volume metrics in cognitively normal older adults. STUDY TYPE: Prospective. POPULATION: A total of 152 cognitively normal older adults aged 53-86 years old, including 41 participants who had follow-up NM-MRI data collected 9-16 months later. FIELD STRENGTH/SEQUENCE: A 3.0 T; NM-MRI turbo spin echo and T1-weighted magnetization-prepared rapid acquisition with gradient echo sequences. ASSESSMENT: NM-MRI images were processed to yield summary measures of volume and signal (contrast-to-noise ratio, CNR) for the substantia nigra (SN) and locus coeruleus (LC) using a recently developed software employing a fully automated algorithm. Change in these metrics over time was also assessed. STATISTICAL TESTS: Mean and standard deviation of NM-MRI metrics were calculated; change over time was tested for significance using 1-sample t-tests. P values < 0.05 were considered statistically significant. RESULTS: At baseline SN signal (CNR) was 10.02% (left) and 10.28% (right) and LC signal was 24.71% (left) and 20.42% (right). Baseline SN volume was 576 mm3 (left) and 540 mm3 (right) and LC volume was 6.31 mm3 (left) and 6.30 mm3 (right). The only NM-MRI metric showing significant change was a decrease in left SN volume (t40  = -2.57, P = 0.014). DATA CONCLUSION: We report normative values for NM-MRI signal and volume in the SN and LC of cognitively normal older adults and explore their change over time. These values may help future efforts to use NM-MRI as a clinical biomarker by facilitating identification of patients with extreme NM-MRI values. TECHNICAL EFFICACY STAGE: 1.

Micapipe: A pipeline for multimodal neuroimaging and connectome analysis.

Multimodal magnetic resonance imaging (MRI) has accelerated human neuroscience by fostering the analysis of brain microstructure, geometry, function, and connectivity across multiple scales and in living brains. The richness and complexity of multimodal neuroimaging, however, demands processing methods to integrate information across modalities and to consolidate findings across different spatial scales. Here, we present micapipe, an open processing pipeline for multimodal MRI datasets. Based on BIDS-conform input data, micapipe can generate i) structural connectomes derived from diffusion tractography, ii) functional connectomes derived from resting-state signal correlations, iii) geodesic distance matrices that quantify cortico-cortical proximity, and iv) microstructural profile covariance matrices that assess inter-regional similarity in cortical myelin proxies. The above matrices can be automatically generated across established 18 cortical parcellations (100-1000 parcels), in addition to subcortical and cerebellar parcellations, allowing researchers to replicate findings easily across different spatial scales. Results are represented on three different surface spaces (native, conte69, fsaverage5), and outputs are BIDS-conform. Processed outputs can be quality controlled at the individual and group level. micapipe was tested on several datasets and is available at https://github.com/MICA-MNI/micapipe, documented at https://micapipe.readthedocs.io/, and containerized as a BIDS App http://bids-apps.neuroimaging.io/apps/. We hope that micapipe will foster robust and integrative studies of human brain microstructure, morphology, function, cand connectivity.

The impact of the Siemens Tim Trio to Prisma upgrade and the addition of volumetric navigators on cortical thickness, structure volume, and 1H-MRS indices: An MRI reliability study with implications for longitudinal study designs.

Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices ("Prisma Upgrade protocol") and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence ("vNav protocol"). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT and amygdala, globus pallidus, hippocampus, and striatum volumes, were observed. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement.

Hippocampal subfield volumes across the healthy lifespan and the effects of MR sequence on estimates.

The hippocampus has been extensively studied in various neuropsychiatric disorders throughout the lifespan. However, inconsistent results have been reported with respect to which subfield volumes are most related to age. Here, we investigate whether these discrepancies may be explained by experimental design differences that exist between studies. Multiple datasets were used to collect 1690 magnetic resonance scans from healthy individuals aged 18-95 years old. Standard T1-weighted (T1w; MPRAGE sequence, 1 mm3 voxels), high-resolution T2-weighted (T2w; SPACE sequence, 0.64 mm3 voxels) and slab T2-weighted (Slab; 2D turbo spin echo, 0.4 × 0.4 × 2 mm3 voxels) images were included. The MAGeT Brain algorithm was used for segmentation of the hippocampal grey matter (GM) subfields and peri-hippocampal white matter (WM) subregions. Linear mixed-effect models and Akaike information criterion were used to examine linear, second or third order natural splines relationship between hippocampal volumes and age. We demonstrated that stratum radiatum/lacunosum/moleculare and fornix subregions expressed the highest relative volumetric decrease, while the cornus ammonis 1 presented a relative volumetric preservation of its volume with age. We also found that volumes extracted from slab images demonstrated different age-related relationships compared to volumes extracted from T1w and T2w images. The current work suggests that although T1w, T2w and slab derived subfield volumetric outputs are largely homologous, modality choice plays a meaningful role in the volumetric estimation of the hippocampal subfields.

Efficient whole-brain tract-specific T1 mapping at 3T with slice-shuffled inversion-recovery diffusion-weighted imaging.

PURPOSE: Most voxels in white matter contain multiple fiber populations with different orientations and levels of myelination. Conventional T1 mapping measures 1 T1 value per voxel, representing a weighted average of the multiple tract T1 times. Inversion-recovery diffusion-weighted imaging (IR-DWI) allows the T1 times of multiple tracts in a voxel to be disentangled, but the scan time is prohibitively long. Recently, slice-shuffled IR-DWI implementations have been proposed to significantly reduce scan time. In this work, we demonstrate that we can measure tract-specific T1 values in the whole brain using simultaneous multi-slice slice-shuffled IR-DWI at 3T. METHODS: We perform simulations to evaluate the accuracy and precision of our crossing fiber IR-DWI signal model for various fiber parameters. The proposed sequence and signal model are tested in a phantom consisting of crossing asparagus pieces doped with gadolinium to vary T1 , and in 2 human subjects. RESULTS: Our simulations show that tract-specific T1 times can be estimated within 5% of the nominal fiber T1 values. Tract-specific T1 values were resolved in subvoxel 2 fiber crossings in the asparagus phantom. Tract-specific T1 times were resolved in 2 different tract crossings in the human brain where myelination differences have previously been reported; the crossing of the cingulum and genu of the corpus callosum and the crossing of the corticospinal tract and pontine fibers. CONCLUSION: Whole-brain tract-specific T1 mapping is feasible using slice-shuffled IR-DWI at 3T. This technique has the potential to improve the microstructural characterization of specific tracts implicated in neurodevelopment, aging, and demyelinating disorders.

A model-based framework for correcting B1+ inhomogeneity effects in magnetization transfer saturation and inhomogeneous magnetization transfer saturation maps.

PURPOSE: In this work, we propose that Δ B1+ -induced errors in magnetization transfer (MT) saturation (MTsat ) maps can be corrected with use of an R1 and B1+ map and through numerical simulations of the sequence. THEORY AND METHODS: One healthy subject was scanned at 3.0T using a partial quantitative MT protocol to estimate the relationship between observed R1 (R1,obs ) and apparent bound pool size ( M0,appB ) in the brain. MTsat values were simulated for a range of B1+ , R1,obs , and M0,appB . An equation was fit to the simulated MTsat , then a linear relationship between R1,obs and M0,appB was generated. These results were used to generate correction factor maps for the MTsat acquired from single-point data. The proposed correction was compared to an empirical correction factor with different MT-preparation schemes. RESULTS: M0,appB was highly correlated with R1,obs (r > 0.96), permitting the use of R1,obs to estimate M0,appB for B1+ correction. All B1+ corrected MTsat maps displayed a decreased correlation with B1+ compared to uncorrected MTsat and MTsat corrected with an empirical factor in the corpus callosum. There was good agreement between the proposed approach and the empirical correction with radiofrequency saturation at 2 kHz, with larger deviations seen when using saturation pulses further off-resonance and in inhomogeneous (ih) MTsat maps. CONCLUSION: The proposed correction decreases the dependence of MTsat on B1+ inhomogeneities. Furthermore, this flexible framework permits the use of different saturation protocols, making it useful for correcting B1+ inhomogeneities in ihMT.

Investigating microstructural variation in the human hippocampus using non-negative matrix factorization.

In this work we use non-negative matrix factorization to identify patterns of microstructural variance in the human hippocampus. We utilize high-resolution structural and diffusion magnetic resonance imaging data from the Human Connectome Project to query hippocampus microstructure on a multivariate, voxelwise basis. Application of non-negative matrix factorization identifies spatial components (clusters of voxels sharing similar covariance patterns), as well as subject weightings (individual variance across hippocampus microstructure). By assessing the stability of spatial components as well as the accuracy of factorization, we identified 4 distinct microstructural components. Furthermore, we quantified the benefit of using multiple microstructural metrics by demonstrating that using three microstructural metrics (T1-weighted/T2-weighted signal, mean diffusivity and fractional anisotropy) produced more stable spatial components than when assessing metrics individually. Finally, we related individual subject weightings to demographic and behavioural measures using a partial least squares analysis. Through this approach we identified interpretable relationships between hippocampus microstructure and demographic and behavioural measures. Taken together, our work suggests non-negative matrix factorization as a spatially specific analytical approach for neuroimaging studies and advocates for the use of multiple metrics for data-driven component analyses.

Altered hippocampal centrality and dynamic anatomical covariance of intracortical microstructure in first episode psychosis.

Hippocampal circuitry has been posited to be fundamental to positive symptoms in psychosis, but its contributions to other factors important for outcome remains unclear. We hypothesized that longitudinal changes in the hippocampal circuit and concomitant changes of intracortical microstructure are altered in first episode psychosis (FEP) patients and that such changes are associated with negative symptoms and verbal memory. Longitudinal brain scans (2-4 visits over 3-15 months) were acquired for 27 FEP and 29 age- and sex-matched healthy controls. Quantitative T1 maps, sensitive to myelin content, were used to sample the microstructure of the hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies), and intracortical regions. Dynamic anatomical covariance in pair-wise regional trajectories were assessed for each subject, and graph theory was used to calculate a participation coefficient metric that quantifies the similarity/divergence between hippocampal and intracortical microstructure. The mean participation coefficient of the hippocampus was significantly reduced in FEP patients compared with controls, reflecting differences in output hippocampal regions. Importantly, lower participation coefficient of the hippocampal circuit was associated with worse negative symptoms, a relationship that was mediated by changes in verbal memory. This study provides evidence for reduced hippocampal centrality in FEP and concomitant changes in intracortical anatomy. Myelin-rich output regions of the hippocampus may be an important biological trigger in early psychosis, with cascading effects on broader cortical networks and resultant clinical profiles.

MR-based age-related effects on the striatum, globus pallidus, and thalamus in healthy individuals across the adult lifespan.

While numerous studies have used magnetic resonance imaging (MRI) to elucidate normative age-related trajectories in subcortical structures across the human lifespan, there exists substantial heterogeneity among different studies. Here, we investigated the normative relationships between age and morphology (i.e., volume and shape), and microstructure (using the T1-weighted/T2-weighted [T1w/T2w] signal ratio as a putative index of myelin and microstructure) of the striatum, globus pallidus, and thalamus across the adult lifespan using a dataset carefully quality controlled, yielding a final sample of 178 for the morphological analyses, and 162 for the T1w/T2w analyses from an initial dataset of 253 healthy subjects, aged 18-83. In accordance with previous cross-sectional studies of adults, we observed age-related volume decrease that followed a quadratic relationship between age and bilateral striatal and thalamic volumes, and a linear relationship in the globus pallidus. Our shape indices consistently demonstrated age-related posterior and medial areal contraction bilaterally across all three structures. Beyond morphology, we observed a quadratic inverted U-shaped relationship between T1w/T2w signal ratio and age, with a peak value occurring in middle age (at around 50 years old). After permutation testing, the Akaike information criterion determined age relationships remained significant for the bilateral globus pallidus and thalamus, for both the volumetric and T1w/T2w analyses. Our findings serve to strengthen and expand upon previous volumetric analyses by providing a normative baseline of morphology and microstructure of these structures to which future studies investigating patients with various disorders can be compared.