Morphological similarity of amygdala-ventral prefrontal pathways represents trait anxiety in younger and older adults.

Stronger amygdala-ventral prefrontal white matter connectivity has been associated with lower trait anxiety, possibly reflecting an increased capacity for efficient communication between the two regions. However, there are also reports arguing against this brain-anxiety association. To address these inconsistencies in the literature, we tested the possibility that idiosyncratic tract morphology may account for meaningful individual differences in trait anxiety, even among those with comparable microstructural integrity. Here, we adopted intersubject representational similarity analysis, an analytic framework that captures multivariate patterns of similarity, to analyze the morphological similarity of amygdala-ventral prefrontal pathways. Data drawn from the Leipzig Study for Mind-Body-Emotion Interactions dataset showed that younger adults (20 to 35 y of age) with low trait anxiety, in contrast to trait-anxious individuals, had consistently similar morphological configurations in their left amygdala-ventral prefrontal pathways. Additional tests on an independent sample of older adults (60 to 75 y of age) validated this finding. Our study reveals a generalizable pattern of brain-anxiety association that is embedded within the shared geometries between fiber tract morphology and trait anxiety data.

Diminished Repetition Suppression Reveals Selective and Systems-Level Face Processing Differences in ASD.

Repeated exposure to a stimulus results in reduced neural response, or repetition suppression, in brain regions responsible for processing that stimulus. This rapid accommodation to repetition is thought to underlie learning, stimulus selectivity, and strengthening of perceptual expectations. Importantly, reduced sensitivity to repetition has been identified in several neurodevelopmental, learning, and psychiatric disorders, including autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by challenges in social communication and repetitive behaviors and restricted interests. Reduced ability to exploit or learn from repetition in ASD is hypothesized to contribute to sensory hypersensitivities, and parallels several theoretical frameworks claiming that ASD individuals show difficulty using regularities in the environment to facilitate behavior. Using fMRI in autistic and neurotypical human adults (females and males), we assessed the status of repetition suppression across two modalities (vision, audition) and with four stimulus categories (faces, objects, printed words, and spoken words). ASD individuals showed domain-specific reductions in repetition suppression for face stimuli only, but not for objects, printed words, or spoken words. Reduced repetition suppression for faces was associated with greater challenges in social communication in ASD. We also found altered functional connectivity between atypically adapting cortical regions and higher-order face recognition regions, and microstructural differences in related white matter tracts in ASD. These results suggest that fundamental neural mechanisms and system-wide circuits are selectively altered for face processing in ASD and enhance our understanding of how disruptions in the formation of stable face representations may relate to higher-order social communication processes.SIGNIFICANCE STATEMENT A common finding in neuroscience is that repetition results in plasticity in stimulus-specific processing regions, reflecting selectivity and adaptation (repetition suppression [RS]). RS is reduced in several neurodevelopmental and psychiatric conditions including autism spectrum disorder (ASD). Theoretical frameworks of ASD posit that reduced adaptation may contribute to associated challenges in social communication and sensory processing. However, the scope of RS differences in ASD is unknown. We examined RS for multiple categories across visual and auditory domains (faces, objects, printed words, spoken words) in autistic and neurotypical individuals. We found reduced RS in ASD for face stimuli only and altered functional connectivity and white matter microstructure between cortical face-recognition areas. RS magnitude correlated with social communication challenges among autistic individuals.

Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial.

AIMS/HYPOTHESIS: The apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV). METHODS: This was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [ΔADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI. RESULTS: Both semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20×10-3 mm2/s [95% CI -0.30, -0.10], p<0.001; empagliflozin: -0.15×10-3 mm2/s [95% CI -0.26, -0.04], p=0.01). No significant change was observed in the combination-therapy group (-0.05×10-3 mm2/s [95%CI -0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed ΔADC significantly from placebo, showing a decrease of -0.13×10-3 mm2/s (95% CI -0.22, -0.04; p=0.01). Compared with placebo, TKV decreased by -3% (95% CI -5%, -0.3%; p=0.04), -3% (95% CI -5%, -0.4%; p=0.02) and -5% (95% CI -8%, -2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA1c. CONCLUSIONS/INTERPRETATION: In a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38.

Microstructural and functional substrates underlying dispositional greed and its link with trait but not state impulsivity.

The interplay between personality traits and impulsivity has long been a central theme in psychology and psychiatry. However, the potential association between Greed Personality Traits (GPT) and impulsivity, encompassing both trait and state impulsivity and future time perspective, remains largely unexplored. To address these issues, we employed questionnaires and an inter-temporal choice task to estimate corresponding trait/state impulsivity and collected multi-modal neuroimaging data (resting-state functional imaging: n = 430; diffusion-weighted imaging: n = 426; task-related functional imaging: n = 53) to investigate the underlying microstructural and functional substrates. Behavioral analyses revealed that GPT mediated the association between time perspective (e.g., present fatalism) and trait impulsivity (e.g., motor impulsivity). Functional imaging analyses further identified that brain activation strengths and patterns related to delay length, particularly in the dorsomedial prefrontal cortex, superior parietal lobule, and cerebellum, were associated with GPT. Moreover, individuals with similar levels of greed exhibited analogous spontaneous brain activity patterns, predominantly in the Default Mode Network (DMN), Fronto-Parietal Network (FPN), and Visual Network (VIS). Diffusion imaging analysis observed specific microstructural characteristics in the spinocerebellar/pontocerebellar fasciculus, internal/external capsule, and corona radiata that support the formation of GPT. Furthermore, the corresponding neural activation pattern, spontaneous neural activity pattern, and analogous functional couplings among the aforementioned brain regions mediated the relationships between time perspective and GPT and between GPT and motor impulsivity. These findings provide novel insights into the possible pathway such as time perspective → dispositional greed → impulsivity and uncover their underlying microstructural and functional substrates.

Distance from main arteries influences microstructural and functional brain tissue characteristics.

Given the substantial dependence of neurons on continuous supply of energy, the distribution of major cerebral arteries opens a question whether the distance from the main supply arteries constitutes a modulating factor for the microstructural and functional properties of brain tissue. To tackle this question, multimodal MRI acquisitions of 102 healthy volunteers over the full adult age span were utilised. Relaxation along a fictitious field in the rotating frame of rank n = 4 (RAFF4), adiabatic T1ρ, T2ρ,  and intracellular volume fraction (fICVF) derived from diffusion-weighted imaging were implemented to quantify microstructural (cellularity, myelin density, iron concentration) tissue characteristics and degree centrality and fractional amplitude of low-frequency fluctuations to probe for functional metrics. Inverse correlation of arterial distance with robust homogeneity was detected for T1ρ, T2ρ and RAFF4 for cortical grey matter and white matter, showing substantial complex microstructural differences between brain tissue close and farther from main arterial trunks. Albeit with wider variability, functional metrics pointed to increased connectivity and neuronal activity in areas farther from main arteries. Surprisingly, multiple of these microstructural and functional distance-based gradients diminished with higher age, pointing to uniformization of brain tissue with ageing. All in all, this pilot study provides a novel insight on brain regionalisation based on artery distance, which merits further investigation to validate its biological underpinnings.

Sex matters: The MouseX DW-ALLEN Atlas for mice diffusion-weighted MR imaging.

Overcoming sex bias in preclinical research requires not only including animals of both sexes in the experiments, but also developing proper tools to handle such data. Recent work revealed sensitivity of diffusion-weighted MRI to glia morphological changes in response to inflammatory stimuli, opening up exciting possibilities to characterize inflammation in a variety of preclinical models of pathologies, the great majority of them available in mice. However, there are limited resources dedicated to mouse imaging, like those required for the data processing and analysis. To fill this gap, we build a mouse MRI template of both structural and diffusion contrasts, with anatomical annotation according to the Allen Mouse Brain Atlas, the most detailed public resource for mouse brain investigation. To achieve a standardized resource, we use a large cohort of animals in vivo, and include animals of both sexes. To prove the utility of this resource to integrate imaging and molecular data, we demonstrate significant association between the mean diffusivity from MRI and gene expression-based glia density. To demonstrate the need of equitable sex representation, we compared across sexes the warp fields needed to match a male-based template, and our template built with both sexes. Then, we use both templates for analysing mice imaging data obtained in animals of different ages, demonstrating that using a male-based template creates spurious significant sex effects, not present otherwise. All in all, our MouseX DW-ALLEN Atlas will be a widely useful resource getting us one step closer to equitable healthcare.

Quantitative characterization of breast lesions and normal fibroglandular tissue using compartmentalized diffusion-weighted model: comparison of intravoxel incoherent motion and restriction spectrum imaging.

BACKGROUND: To compare the compartmentalized diffusion-weighted models, intravoxel incoherent motion (IVIM) and restriction spectrum imaging (RSI), in characterizing breast lesions and normal fibroglandular tissue. METHODS: This prospective study enrolled 152 patients with 157 histopathologically verified breast lesions (41 benign and 116 malignant). All patients underwent a full-protocol preoperative breast MRI, including a multi-b-value DWI sequence. The diffusion parameters derived from the mono-exponential model (ADC), IVIM model (Dt, Dp, f), and RSI model (C1, C2, C3, C1C2, F1, F2, F3, F1F2) were quantitatively measured and then compared among malignant lesions, benign lesions and normal fibroglandular tissues using Kruskal-Wallis test. The Mann-Whitney U-test was used for the pairwise comparisons. Diagnostic models were built by logistic regression analysis. The ROC analysis was performed using five-fold cross-validation and the mean AUC values were calculated and compared to evaluate the discriminative ability of each parameter or model. RESULTS: Almost all quantitative diffusion parameters showed significant differences in distinguishing malignant breast lesions from both benign lesions (other than C2) and normal fibroglandular tissue (all parameters) (all P < 0.0167). In terms of the comparisons of benign lesions and normal fibroglandular tissues, the parameters derived from IVIM (Dp, f) and RSI (C1, C2, C1C2, F1, F2, F3) showed significant differences (all P < 0.005). When using individual parameters, RSI-derived parameters-F1, C1C2, and C2 values yielded the highest AUCs for the comparisons of malignant vs. benign, malignant vs. normal tissue and benign vs. normal tissue (AUCs = 0.871, 0.982, and 0.863, respectively). Furthermore, the combined diagnostic model (IVIM + RSI) exhibited the highest diagnostic efficacy for the pairwise discriminations (AUCs = 0.893, 0.991, and 0.928, respectively). CONCLUSIONS: Quantitative parameters derived from the three-compartment RSI model have great promise as imaging indicators for the differential diagnosis of breast lesions compared with the bi-exponential IVIM model. Additionally, the combined model of IVIM and RSI achieves superior diagnostic performance in characterizing breast lesions.

Prevalence of TERT Promoter Mutations in Orbital Solitary Fibrous Tumors.

The orbital manifestation of a solitary fibrous tumor (SFT) is exceptionally rare and poses specific challenges in diagnosis and treatment. Its rather exceptional behavior among all SFTs comprises a high tendency towards local recurrence, but it rarely culminates in metastatic disease. This raises the question of prognostic factors in orbital SFTs (oSFTs). Telomerase reverse transcriptase (TERT)-promoter mutations have previously been linked to an unfavorable prognosis in SFTs of other locations. We analyzed the prevalence of TERT promoter mutations of SFTs in the orbital compartment. We performed a retrospective, descriptive clinico-histopathological analysis of nine cases of oSFTs between the years of 2017 and 2021. A TERT promoter mutation was present in one case, which was classified with intermediate metastatic risk. Local recurrence or progress occurred in six cases after primary resection; no distant metastases were reported. Multimodal imaging repeatedly showed particular morphologic patterns, including tubular vascular structures and ADC reduction. The prevalence of the TERT promoter mutation in oSFT was 11%, which is similar to the prevalence of extra-meningeal SFTs of the head and neck and lower than that in other extra-meningeal compartments. In the present study, the TERT promoter mutation in oSFT manifested in a case with an unfavorable prognosis, comprising aggressive local tumor growth, local recurrence, and eye loss.

Neurite density of the hippocampus is associated with trace eyeblink conditioning latency in 4- to 6-year-olds.

Limited options exist to evaluate the development of hippocampal function in young children. Research has established that trace eyeblink conditioning (EBC) relies on a functional hippocampus. Hence, we set out to investigate whether trace EBC is linked to hippocampal structure, potentially serving as a valuable indicator of hippocampal development. Our study explored potential associations between individual differences in hippocampal volume and neurite density with trace EBC performance in young children. We used onset latency of conditioned responses (CR) and percentage of conditioned responses (% CR) as measures of hippocampal-dependent associative learning. Using a sample of typically developing children aged 4 to 6 years (N = 30; 14 girls; M = 5.70 years), participants underwent T1- and diffusion-weighted MRI scans and completed a 15-min trace eyeblink conditioning task conducted outside the MRI. % CR and CR onset latency were calculated based on all trials involving tone-puff presentations and tone-alone trials. Findings revealed a connection between greater left hippocampal neurite density and delayed CR onset latency. Children with higher neurite density in the left hippocampus tended to blink closer to the onset of the unconditioned stimulus, indicating that structural variations in the hippocampus were associated with more precise timing of conditioned responses. No other relationships were observed between hippocampal volume, cerebellum volume or neurite density, hippocampal white matter connectivity and any EBC measures. Preliminary results suggest that trace EBC may serve as a straightforward yet innovative approach for studying hippocampal development in young children and populations with atypical development.

Comparison of T1-weighted landmark placement and ROI transfer onto diffusion-weighted EPI sequences for targeted tractography tasks in the optic nerve.

Diffusion-based tractography in the optic nerve requires sampling strategies assisted by anatomical landmark information (regions of interest [ROIs]). We aimed to investigate the feasibility of expert-placed, high-resolution T1-weighted ROI-data transfer onto lower spatial resolution diffusion-weighted images. Slab volumes from 20 volunteers were acquired and preprocessed including distortion bias correction and artifact reduction. Constrained spherical deconvolution was used to generate a directional diffusion information grid (fibre orientation distribution-model [FOD]). Three neuroradiologists marked landmarks on both diffusion imaging variants and structural datasets. Structural ROI information (volumetric interpolated breath-hold sequence [VIBE]) was respectively registered (linear with 6/12 degrees of freedom [DOF]) onto single-shot EPI (ss-EPI) and readout-segmented EPI (rs-EPI) volumes, respectively. All eight ROI/FOD-combinations were compared in a targeted tractography task of the optic nerve pathway. Inter-rater reliability for placed ROIs among experts was highest in VIBE images (lower confidence interval 0.84 to 0.97, mean 0.91) and lower in both ss-EPI (0.61 to 0.95, mean 0.79) and rs-EPI (0.59 to 0.86, mean 0.70). Tractography success rate based on streamline selection performance was highest in VIBE-drawn ROIs registered (6-DOF) onto rs-EPI FOD (70.0% over 5%-threshold, capped to failed ratio 39/16) followed by both 12-DOF-registered (67.5%; 41/16) and nonregistered VIBE (67.5%; 40/23). On ss-EPI FOD, VIBE-ROI-datasets obtained fewer streamlines overall with each at 55.0% above 5%-threshold and with lower capped to failed ratio (6-DOF: 35/36; 12-DOF: 34/34, nonregistered 33/36). The combination of VIBE-placed ROIs (highest inter-rater reliability) with 6-DOF registration onto rs-EPI targets (best streamline selection performance) is most suitable for white matter template generation required in group studies.

Clarifying Human White Matter.

Progress in magnetic resonance imaging (MRI) now makes it possible to identify the major white matter tracts in the living human brain. These tracts are important because they carry many of the signals communicated between different brain regions. MRI methods coupled with biophysical modeling can measure the tissue properties and structural features of the tracts that impact our ability to think, feel, and perceive. This review describes the fundamental ideas of the MRI methods used to identify the major white matter tracts in the living human brain.

A practical evaluation of measures derived from compressed sensing diffusion spectrum imaging.

Diffusion Spectrum Imaging (DSI) using dense Cartesian sampling of q-space has been shown to provide important advantages for modeling complex white matter architecture. However, its adoption has been limited by the lengthy acquisition time required. Sparser sampling of q-space combined with compressed sensing (CS) reconstruction techniques has been proposed as a way to reduce the scan time of DSI acquisitions. However prior studies have mainly evaluated CS-DSI in post-mortem or non-human data. At present, the capacity for CS-DSI to provide accurate and reliable measures of white matter anatomy and microstructure in the living human brain remains unclear. We evaluated the accuracy and inter-scan reliability of 6 different CS-DSI schemes that provided up to 80% reductions in scan time compared to a full DSI scheme. We capitalized on a dataset of 26 participants who were scanned over eight independent sessions using a full DSI scheme. From this full DSI scheme, we subsampled images to create a range of CS-DSI images. This allowed us to compare the accuracy and inter-scan reliability of derived measures of white matter structure (bundle segmentation, voxel-wise scalar maps) produced by the CS-DSI and the full DSI schemes. We found that CS-DSI estimates of both bundle segmentations and voxel-wise scalars were nearly as accurate and reliable as those generated by the full DSI scheme. Moreover, we found that the accuracy and reliability of CS-DSI was higher in white matter bundles that were more reliably segmented by the full DSI scheme. As a final step, we replicated the accuracy of CS-DSI in a prospectively acquired dataset (n = 20, scanned once). Together, these results illustrate the utility of CS-DSI for reliably delineating in vivo white matter architecture in a fraction of the scan time, underscoring its promise for both clinical and research applications.

Increased white matter fibre dispersion and lower IQ scores in adults born preterm.

Preterm birth has been associated with altered microstructural properties of the white matter and lower cognitive ability in childhood and adulthood. Due to methodological limitations of the diffusion tensor model, it is not clear whether alterations in myelination or variation in fibre orientation are driving these differences. Novel models applied to multi-shell diffusion imaging have been used to disentangle these effects, but to date this has not been used to study the preterm brain in adulthood. This study investigated whether novel advanced diffusion MRI metrics such as microscopic anisotropy and orientation dispersion are altered in adults born preterm, and whether this was associated with cognitive performance. Seventy-two preterm born participants (<37 weeks gestational age) were recruited from a 1982-1984 cohort (33 males, mean age 33.5 ± 1.0 years). Seventy-two term born (>37 weeks gestational age) controls (34 males, mean age 30.9 ± 4.0 years) were recruited from the general population. Tensor FA was calculated with FSL, while microscopic FA and orientation dispersion entropy (ODE) were estimated using the Spherical Mean Technique (SMT). Estimated Full Scale IQ (FSIQ), Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI) were obtained from the WASI-II (abbreviated) IQ test. Voxel-wise comparisons using FSL's tract-based spatial statistics were performed to test between-group differences in diffusion MRI metrics as well as within-group associations of diffusion MRI metrics and IQ outcomes. The preterm group had significantly lower FSIQ, VCI and PRI scores. Preterm subjects demonstrated widespread decreases in ODE reflecting increased fibre dispersion, but no differences in microscopic FA. Tensor FA was increased in a small area in the anterior corona radiata. Lower FA values in the preterm population were associated with lower FSIQ and PRI scores. An increase in fibre dispersion in white matter and lower IQ scores after preterm birth exist in adulthood. Advanced diffusion MRI metrics such as the orientation dispersion entropy can be used to monitor white matter alterations across the lifespan in preterm born individuals. Although not significantly different between preterm and term groups, tensor FA values in the preterm group were associated with cognitive outcome.

Fibre orientation atlas guided rapid segmentation of white matter tracts.

Fibre tract delineation from diffusion magnetic resonance imaging (MRI) is a valuable clinical tool for neurosurgical planning and navigation, as well as in research neuroimaging pipelines. Several popular methods are used for this task, each with different strengths and weaknesses making them more or less suited to different contexts. For neurosurgical imaging, priorities include ease of use, computational efficiency, robustness to pathology and ability to generalise to new tracts of interest. Many existing methods use streamline tractography, which may require expert neuroimaging operators for setting parameters and delineating anatomical regions of interest, or suffer from as a lack of generalisability to clinical scans involving deforming tumours and other pathologies. More recently, data-driven approaches including deep-learning segmentation models and streamline clustering methods have improved reproducibility and automation, although they can require large amounts of training data and/or computationally intensive image processing at the point of application. We describe an atlas-based direct tract mapping technique called 'tractfinder', utilising tract-specific location and orientation priors. Our aim was to develop a clinically practical method avoiding streamline tractography at the point of application while utilising prior anatomical knowledge derived from only 10-20 training samples. Requiring few training samples allows emphasis to be placed on producing high quality, neuro-anatomically accurate training data, and enables rapid adaptation to new tracts of interest. Avoiding streamline tractography at the point of application reduces computational time, false positives and vulnerabilities to pathology such as tumour deformations or oedema. Carefully filtered training streamlines and track orientation distribution mapping are used to construct tract specific orientation and spatial probability atlases in standard space. Atlases are then transformed to target subject space using affine registration and compared with the subject's voxel-wise fibre orientation distribution data using a mathematical measure of distribution overlap, resulting in a map of the tract's likely spatial distribution. This work includes extensive performance evaluation and comparison with benchmark techniques, including streamline tractography and the deep-learning method TractSeg, in two publicly available healthy diffusion MRI datasets (from TractoInferno and the Human Connectome Project) in addition to a clinical dataset comprising paediatric and adult brain tumour scans. Tract segmentation results display high agreement with established techniques while requiring less than 3 min on average when applied to a new subject. Results also display higher robustness than compared methods when faced with clinical scans featuring brain tumours and resections. As well as describing and evaluating a novel proposed tract delineation technique, this work continues the discussion on the challenges surrounding the white matter segmentation task, including issues of anatomical definitions and the use of quantitative segmentation comparison metrics.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Neuroscience meets behavior: A systematic literature review on magnetic resonance imaging of the brain combined with real-world digital phenotyping.

A primary goal of neuroscience is to understand the relationship between the brain and behavior. While magnetic resonance imaging (MRI) examines brain structure and function under controlled conditions, digital phenotyping via portable automatic devices (PAD) quantifies behavior in real-world settings. Combining these two technologies may bridge the gap between brain imaging, physiology, and real-time behavior, enhancing the generalizability of laboratory and clinical findings. However, the use of MRI and data from PADs outside the MRI scanner remains underexplored. Herein, we present a Preferred Reporting Items for Systematic Reviews and Meta-Analysis systematic literature review that identifies and analyzes the current state of research on the integration of brain MRI and PADs. PubMed and Scopus were automatically searched using keywords covering various MRI techniques and PADs. Abstracts were screened to only include articles that collected MRI brain data and PAD data outside the laboratory environment. Full-text screening was then conducted to ensure included articles combined quantitative data from MRI with data from PADs, yielding 94 selected papers for a total of N = 14,778 subjects. Results were reported as cross-frequency tables between brain imaging and behavior sampling methods and patterns were identified through network analysis. Furthermore, brain maps reported in the studies were synthesized according to the measurement modalities that were used. Results demonstrate the feasibility of integrating MRI and PADs across various study designs, patient and control populations, and age groups. The majority of published literature combines functional, T1-weighted, and diffusion weighted MRI with physical activity sensors, ecological momentary assessment via PADs, and sleep. The literature further highlights specific brain regions frequently correlated with distinct MRI-PAD combinations. These combinations enable in-depth studies on how physiology, brain function and behavior influence each other. Our review highlights the potential for constructing brain-behavior models that extend beyond the scanner and into real-world contexts.

Phase stabilization with motion compensated diffusion weighted imaging.

PURPOSE: Diffusion encoding gradient waveforms can impart intra-voxel and inter-voxel dephasing owing to bulk motion, limiting achievable signal-to-noise and complicating multishot acquisitions. In this study, we characterize improvements in phase consistency via gradient moment nulling of diffusion encoding waveforms. METHODS: Healthy volunteers received neuro ( N = 10 $$ N=10 $$ ) and cardiac ( N = 10 $$ N=10 $$ ) MRI. Three gradient moment nulling levels were evaluated: compensation for position ( M 0 $$ {M}_0 $$ ), position + velocity ( M 1 $$ {M}_1 $$ ), and position + velocity + acceleration ( M 1 + M 2 $$ {M}_1+{M}_2 $$ ). Three experiments were completed: (Exp-1) Fixed Trigger Delay Neuro DWI; (Exp-2) Mixed Trigger Delay Neuro DWI; and (Exp-3) Fixed Trigger Delay Cardiac DWI. Significant differences ( p < 0 . 05 $$ p<0.05 $$ ) of the temporal phase SD between repeated acquisitions and the spatial phase gradient across a given image were assessed. RESULTS: M 0 $$ {M}_0 $$ moment nulling was a reference for all measures. In Exp-1, temporal phase SD for G z $$ {G}_z $$ diffusion encoding was significantly reduced with M 1 $$ {M}_1 $$ (35% of t-tests) and M 1 + M 2 $$ {M}_1+{M}_2 $$ (68% of t-tests). The spatial phase gradient was reduced in 23% of t-tests for M 1 $$ {M}_1 $$ and 2% of cases for M 1 + M 2 $$ {M}_1+{M}_2 $$ . In Exp-2, temporal phase SD significantly decreased with M 1 + M 2 $$ {M}_1+{M}_2 $$ gradient moment nulling only for G z $$ {G}_z $$ (83% of t-tests), but spatial phase gradient significantly decreased with only M 1 $$ {M}_1 $$ (50% of t-tests). In Exp-3, M 1 + M 2 $$ {M}_1+{M}_2 $$ gradient moment nulling significantly reduced temporal phase SD and spatial phase gradients (100% of t-tests), resulting in less signal attenuation and more accurate ADCs. CONCLUSION: We characterized gradient moment nulling phase consistency for DWI. Using M1 for neuroimaging and M1 + M2 for cardiac imaging minimized temporal phase SDs and spatial phase gradients.

Reproducibility of intravoxel incoherent motion quantification in the liver across field strengths and gradient hardware.

PURPOSE: To evaluate reproducibility and interlobar agreement of intravoxel incoherent motion (IVIM) quantification in the liver across field strengths and MR scanners with different gradient hardware. METHODS: Cramer-Rao lower bound optimization was performed to determine optimized monopolar and motion-robust 2D (b-value and first-order motion moment [M1]) IVIM-DWI acquisitions. Eleven healthy volunteers underwent diffusion MRI of the liver, where each optimized acquisition was obtained five times across three MRI scanners. For each data set, IVIM estimates (diffusion coefficient (D), pseudo-diffusion coefficients ( d 1 * $$ {d}_1^{\ast } $$ and d 2 * $$ {d}_2^{\ast } $$ ), blood velocity SDs (Vb1 and Vb2), and perfusion fractions [f1 and f2]) were obtained in the right and left liver lobes using two signal models (pseudo-diffusion and M1-dependent physical) with and without T2 correction (fc1 and fc2) and three fitting techniques (tri-exponential region of interest-based full and segmented fitting and blood velocity SD distribution fitting). Reproducibility and interlobar agreement were compared across methods using within-subject and pairwise coefficients of variation (CVw and CVp), paired sample t-tests, and Bland-Altman analysis. RESULTS: Using a combination of motion-robust 2D (b-M1) data acquisition, M1-dependent physical signal modeling with T2 correction, and blood velocity SD distribution fitting, multiscanner reproducibility with median CVw = 5.09%, 11.3%, 9.20%, 14.2%, and 12.6% for D, Vb1, Vb2, fc1, and fc2, respectively, and interlobar agreement with CVp = 8.14%, 11.9%, 8.50%, 49.9%, and 42.0%, respectively, was achieved. CONCLUSION: Recently proposed advanced IVIM acquisition, signal modeling, and fitting techniques may facilitate reproducible IVIM quantification in the liver, as needed for establishment of IVIM-based quantitative biomarkers for detection, staging, and treatment monitoring of diseases.

Distortion-free water-fat separated diffusion-weighted imaging using spatiotemporal joint reconstruction.

PURPOSE: Diffusion-weighted imaging (DWI) suffers from geometric distortion and chemical shift artifacts due to the commonly used Echo Planar Imaging (EPI) trajectory. Even with fat suppression in DWI, severe B0 and B1 variations can result in residual fat, which becomes both a source of image artifacts and a confounding factor in diffusion-weighted contrast in distinguishing benign and malignant tissues. This work presents a method for acquiring distortion-free diffusion-weighted images using spatiotemporal acquisition and joint reconstruction. Water-fat separation is performed by chemical-shift encoding. METHODS: Spatiotemporal acquisition is employed to obtain distortion-free images at a series of echo times. Chemical-shift encoding is used for water-fat separation. Reconstruction and separation are performed jointly in the spat-spectral domain. To address the shot-to-shot motion-induced phase in DWI, an Fast Spin Echo (FSE)-based phase navigator is incorporated into the sequence to obtain distortion-free phase information. The proposed method was validated in phantoms and in vivo for the brain, head and neck, and breast. RESULTS: The proposed method enables the acquisition of distortion-free diffusion-weighted images in the presence of B0 field inhomogenieties commonly observed in the body. Water and fat components are separated with no obvious spectral leakage artifacts. The estimated Apparent Diffusion Coefficient (ADC) is comparable to that of multishot DW-EPI. CONCLUSION: Distortion-free, water-fat separated diffusion-weighted images in body can be obtained through the utilization of spatiotemporal acquisition and joint reconstruction methods.

Motion-compensated diffusion encoding in multi-shot human brain acquisitions: Insights using high-performance gradients.

PURPOSE: To evaluate the utility of up to second-order motion-compensated diffusion encoding in multi-shot human brain acquisitions. METHODS: Experiments were performed with high-performance gradients using three forms of diffusion encoding motion-compensated through different orders: conventional zeroth-order-compensated pulsed gradients (PG), first-order-compensated gradients (MC1), and second-order-compensated gradients (MC2). Single-shot acquisitions were conducted to correlate the order of motion compensation with resultant phase variability. Then, multi-shot acquisitions were performed at varying interleaving factors. Multi-shot images were reconstructed using three levels of shot-to-shot phase correction: no correction, channel-wise phase correction based on FID navigation, and correction based on explicit phase mapping (MUSE). RESULTS: In single-shot acquisitions, MC2 diffusion encoding most effectively suppressed phase variability and sensitivity to brain pulsation, yielding residual variations of about 10° and of low spatial order. Consequently, multi-shot MC2 images were largely satisfactory without phase correction and consistently improved with the navigator correction, which yielded repeatable high-quality images; contrarily, PG and MC1 images were inadequately corrected using the navigator approach. With respect to MUSE reconstructions, the MC2 navigator-corrected images were in close agreement for a standard interleaving factor and considerably more reliable for higher interleaving factors, for which MUSE images were corrupted. Finally, owing to the advanced gradient hardware, the relative SNR penalty of motion-compensated diffusion sensitization was substantially more tolerable than that faced previously. CONCLUSION: Second-order motion-compensated diffusion encoding mitigates and simplifies shot-to-shot phase variability in the human brain, rendering the multi-shot acquisition strategy an effective means to circumvent limitations of retrospective phase correction methods.