Perivascular space enlargement accelerates in ageing and Alzheimer's disease pathology: evidence from a three-year longitudinal multicentre study.

BACKGROUND: Perivascular space (PVS) enlargement in ageing and Alzheimer's disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD. METHODS: We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; meanage = 70.78 ± 5.78) of the ongoing observational multicentre "DZNE Longitudinal Cognitive Impairment and Dementia Study" (DELCODE) cohort. We analysed data from subjects who were cognitively unimpaired (n = 401), had amnestic mild cognitive impairment (n = 71), or had AD (n = 31). We used linear mixed-effects modelling to test for changes of PVS volumes in relation to cross-sectional and longitudinal age, as well as sex, years of education, hypertension, white matter hyperintensities, AD diagnosis, and cerebrospinal-fluid-derived amyloid (A) and tau (T) status (available for 46.71%; A-T-/A + T-/A + T + n = 143/48/39). RESULTS: PVS volumes increased significantly over follow-ups (CSO: B = 0.03 [0.02, 0.05], p < 0.001; BG: B = 0.05 [0.03, 0.07], p < 0.001). PVS enlargement rates varied substantially across subjects and depended on the participant's age, white matter hyperintensities volumes, and amyloid and tau status. PVS volumes were higher across elderly participants, regardless of region of interest (CSO: B = 0.12 [0.02, 0.21], p = 0.017; BG: B = 0.19 [0.09, 0.28], p < 0.001). Faster BG-PVS enlargement related to lower baseline white matter hyperintensities volumes (ρspearman = -0.17, pFDR = 0.001) and was more pronounced in individuals who presented with combined amyloid and tau positivity versus negativity (A + T + > A-T-, pFDR = 0.004) or who were amyloid positive but tau negative (A + T + > A + T-, pFDR = 0.07). CSO-PVS volumes increased at a faster rate with amyloid positivity as compared to amyloid negativity (A + T-/A + T + > A-T-, pFDR = 0.021). CONCLUSION: Our longitudinal evidence supports the relevance of PVS enlargement in presumably healthy ageing as well as in AD pathology. We further discuss the region-specific involvement of white matter hyperintensities and neurotoxic waste accumulation in PVS enlargement and the possibility of additional factors contributing to PVS progression. A comprehensive understanding of PVS dynamics could facilitate the understanding of pathological cascades and might inform targeted treatment strategies. TRIAL REGISTRATION: German Clinical Trials Register DRKS00007966. Registered 04.05.2015 - retrospectively registered, https://drks.de/search/en/trial/DRKS00007966 .

Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults.

BACKGROUND: For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce. METHODS: We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period. For this purpose, we leveraged longitudinal MRI data from 451 cognitively unimpaired participants (DELCODE; median age 69.71 [IQR 65.51, 75.50] years; 52.32% female). Participants underwent MRI sessions annually over a four-year period (1815 sessions in total, with roughly four MRI sessions per participant). We adjusted all models for demographics and cardiovascular risk. RESULTS: Our findings were three-fold. First, larger WMH volumes were linked to lower cortical thickness (σ = -0.165, SE = 0.047, Z = -3.515, P < 0.001). Second, individuals with higher WMH volumes experienced more rapid cortical thinning (σ = -0.226, SE = 0.093, Z = -2.443, P = 0.007), particularly in temporal, cingulate, and insular regions. Similarly, those with lower initial cortical thickness had faster WMH progression (σ = -0.141, SE = 0.060, Z = -2.336, P = 0.009), with this effect being most pronounced in temporal, cingulate, and insular cortices. Third, faster WMH progression was associated with accelerated cortical thinning (σ = -0.239, SE = 0.139, Z = -1.710, P = 0.044), particularly in frontal, occipital, and insular cortical regions. CONCLUSIONS: Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00007966, 04/05/2015).

Signal-to-noise ratio versus field strength for small surface coils.

The increasing signal-to-noise ratio (SNR) is the main reason to use ultrahigh field MRI. Here, we investigate the dependence of the SNR on the magnetic field strength, especially for small animal applications, where small surface coils are used and coil noise cannot be ignored. Measurements were performed at five field strengths from 3 to 14.1 T, using 2.2-cm surface coils with an identical coil design for transmit and receive on two water samples with and without salt. SNR was measured in a series of spoiled gradient echo images with varying flip angle and corrected for saturation based on a series of flip angle and T1 measurements. Furthermore, the noise figure of the receive chain was determined and eliminated to remove instrument dependence. Finally, the coil sensitivity was determined based on the principle of reciprocity to obtain a measure for ultimate SNR. Before coil sensitivity correction, the SNR increase in nonconductive samples is highly supralinear with B0 1.6-2.7, depending on distance to the coil, while in the conductive sample, the growth is smaller, being around linear close to the surface coil and increasing up to a B0 2.0 dependence when moving away from the coil. After sensitivity correction, the SNR increase is independent of loading with B0 2.1. This study confirms the supralinear increase of SNR with increasing field strengths. Compared with most human measurements with larger coil sizes, smaller surface coils, as mainly used in animal studies, have a higher contribution of coil noise and thus a different behavior of SNR at high fields.

Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks.

BACKGROUND: Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. OBJECTIVE: This cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks. METHODS: We assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds. RESULTS: Older participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks. CONCLUSION: We show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00007966, 04/05/2015).

Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum.

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants' whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aß-positive and Aß-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

Inferior Frontal Sulcal Hyperintensities on Brain MRI Are Associated with Amyloid Positivity beyond Age-Results from the Multicentre Observational DELCODE Study.

Inferior frontal sulcal hyperintensities (IFSHs) on fluid-attenuated inversion recovery (FLAIR) sequences have been proposed to be indicative of glymphatic dysfunction. Replication studies in large and diverse samples are nonetheless needed to confirm them as an imaging biomarker. We investigated whether IFSHs were tied to Alzheimer's disease (AD) pathology and cognitive performance. We used data from 361 participants along the AD continuum, who were enrolled in the multicentre DELCODE study. The IFSHs were rated visually based on FLAIR magnetic resonance imaging. We performed ordinal regression to examine the relationship between the IFSHs and cerebrospinal fluid-derived amyloid positivity and tau positivity (Aß42/40 ratio ≤ 0.08; pTau181 ≥ 73.65 pg/mL) and linear regression to examine the relationship between cognitive performance (i.e., Mini-Mental State Examination and global cognitive and domain-specific performance) and the IFSHs. We controlled the models for age, sex, years of education, and history of hypertension. The IFSH scores were higher in those participants with amyloid positivity (OR: 1.95, 95% CI: 1.05-3.59) but not tau positivity (OR: 1.12, 95% CI: 0.57-2.18). The IFSH scores were higher in older participants (OR: 1.05, 95% CI: 1.00-1.10) and lower in males compared to females (OR: 0.44, 95% CI: 0.26-0.76). We did not find sufficient evidence linking the IFSH scores with cognitive performance after correcting for demographics and AD biomarker positivity. IFSHs may reflect the aberrant accumulation of amyloid ß beyond age.

A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings.

Memory clinic patients are a heterogeneous population representing various aetiologies of pathological ageing. It is not known whether divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± standard deviation, age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (n = 342), mild cognitive impairment (n = 118) or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid Alzheimer's disease biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5) as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test whether baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and mild cognitive impairment conversion rates of cognitively unimpaired participants and those with subjective cognitive decline. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy initially affected the medial temporal lobes, followed by further temporal regions and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological Alzheimer's disease biomarker levels, APOE ε4 carriership and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe, with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive Alzheimer's disease biomarkers and was associated with more generalized cognitive impairment. Limbic-predominant atrophy, in all participants and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of mild cognitive impairment conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, at both the subject and the group level, was excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for Alzheimer's disease in applied settings. The implementation of atrophy subtype- and stage-specific end points might increase the statistical power of pharmacological trials targeting early Alzheimer's disease.

Contrast Agents Based on Human Serum Albumin and Nitroxides for 1H-MRI and Overhauser-Enhanced MRI.

In cancer diagnostics, magnetic resonance imaging (MRI) uses contrast agents to enhance the distinction between the target tissue and background. Several promising approaches have been developed to increase MRI sensitivity, one of which is Overhauser dynamic nuclear polarization (ODNP)-enhanced MRI (OMRI). In this study, a macromolecular construct based on human serum albumin and nitroxyl radicals (HSA-NIT) was developed using a new synthesis method that significantly increased the modification to 21 nitroxide residues per protein. This was confirmed by electron paramagnetic resonance (EPR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry. Gel electrophoresis and circular dichroism showed no significant changes in the structure of HSA-NITs, and no oligomers were formed during modification. The cytotoxicity of HSA-NITs was comparable to that of native albumin. HSA-NITs were evaluated as potential "metal-free" organic radical relaxation-based contrast agents for 1H-MRI and as hyperpolarizing contrast agents for OMRI. Relaxivities (longitudinal and transversal relaxation rates r1 and r2) for HSA-NITs were measured at different magnetic field strengths (1.88, 3, 7, and 14 T). Phantoms were used to demonstrate the potential use of HSA-NIT as a T1- and T2-weighted relaxation-based contrast agent at 3 T and 14 T. The efficacy of 1H Overhauser dynamic nuclear polarization (ODNP) in liquids at an ultralow magnetic field (ULF, B0 = 92 ± 0.8 µT) was investigated for HSA-NIT conjugates. The HSA-NITs themselves did not show ODNP enhancement; however, under the proteolysis conditions simulating cancer tissue, HSA-NIT conjugates were cleaved into lower-molecular-weight (MW) protein fragments that activate ODNP capabilities, resulting in a maximum achievable enhancement |Emax| of 40-50 and a radiofrequency power required to achieve half of Emax, P1/2, of 21-27 W. The HSA-NIT with a higher degree of modification released increased the number of spin probes upon biodegradation, which significantly enhanced the Overhauser effect. Thus, HSA-NITs may represent a new class of MRI relaxation-based contrast agents as well as novel cleavable conjugates for use as hyperpolarizing contrast agents (HCAs) in OMRI.

Intra-scan RF power amplifier drift correction.

PURPOSE: The drift in radiofrequency (RF) power amplifiers (RFPAs) is assessed and several contributing factors are investigated. Two approaches for prospective correction of drift are proposed and their effectiveness is evaluated. METHODS: RFPA drift assessment encompasses both intra-pulse and inter-pulse drift analyses. Scan protocols with varying flip angle (FA), RF length, and pulse repetition time (TR) are used to gauge the influence of these parameters on drift. Directional couplers (DICOs) monitor the forward waveforms of the RFPA outputs. DICOs data is stored for evaluation, allowing calculation of correction factors to adjust RFPAs' transmit voltage. Two correction methods, predictive and run-time, are employed: predictive correction necessitates a calibration scan, while run-time correction calculates factors during the ongoing scan. RESULTS: RFPA drift is indeed influenced by the RF duty-cycle, and in the cases examined with a maximum duty-cycle of 66%, the potential drift is approximately 41% or 15%, depending on the specific RFPA revision. Notably, in low transmit voltage scenarios, FA has minimal impact on RFPA drift. The application of predictive and run-time drift correction techniques effectively reduces the average drift from 10.0% to less than 1%, resulting in enhanced MR signal stability. CONCLUSION: Utilizing DICO recordings and implementing a feedback mechanism enable the prospective correction of RFPA drift. Having a calibration scan, predictive correction can be utilized with fewer complexity; for enhanced performance, a run-time approach can be employed.

Submillimeter balanced SSFP BOLD-functional MRI accelerated with 3D stack-of-spirals at 9.4 T.

PURPOSE: This work aims to improve the speed of balanced SSFP (bSSFP) acquisition with segmented 3D stack-of-spirals for functional brain studies at ultrahigh field. METHODS: Functional experiments were performed with an accelerated 3D stack-of-spirals sequence with water excitation for fat suppression. The resulting data were reconstructed using an iterative algorithm with corrections for system imperfections such as trajectory deviations and B0 inhomogeneity. In the first set of experiments, we evaluated the signal change and stability with respect to echo and TR for a full-field checkerboard stimulus. To demonstrate the high spatio-temporal resolution of the developed method, the results of three optimized protocols at submillimeter resolution (0.6-mm isotropic and 0.8-mm isotropic) and at 1.2 mm isotropic resolution for whole-brain coverage were shown. RESULTS: Water excitation and the model-based iterative reconstruction improved image quality. The BOLD-related signal changes increased with longer TE and longer TR. We observed an increase in thermal noise performance at lower TE and higher TR. However, signal stability deteriorates at higher TE and TR. Therefore, optimized protocols used shorter TE and moderately long TR to maximize the sensitivity and speed. Reproducible activations were detected along the gray-matter gyri in the submillimeter protocols with a median signal change of approximately 4% across subjects. CONCLUSIONS: Three-dimensional stack-of-spirals enables passband balanced SSFP functional imaging at a much higher spatial and temporal scale, compared with conventional spoiled gradient-echo train sequences.

Dynamic parallel imaging at 9.4 T using reconfigurable receive coaxial dipoles.

Parallel imaging is one of the key MRI technologies that allow reduction of image acquisition time. However, the parallel imaging reconstruction commonly leads to a signal-to-noise ratio (SNR) drop evaluated using a so-called geometrical factor (g-factor). The g-factor is minimized by increasing the number of array elements and their spatial diversity. At the same time, increasing the element count requires a decrease in their size. This may lead to insufficient coil loading, an increase in the relative noise contribution from the RF coil itself, and hence SNR reduction. Previously, instead of increasing the channel number, we introduced the concept of electronically switchable time-varying sensitivities, which was shown to improve parallel imaging performance. In this approach, each reconfigurable receive element supports two spatially distinct sensitivity profiles. In this work, we developed and evaluated a novel eight-element human head receive-only reconfigurable coaxial dipole array for human head imaging at 9.4 T. In contrast to the previously reported reconfigurable dipole array, the new design does not include direct current (DC) control wires connected directly to the dipoles. The coaxial cable itself is used to deliver DC voltage to the PIN diodes located at the ends of the antennas. Thus, the novel reconfigurable coaxial dipole design opens a way to scale the dynamic parallel imaging up to a realistic number of channels, that is, 32 and above. The novel array was optimized and tested experimentally, including in vivo studies. It was found that dynamic sensitivity switching provided an 8% lower mean and 33% lower maximum g-factor (for Ry × Rz = 2 × 2 acceleration) compared with conventional static sensitivities.

Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia.

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.

13C MRI of hyperpolarized pyruvate at 120 µT.

Nuclear spin hyperpolarization increases the sensitivity of magnetic resonance dramatically, enabling many new applications, including real-time metabolic imaging. Parahydrogen-based signal amplification by reversible exchange (SABRE) was employed to hyperpolarize [1-13C]pyruvate and demonstrate 13C imaging in situ at 120 µT, about twice Earth's magnetic field, with two different signal amplification by reversible exchange variants: SABRE in shield enables alignment transfer to heteronuclei (SABRE-SHEATH), where hyperpolarization is transferred from parahydrogen to [1-13C]pyruvate at a magnetic field below 1 µT, and low-irradiation generates high tesla (LIGHT-SABRE), where hyperpolarization was prepared at 120 µT, avoiding magnetic field cycling. The 3-dimensional images of a phantom were obtained using a superconducting quantum interference device (SQUID) based magnetic field detector with submillimeter resolution. These 13C images demonstrate the feasibility of low-field 13C metabolic magnetic resonance imaging (MRI) of 50 mM [1-13C]pyruvate hyperpolarized by parahydrogen in reversible exchange imaged at about twice Earth's magnetic field. Using thermal 13C polarization available at 120 µT, the same experiment would have taken about 300 billion years.

MP2RAGE vs. MPRAGE surface-based morphometry in focal epilepsy.

In drug-resistant focal epilepsy, detecting epileptogenic lesions using MRI poses a critical diagnostic challenge. Here, we assessed the utility of MP2RAGE-a T1-weighted sequence with self-bias correcting properties commonly utilized in ultra-high field MRI-for the detection of epileptogenic lesions using a surface-based morphometry pipeline based on FreeSurfer, and compared it to the common approach using T1w MPRAGE, both at 3T. We included data from 32 patients with focal epilepsy (5 MRI-positive, 27 MRI-negative with lobar seizure onset hypotheses) and 94 healthy controls from two epilepsy centres. Surface-based morphological measures and intensities were extracted and evaluated in univariate GLM analyses as well as multivariate unsupervised 'novelty detection' machine learning procedures. The resulting prediction maps were analyzed over a range of possible thresholds using alternative free-response receiver operating characteristic (AFROC) methodology with respect to the concordance with predefined lesion labels or hypotheses on epileptogenic zone location. We found that MP2RAGE performs at least comparable to MPRAGE and that especially analysis of MP2RAGE image intensities may provide additional diagnostic information. Secondly, we demonstrate that unsupervised novelty-detection machine learning approaches may be useful for the detection of epileptogenic lesions (maximum AFROC AUC 0.58) when there is only a limited lesional training set available. Third, we propose a statistical method of assessing lesion localization performance in MRI-negative patients with lobar hypotheses of the epileptogenic zone based on simulation of a random guessing process as null hypothesis. Based on our findings, it appears worthwhile to study similar surface-based morphometry approaches in ultra-high field MRI (≥ 7 T).

Different inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition.

Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, Aß42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295); a longitudinal observational study focusing on at-risk stages of AD. Volumetric maps of gray and white matter (GM/WM; n = 261) and white matter hyperintensities (WMHs, n = 249) were derived from baseline MRIs. Cognitive decline (n = 204) and the rate of change in GM volume was measured in subjects with at least 3 visits (n = 175). A principal component analysis on the CSF markers revealed four inflammatory components (PCs). Of these, the first component PC1 (highly loading on sTyro3, sAXL, sTREM2, YKL-40, and C1q) was associated with older age and higher p-tau levels, but with less pathological Aß when controlling for p-tau. PC2 (highly loading on CRP, IL-18, complement factor F/H and C4) was related to male gender, higher body mass index and greater vascular risk. PC1 levels, adjusted for AD markers, were related to higher GM and WM volumes, less WMHs, better baseline memory, and to slower atrophy rates in AD-related areas and less cognitive decline. In contrast, PC2 related to less GM and WM volumes and worse memory at baseline. Similar inflammatory signatures and associations were identified in the independent F.ACE cohort. Our data suggest that there are beneficial and detrimental signatures of inflammatory CSF biomarkers. While higher levels of TAM receptors (sTyro/sAXL) or sTREM2 might reflect a protective glia response to degeneration related to phagocytic clearance, other markers might rather reflect proinflammatory states that have detrimental impact on brain integrity.

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.

FastPtx: a versatile toolbox for rapid, joint design of pTx RF and gradient pulses using Pytorch's autodifferentiation.

OBJECTIVE: With modern optimization methods, free optimization of parallel transmit pulses together with their gradient waveforms can be performed on-line within a short time. A toolbox which uses PyTorch's autodifferentiation for simultaneous optimization of RF and gradient waveforms is presented and its performance is evaluated. METHODS: MR measurements were performed on a 9.4T MRI scanner using a 3D saturated single-shot turboFlash sequence for [Formula: see text] mapping. RF pulse simulation and optimization were done using a Python toolbox and a dedicated server. An RF- and Gradient pulse design toolbox was developed, including a cost function to balance different metrics and respect hardware and regulatory limits. Pulse performance was evaluated in GRE and MPRAGE imaging. Pulses for non-selective and for slab-selective excitation were designed. RESULTS: Universal pulses for non-selective excitation reduced the flip angle error to an NRMSE of (12.3±1.7)% relative to the targeted flip angle in simulations, compared to (42.0±1.4)% in CP mode. The tailored pulses performed best, resulting in a narrow flip angle distribution with NRMSE of (8.2±1.0)%. The tailored pulses could be created in only 66 s, making it feasible to design them during an experiment. A 90° pulse was designed as preparation pulse for a satTFL sequence and achieved a NRMSE of 7.1%. We showed that both MPRAGE and GRE imaging benefited from the pTx pulses created with our toolbox. CONCLUSION: The pTx pulse design toolbox can freely optimize gradient and pTx RF waveforms in a short time. This allows for tailoring high-quality pulses in just over a minute.

A predictor-corrector phase unwrapping algorithm for temporally undersampled gradient-echo MRI.

PURPOSE: To develop a method for unwrapping temporally undersampled and nonlinear gradient recalled echo (GRE) phase. THEORY AND METHODS: Temporal unwrapping is performed as a sequential one step prediction of the echo phase, followed by a correction to the nearest integer wrap-count. A spatio-temporal extension of the 1D predictor corrector unwrapping (PCU) algorithm improves the prediction accuracy, and thereby maintains spatial continuity. The proposed method is evaluated using numerical phantom, physical phantom, and in vivo brain data at both 3 T and 9.4 T. The unwrapping performance is compared with the state-of-the-art temporal and spatial unwrapping algorithms, and the spatio-temporal iterative virtual-echo based Nyquist sampled (iVENyS) algorithm. RESULTS: Simulation results showed significant reduction in unwrapping errors at higher echoes compared with the state-of-the-art algorithms. Similar to the iVENyS algorithm, the PCU algorithm was able to generate spatially smooth phase images for in vivo data acquired at 3 T and 9.4 T, bypassing the use of additional spatial unwrapping step. A key advantage over iVENyS algorithm is the superior performance of PCU algorithm at higher echoes. CONCLUSION: PCU algorithm serves as a robust phase unwrapping method for temporally undersampled and nonlinear GRE phase, particularly in the presence of high field gradients.

Alpha-180 spin-echo based line-scanning method for high resolution laminar-specific fMRI.

Laminar-specific functional magnetic resonance imaging (fMRI) has been widely used to study circuit-specific neuronal activity by mapping spatiotemporal fMRI response patterns across cortical layers. Hemodynamic responses reflect indirect neuronal activity given limit of spatial and temporal resolution. Previous gradient-echo based line-scanning fMRI (GELINE) method was proposed with high temporal (50 ms) and spatial (50 µm) resolution to better characterize the fMRI onset time across cortical layers by employing 2 saturation RF pulses. However, the imperfect RF saturation performance led to poor boundary definition of the reduced region of interest (ROI) and aliasing problems outside of the ROI. Here, we propose α (alpha)-180 spin-echo-based line-scanning fMRI (SELINE) method to resolve this issue by employing a refocusing 180° RF pulse perpendicular to the excitation slice. In contrast to GELINE signals peaked at the superficial layer, we detected varied peaks of laminar-specific BOLD signals across deeper cortical layers with the SELINE method, indicating the well-defined exclusion of the large drain-vein effect with the spin-echo sequence. Furthermore, we applied the SELINE method with 200 ms TR to sample the fast hemodynamic changes across cortical layers with a less draining vein effect. In summary, this SELINE method provides a novel acquisition scheme to identify microvascular-sensitive laminar-specific BOLD responses across cortical depth.

Distribution of corpora amylacea in the human midbrain: using synchrotron radiation phase-contrast microtomography, high-field magnetic resonance imaging, and histology.

Corpora amylacea (CA) are polyglucosan aggregated granules that accumulate in the human body throughout aging. In the cerebrum, CA have been found in proximity to ventricular walls, pial surfaces, and blood vessels. However, studies showing their three-dimensional spatial distribution are sparse. In this study, volumetric images of four human brain stems were obtained with MRI and phase-contrast X-ray microtomography, followed up by Periodic acid Schiff stain for validation. CA appeared as hyperintense spheroid structures with diameters up to 30 µm. An automatic pipeline was developed to segment the CA, and the spatial distribution of over 200,000 individual corpora amylacea could be investigated. A threefold-or higher-density of CA was detected in the dorsomedial column of the periaqueductal gray (860-4,200 CA count/mm3) than in the superior colliculus (150-340 CA count/mm3). We estimated that about 2% of the CA were located in the immediate vicinity of the vessels or in the peri-vascular space. While CA in the ependymal lining of the cerebral aqueduct was rare, the sub-pial tissue of the anterior and posterior midbrain contained several CA. In the sample with the highest CA density, quantitative maps obtained with MRI revealed high R2* values and a diamagnetic shift in a region which spatially coincided with the CA dense region.