PURPOSE:To investigate dipole antennas with electronically switchable transmit field patterns to improve flip angle homogeneity in ultra-high field MRI. METHODS:Reconfigurable dipole elements that could produce two distinct electronically switchable B 1 + field profiles were conceptualized and constructed. Eight such elements were combined into an array. Alteration of the field profiles was accomplished by modulating the currents along the dipoles using a combination of PIN diodes and lumped inductors. The behavior of these reconfigurable elements was studied in numerical electromagnetic simulations and 9.4T MRI measurements, investigating rapid switching of transmit sensitivities during excitation pulses in both single-channel and pTx mode operation. RESULTS:For the simulated dipole elements, modulating the current densities along the dipole's axis causes a ∼ 30% change of the B 1 + field between superior and inferior regions of the brain. When rapidly switched during excitation pulses, this degree of freedom can improve flip angle homogeneity, e.g., by a factor of ∼ 2.2 for a two kT points pTx pulse. For the constructed prototype array, the switching effect was observable but weaker, causing ∼ 10% superior-inferior B 1 + variation. CONCLUSIONS:The proposed coaxial dipole array with switchable transmit sensitivities offers a novel degree of freedom for designing excitation pulses. The approach has the potential to improve flip angle homogeneity without necessitating an expensive increase in the number of independent transmit channels.

Purpose Low- and ultralow-field magnetic resonance imaging (ULF MRI) have inherently low signal-to-noise ratio (SNR) by design. Overhauser dynamic nuclear polarization (ODNP) stands out as an effective solution for continuous signal enhancement. To accelerate imaging and reduce radiofrequency (RF) power deposition-which is critical due to the high-frequency RF fields required for ODNP-efficient pulse sequences are essential. For instance, a balanced steady-state free precession (bSSFP) sequence offers high signal efficiency. However, conventional bSSFP sequences are susceptible to B0 inhomogeneities and temporal field drifts, which can lead to banding artifacts.Methods In this work, we mitigated the limitations of banding artifacts by developing a modified bSSFP sequence (bSSFP180) that allows interleaved polarization and acquisition, thereby tailoring it for ODNP-enhanced ULF MRI. The unmodified and modified sequences are compared in an imaging experiment.Results The proposed sequence effectively suppresses banding artifacts and demonstrates robust performance under inhomogeneous field conditions. Experimental MRI results demonstrated that bSSFP 180 achieves banding artifact-free performance.Conclusion The banding artifact-free bSSFP180 images represent a significant advancement toward the practical and reliable use of ODNP-enhanced imaging in future biomedical applications. This is particularly relevant for MRI experiments that employ lightweight, cost-efficient, permanent magnet systems in low-field environments, which often face challenges related to field instability and inhomogeneity.

Research on visual episodic memory impairment in Alzheimer's disease often focuses on memory processes rather than the specific content of image being remembered. We previously showed that patients with mild cognitive impairment (MCI), a transitional stage that may precede Alzheimer's disease, can memorize certain images well, indicating that episodic memory is not uniformly impaired. Conversely, other specific images could not be memorized by MCI patients and were instead diagnostic for distinguishing MCI from healthy older adults. In this study, we investigate whether poor memory for these diagnostic images relates to impaired neural processing in specific brain regions and Alzheimer's biomarker pathology. We assessed 64 healthy controls and 48 MCI participants from the DZNE Longitudinal Cognitive Impairment and Dementia Study. Participants performed a visual scene memory task during fMRI and provided CSF biomarker data for amyloid and tau. Diagnostic images demonstrated significantly larger behavior-biomarker correlations (total tau, phospho-tau, Aβ42/Aβ40, and Aβ42/phospho-tau) compared with nondiagnostic images. This suggests memory for these specific diagnostic images is more affected by Alzheimer's disease pathology. The fMRI data revealed an interaction effect between group membership (healthy control/MCI) and image diagnosticity (diagnostic/nondiagnostic). MCI participants exhibited higher activation in specific scene-processing regions (parahippocampal place area, retrosplenial cortex, and occipital place area) for diagnostic compared with nondiagnostic images. Healthy controls, however, showed no processing differences between diagnostic and nondiagnostic images. These findings suggest MCI individuals may engage in inefficiently heightened encoding activation for diagnostic images. Our results show that special "diagnostic" images exist that can reliably reveal underlying amyloid and tau pathology alongside altered neural activity in scene regions.

Purpose To investigate how the relaxation rates (R1, R2) and asymmetry indices (AI), derived from phase-cycled balanced steady-state free precession (pc-bSSFP) data, depend on the orientation of white matter (WM) fiber tracts at different field strengths.Methods Phase-cycled bSSFP data acquired at 3 and 9.4T in the healthy human brain were processed using motion-insensitive rapid configuration relaxometry (MIRACLE) and a frequency response analysis to derive R1, R2, and AI values, respectively. Fractional anisotropy (FA) and fiber-to-field angle (theta) were estimated based on 3T diffusion tensor imaging. The orientation dependence of R1, R2, and AI in WM was characterized using literature model fits as well as Monte Carlo random walk simulations to explore the influence of field strength and susceptibility effects.Results R2 and AI exhibited a pronounced orientation dependence while the influence of anisotropy on R1 was weaker, but noticeable. The observed anisotropy increased systematically from 3 to 9.4T. Literature models assuming either a susceptibility or a generalized magic angle effect described the R2 and AI anisotropy to a high degree (R2 >= 0.99). The calculated partial contributions of susceptibility to R2 anisotropy increased from 24.0%-39.0% at 3T to 77.0%-87.1% at 9.4T. The Monte Carlo simulations were able to reproduce the characteristics of R2 anisotropy, but not its strength.Conclusion Microstructure-driven relaxation anisotropy considerably affects pc-bSSFP relaxometry, in particular R2. The findings indicate that R2 anisotropy is driven by susceptibility at ultra-high fields whereas additional mechanisms likely contribute at lower field strengths.

1. Abstract Background The detection of subtle epileptogenic lesions such as focal cortical dysplasias (FCDs) is a clinical challenge in the management of drug-resistant focal epilepsy (DRFE). Ultra-high field (UHF) MRI offers increased signal-to-noise ratios and spatial resolution compared to 3 Tesla (T) MRI and may improve diagnostic yield. Here, we present a 9.4T MRI cohort study of patients with DRFE. Methods We recruited n=21 DRFE patients (with 3T-MRI findings: 2 positive, 3 equivocal, 16 negative) undergoing presurgical workup, and n=20 healthy controls for 9.4T MRI (0.8 mm isotropic MP2RAGE, slabs of 0.375 × 0.375 × 0.8 mm T2*-weighted GRE) and 3T MRI (MP2RAGE, FLAIR) acquisitions. Visual review for possible epileptogenic lesions was performed by clinical experts. For histopathologically confirmed FCD lesions, we extracted surface-based quantitative features (cortical thickness, qT1, FLAIR, T2*, and QSM values) across cortical depths and distances from the lesion centre and performed high-resolution cortical profiling of 9.4T T2* values. Results No new epileptogenic lesions were visually identified at 9.4T in 3T MRI negative patients. In the two patients with histopathologically confirmed lesions, the FCD IIb lesions were visible with distinct qualitative and quantitative features at both field strengths. One of these FCD IIb showed a focal cortical T2* reduction at 9.4T that could here be quantified via automated cortical profiling, consistent with the previously described “black line sign”. Conclusion 9.4T MRI findings in epileptogenic lesions underlying DRFE are consistent with those on 3T MRI. While additional lesions were not identified in patients with negative 3T MRI, higher resolution T2*-weighted sequences can reveal a feature not seen at 3T: Cortical profiling of FCDs highlights the black line sign and can possibly help refine surgical or ablation targeting for some FCDs. Further optimization of UHF protocols and analysis methods on larger cohorts may reveal clinically applicable diagnostic benefits. Key Points - 9.4T MRI shows focal cortical dysplasia (FCD) IIb with distinct qualitative and quantitative features that are consistent with 3T MRI. - High-resolution quantitative T2* maps at 9.4T may provide additional information for defining resection or ablation targets in FCDs. - Without using parallel transmit technology, artefacts in the temporal lobes pose a limitation of 9.4T MRI in presurgical epilepsy workup.

Access to magnetic resonance imaging (MRI) remains severely limited in low- and middle-income countries, especially in sub-Saharan Africa, despite rising rates of non-communicable diseases. Low-field MRI presents an affordable, locally developable diagnostic solution, but its performance is constrained by magnetic field instability. We present a novel NMR field probe designed to overcome these challenges using a rapid non-adiabatic switch-off of a pre-polarization field resulting in precessing spin magnetization. Achieved by first use of high-voltage silicon carbide transistors operating in controlled avalanche breakdown, it measures the Larmor frequency without prior field knowledge, unlike conventional probes. This capability is crucial during magnet development with often unknown fields, allowing early detection of magnet issues, and offering an urgently needed tool for magnet design and image-quality improvement. Validated from 1 mT to 45 mT (up to 1,000 times stronger than similar systems) its low-cost, modular design supports replication, upgrades, and enhanced field control, helping expand global MRI access.

Quantitative MRI enables the detection of subtle microstructural alterations in normal-appearing white matter (NAWM) associated with pathological conditions such as multiple sclerosis. Quantitative metrics including R 1 , R 2 , and the bSSFP asymmetry index (AI) were evaluated in the WM of 20 relapsing-remitting multiple sclerosis (RRMS) patients and 10 healthy controls (HC). A multi-parametric frame-work based on a phase-cycled balanced steady-state free precession (pc-bSSFP) sequence was used. Diffusion tensor imaging–derived measures, including fiber-to-field angle, number of fiber orientations, and fractional anisotropy, were incorporated to assess parameter anisotropy. Statistical analysis was performed using linear mixed-effects models to test for group, ROI, and group-by-ROI effects for each metric, with ROI-specific group comparisons derived from the model. Significant main effects of group, ROI, and group-by-ROI interaction were observed for both R 1 and R 2 , whereas for AI only the ROI effect reached significance (group p= 0.462; group-by-ROI p = 0.786). Fourteen of sixteen ROIs demonstrated significantly lower R 1 and R 2 values in RRMS compared with HC. No ROI showed significant differences in AI. In conclusion, pc-bSSFP–based relaxometry reveals predominantly white matter alterations in RRMS, while enabling a comprehensive whole-brain assessment that also encompasses gray matter.

Abstract High‑temperature superconductors (HTS) cooled with liquid nitrogen are promising for low‑field magnetic resonance imaging (LFMRI) due to improved efficiency and stability. However, the impact of HTS‑induced magnetic noise on image quality must be evaluated. A HTS sample was cooled to 77 K, and its magnetic noise was measured using a SQUID system. The measured 1/ f 2 noise behavior indicates Brownian flux creep from trapped Abrikosov vortices. When extrapolated to a modelled HTS‑based LFMRI magnet, the expected HTS noise was found to be significantly lower than the typical receiver Nyquist noise. Therefore, HTS noise is negligible, and SNR optimization should focus on receiver and sample noise in LFMRI.

Alzheimer's disease (AD) is a major cause of dementia and cognitive decline. Here, we assessed how episodic memory (EM) network dysfunction, a hallmark of AD, is related to the longitudinal progression of AD biomarkers, neurodegeneration and cognition using data from the DZNE DELCODE study. This data set includes over 1000 longitudinal functional magnetic resonance imaging measurements of EM network function. We related activation and deactivation of EM to individual disease progression scores from a disease progression model. Voxel-wise analyses revealed widespread loss of deactivation and activation with disease progression. Trajectories for the loss of deactivation were nonlinear, associated with amyloid- and tau-positivity and visually preceded trajectories of cognitive decline. The relationship between deactivation and cognitive decline was partly independent of neurodegeneration. Our results provide evidence that synaptic dysfunction and neurodegeneration are independent drivers of cognitive decline, providing a rationale for targeting synaptic dysfunction along the AD cascade.

Purpose: Pushing MRI speed further demands more spatially-encoded information captured per unit time, e.g., by superimposing additional field modulations during oversampled readout. However, this can introduce calibration errors and increase reconstruction time. Thus, we propose a continuous field calibration approach and an efficient k-space reconstruction technique. Theory and Methods: Our auto-calibration generalizes GRAPPA kernels to explicitly extract continuous B0 modulation kernels, solving interpolation relationships between two ACS regions differing only in the extra field modulation. The k-space locations sharing the same instantaneous image-space modulation are grouped, so that subsets of time-invariant kernels can be separately estimated, as a generalized solution for Wave-CAIPI/FRONSAC-type scans. This view further inspires a k-space subregion-wise reconstruction technique, as an efficient alternative to conventional hybrid-space reconstruction. At 9.4T, FLASH accelerated by a local B0 coil array and Wave-CAIPI were tested with retrospective undersampling. Results: Artifact-free images were reconstructed, under diverse rapid B0 modulation schemes, reaching maximum acceleration factors of 8-fold in 2D and 14.6-fold in 3D. Some nonlinear gradients modulation schemes reach similar sampling efficiency as linear gradients modulation. The proposed reconstruction shows potentials in reducing reconstruction time. Conclusion: Rapid B0 modulations and widely-adopted parallel imaging can share a common mathematical framework, and consequently, achieve similarly-robust reconstructions. Specifically, for scans using dynamic B0 and static RF kernels, not only signal encoding, but also auto-calibration and reconstruction can be performed in k-space. This paves the way to robustly remove eddy currents, and explore more complex B0 modulation strategies towards ultimate MRI speed.

Brain maintenance - the preservation of brain structure or function relevant to cognitive performance - remains challenging to quantify. Here, we propose a domain-general brain maintenance index derived by jointly modelling the longitudinal co-evolution of ageing-related atrophy (via medial temporal lobe to ventricle ratio, MTLV-ratio), white matter hyperintensities (WMH), and global cognition assessed by the preclinical Alzheimer's cognitive composite (PACC5) using latent growth curve modelling. We demonstrate its utility in 543 cognitively unimpaired older adults from the DELCODE cohort, followed annually over four years. We show that changes in MTLV-ratio and WMH additively predict cognitive change. We further show that higher neuroticism, depressive symptoms, lower openness, and faster biological ageing are related to unfavourable domain-specific trajectories and poorer brain maintenance. Our findings highlight the combined relevance of WMH and ageing-related atrophy dynamics for brain maintenance. Maintaining cerebrovascular and mental health alongside cognitive engagement could promote brain maintenance, delay cognitive decline and dementia.

PURPOSE:To accelerate MRI further, rapid B0 field modulations can be applied during oversampled readout to capture additional physical information, as in Wave-CAIPI/FRONSAC/local B0 coils modulation techniques. These methods, however, turn the Fourier readout into a non-Fourier-encoded dimension that cannot be reconstructed by FFT, posing significant reconstruction challenges especially in compressed-sensing or neural-network frameworks. THEORY AND METHODS:Because the rapid B0 modulations still vary slowly relative to the oversampled ADC dwell time, we exploit this encoding redundancy by compressing k-space patch-by-patch across subregions, each of which is jointly encoded by a distinct subset of B0 and RF (receive) spatial encoding functions. For each subset, a compression matrix is computed once and reused to compress all patches encoded by the same B0-RF spatial modulations. This can be implemented by feeding subsets of B0 and RF spatial encoding maps into an adapted conventional RF array compression algorithm, mimicking an expanded set of virtual receiver channels. This approach was evaluated on human brain scans at 9.4 T/3 T. RESULTS:The proposed group-patch joint compression achieves substantially higher compression factors than conventional RF-only compression, while minimally compromising encoding efficiency. Typically, joint compression factors of 11×-20× led to negligible encoding loss, dramatically reducing reconstruction time and peak memory usage. For example, compressed-sensing reconstruction took 1.4-5.1 s/2D slice, 177 s-10.1 min/3D volume on a high-memory CPU node. CONCLUSION:Given joint encoding of dynamic B0 and static RF fields, compressing multidimensional k-space patches in separate groups outperforms compressing RF receivers alone. This substantially mitigates a fundamental computational bottleneck when combining rapid B0 and RF-receiver modulations.

The bed nucleus of the stria terminalis (BST) and the ventromedial striatum (consisting of the head of the caudate nucleus (hCN) and the nucleus accumbens (NAcc)) are both part of complex, foremost limbic networks involved in a variety of neuropsychiatric conditions. However, data on functional or structural connections between the BST and hCN in humans are scarce. In an earlier study using both diffusion tensor magnetic resonance imaging (DTI) and conventional histology we found a pathway from the BST to the orbitofrontal cortex apparently passing directly through the hCN. To confirm this finding, we now examined the hCN in human ex-vivo brain tissue using polarized light microscopy (PLM), a method particularly suitable for depicting myelinated nerve fibers. We further examined whether differences in fiber distribution inside the hCN could be depicted using high-resolution DTI data. PLM revealed different fiber populations inside the hCN and the NAcc. Fibers in the hCN were mostly related to the anterior limb of the internal capsule (ALIC) with some apparently terminating in the hCN while the majority exited the hCN to enter the prefrontal white matter. Fibers originating from the BST were only scarcely seen on this level and appeared to either terminate inside the hCN or join the ALIC. On levels below the anterior commissure, the BST strongly connected 1) to other basal forebrain structures including the NAcc, and 2) with the white matter of the medial prefrontal cortex. Differences in fiber density within the hCN could be reproduced on MRI data but with strong interindividual variation. In summary, PLM revealed a much more complex fiber architecture in the region of interest than suggested by our earlier DTI findings. The study at hand shows that PLM can be a valuable tool for the verification of unclear or ambiguous DTI fiber tracking results.

The UltraCortex repository houses magnetic resonance imaging data of the human brain obtained at an ultra-high field strength of 9.4 T. It contains 86 structural MR images with spatial resolutions ranging from 0.6 to 0.8 mm. Additionally, the repository includes segmentations of 12 brains into gray and white matter compartments. These segmentations have been independently validated by two expert neuroradiologists, thus establishing them as a reliable gold standard. This resource provides researchers with access to high-quality brain imaging data and validated segmentations, facilitating neuroimaging studies and advancing our understanding of brain structure and function. Existing repositories do not accommodate field strengths beyond 7 T, nor do they offer validated segmentations, underscoring the significance of this new resource.

Subjective cognitive decline (SCD) is proposed as an indicator of transitional disease stage 2 in the Alzheimer’s disease (AD) continuum. However, molecular and particularly longitudinal fluid biomarker data for this stage are still limited. This study aimed to determine whether blood-based biomarkers in amyloid-positive individuals with SCD (A + SCD) support the notion of stage 2 as a distinct stage between stages 1 and 3 of AD and to identify those at high risk for clinical progression. In a prospective multicenter study (DELCODE) involving 457 participants across the AD continuum, we analyzed plasma phospho-tau 181 (p181) and neurofilament light chain (NfL) and assessed their association with longitudinal cognition, hippocampal atrophy, and AD clinical stage transition. The results showed that baseline plasma p181 levels were elevated and increased more rapidly in A + SCD individuals compared to amyloid-positive cognitively unimpaired (A + CU) individuals (stage 1). NfL levels rose across A + CU, A + SCD, and amyloid-positive mild cognitive impairment (A + MCI, stage 3). In A + SCD, but not in A + CU, higher p181 levels predicted cognitive decline (PACC5) and transition to MCI. In conclusion, plasma p181 provides molecular biomarker evidence supporting A + SCD as a pre-dementia AD stage (stage 2) distinct from A + CU (stage 1) and helps identify individuals at risk for cognitive decline early in the AD continuum.

The draining-vein bias of T2*-weighted sequences, like gradient echo echo-planar imaging (GRE-EPI), can limit the spatial specificity of functional MRI (fMRI). The underlying extravascular signal changes increase with field strength (B0) and the perpendicularity of draining veins to the main axis of B0, and are, therefore, particularly problematic at ultra-high field (UHF). In contrast, simulations showed that T2-weighted sequences are less affected by the draining-vein bias, depending on the amount of rephasing of extravascular signal. As large pial veins on the cortical surface follow the cortical folding tightly, their orientation can be approximated by the cortical orientation to B 0 → . In our work, we compare the influence of the cortical orientation to B 0 → on the resting-state fMRI signal of three sequences aiming to understand their macrovascular contribution. While 2D GRE-EPI and 3D GRE-EPI (both T2*-weighted) showed a high dependence on the cortical orientation to B 0 → , especially on the cortical surface, this was not the case for 3D balanced steady-state free precession (bSSFP) (T2/T1-weighted). Here, a slight increase of orientation dependence was shown in depths closest to white matter (WM). And while orientation dependence decreased with increased distance to the veins for both EPI sequences, no change in orientation dependence was observed in bSSFP. This indicates the low macrovascular contribution to the bSSFP signal, making it a promising sequence for layer fMRI at UHF.

We aimed at validating the Mini Social Cognition and Emotional Assessment (Mini-SEA) in a German cohort of mildly impaired behavioural-variant frontotemporal dementia (bvFTD) patients and healthy controls. The Mini-SEA comprises the Facial Emotion Recognition Test (FERT) and the Faux Pas Test (FPT) measuring Theory of Mind (ToM) abilities in social norm-related real-life stories. We examined the diagnostic performance of the Mini-SEA alongside other neuropsychological assessments and investigated its structural neural correlates. We included 32 bvFTD patients and 54 controls in logistic regression models with forward-stepwise selection containing demographics, standard neuropsychological battery (CERAD-NAB+) and the Mini-SEA scores to identify the most relevant variables. Demographic, neuropsychological and daily-life activity associations were explored. Voxel-based morphometry analysis was conducted in a subsample (14 bvFTD and 14 controls) on regions previously linked to emotion processing and ToM functions. The Mini-SEA yielded a very good performance, being in the best-fitting model with a high odds ratio alongside the executive-language and memory measures. Specifically, the FERT indicated the strongest effect in the group differentiation. Mini-SEA showed significant associations with executive-language tests and daily-life activities. In canonical emotion processing brain regions, we found associations of the Mini-SEA composite and the FERT with grey matter volumes in the left insula and lentiform nucleus of putamen. Within ToM regions, associations were found for the Mini-SEA composite and the FPT in cerebellar regions. The German Mini-SEA discriminates well between mildly impaired bvFTD patients and controls. We also demonstrated its significant value for neuropsychological assessment and neuro-behavioural associations in regions underlying emotion processing and ToM.

We demonstrated the feasibility of using bSSFP acquisitions for off-resonance insensitive high-resolution [6,6'-2H2]-glucose deuterium metabolic imaging (DMI) studies in the healthy human brain at 9.4T. Balanced SSFP acquisitions have potential to improve the sensitivity of DMI despite the SNR loss of phase-cycling and other human scanner constraints.We investigated two variants of bSSFP acquisitions, namely uniform-weighted multi echo and acquisition-weighted CSI to improve the SNR of deuterium metabolic imaging (DMI) in the brain with oral labelled-glucose intake. Phase-cycling was introduced to make bSSFP acquisitions less sensitive to B0 inhomogeneity. Two SNR optimal methods for obtaining metabolite amplitudes from the phase-cycled data were proposed. The SNR performance of the two bSSFP variants was compared with a standard gradient-spoiled CSI acquisition and subsequent IDEAL processing. In addition, in vivo T1 and T2 of water, glucose and Glx (glutamate+glutamine) were estimated from non-localized inversion recovery and spin-echo measurements.High-resolution whole-brain dynamic quantitative DMI maps were successfully obtained for all three acquisitions. Phase-cycling improved the quality of bSSFP metabolite estimation and provided additional spectral encoding. The SNR improvement was only observed for the CSI variant of bSSFP acquisitions with an average increase of 18 respectively, compared to the vendor's CSI. ME-bSSFP acquisition achieved higher resolutions than acquisition-weighted CSI and exhibited several qualitative improvements.

PURPOSE:The aim was to improve the sensitivity and robustness against B0 inhomogeneities of deuterium metabolic imaging (DMI) using phase-cycled balanced SSFP (bSSFP) methods at 9.4 T. METHODS:We investigated two variants of phase-cycled bSSFP acquisitions, namely uniformly weighted multi-echo and acquisition-weighted chemical shift imaging (CSI) to improve the SNR of DMI in the brain after oral [6,6'-2H2]-glucose intake. Phase-cycling was introduced to reduce the off-resonance sensitivity of bSSFP, incurring a moderate SNR loss. Two SNR optimal methods for obtaining metabolite amplitudes from the phase-cycled bSSFP data were proposed. The SNR performance of the two bSSFP variants was compared with the SNR-optimized vendor's standard CSI. Additionally, in vivo T1 and T2 of deuterium metabolites were estimated. RESULTS:High-resolution whole-brain dynamic DMI maps were obtained for all acquisitions. The CSI variant of phase-cycled bSSFP achieved an average SNR increase of 16% and 25% for glucose and glutamate + glutamine (Glx), respectively, compared to the SNR-optimized vendor's standard CSI. Phase-cycling improved the bSSFP metabolite estimation and provided additional spectral encoding at the cost of a 10% to 20% SNR loss. Compared to the CSI variant of bSSFP acquisition, the multi-echo variant exhibited up to 35% lower SNR performance because of uniform k-space weighting and less efficient readout. However, it achieved higher resolutions than acquisition-weighted CSI protocols and showed several qualitative improvements. CONCLUSION:We demonstrated the feasibility of using two phase-cycled bSSFP acquisitions for off-resonance insensitive high-resolution [6,6'-2H2]-glucose DMI studies in the human brain. bSSFP acquisitions have potential to improve the sensitivity of DMI despite the SNR loss of phase-cycling and other human scanner constraints.

Alzheimer’s disease (AD) is characterised by the accumulation of beta-amyloid (Aβ) and tau proteins, leading to neurodegeneration and cognitive decline. While Aβ and tau are known to disrupt synaptic function, the mechanisms linking these molecular pathologies to network-level dysfunction and memory impairment remain poorly understood. Here we investigated the effects of Aβ and tau pathology (CSF Aβ42/40 ratio and tau phosphorylated at position 181, p-tau-181, respectively) on effective connectivity (EC) related to memory encoding, which may constitute a link between synaptic pathology and cognitive outcomes. Functional magnetic resonance imaging (fMRI) during visual memory encoding was acquired from participants of the multicentric DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE), including 203 cognitively normal older participants (CN) as well as individuals with subjective cognitive decline (SCD; N = 204), mild cognitive impairment (MCI; N = 65), and early dementia due to AD (DAT; N = 21). EC was assessed by applying Dynamic causal modelling (DCM) to the fMRI data, using brain regions previously implicated in memory-encoding: the parahippocampal place area (PPA), the hippocampus (HC) and the precuneus (PCU). Disruptions in forward connectivity from the PPA to the HC and PCU were associated with both memory impairment and indices of AD pathology. Specifically, reduced excitatory EC from the PPA to the HC was associated with higher p-tau-181 levels and correlated with poorer memory performance. Diminished inhibitory EC from the PPA to the PCU was driven by both tau and amyloid pathology and was likewise linked to memory decline. Our findings suggest that disrupted forward connectivity within the temporo-parietal memory network constitutes a candidate mechanism mediating the relationship between molecular pathology and cognitive dysfunction. ### Competing Interest Statement E.D. is one of co-founders of neotiv GmbH and conducted paid consultancy work for Eisai, Lilly, Biogen, Roche and RoxHealth (unrelated to this study). C.B. received honoraria as a commercial advisory board member for Lilly (April 2024); honoria for lectures from Boehringer Ingelheim (September 2024), Roche (June 2021), Lilly (March 2025) and Eisai (April 2024); and funding from the German Alzheimer Association (DAlzG; 2021-2023). * AB : beta-amyloid AD : Alzheimer’s disease CN : cognitively normal DAT : dementia of Alzheimer’s type DCM : Dynamic causal modelling DELCODE : DZNE - Longitudinal Cognitive Impairment and Dementia Study DZNE : German Centre for Neurodegenerative Diseases GAMs : Generalised additive models HC : hippocampus MCI : mild cognitive impairment PPA : parahippocampal place area PCU : precuneus p-tau : phosphorylated tau SCD : subjective cognitive decline Deutsche Forschungsgemeinschaft, 362321501/RTG 2413 'SynAGE', 374011584/3T Ganzkörper MR-Tomograf, CRC 1436, projects C01, B02, and A05 German Center for Neurodegenerative Diseases, https://ror.org/043j0f473, BN012