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1.
Nat Methods ; 19(11): 1500-1509, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36253644

RESUMO

Forming a complete picture of the relationship between neural activity and skeletal kinematics requires quantification of skeletal joint biomechanics during free behavior; however, without detailed knowledge of the underlying skeletal motion, inferring limb kinematics using surface-tracking approaches is difficult, especially for animals where the relationship between the surface and underlying skeleton changes during motion. Here we developed a videography-based method enabling detailed three-dimensional kinematic quantification of an anatomically defined skeleton in untethered freely behaving rats and mice. This skeleton-based model was constrained using anatomical principles and joint motion limits and provided skeletal pose estimates for a range of body sizes, even when limbs were occluded. Model-inferred limb positions and joint kinematics during gait and gap-crossing behaviors were verified by direct measurement of either limb placement or limb kinematics using inertial measurement units. Together we show that complex decision-making behaviors can be accurately reconstructed at the level of skeletal kinematics using our anatomically constrained model.


Assuntos
Marcha , Roedores , Animais , Ratos , Camundongos , Fenômenos Biomecânicos , Amplitude de Movimento Articular
2.
Mol Psychiatry ; 29(4): 992-1004, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38216727

RESUMO

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.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Encéfalo , Cognição , Disfunção Cognitiva , Inflamação , Imageamento por Ressonância Magnética , Substância Branca , Proteínas tau , Humanos , Masculino , Feminino , Biomarcadores/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/patologia , Pessoa de Meia-Idade , Encéfalo/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Cognição/fisiologia , Inflamação/líquido cefalorraquidiano , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/líquido cefalorraquidiano , Substância Branca/patologia , Proteínas tau/líquido cefalorraquidiano , Estudos Longitudinais , Substância Cinzenta/patologia , Estudos de Coortes
3.
PLoS Biol ; 20(12): e3001951, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36577117

RESUMO

[This corrects the article DOI: 10.1371/journal.pbio.3000923.].

4.
Brain ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743817

RESUMO

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.

5.
Brain ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38654513

RESUMO

Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) 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 ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD 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 if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD 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 AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all 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 MCI 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, both on the subject and group level, were 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 AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.

6.
Magn Reson Med ; 91(4): 1707-1722, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38084410

RESUMO

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.


Assuntos
Algoritmos , Encéfalo , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cabeça , Simulação por Computador
7.
Magn Reson Med ; 92(1): 186-201, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38440956

RESUMO

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.


Assuntos
Algoritmos , Encéfalo , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento Tridimensional/métodos , Encéfalo/diagnóstico por imagem , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador/métodos , Mapeamento Encefálico/métodos , Reprodutibilidade dos Testes , Razão Sinal-Ruído
8.
Magn Reson Med ; 92(2): 645-659, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38469935

RESUMO

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.


Assuntos
Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/instrumentação , Humanos , Imagens de Fantasmas , Amplificadores Eletrônicos , Ondas de Rádio , Algoritmos , Reprodutibilidade dos Testes , Artefatos , Desenho de Equipamento
9.
NMR Biomed ; : e5168, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716493

RESUMO

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.

10.
NMR Biomed ; 37(6): e5118, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38342102

RESUMO

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.


Assuntos
Imageamento por Ressonância Magnética , Razão Sinal-Ruído , Imageamento por Ressonância Magnética/instrumentação , Humanos , Imagens de Fantasmas , Desenho de Equipamento , Encéfalo/diagnóstico por imagem
11.
PLoS Biol ; 19(9): e3000923, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499636

RESUMO

Current approaches to high-field functional MRI (fMRI) provide 2 means to map hemodynamics at the level of single vessels in the brain. One is through changes in deoxyhemoglobin in venules, i.e., blood oxygenation level-dependent (BOLD) fMRI, while the second is through changes in arteriole diameter, i.e., cerebral blood volume (CBV) fMRI. Here, we introduce cerebral blood flow-related velocity-based fMRI, denoted CBFv-fMRI, which uses high-resolution phase contrast (PC) MRI to form velocity measurements of flow. We use CBFv-fMRI in measure changes in blood velocity in single penetrating microvessels across rat parietal cortex. In contrast to the venule-dominated BOLD and arteriole-dominated CBV fMRI signals, CBFv-fMRI is comparable from both arterioles and venules. A single fMRI platform is used to map changes in blood pO2 (BOLD), volume (CBV), and velocity (CBFv). This combined high-resolution single-vessel fMRI mapping scheme enables vessel-specific hemodynamic mapping in animal models of normal and diseased states and further has translational potential to map vascular dementia in diseased or injured human brains with ultra-high-field fMRI.


Assuntos
Velocidade do Fluxo Sanguíneo , Circulação Cerebrovascular , Imageamento por Ressonância Magnética/métodos , Animais , Encéfalo/irrigação sanguínea , Masculino , Oxigênio/sangue , Ratos Sprague-Dawley
12.
Brain ; 146(5): 2075-2088, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36288546

RESUMO

Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Doença de Alzheimer/psicologia , Encéfalo , Disfunção Cognitiva/psicologia , Colinérgicos
13.
MAGMA ; 37(1): 127-138, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38064137

RESUMO

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.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Algoritmos , Simulação por Computador , Imagens de Fantasmas
14.
MAGMA ; 37(2): 169-183, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38197908

RESUMO

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.


Assuntos
Imageamento por Ressonância Magnética , Imãs , Imageamento por Ressonância Magnética/métodos
15.
Int J Mol Sci ; 25(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38612851

RESUMO

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.


Assuntos
Neoplasias , Óxidos de Nitrogênio , Albumina Sérica Humana , Humanos , Meios de Contraste , Imageamento por Ressonância Magnética
16.
Nat Methods ; 17(1): 64-67, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31768059

RESUMO

Magnetic resonance imaging and spectroscopy are versatile methods for probing brain physiology, but their intrinsically low sensitivity limits the achievable spatial and temporal resolution. Here, we introduce a monolithically integrated NMR-on-a-chip needle that combines an ultra-sensitive 300 µm NMR coil with a complete NMR transceiver, enabling in vivo measurements of blood oxygenation and flow in nanoliter volumes at a sampling rate of 200 Hz.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética/métodos , Oxigênio/metabolismo , Animais , Velocidade do Fluxo Sanguíneo , Masculino , Ratos , Ratos Sprague-Dawley
17.
Magn Reson Med ; 89(1): 322-330, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36120984

RESUMO

PURPOSE: To evaluate the usage of three-dimensional (3D) presaturated TurboFLASH (satTFL) for B 1 + $$ {\mathrm{B}}_1^{+} $$ and B 0 $$ {\mathrm{B}}_0 $$ mapping on single channel and parallel transmission (pTx) systems. METHODS: B 1 + $$ {\mathrm{B}}_1^{+} $$ maps recorded with 3D satTFL were compared to maps from three other 3D B 1 + $$ {\mathrm{B}}_1^{+} $$ mapping sequences in an agar phantom. Furthermore, individual-channel B 1 + $$ {\mathrm{B}}_1^{+} $$ maps of 18 human subjects were recorded with 3D satTFL using B 1 + $$ {\mathrm{B}}_1^{+} $$ interferometry. A neural network was trained for masking of the maps. RESULTS: Out of the sequences compared satTFL was the only one with a mapping range exceeding well over 90°. In regions with lower flip angles there was high correspondence between satTFL and AFI. DREAM and double angle method also showed high qualitative similarity, however the magnitude differed from the other two measurements. The individual-channel B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were successfully used for pTx pulse calculation in a separate study. CONCLUSION: 3D satTFL can record high-quality B 1 + $$ {\mathrm{B}}_1^{+} $$ maps with a high dynamic range in a short time. Correspondence with AFI maps is high, while measurement duration is reduced drastically.


Assuntos
Algoritmos , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Fluxo de Trabalho , Imagens de Fantasmas , Encéfalo
18.
Magn Reson Med ; 90(4): 1713-1727, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37332195

RESUMO

PURPOSE: To extend the concept of 3D dynamic parallel imaging, we developed a prototype of an electronically reconfigurable dipole array that provides sensitivity alteration along the dipole length. METHODS: We developed a radiofrequency array coil consisting of eight reconfigurable elevated-end dipole antennas. The receive sensitivity profile of each dipole can be electronically shifted toward one or the other end by electrical shortening or lengthening the dipole arms using positive-intrinsic-negative-diode lump-element switching units. Based on the results of electromagnetic simulations, we built the prototype and tested it at 9.4 T on phantom and healthy volunteer. A modified 3D SENSE reconstruction was used, and geometry factor (g-factor) calculations were performed to assess the new array coil. RESULTS: Electromagnetic simulations showed that the new array coil was capable of alteration of its receive sensitivity profile along the dipole length. Electromagnetic and g-factor simulations showed closely agreeing predictions when compared to the measurements. The new dynamically reconfigurable dipole array provided significant improvement in geometry factor compared to static dipoles. We obtained up to 220% improvement for 3 × 2 (Ry × Rz ) acceleration compared to the static configuration case in terms of maximum g-factor and up to 54% in terms of mean g-factor for the same acceleration. CONCLUSION: We presented an 8-element prototype of a novel electronically reconfigurable dipole receive array that permits rapid sensitivity modulations along the dipole axes. Applying dynamic sensitivity modulation during image acquisition emulates two virtual rows of receive elements along the z-direction, and therefore improves parallel imaging performance for 3D acquisitions.


Assuntos
Campos Magnéticos , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Desenho de Equipamento , Imageamento Tridimensional , Imagens de Fantasmas , Ondas de Rádio
19.
Magn Reson Med ; 90(5): 1874-1888, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37392412

RESUMO

PURPOSE: Clinical use of transcranial electrical stimulation (TES) requires accurate knowledge of the injected current distribution in the brain. MR current density imaging (MRCDI) uses measurements of the TES-induced magnetic fields to provide this information. However, sufficient sensitivity and image quality in humans in vivo has only been documented for single-slice imaging. METHODS: A recently developed, optimally spoiled, acquisition-weighted, gradient echo-based 2D-MRCDI method has now been advanced for volume coverage with densely or sparsely distributed slices: The 3D rectilinear sampling (3D-DENSE) and simultaneous multislice acquisition (SMS-SPARSE) were optimized and verified by cable-loop experiments and tested with 1-mA TES experiments for two common electrode montages. RESULTS: Comparisons between the volumetric methods against the 2D-MRCDI showed that relatively long acquisition times of 3D-DENSE using a single slab with six slices hindered the expected sensitivity improvement in the current-induced field measurements but improved sensitivity by 61% in the Laplacian of the field, on which some MRCDI reconstruction methods rely. Also, SMS-SPARSE acquisition of three slices, with a factor 2 CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) acceleration, performed best against the 2D-MRCDI with sensitivity improvements for the ∆ B z , c $$ \Delta {B}_{z,c} $$ and Laplacian noise floors of 56% and 78% (baseline without current flow) as well as 43% and 55% (current injection into head). SMS-SPARSE reached a sensitivity of 67 pT for three distant slices at 2 × 2 × 3 mm3 resolution in 10 min of total scan time, and consistently improved image quality. CONCLUSION: Volumetric MRCDI measurements with high sensitivity and image quality are well suited to characterize the TES field distribution in the human brain.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cabeça , Imagens de Fantasmas , Campos Magnéticos , Processamento de Imagem Assistida por Computador/métodos
20.
Magn Reson Med ; 90(4): 1345-1362, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37357374

RESUMO

PURPOSE: An end-to-end differentiable 2D Bloch simulation is used to reduce T2 induced blurring in single-shot turbo spin echo sequences, also called rapid imaging with refocused echoes (RARE) sequences, by using a joint optimization of refocusing flip angles and a convolutional neural network. METHODS: Simulation and optimization were performed in the MR-zero framework. Variable flip angle train and DenseNet parameters were optimized jointly using the instantaneous transverse magnetization, available in our simulation, at a certain echo time, which serves as ideal blurring-free target. Final optimized sequences were exported for in vivo measurements at a real system (3 T Siemens, PRISMA) using the Pulseq standard. RESULTS: The optimized RARE was able to successfully lower T2 -induced blurring for single-shot RARE sequences in proton density-weighted and T2 -weighted images. In addition to an increased sharpness, the neural network allowed correction of the contrast changes to match the theoretical transversal magnetization. The optimization found flip angle design strategies similar to existing literature, however, visual inspection of the images and evaluation of the respective point spread function demonstrated an improved performance. CONCLUSIONS: This work demonstrates that when variable flip angles and a convolutional neural network are optimized jointly in an end-to-end approach, sequences with more efficient minimization of T2 -induced blurring can be found. This allows faster single- or multi-shot RARE MRI with longer echo trains.


Assuntos
Imageamento por Ressonância Magnética , Redes Neurais de Computação , Imageamento por Ressonância Magnética/métodos , Simulação por Computador , Fatores de Tempo , Prótons
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