NMR in Biomedicine最新文献

Compositional changes can occur in the osteochondral junction (OCJ) during the early stages and progressive disease evolution of knee osteoarthritis (OA). However, conventional magnetic resonance imaging (MRI) sequences are not able to image these regions efficiently because of the OCJ region's rapid signal decay. The development of new sequences able to image and quantify OCJ region is therefore highly desirable. We developed a comprehensive ultrashort echo time (UTE) MRI protocol for quantitative assessment of OCJ region in the knee joint, including UTE variable flip angle technique for T₁ mapping, UTE magnetization transfer (UTE-MT) modeling for macromolecular proton fraction (MMF) mapping, UTE adiabatic T_1ρ (UTE-AdiabT_1ρ) sequence for T_1ρ mapping, and multi-echo UTE sequence for T₂* mapping. B₁ mapping based on the UTE actual flip angle technique was utilized for B₁ correction in T₁, MMF, and T_1ρ measurements. Ten normal and one abnormal cadaveric human knee joints were scanned on a 3T clinical MRI scanner to investigate the feasibility of OCJ imaging using the proposed protocol. Volumetric T₁, MMF, T_1ρ, and T₂* maps of the OCJ, as well as the superficial and full-thickness cartilage regions, were successfully produced using the quantitative UTE imaging protocol. Significantly lower T₁, T_1ρ, and T₂* relaxation times were observed in the OCJ region compared with those observed in both the superficial and full-thickness cartilage regions, whereas MMF showed significantly higher values in the OCJ region. In addition, all four UTE biomarkers showed substantial differences in the OCJ region between normal and abnormal knees. These results indicate that the newly developed 3D quantitative UTE imaging techniques are feasible for T₁, MMF, T_1ρ, and T₂* mapping of knee OCJ, representative of a promising approach for the evaluation of compositional changes in early knee OA.

Magnetic resonance imaging (MRI) was applied to determine the sex of polar cod (Boreogadus saida Lepechin, 1774) (Actinopterygii: Gadidae) and to follow the gonadal development in individual animals over time. Individual unanaesthetised fish were transferred to a measurement chamber inside a preclinical 9.4 T MRI scanner and continuously perfused with aerated seawater. A screening procedure at an average of 3.5 h, consisting of a set of MRI scans of different orientations, was repeated every 4 weeks on the same set of reproducing B. saida (n = 10) with a body length of about 20 cm. Adapted multi-slice flow-compensated fast low-angle shot (FcFLASH) and rapid acquisition with relaxation enhancement (RARE) protocols with an in-plane resolution of 313 μm and an acquisition time of 2.5 min were used to visualise the morphology of various organs, including the gonads within the field of view (FOV). The MR images provided high resolution, enabling specific sex determination, calculation of gonad volumes, and determination of oocyte sizes. Gonad maturation was followed over 4 months from November 2021 until shortly before spawning in February 2022. The gonad volume increased by 2.3-25.5% for males and by 11.5-760.7% for females during the observation period. From October to February, the oocyte diameter increased from 427 μm (n = 1) to 1346 ± 27 μm (n = 4). Interestingly, individual oocytes showed changes in MR contrast over time that can be attributed to the morphological development of the oocytes. The results fit well with previous literature data from classical invasive studies. The presented approach has great potential for various ecophysiological applications such as monitoring natural or delayed development of internal organs or sex determination under different environmental conditions.

Iron and myelin are primary susceptibility sources in the human brain. These substances are essential for a healthy brain, and their abnormalities are often related to various neurological disorders. Recently, an advanced susceptibility mapping technique, which is referred to as χ-separation (pronounced as "chi"-separation), has been proposed, successfully disentangling paramagnetic iron from diamagnetic myelin. This method provided a new opportunity for generating high-resolution iron and myelin maps of the brain. Utilizing this technique, this study constructs a normative χ-separation atlas from 106 healthy human brains. The resulting atlas provides detailed anatomical structures associated with the distributions of iron and myelin, clearly delineating subcortical nuclei, thalamic nuclei, and white matter fiber bundles. Additionally, susceptibility values in a number of regions of interest are reported along with age-dependent changes. This atlas may have direct applications such as localization of subcortical structures for deep brain stimulation or high-intensity focused ultrasound and also serve as a valuable resource for future research.

Sensitivity analysis enables the identification of influential parameters and the optimisation of model composition. Such methods have not previously been applied systematically to models describing hyperpolarised ¹²⁹Xe gas exchange in the lung. Here, we evaluate the current ¹²⁹Xe gas exchange models to assess their precision for identifying alterations in pulmonary vascular function and lung microstructure. We assess sensitivity using established univariate methods and scatter plots for parameter interactions. We apply them to the model described by Patz et al and the Model of Xenon Exchange (MOXE), examining their ability to measure: i) importance (rank), ii) temporal dependence and iii) interaction effects of each parameter across healthy and diseased ranges. The univariate methods and scatter plot analyses demonstrate consistently similar results for the importance of parameters common to both models evaluated. Alveolar surface area to volume ratio is identified as the parameter to which model signals are most sensitive. The alveolar-capillary barrier thickness is identified as a low-sensitivity parameter for the MOXE model. An acquisition window of at least 200 ms effectively demonstrates model sensitivity to most parameters. Scatter plots reveal interaction effects in both models, impacting output variability and sensitivity. Our sensitivity analysis ranks the parameters within the model described by Patz et al and within the MOXE model. The MOXE model shows low sensitivity to alveolar-capillary barrier thickness, highlighting the need for designing acquisition protocols optimised for the measurement of this parameter. The presence of parameter interaction effects highlights the requirement for care in interpreting model outputs.

Functional magnetic resonance spectroscopy (fMRS) measures dynamic changes in metabolite concentration in response to neural stimulation. The biophysical basis of these changes remains unclear. One hypothesis suggests that an increase or decrease in the glutamate signal detected by fMRS could be due to neurotransmitter movements between cellular compartments with different T₂ relaxation times. Previous studies reporting glutamate (Glu) T₂ values have generally sampled at echo times (TEs) within the range of 30-450 ms, which is not adequate to observe a component with short T₂ (<20 ms). Here, we acquire MRS measurements for Glu, (t) total creatine (tCr) and total N-acetylaspartate (tNAA) from the visual cortex in 14 healthy participants at a range of TE values between 9.3-280 ms during short blocks (64 s) of flickering checkerboards and rest to examine both the short- and long-T₂ components of the curve. We fit monoexponential and biexponential Glu, tCr and tNAA T₂ relaxation curves for rest and stimulation and use Akaike information criterion to assess best model fit. We also include power calculations for detection of a 2% shift of Glu between compartments for each TE. Using pooled data over all participants at rest, we observed a short Glu T₂-component with T₂ = 10 ms and volume fraction of 0.35, a short tCr T₂-component with T₂ = 26 ms and volume fraction of 0.25 and a short tNAA T₂-component around 15 ms with volume fraction of 0.34. No statistically significant change in Glu, tCr and tNAA signal during stimulation was detected at any TE. The volume fractions of short-T₂ component between rest and active conditions were not statistically different. This study provides evidence for a short T₂-component for Glu, tCr and tNAA but no evidence to support the hypothesis of task-related changes in glutamate distribution between short and long T₂ compartments.

In recent years, diffusion models have made significant progress in accelerating magnetic resonance imaging. Nevertheless, it still has inherent limitations, such as prolonged iteration times and sluggish convergence rates. In this work, we present a novel generalized map generation model based on mean-reverting SDE, called GM-SDE, to alleviate these shortcomings. Notably, the core idea of GM-SDE is optimizing the initial values of the iterative algorithm. Specifically, the training process of GM-SDE diffuses the original k-space data to an intermediary degraded state with fixed Gaussian noise, while the reconstruction process generates the data by reversing this process. Based on the generalized map, three variants of GM-SDE are proposed to learn k-space data with different structural characteristics to improve the effectiveness of model training. GM-SDE also exhibits flexibility, as it can be integrated with traditional constraints, thereby further enhancing its overall performance. Experimental results showed that the proposed method can reduce reconstruction time and deliver excellent image reconstruction capabilities compared to the complete diffusion-based method.

This work aims to develop and implement a pulse-acquire sequence for three-dimensional (3D) single-voxel localized ¹³C MRS in humans at 7 T, in conjunction with bilevel broadband ¹H decoupling, and to test its feasibility in vitro and in vivo in human calf muscle with emphasis on the detection of glycogen C₁-C₆. A localization scheme suitable for measuring fast-relaxing ¹³C signals in humans at 7 T was developed and implemented using the outer volume suppression (OVS) and one-dimensional image selected in vivo spectroscopy (ISIS-1D) schemes, similar to that which was previously reported in humans at 4 T. The 3D ¹³C localization scheme was followed by uniform ¹³C adiabatic excitation, all complemented with an option for bilevel broadband ¹H decoupling to improve both ¹³C sensitivity and spectral resolution at 7 T. The performance of the pulse-acquire sequence was investigated in vitro on phantoms and in vivo in the human calf muscle of three healthy volunteers, while measuring glycogen C₁-C₆. In addition, T₁ and T₂ of glycogen C₁-C₆ were measured in vitro at 7 T, as well as T₁ of glycogen C₁ in vivo. The glycerol C₂ and C_1,3 lipid resonances were efficiently suppressed in vitro at 7 T using the OVS and ISIS-1D schemes, allowing distinct detection of glycogen C₂-C₆. While some glycerol remained in calf muscle in vivo, the intense lipid at 130 ppm was efficiently suppressed. The ¹³C sensitivity and spectral resolution of glycogen C₁-C₆ in vitro and glycogen C₁ in vivo were improved at 7 T using bilevel broadband ¹H decoupling. The T₁ and T₂ of glycogen C₁-C₆ in vitro at 7 T were consistent compared with those at 8.5 T, while the T₁ of glycogen C₁ in vivo at 7 T resulted similar to that in vitro. Localized ¹³C MRS is feasible in human calf muscle in vivo at 7 T, and this will allow further extension of this method for ¹³C MRS measurements such as in the brain.

Slice-to-volume registration and super-resolution reconstruction are commonly used to generate 3D volumes of the fetal brain from 2D stacks of slices acquired in multiple orientations. A critical initial step in this pipeline is to select one stack with the minimum motion among all input stacks as a reference for registration. An accurate and unbiased motion assessment (MA) is thus crucial for successful selection. Here, we presented an MA method that determines the minimum motion stack based on 3D low-rank approximation using CANDECOMP/PARAFAC (CP) decomposition. Compared to the current 2D singular value decomposition (SVD) based method that requires flattening stacks into matrices to obtain ranks, in which the spatial information is lost, the CP-based method can factorize 3D stack into low-rank and sparse components in a computationally efficient manner. The difference between the original stack and its low-rank approximation was proposed as the motion indicator. Experiments on linearly and randomly simulated motion illustrated that CP demonstrated higher sensitivity in detecting small motion with a lower baseline bias, and achieved a higher assessment accuracy of 95.45% in identifying the minimum motion stack, compared to the SVD-based method with 58.18%. CP also showed superior motion assessment capabilities in real-data evaluations. Additionally, combining CP with the existing SRR-SVR pipeline significantly improved 3D volume reconstruction. The results indicated that our proposed CP showed superior performance compared to SVD-based methods with higher sensitivity to motion, assessment accuracy, and lower baseline bias, and can be used as a prior step to improve fetal brain reconstruction.

Understanding the effects of white matter (WM) axon fibre microstructure on T1 relaxation is important for neuroimaging. Here, we have studied the interrelationship between T1 and axon fibre configurations at 3T and 7T. T1 and S0 (=signal intensity at zero TI) were computed from MP2RAGE images acquired with six inversion recovery times. Multishell diffusion MRI images were analysed for fractional anisotropy (FA); MD; V1; the volume fractions for the first (f₁), second (f₂) and third (f₃) fibre configuration; and fibre density cross-section images for the first (fdc₁), second (fdc₂) and third (fdc₃) fibres. T1 values were plotted as a function of FA, f₁, f₂, f₃, fdc₁, fdc₂ and fdc₃ to examine interrelationships between the longitudinal relaxation and the diffusion MRI microstructural measures. T1 values decreased with increasing FA, f₁ and f₂ in a nonlinear fashion. At low FA values (from 0.2 to 0.4), a steep shortening of T1 was followed by a shallow shortening by 6%-10% at both fields. The steep shortening was associated with decreasing S0 and MD. T1 also decreased with increasing fdc₁ values in a nonlinear fashion. Instead, only a small T1 change as a function of either f₃ or fdc₃ was observed. In WM areas selected by fdc₁ only masks, T1 was shorter than in those with fdc₂/fdc₃. In WM areas with high single fibre populations, as delineated by f₁/fdc₁ masks, T1 was shorter than in tissue with high complex fibre configurations, as segmented by f₂/fdc₂ or f₃/fdc₃ masks. T1 differences between these WM areas are attributable to combined effects by T1 anisotropy and lowered FA. The current data show strong interrelationships between T1, axon fibre configuration and orientation in healthy WM. It is concluded that diffusion MRI microstructural measures are essential in the effort to interpret quantitative T1 images in terms of tissue state in health and disease.

Leukemia is a group of blood cancers that are classified in four major classes. Within these four classes, many different subtypes exists with similar origin, genetic mutations, and level of maturity, which can make them difficult to distinguish. Despite their similarities, they might respond differently to treatment, and therefore distinguishing between them is of crucial importance. A deranged metabolic phenotype (Warburg effect) is often seen in cancer cells, leukemia cells included, and is increasingly a target for improved diagnosis and treatment. In this study, hyperpolarized ¹³C NMR spectroscopy was used to characterize the metabolic signatures of the six leukemia cell lines ML-1, CCRF-CEM, THP-1, MOLT-4, HL-60, and K562. This was done using [1-¹³C]pyruvate and [1-¹³C]alanine as bioprobes for downstream metabolite quantification and kinetic analysis on cultured cells with and without 2-deoxy-D-glucose treatment. The metabolic signatures of similar leukemia subtypes could be readily distinguished. This includes ML-1 and THP-1, which are of the similar M4 and M5 AML subtypes, CCRF-CEM and MOLT-4, which are of the similar T-ALL lineage at different maturation states, and HL-60 and K562, which are of the closely related M1 and M2 AML subtypes. The data presented here demonstrate the potential of hyperpolarized ¹³C NMR spectroscopy as a method to differentiate between leukemia subtypes of similar origin. Combining this method with bioreactor setups could potentially allow for better leukemia disease management as metabolic signatures could be acquired from a single biopsy through repeated experimentation and intervention.