NMR in Biomedicine最新文献

Since the overall glioma mass and its subcomponents-enhancing region (malignant part of the tumor), non-enhancing (less aggressive tumor cells), necrotic core (dead cells), and edema (water deposition)-are complex and irregular structures, non-Euclidean geometric measures such as fractal dimension (FD or "fractality") and lacunarity are needed to quantify their structural complexity. Fractality measures the extent of structural irregularity, while lacunarity measures the spatial distribution or gaps. The complex geometric patterns of the glioma subcomponents may be closely associated with the grade and molecular landscape. Therefore, we measured FD and lacunarity in the glioma subcomponents and developed machine learning models to discriminate between tumor grades and isocitrate dehydrogenase (IDH) gene status. 3D fractal dimension (FD3D) and lacunarity (Lac3D) were measured for the enhancing, non-enhancing plus necrotic core, and edema-subcomponents using preoperative structural-MRI obtained from the The Cancer Genome Atlas (TCGA) and University of California San Francisco Preoperative Diffuse Glioma MRI (UCSF-PDGM) glioma cohorts. The FD3D and Lac3D measures of the tumor-subcomponents were then compared across glioma grades (HGGs: high-grade gliomas vs. LGGs: low-grade gliomas) and IDH status (mutant vs. wild type). Using these measures, machine learning platforms discriminative of glioma grade and IDH status were developed. Kaplan-Meier survival analysis was used to assess the prognostic significance of FD3D and Lac3D measurements. HGG exhibited significantly higher fractality and lower lacunarity in the enhancing subcomponent, along with lower fractality in the non-enhancing subcomponent compared to LGG. This suggests that a highly irregular and complex geometry in the enhancing-subcomponent is a characteristic feature of HGGs. A comparison of FD3D and Lac3D between IDH-wild type and IDH-mutant gliomas revealed that mutant gliomas had ~2.5-fold lower FD3D in the enhancing-subcomponent and higher FD3D with lower Lac3D in the non-enhancing subcomponent, indicating a less complex and smooth enhancing subcomponent, and a more continuous non-enhancing subcomponent as features of IDH-mutant gliomas. Supervised ML models using FD3D from both the enhancing and non-enhancing subcomponents together demonstrated high-sensitivity in discriminating glioma grades (~97.9%) and IDH status (~94.4%). A combined fractal estimation of the enhancing and non-enhancing subcomponents using MR images could serve as a non-invasive, precise, and quantitative measure for discriminating glioma grade and IDH status. The combination of 2-hydroxyglutarate-magnetic resonance spectroscopy (2HG-MRS) with FD3D and Lac3D quantification may be established as a robust imaging signature for glioma subtyping.

Hyperpolarized carbon-13 (¹³C) magnetic resonance imaging (MRI) has shown promise for non-invasive assessment of the cerebral metabolism of [1-¹³C]pyruvate in both healthy volunteers and patients. The exchange of pyruvate to lactate catalysed by lactate dehydrogenase (LDH) and that of pyruvate flux to bicarbonate through pyruvate dehydrogenase (PDH) are the most widely studied reactions in vivo. Here we show the potential of the technique to probe additional enzymatic activity within the brain. Approximately 50 s after intravenous injection of hyperpolarized pyruvate, high-flip-angle pulses were used to detect cerebral ¹³C-labelled carbon dioxide (¹³CO₂), in addition to the ¹³C-bicarbonate (H¹³CO₃ ^-) subsequently formed by carbonic anhydrase (CA). Brain pH measurements, which were weighted towards the extracellular compartment, were calculated from the ratio of H¹³CO₃ ^- to ¹³CO₂ in seven volunteers using the Henderson-Hasselbalch equation, demonstrating an average pH ± SD of 7.40 ± 0.02, with inter-observer reproducibility of 0.04. In addition, hyperpolarized [1-¹³C]aspartate was also detected, demonstrating irreversible pyruvate carboxylation to oxaloacetate by pyruvate carboxylase (PC) and subsequent transamination by aspartate aminotransferase (AST), with the average flux being on average 11% ± 3% of that through PDH. A hyperpolarized [1-¹³C]alanine signal was also detected, but this was localized to extracranial muscle tissue in keeping with skeletal alanine aminotransferase (ALT) activity. The results demonstrate the potential of hyperpolarized ¹³C-MRI to assess cerebral and extracerebral [1-¹³C]pyruvate metabolism in addition to LDH and PDH activity. Non-invasive measurements of brain pH could be particularly important in assessing cerebral pathology given the wide range of disease processes that alter acid-base balance.

Non-contrast enhanced ¹H magnetic resonance imaging (MRI) is promising for ventilation/perfusion (V/Q) assessment of the lung but the influence of the echo time (TE) on V/Q parameters is lacking. Therefore, the purpose of this study was to investigate the influence of different TEs on pulmonary V/Q parameters derived by phase-resolved functional lung (PREFUL) MRI using a multi-echo ultrashort TE (UTE) acquisition. A 2D multi-echo UTE sequence with radial center out readout and tiny golden angle increment was developed. Forty-eight participants were enrolled in this study: 25 healthy subjects, six patients with asthma, and 17 patients with pulmonary fibrosis. Participants underwent two acquisitions of 2D multi-echo UTE MRI with three TEs per acquisition (TE_1-6: 0.07, 0.82, 1.72, 2.47, 3.37, and 4.12 ms). Regional ventilation (RVent), flow-volume loop cross-correlation metric (FVL-CM), and normalized perfusion-weighted signal (QN) maps were calculated. V/Q defect percentages (VDP/QDP) were determined. To assess repeatability, the measurement was repeated in healthy subjects. Median and interquartile range of RVent, FVL-CM, QN, VDP, and QDP were calculated. To assess significant differences between parameters obtained at different TEs, Friedman's test and Dunnett's test were performed. Pearson correlation coefficients between RVent derived at TE₁ and the difference in RVent between TE_2,3 and TE₁ were calculated. For repeatability assessment, coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were determined. Significant differences were found comparing V/Q parameters obtained at TE_3-6 compared to TE₁. CoV increased with TE. For ICC, values between 0.35 (QDP at TE₁) and 0.83 (VDP_RVent at TE₂) were obtained for T_1,2. Statistically significant differences for ventilation and perfusion parameters derived by PREFUL were found for TE_3-6 compared to TE₁. All V/Q parameters were well repeatable for TE_1-2. With increasing TE and respiratory volume, RVent shows a T2*-dependency leading to biased ventilation assessment compared to TE₁.

Calcium sulfate is an established carrier for localized drug delivery, but a means to non-invasively measure drug release, which would improve our understanding of localized delivery, remains an unmet need. We aim to quantitatively estimate the diffusion-controlled release of small molecules loaded into a calcium sulfate carrier through a gadobutrol-based contrast agent, which acts as a surrogate small molecule. A central cylindrical core made of calcium sulfate, either alone or within a metal scaffold, is loaded with contrast agents that release into agar. Multi-echo scans are acquired at multiple time points over 4 weeks and processed into R2* and quantitative susceptibility mapping (QSM) maps. Mean R2* values are fit to a known drug delivery model, which are then compared with the decrease in core QSM. Fitting R2* measurements of calcium sulfate core while constraining constants to a drug release model results in an R²-value of 0.991, yielding a diffusion constant of 4.59 × 10^-11 m² s^-1. Incorporating the carrier within a metal scaffold results in a slower release. QSM shows the resulting loss of susceptibility in the non-metal core but is unreliable around metal. R2* characterizes the released gadobutrol, and QSM detects the resulting decrease in core susceptibility. The addition of a porous metal scaffold slows the release of gadobutrol, as expected.

Efficient abdominal coverage with T1-mapping methods currently available in the clinic is limited by the breath hold period (BHP) and the time needed for T1 recovery. This work develops a T1-mapping framework for efficient abdominal coverage based on rapid T1 recovery curve (T1RC) sampling, slice-selective inversion, optimized slice interleaving, and a convolutional neural network (CNN)-based T1 estimation. The effect of reducing the T1RC sampling was evaluated by comparing T1 estimates from T1RC ranging from 0.63 to 2.0 s with reference T1 values obtained from T1RC = 2.5-5 s. Slice interleaving methodologies were evaluated by comparing the T1 variation in abdominal organs across slices. The repeatability of the proposed framework was demonstrated by performing acquisition on test subjects across imaging sessions. Analysis of in vivo data based on retrospectively shortening the T1RC showed that with the CNN framework, a T1RC = 0.84 s yielded T1 estimates without significant changes in mean T1 (p > 0.05) or significant increase in T1 variability (p > 0.48) compared to the reference. Prospectively acquired data using T1RC = 0.84 s, an optimized slice interleaving scheme, and the CNN framework enabled 21 slices in a 20 s BHP. Analyses across abdominal organs produced T1 values within 2% of the reference. Repeatability experiments yielded Pearson's correlation, repeatability coefficient, and coefficient of variation of 0.99, 2.5%, and 0.12%, respectively. The proposed T1 mapping framework provides full abdominal coverage within a single BHP.

The divided subtracted inversion recovery (dSIR) is a high T₁ contrast technique that shows changes in white matter in patients with traumatic brain injury and hypoxic injury. The changes can be explained by small differences in T₁; however, to date, there has been no independent validation of the technique using a standard reference. The present study develops the theory of the dSIR signal and performs validation using the NIST/ISMRM T₁ phantom. Non-idealities are explored, including the influence of noise bias and finite repetition time (TR), which leads to the introduction of an optimally efficient TR for inversion recovery acquisitions. Results show excellent agreement with theoretical calculations.

This study aims to develop methods to design the complete magnetic system for a truly portable MRI scanner for neurological and musculoskeletal (MSK) applications, optimized for field homogeneity, field of view (FoV), and gradient performance compared to existing low-weight configurations. We explore optimal elliptic-bore Halbach configurations based on discrete arrays of permanent magnets. In this way, we seek to improve the field homogeneity and remove constraints to the extent of the gradient coils typical of Halbach magnets. Specifically, we have optimized a tightly packed distribution of magnetic Nd₂Fe₁₄B cubes with differential evolution algorithms and a second array of shimming magnets with interior point and differential evolution methods. We have also designed and constructed an elliptical set of gradient coils that extend over the whole magnet length, maximizing the distance between the lobe centers. These are optimized with a target field method minimizing a cost function that considers also heat dissipation. We have employed the new toolbox to build the main magnet and gradient modules for a portable MRI scanner designed for point-of-care and residential use. The elliptical Halbach bore has semi-axes of 10 and 14& cm, and the magnet generates a field of 87& mT homogeneous down to 5700& ppm (parts per million) in a 20-cm diameter FoV; it weighs 216& kg and has a width of 65& cm and a height of 72& cm. Gradient efficiencies go up to around 0.8& mT/m/A, for a maximum of 12& mT/m within 0.5& ms with 15& A and 15& V amplifier. The distance between lobes is 28& cm, significantly increased with respect to other Halbach-based scanners. Heat dissipation is around 25& W at maximum power, and gradient deviations from linearity are below 20% in a 20-cm sphere. Elliptic-bore Halbach magnets enhance the ergonomicity and field distribution of low-cost portable MRI scanners, while allowing for full-length gradient support to increase the FoV. This geometry can be potentially adapted for a prospective low-cost whole-body technology.

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.

Respiratory motion-induced image blurring and artifacts can compromise image quality in dynamic contrast-enhanced MRI (DCE-MRI) of the liver. Despite remarkable advances in respiratory motion detection and compensation in past years, these techniques have not yet seen widespread clinical adoption. The accuracy of image-based motion detection can be especially compromised in the presence of contrast enhancement and/or in situations involving deep and/or irregular breathing patterns. This work proposes a framework that combines GRASP-Pro (Golden-angle RAdial Sparse Parallel MRI with imProved performance) MRI with a new radial sampling scheme called navi-stack-of-stars for free-breathing DCE-MRI of the liver without the need for explicit respiratory motion compensation. A prototype 3D golden-angle radial sequence with a navi-stack-of-stars sampling scheme that intermittently acquires a 2D navigator was implemented. Free-breathing DCE-MRI of the liver was conducted in 24 subjects at 3T including 17 volunteers and 7 patients. GRASP-Pro reconstruction was performed with a temporal resolution of 0.34-0.45 s per volume, whereas standard GRASP reconstruction was performed with a temporal resolution of 15 s per volume. Motion compensation was not performed in all image reconstruction tasks. Liver images in different contrast phases from both GRASP and GRASP-Pro reconstructions were visually scored by two experienced abdominal radiologists for comparison. The nonparametric paired two-tailed Wilcoxon signed-rank test was used to compare image quality scores, and the Cohen's kappa coefficient was calculated to evaluate the inter-reader agreement. GRASP-Pro MRI with sub-second temporal resolution consistently received significantly higher image quality scores (P < 0.05) than standard GRASP MRI throughout all contrast enhancement phases and across all assessment categories. There was a substantial inter-reader agreement for all assessment categories (ranging from 0.67 to 0.89). The proposed technique using GRASP-Pro reconstruction with navi-stack-of-stars sampling holds great promise for free-breathing DCE-MRI of the liver without respiratory motion compensation.

Conventional diffusion-weighted imaging (DWI) sequences employing a spin echo or stimulated echo sensitize diffusion with a specific b-value at a fixed diffusion direction and diffusion time (Δ). To compute apparent diffusion coefficient (ADC) and other diffusion parameters, the sequence needs to be repeated multiple times by varying the b-value and/or gradient direction. In this study, we developed a single-shot multi-b-value (SSMb) diffusion MRI technique, which combines a spin echo and a train of stimulated echoes produced with variable flip angles. The method involves a pair of 90° radio frequency (RF) pulses that straddle a diffusion gradient lobe (G_D), to rephase the magnetization in the transverse plane, producing a diffusion-weighted spin echo acquired by the first echo-planar imaging (EPI) readout train. The magnetization stored along the longitudinal axis is successively re-excited by a series of n variable-flip-angle pulses, each followed by a diffusion gradient lobe G_D and a subsequent EPI readout train to sample n stimulated-echo signals. As such, (n + 1) diffusion-weighted images, each with a distinct b-value, are acquired in a single shot. The SSMb sequence was demonstrated on a diffusion phantom and healthy human brain to produce diffusion-weighted images, which were quantitative analyzed using a mono-exponential model. In the phantom experiment, SSMb provided similar ADC values to those from a commercial spin-echo EPI (SE-EPI) sequence (r = 0.999). In the human brain experiment, SSMb enabled a fourfold scan time reduction and yielded slightly lower ADC values (0.83 ± 0.26 μm²/ms) than SE-EPI (0.88 ± 0.29 μm²/ms) in all voxels excluding cerebrospinal fluid, likely due to the influence of varying diffusion times. The feasibility of using SSMb to acquire multiple images in a single shot for intravoxel incoherent motion (IVIM) analysis was also demonstrated. In conclusion, despite a relatively low signal-to-noise ratio, the proposed SSMb technique can substantially increase the data acquisition efficiency in DWI studies.