Magnetic Resonance Spectroscopy (MRS) offers a unique non-invasive window into metabolic processes, yet its potential remains strictly constrained by severe spectral congestion and intrinsic insensitivity. Traditional pulse sequence design, tethered to human intuition, predominantly targets simple quantum states, thereby overlooking the vast majority of the exponentially scaling operator space which consists of complex spin superpositions. Here, we introduce a spectrum-driven, end-to-end differentiable physical framework that transcends these heuristic limitations. By integrating physical laws with automatic differentiation algorithm, our approach directly navigates the high-dimensional spin dynamics space, bypassing the intractable inverse problem of state preparation. This enables the discovery of non-intuitive, complex mixed states that simultaneously satisfy the dual objectives of selective excitation and interferometric signal enhancement. We validate this paradigm by achieving the robust separation of Glutamate and Glutamine, which is a longstanding neuroimaging challenge, in the human brain at 3T, demonstrating spectral fidelity superior to conventional methods. By unlocking the "dark" informational content of nuclear spin ensembles, our work establishes a generalizable paradigm for goal-driven quantum state engineering in magnetic resonance and beyond.

PURPOSE:In vivo quantification of brain glutathione (GSH) is severely confounded by extreme spectral overlap in conventional 1H MRS. We developed a novel StepWIse FilTering Point-Resolved Spectroscopy (SWIFT-PRESS) sequence to fundamentally address this inherent limitation. METHODS:Transposing the stepwise filtering strategy from classical signal processing into quantum spin dynamics, SWIFT-PRESS concatenates multiple customized filter modules. This cascaded architecture circumvents the inherent inability of single-pass filters to simultaneously preserve target signals and completely eradicate interference. The proposed sequence was rigorously benchmarked against conventional PRESS and MEGA-PRESS. RESULTS:Simulations and phantom validations demonstrated that SWIFT-PRESS successfully eradicated the dominant creatine-derived interference while maintaining a highly acceptable GSH retention yield of ˜70%. In vivo human brain acquisitions confirmed its exceptional selectivity and robustness in both the parietal lobe and the magnetically complex basal ganglia, yielding precise mean GSH concentrations of 2.45 mM and 2.88 mM, respectively. Crucially, SWIFT-PRESS uncovered a pronounced inhomogeneous GSH distribution within the basal ganglia, directly reflecting underlying micro-regional metabolic heterogeneity. CONCLUSION:Transcending the limitations of conventional spectral editing, SWIFT-PRESS enables the highly specific, stable, and quantitative in vivo detection of brain GSH. By illuminating previously obscured spatial metabolic nuances, this technique establishes a robust methodological foundation for advanced clinical investigations of oxidative stress-related disorders.

2-hydroxyglutarate (2-HG) is a key metabolic biomarker for identifying IDH-mutant gliomas. Non-invasive and accurate detection of 2-HG is of great significance for the early diagnosis of diseases and dynamic monitoring of therapeutic efficacy. However, conventional magnetic resonance spectroscopy (MRS) faces challenges in detecting 2-HG in vivo, mainly due to the overlap of its resonance peaks with those of metabolites such as glutamate (Glu) and N-acetylaspartate (NAA). Although the long echo time (TE) filtering method can separate signals to a certain extent, it is often accompanied by peak distortion and signal attenuation, which limits its clinical application. To address this problem, this study proposes a 2-HG-targeted detection sequence based on optimal control pulses. By applying optimal control pulses to regulate the state evolution of a 14-spin system composed of 2-HG, Glu, and NAA molecules, the study achieves selective retention of 2-HG signals and suppression of other molecular signals. In experimental verification conducted on phantoms and IDH-mutant glioma animal models, the targeted sequence exhibited excellent signal resolution performance: it efficiently retained 2-HG signals and achieved approximately 95% and 98% suppression of Glu and NAA signals, respectively. To further verify the quantitative reliability of the targeted sequence, the 2-HG concentrations measured by this sequence were compared with those obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A high linear correlation was found between the two sets of results, which fully confirms the accuracy of non-invasive quantitative detection of 2-HG using the targeted sequence.

Lactate can provide a large amount of energy to the body to maintain the stability of the cellular nervous system. In medicine, lactate is often used as a signaling molecule to monitor the health level of the body in a timely manner. Accurately and efficiently detecting changes in the content of lactate in living tissues can provide important information about the physiological functions and health status of the organism, and also has certain significance for the early diagnosis of diseases. Several methods for detecting lactate using magnetic resonance spectroscopy techniques have been reported in literature, including long TE filtering technology and multiple quantum filtering technology, which have certain limitations in signal selectivity and efficiency. Here we propose a new method for selectively filtering lactate signals, which uses optimized control pulses to specifically transform the four hydrogen protons on the methyl and methine of lactate molecules into a two-spin Zeeman order, achieving efficient and highly selective detection of the methyl signal of lactate. Using this pulse sequence method, we have successively achieved selective detection of the signals of lactate or similar chemical groups in mixtures and polymer samples. This study provides new ideas and methods for efficiently selecting the signals of lactate in complex systems.

BACKGROUND:Glycine (Gly) is a key metabolic intermediate in the proliferation of tumor cells. Monitoring the concentration of Gly in tumor tissues is of great importance for understanding the growth status of tumors. At present, magnetic resonance spectroscopy (MRS) is the only method to non-invasively measure Gly concentration in human tissues. However, in conventional MR spectra the 1H signal of Gly overlaps with those of other molecules. This makes conventional MRS difficult to accurately measure the Gly concentration in human tissues. PURPOSE:To develop a pulse sequence, Gly-MRS, which can accurately measure Gly concentrations without the influence of the signal overlapping from other molecules in subjects with glioma. STUDY TYPE:Prospective. SUBJECTS/PHANTOMS:A phantom of the glycine (Gly), myo-inositol (MI) and glutamate (Glu) mixture aqueous solution and 6 phantoms of Gly aqueous solution (pH = 7.2 ± 0.1), 6 subjects with glioma (3 females and 3 males, BMI: 20 ± 4 kg/m2, age: 50 ± 10 years). FIELD STRENGTH/SEQUENCE:3 Tesla/A Gly-targeted magnetic resonance spectroscopy pulse sequence, Gly-MRS, using Point-RESolved Spectroscopy (PRESS) for single voxel signal selection. ASSESSMENT:By applying the developed pulse sequences to the phantoms and the subjects with glioma, the Gly 1H signals were successfully selectively probed. Quantification of the signals yields the concentrations of Gly in the regions of the tumor tissues of the subjects with glioma. STATISTICAL TESTS:Numerical data only. RESULTS:The Gly 1H signals were detected in the tumor regions of 6 subjects with glioma, at a mean concentration of 5.20 mM (standard deviation, ± 3.29 mM). One subject exhibited a clear spatial distribution in the Gly concentrations in the tumor regions. DATA CONCLUSION:The Gly-MRS pulse sequence developed in this work might be useful for the accurate in vivo detection of the 1H signal of Gly in gliomas of human beings. EVIDENCE LEVEL:2. TECHNICAL EFFICACY:Stage 3.

Nuclear spin singlet is a special quantum state that lasts longer than T1 and can be used to study slow diffusion and motion between molecules. The preparation of singlet states is the key to their successful application. Currently, various methods for preparing singlet states have been reported in the literature, which are mainly applicable to isolated two-spin systems. When the nuclear spin involved in the singlet state is coupled to other spins, the preparation efficiency of the singlet state often decreases. In this paper, taking a three-spin system as an example, we studied the effect of non-singlet spin coupling on the preparation efficiency of singlet states under different coupling configurations. The simulation results show that as the singlet spin changes from weak coupling to strong coupling, the preparation efficiency of the singlet state will maintain a certain stability when the coupling between the singlet spin and the non-singlet spin is symmetrical. This characteristic can provide a reference for selecting appropriate spins to prepare singlet states in complex systems. We experimentally verified this conclusion using a three-spin system in the N-acetyl-L-aspartic acid (NAA) molecule. By adjusting the pH of the NAA molecule, the three-spin system can transfer from weak coupling to strong coupling. The experimental results show that the preparation efficiency of the singlet state is significantly higher when the three spins are in strong coupling than that when the spins are in weak coupling.

1H NMR spectral features of hydrogen molecules in the stacking interstices of silicon dioxide (SiO2) microspheres with different sizes are studied in the present article. The chemical shift of hydrogen molecules is observed to gradually shift towards higher fields as the size of the stacking interstices decreases. Combined with experimental results of variable temperature hydrogen spectroscopy, self-diffusion coefficients measurement, and scanning electron microscopy, the observed phenomenon is attributed to two factors, namely, 1) the microsphere size-dependent local magnetic field inhomogeneity in the stacking interstices caused by the diamagnetic SiO2 microspheres; and 2) the rapid exchange among hydrogen molecules experiencing different local fields within the microsphere interstices. The results of this study demonstrate the potential of hydrogen gas as a probe molecule for measuring micro- and nano-scale pore sizes.

Parahydrogen-induced polarization (PHIP) technique can greatly enhance the sensitivity of nuclear magnetic resonance (NMR) signals, and has been applied in the fields of magnetic resonance imaging, in situ chemical reaction monitoring, etc. In addition to improving the sensitivity of different molecules in the PHIP, it is also crucial to extend and preserve the high polarization state. To achieve this, a possible approach is to transfer the polarized state into a nuclear spin singlet state. Here, we focus on the singlet states preparation in hexene molecule that can be polarized by PHIP. By designing optimal control pulses, a five-spin system in hexene molecule was manipulated, and various quantum states were prepared respectively. Our results show that three different nuclear spin singlet states could be prepared with the group CH2=CH- in hexene. The three different nuclear spin singlet states have longer lifetime than that of the initial state polarized by PHIP, and thus can be utilized as the intermediate states to delay the decay of the polarization state. By comparing the lifetime of the singlet state with the longitudinal relaxation time of the corresponding spin, it is deduced that converting the state of the polarized hexene to longitudinal magnetization may also be an effective way to preserve the polarizability.

BACKGROUND Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in human brains, playing a role in the pathogenesis of various psychiatric disorders. Current methods have some non-neglectable shortcomings and noninvasive and accurate detection of GABA in human brains is long-term challenge. PURPOSE To develop a pulse sequence capable of selectively detecting and quantifying the 1 H signal of GABA in human brains based on optimal controlled spin singlet order. STUDY TYPE Prospective. SUBJECTS/PHANTOM A phantom of GABA (pH = 7.3 ± 0.1) and 11 healthy subjects (5 females and 6 males, body mass index: 21 ± 3 kg/m2 , age: 25 ± 4 years). FIELD STRENGTH/SEQUENCE 7 Tesla, 3 Tesla, GABA-targeted magnetic resonance spectroscopy (GABA-MRS-7 T, GABA-MRS-3 T), magnetization prepared two rapid acquisition gradient echoes sequence. ASSESSMENT By using the developed pulse sequences applied on the phantom and healthy subjects, the signals of GABA were successfully selectively probed. Quantification of the signals yields the concentration of GABA in the dorsal anterior cingulate cortex (dACC) in human brains. STATISTICAL TESTS Frequency. RESULTS The 1 H signals of GABA in the phantom and in the human brains of healthy subjects were successfully detected. The concentration of GABA in the dACC of human brains was 3.3 ± 1.5 mM. DATA CONCLUSION The developed pulse sequences can be used to selectively probe the 1 H MR signals of GABA in human brains in vivo. EVIDENCE LEVEL 1 TECHNICAL EFFICACY STAGE: 1.

Purpose The signals of glutamate (Glu) and glutamine (Gln) are often significantly overlapped in routine 1 H‐MR spectra of human brain in vivo. Selectively probing the signals of Glu and Gln in vivo is very important for the study of the metabolisms in which Glu and Gln are involved. Methods The Glu−/Gln‐ targeted pulse sequences are developed to selectively probe the signals of Glu and Gln. The core part of the Glu−/Gln‐ targeted pulse sequences lies on the preparation of the nuclear spin singlet orders (SSOs) of the five‐spin systems of Glu and Gln. The optimal control method is used to prepare the SSOs of Glu and Gln with high efficiency. Results The Glu−/Gln‐ targeted pulse sequences have been applied on phantoms to selectively probe the signals of Glu and Gln. Moreover, in the in vivo experiments, the signals of Glu and Gln in human brains of healthy subjects have been successfully probed separately. Conclusion The developed Glu−/Gln‐ targeted pulse sequences can be used to distinguish the 1 H‐MR signals of Glu and Gln in human brains in vivo. The optimal control method provides an effective way to prepare the SSO of a specific spin system with high efficiency and in turn selectively probe the signals of a targeted molecule.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have made great successes in clinical diagnosis, medical research, and neurological science. MRI provides high resolution anatomical images of tissues/organs, and MRS provides information of the functional molecules related to a specific tissue/organ. However, it is difficult for classic MRI/MRS to selectively image/probe a specific metabolite molecule other than the water or fat in tissues/organs. This greatly limits their applications on the study of the molecular mechanism(s) of metabolism and disease. Herein, we report a series of molecularly targeted MRI/MRS methods to target specific molecules. The optimal control method was used to efficiently prepare the singlet spin orders of varied multi-spin systems and in turn greatly expand the choice of the targeted molecules in the molecularly targeted MRI/MRS. Several molecules, such as N-acetyl-L-aspartic acid (NAA), dopamine (DA), and a tripeptide (alanine-glycine-glycine, AGG), have been used as targeted molecules for molecularly targeted MRI and MRS. We show in vivo NAA-targeted 1H MRS spectrum of a human brain. The high-resolution signal of NAA suggests a promising way to study important issues in molecular biology at the molecular level, e.g., measuring the local pH value of tissue in vivo, demonstrating the high potential of such methods in medicine.

Nuclear spin singlet state is a special spin state, whose main characteristic is that its lift-time can be much longer than the corresponding longitudinal/transverse relaxation time. It can be used to study molecular slow diffusion, slow motion, special signal selection or other molecular motion. In the literature, singlet states are mainly studied in an isolated two-spin system. Here we discuss the nuclear spin singlet state preparation in a three-spin system. The system consisting of three protons in the molecule N-acetyl aspartic acid (NAA) was used as an example. Specifically, we used optimal control theory and numerical calculation method to design the pulse sequence and to transfer the two spins in methylene group into singlet state. The shaped pulses including and not including the proton in the methyne group were designed respectively. Our simulation results indicate that to ensure a high efficiency for the singlet state preparation, the coupling of the proton in the methyne group should be included in the pulse calculation. Furthermore, the singlet state can be combined with two-dimensional pulse sequences such as COSY and NOESY. The experimental results show that some correlation peaks could be selectively observed in the two-dimensional spectrum based on singlet state. It will be useful for the spectral peak assignment especially in the case of serious spectral overlap.

Selectively probing specific molecules in complex mixtures with nuclear magnetic resonance promises new insights into molecular structures or molecular interaction. Such a study often can be further facilitated when two or more objects in chemical moieties of interest can be precisely targeted. Herein, we proposed a novel method to implement the multiple-targeting signal selection by optimal control of the spin singlets of two or more targeted spin systems from one or more molecules. This method can endow the conventional nuclear magnetic resonance (NMR), magnetic resonance image (MRI) and magnetic resonance spectrum (MRS) with the multiple-targeting signal selectivity to selectively probe several targeted molecules and/or chemical groups simultaneously.

The development of an efficient and durable photocatalyst is the key to the degradation of tetracycline (TC). However, the ability to monitor the concentration of TC accurately remains a significant challenge. The present work addresses this issue by applying an operando H-1 NMR spectroscopy technology for monitoring the TC concentration using TiO2 photocatalysts with different oxygen vacancy concentrations. The application of operando NMR spectra compensates for the experimental error inherent in UV-vis spectrophotometry analyses caused by the destruction of the chromogenic group and thereby can accurately reflect the true degree of degradation. The TC degradation performances of the photocatalysts are evaluated systematically, and the obtained benzene ring concentrations are observed to contrast sharply with the corresponding TC concentration results obtained by UV-vis spectrophotometry. This research increases the availability, reliability, and accuracy of the test methods employed in TC degradation research and provides an experimental reference for the design of high-efficiency catalysts.

Most current approaches applied for the essential identification of adulteration in edible vegetable oils are of limited practical benefit because they require long analysis times, professional training, and costly instrumentation. The present work addresses this issue by developing a novel simple, accurate, and rapid identification approach based on the magnetic resonance relaxation fingerprints obtained from low-field nuclear magnetic resonance spectroscopy measurements of edible vegetable oils. The relaxation fingerprints obtained for six types of edible vegetable oil, including flaxseed oil, olive oil, soybean oil, corn oil, peanut oil, and sunflower oil, are demonstrated to have sufficiently unique characteristics to enable the identification of the individual types of oil in a sample. By using principal component analysis, three characteristic regions in the fingerprints were screened out to create a novel three-dimensional characteristic coordination system for oil discrimination and adulteration identification. Univariate analysis and partial least squares regression were used to successfully quantify the oil adulteration in adulterated binary oil samples, indicating the great potential of the present approach on both identification and quantification of edible oil adulteration.

The preparation and detection of the nuclear singlet state are valuable and prospective for many applications related with compound molecular analysis. In this work, a proton spin coupled system containing two H nuclei in tripeptide (Ala-Gly-Gly, AGG) was selected as research object, and singlets were prepared with three sets of different pulse sequences based on different principles. The lifetime of those singlets were measured, and the singlet preparation efficiencies of different sequences were compared. The results indicated that for the same spin coupling system of the same molecule, there is no significant difference in the lifetime of the singlet state prepared by different pulse sequences, while their preparation efficiencies could be relatively different.

The reaction of heterogeneous benzene hydrogenation reaction in a real solid-liquid-gas environment was studied by operando nuclear magnetic resonance (NMR) spectroscopy. During the reaction process, the products need not be separated before the test. Different catalysts (Pd nanoparticles and Pd with different crystal morphology) were performed to investigate the effects of pressure, reaction time and catalyst surface properties on benzene hydrogenation reaction. It was found that the pressure and the reaction time can affect the productivity of hydrogenation reaction, and the products of benzene hydrogenation reaction are determined by the exposed crystal surface of Pd catalysts. This operando NMR method provides a good opportunity to study the mechanism of solid-liquid-gas heterogeneous hydrogenation reaction.

The long-life nuclear spin singlet states (LLSs) have broad application prospects due to the unique nature of their long lifetime. Herein, in a solution of alanylglycylgcine (AGG), the nuclear spin singlet state of a two-spin system far from the chiral carbon in the structure is prepared. Then, the effects of sample concentration, temperature, radiofrequency (RF) center, J-coupling value and magnetic field inhomogeneity on conversion efficiency and lifetime of the LLSs were investigated. The experimental results showed that the conversion efficiency and lifetime of the singlet state were not affected by the sample concentration and magnetic field inhomogeneity, but increased with increasing experimental temperature. The influence of the position of RF center on the singlet state was not obvious when it changed within a small range, but the conversion efficiency and lifetime reduced significantly when the changes were large. Moreover, the singlet state was found to be sensitive to the changes of J-coupling value. The conversion efficiency and lifetime reduced significantly with choose of non-accurate J-coupling constant.

The lifetime Ts of a long-lived nuclear spin state (LLS) could be much longer than the longitudinal order T1 . Many spin systems were used to produce long-lived states, including two or more homonuclear spins that couple to each other. For multiple homonuclear spins with rather small chemical shift difference, normally it is difficult to selectively control the spins and then to prepare a LLS. Herein, we present a scheme that prepares different spin orders in a multi-spin system by using optimal control and numerical calculation. By experimentally measuring the lifetime of the states, we find that for a three-spin physical system, although there are many forms of state combinations with different spin orders, each component has its own lifetime.

This study developed a molecularly targeted magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) method to selectively probe a specific metabolite molecule of tissues/organs in vivo. Several biomolecules have been used for molecularly targeted MRI and MRS. We used N-acetyl aspartate (NAA)- and glutamate (GLU)-targeted 1H MRS spectra of the human brain and reported a novel approach to measure the local pH values of tissue in vivo.