2D 1H sLASER Long-TE and 3D 31P Chemical Shift Imaging at 3 T for Monitoring Fasting-Induced Changes in Brain Tumor Tissue.

BACKGROUND: Emerging evidence suggests that fasting could play a key role in cancer treatment. Its metabolic effects on gliomas require further investigation. PURPOSE: To design a multi-voxel 1H/31P MR-spectroscopic imaging (MRSI) protocol for noninvasive metabolic monitoring of cerebral, fasting-induced changes on an individual patient/tumor level, and to assess its technical reliability/reproducibility. STUDY TYPE: Prospective. POPULATION: MRS phantom. Twenty-two patients (mean age = 61, 6 female) with suspected WHO grade II-IV glioma examined before and after 72-hour-fasting prior to biopsy/resection. FIELD STRENGTH/SEQUENCE: 3-T, 1H decoupled 3D 31P MRSI, 2D 1H sLASER MRSI at an echo time of 144 msec, 2D 1H MRSI (as water reference), T1-weighted, T1-weighted contrast-enhanced, T2-weighted, and FLAIR. sLASER and PRESS sequences were used for phantom measurements. ASSESSMENT: Phantom measurements and spectral simulations were performed with various echo-times for protocol optimization. In vivo spectral analyses were conducted using LCModel and AMARES, obtaining quality/fitting parameters (linewidth, signal-to-noise-ratio, and uncertainty measures of fitting) and metabolite intensities. The volume of glioma sub-regions was calculated and correlated with MRS findings. Ex-vivo spectra of necrotic tumor tissues were obtained using high-resolution magic-angle spinning (HR-MAS) technique. STATISTICAL TESTS: Wilcoxon signed-rank test, Bland-Altman plots, and coefficient of variation were used for repeatability analysis of quality/fitting parameters and metabolite concentrations. Spearman ρ correlation for the concentration of ketone bodies with volumes of glioma sub-regions was determined. A P-value <0.05 was considered statistically significant. RESULTS: 1H and 31P repeatability measures were highly consistent between the two sessions. ß-hydroxybutyrate and acetoacetate were detectable (fitting-uncertainty <50%) in glioma sub-regions of all patients who completed the 72-hour-fasting cycle. ß-hydroxybutyrate accumulation was significantly correlated with the necrotic/non-enhancing tumor core volume (ρ = 0.81) and validated using ex-vivo 1H HR-MAS. DATA CONCLUSION: We propose a comprehensive MRS protocol that may be used for monitoring cerebral, fasting-induced changes in patients with glioma. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Zero- to low-field relaxometry of chemical and biological fluids.

Nuclear magnetic resonance (NMR) relaxometry is an analytical method that provides information about molecular environments, even for NMR "silent" molecules (spin-0), by analyzing the properties of NMR signals versus the magnitude of the longitudinal field. Conventionally, this technique is performed at fields much higher than Earth's magnetic field, but our work focuses on NMR relaxometry at zero and ultra-low magnetic fields (ZULFs). Operating under such conditions allows us to investigate slow (bio)chemical processes occurring on a timescale from milliseconds to seconds, which coincide with spin evolution. ZULFs also minimize T2 line broadening in heterogeneous samples resulting from magnetic susceptibility. Here, we use ZULF NMR relaxometry to analyze (bio)chemical compounds containing 1H-13C, 1H-15N, and 1H-31P spin pairs. We also detected high-quality ULF NMR spectra of human whole-blood at 0.8 µT, despite a shortening of spin relaxation by blood proteomes (e.g., hemoglobin). Information on proton relaxation times of blood, a potential early biomarker of inflammation, can be acquired in under a minute using inexpensive, portable/small-size NMR spectrometers based on atomic magnetometers.

Detection of pyridine derivatives by SABRE hyperpolarization at zero field.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical tool used in modern science and technology. Its novel incarnation, based on measurements of NMR signals without external magnetic fields, provides direct access to intramolecular interactions based on heteronuclear scalar J-coupling. The uniqueness of these interactions makes each zero-field NMR spectrum distinct and useful in chemical fingerprinting. However, the necessity of heteronuclear coupling often results in weak signals due to the low abundance of certain nuclei (e.g., 15N). Hyperpolarization of such compounds may solve the problem. In this work, we investigate molecules with natural isotopic abundance that are polarized using non-hydrogenative parahydrogen-induced polarization. We demonstrate that spectra of hyperpolarized naturally abundant pyridine derivatives can be observed and uniquely identified whether the same substituent is placed at a different position of the pyridine ring or different constituents are placed at the same position. To do so, we constructed an experimental system using a home-built nitrogen vapor condenser, which allows for consistent long-term measurements, crucial for identifying naturally abundant hyperpolarized molecules at a concentration level of ~1 mM. This opens avenues for future chemical detection of naturally abundant compounds using zero-field NMR.

Zero-Field NMR of Urea: Spin-Topology Engineering by Chemical Exchange.

Well-resolved and information-rich J-spectra are the foundation for chemical detection in zero-field NMR. However, even for relatively small molecules, spectra exhibit complexity, hindering the analysis. To address this problem, we investigate an example biomolecule with a complex J-coupling network─urea, a key metabolite in protein catabolism─and demonstrate ways of simplifying its zero-field spectra by modifying spin topology. This goal is achieved by controlling pH-dependent chemical exchange rates of 1H nuclei and varying the composition of the D2O/H2O mixture used as a solvent. Specifically, we demonstrate that by increasing the proton exchange rate in the [13C,15N2]-urea solution, the spin system simplifies, manifesting through a single narrow spectral peak. Additionally, we show that the spectra of 1H/D isotopologues of [15N2]-urea can be understood easily by analyzing isolated spin subsystems. This study paves the way for zero-field NMR detection of complex biomolecules, particularly in biofluids with a high concentration of water.

Zero-Field NMR J-Spectroscopy of Organophosphorus Compounds.

Organophosphorus compounds are a wide and diverse class of chemicals playing a crucial role in living organisms. This aspect has been often investigated using nuclear magnetic resonance (NMR), which provides information about molecular structure and function. In this paper, we report the results of theoretical and experimental studies on basic organophosphorus compounds using zero-field NMR, where spin dynamics are investigated in the absence of a magnetic field with the dominant heteronuclear J-coupling. We demonstrate that the zero-field NMR enables distinguishing the chemicals owing to their unique electronic environment even though their spin systems have the same alphabetic designation. Such information can be obtained just in a single measurement, while amplitudes and widths of observed low-field NMR resonances enable the study of processes affecting spin dynamics. An excellent agreement between simulations and measurements of the spectra, particularly in the largest frequency J-couplings range ever reported in zero-field NMR, is demonstrated.

False-positive I-131 Uptakes at Pulmonary Wedge-resection Site and Soft Tissue Lateral to the Femoral Heads in a Patient with Papillary Thyroid Carcinoma

A hyper-metabolic pulmonary nodule was detected on 18F-FDG PET/CT in a 65-year-old woman who had been followed up for 12 years without any complaints following treatment for papillary thyroid cancer (PTC). Wedge resection was performed to the pulmonary nodule and the pathologic examination revealed PTC metastasis. On the post-therapeutic I-131 scan after radioiodine treatment, focal I-131 uptake was detected at the site of pulmonary wedge resection. At first, this finding was thought to be related to the residual lesion but diagnostic CT demonstrated only focal traction bronchiectasis at that region. In addition, a false-positive I-131 uptake was also detected at the soft tissue just lateral to the femoral heads probably due to inflammation.