Metabolic profiling of colorectal cancer organoids: A comparison between high-resolution magic angle spinning magnetic resonance spectroscopy and solution nuclear magnetic resonance spectroscopy of polar extracts

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31P T2s of phosphomonoesters, phosphodiesters, and inorganic phosphate in the human brain at 7T

Purpose: To determine the phosphorus-31 T2s of phosphomonoesters, phosphodiesters, and inorganic phosphate in the healthy human brain at 7T. Methods: A 3D chemical shift imaging multi-echo sequence with composite block pulses for refocusing was used to measure one free induction decay (FID) and seven full echoes with an echo spacing of 45 ms on the brain of nine healthy volunteers (age range 22–45 years; average age 27 ± 8 years). Spectral fitting was used to determine the change in metabolic signal amplitude with echo time. Results: The average apparent T2s with their standard deviation were 202 ± 6 ms, 129 ± 6 ms, 86 ± 2 ms, 214 ± 10 ms, and 213 ± 11 ms for phosphoethanolamine, phosphocholine, inorganic phosphate, glycerophosphoethanolamine, and glycerophosphocholine, respectively. Conclusion: The determined apparent T2 for phosphoethanolamine, glycerophosphocholine, and glycerophosphoethanolamine is approximately 200 ms. The lower apparent T2 value for phosphocholine is attributed to the overlap of this resonance with the 3-phosphorous resonance of 2,3-diphosphoglycerate from blood, with an apparent shorter T2. Omitting the FID signal and the first echo of phosphocholine leads to a T2 of 182 ± 7 ms, whereas a biexponential analysis leads to 203 ± 4 ms. These values are more in line with phosphoethanolamine and the phosphodiesters. The short T2 of inorganic phosphate is subscribed to the fast reversible exchange with γ-adenosine triphosphate, which is mediated by glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase within the glycolytic pathway. Magn Reson Med 80:29–35, 2018

Analysis of chemical exchange saturation transfer contributions from brain metabolites to the Z-spectra at various field strengths and pH

Chemical exchange saturation transfer (CEST) exploits the chemical exchange of labile protons of an endogenous or exogenous compound with water to image the former indirectly through the water signal. Z-spectra of the brain have traditionally been analyzed for two most common saturation phenomena: downfield amide proton transfer (APT) and upfield nuclear Overhauser enhancement (NOE). However, a great body of brain metabolites, many of interest in neurology and oncology, contributes to the downfield saturation in Z-spectra. The extraction of these “hidden” metabolites from Z-spectra requires careful design of CEST sequences and data processing models, which is only possible by first obtaining CEST signatures of the brain metabolites possessing labile protons. In this work, we measured exchange rates of all major-for-CEST brain metabolites in the physiological pH range at 37 °C. Analysis of their contributions to Z-spectra revealed that regardless of the main magnetic field strength and pH, five main contributors, i.e. myo-inositol, creatine, phosphocreatine, glutamate, and mobile (poly)peptides, account for ca. 90% of downfield CEST effect. The fundamental CEST parameters presented in this study can be exploited in the design of novel CEST sequences and Z-spectra processing models, which will enable simultaneous and quantitative CEST imaging of multiple metabolites: multicolor CEST

SNR optimized P-31 functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

Summary: Energy metabolism of the human visual cortex was investigated by performing 31P functional MRS. Introduction: The human brain is known to be the main glucose demanding organ of the human body and neuronal activity can increase this energy demand. In this study we investigate whether alterations in pH during activation of the brain can be observed with MRS, focusing on the mitochondrial inorganic phosphate (Pi) pool as potential marker of energy demand. Methods: Six participants were scanned with 16 consecutive 31P-MRSI scans, which were divided in 4 blocks of 8:36 minutes of either rest or visual stimulation. Since the signals from the mitochondrial compartments of Pi are low, multiple approaches to achieve high SNR 31P measurements were combined. This included: a close fitting 31P RF coil, a 7 T-field strength, Ernst angle acquisitions and a stimulus with a large visual angle allowing large spectroscopy volumes containing activated tissue. Results: The targeted resonance downfield of the main Pi peak could be distinguished, indicating the high SNR of the 31P spectra. The peak downfield of the main Pi peak is believed to be connected to mitochondrial performance. In addition, a BOLD effect in the PCr signal was observed as a signal increase of 2–3% during visual stimulation as compared to rest. When averaging data over multiple volunteers, a small subtle shift of about 0.1 ppm of the downfield Pi peak towards the main Pi peak could be observed in the first 4 minutes of visual stimulation, but no longer in the 4 to 8 minute scan window. Indications of a subtle shift during visual stimulation were found, but this effect remains small and should be further validated. Conclusion: Overall, the downfield peak of Pi could be observed, revealing opportunities and considerations to measure specific acidity (pH) effects in the human visual cortex

2D AMESING multi-echo (31)P-MRSI of the liver at 7T allows transverse relaxation assessment and T2-weighted averaging for improved SNR

PURPOSE: Liver diseases are a major global health concern often requiring invasive assessment by needle biopsy. (31)P magnetic resonance spectroscopic imaging (MRSI) allows non-invasive probing of important liver metabolites. Recently, the adiabatic multi-echo spectroscopic imaging sequence with spherical k-space sampling (AMESING) was introduced at 7T, enabling acquisition of T2 information. T2-weighed averaging of the multiple echoes improves signal-to-noise ratio (SNR). The purpose of our study was to implement AMESING MRSI of the liver at 3T and 7T, derive localized T2 information and compare T2-weighted average spectra in terms of SNR. METHODS: Ten male volunteers underwent 2D AMESING MRSI at 3T and 7T after a minimum four-hour fast. SNR was calculated for PC, PE, Pi, GPE, GPC and α-ATP using maximum peak amplitudes and the SD of the noise. Metabolite peak ratios were calculated after fitting in jMRUI. SNR values and peak ratios were compared with the Wilcoxon signed-rank test. RESULTS: For the first time liver metabolites' T2 values at 7T were measured: PE (55.6±3.5 ms), PC (51.2±2.3 ms), Pi (46.4±1.1 ms), GPE (44.0±0.8 ms), GPC (50.4±0.8 ms) and α-ATP (18.2±0.4 ms). SNR gain using T2-weighted averaging at 7T resulted in a 1.2× SNR gain. In conjunction with higher field strength and improved coil set-up T2-weighted averaging at 7T allowed a total 3.2× SNR gain compared to 3T FID-only. CONCLUSION: AMESING 2D MRSI of the liver at 7T provides T2 values that allow T2-weighted averaging of data from multiple echoes resulting in improved SNR

MRI and P-31 Magnetic Resonance Spectroscopy Hardware for Axillary Lymph Node Investigation at 7T

PurposeNeoadjuvant treatment response in lymph nodes predicts patient outcome, but existing methods do not track response during therapy accurately. In this study, specialized hardware was used to adapt high-field (7T) P-31 magnetic resonance spectroscopy (MRS), which has been shown to track treatment response in small breast tumors, to monitor axillary lymph nodes. MethodA dual-tuned quadrature coil that is a P-31 (120 MHz) transceiver and a H-1 (300 MHz) receiver was designed using a novel detune circuit. The transceiver/receiver coil in the axilla is used with a fractionated dipole antenna on the back of the subject and the conventional breast coil for transmit. ResultsThe novel circuit detuned the H-1 resonance without disturbing the P-31 resonance. In vivo demonstrations included: >80% homogeneous B-1(+) for H-1 over the axilla, identification of a small (3-mm diameter) lymph node, and P-31 MR spectra from a single healthy lymph node. The setup can detect ConclusionsThe first P-31 MR spectrum from an in vivo lymph node indicates that the presented design may be sufficiently sensitive to detect metabolic response to neoadjuvant therapy. Multinuclei MRS of the lymph nodes at 7T is possible through combining lightweight antenna elements with dual-tuned transceiver/receive-only coils. Magn Reson Med 73:2038-2046, 2015. (c) 2014 Wiley Periodicals, Inc

1H/31P polarization transfer at 9.4 Tesla for improved specificity of detecting phosphomonoesters and phosphodiesters in breast tumor models.

To assess the ability of a polarization transfer (PT) magnetic resonance spectroscopy (MRS) technique to improve the detection of the individual phospholipid metabolites phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), and glycerophosphoethanolamine (GPE) in vivo in breast tumor xenografts.The adiabatic version of refocused insensitive nuclei enhanced by polarization transfer (BINEPT) MRS was tested at 9.4 Tesla in phantoms and animal models. BINEPT and pulse-acquire (PA) 31P MRS was acquired consecutively from the same orthotopic MCF-7 (n = 10) and MDA-MB-231 (n = 10) breast tumor xenografts. After in vivo MRS measurements, animals were euthanized, tumors were extracted and high resolution (HR)-MRS was performed. Signal to noise ratios (SNRs) and metabolite ratios were compared for BINEPT and PA MRS, and were also measured and compared with that from HR-MRS.BINEPT exclusively detected metabolites with 1H-31P coupling such as PC, PE, GPC, and GPE, thereby creating a significantly improved, flat baseline because overlapping resonances from immobile and partly mobile phospholipids were removed without loss of sensitivity. GPE and GPC were more accurately detected by BINEPT in vivo, which enabled a reliable quantification of metabolite ratios such as PE/GPE and PC/GPC, which are important markers of tumor aggressiveness and treatment response.BINEPT is advantageous over PA for detecting and quantifying the individual phospholipid metabolites PC, PE, GPC, and GPE in vivo at high magnetic field strength. As BINEPT can be used clinically, alterations in these phospholipid metabolites can be assessed in vivo for cancer diagnosis and treatment monitoring

Radiofrequency configuration to facilitate bilateral breast 31P MR spectroscopic imaging and high-resolution MRI at 7 Tesla

PURPOSE: High-resolution MRI combined with phospholipid detection may improve breast cancer grading. Currently, configurations are optimized for either high-resolution imaging or 31 P spectroscopy. To be able to perform both imaging as well as spectroscopy in a single session, we integrated a 1 H receiver array into a 1 H-31 P transceiver at 7T. To ensure negligible signal loss due to coupling between elements, we investigated the use of a floating decoupling loop to enable bilateral MRI and 31P MRS. METHODS: Two quadrature double-tuned radiofrequency coils were designed for bilateral breast MR with active detuning at the 1 H frequency. The two coils were placed adjacent to each other and decoupled for both frequencies with a single resonant floating loop. Sensitivity of the bilateral configuration, facilitating space for a 26-element 1 H receive array, was compared with a transceiver configuration. RESULTS: The floating loop was able to decouple the elements over 20 dB for both frequencies. Enlargement of the elements, to provide space for the receivers, and the addition of detuning electronics altered the 31 P sensitivity by 0.4 dB. CONCLUSION: Dynamic contrast-enhanced scans of 0.7 mm isotropic, diffusion-weighted imaging, and 31 P MR spectroscopic imaging can be acquired at 7T in a single session as demonstrated in a patient with invasive ductal carcinom

Proton and phosphorus magnetic resonance spectroscopy of the healthy human breast at 7 T

In vivo water- and fat-suppressed (1) H magnetic resonance spectroscopy (MRS) and (31) P magnetic resonance adiabatic multi-echo spectroscopic imaging were performed at 7 T in duplicate in healthy fibroglandular breast tissue of a group of eight volunteers. The transverse relaxation times of (31) P metabolites were determined, and the reproducibility of (1) H and (31) P MRS was investigated. The transverse relaxation times for phosphoethanolamine (PE) and phosphocholine (PC) were fitted bi-exponentially, with an added short T2 component of 20 ms for adenosine monophosphate, resulting in values of 199 ± 8 and 239 ± 14 ms, respectively. The transverse relaxation time for glycerophosphocholine (GPC) was also fitted bi-exponentially, with an added short T2 component of 20 ms for glycerophosphatidylethanolamine, which resonates at a similar frequency, resulting in a value of 177 ± 6 ms. Transverse relaxation times for inorganic phosphate, γ-ATP and glycerophosphatidylcholine mobile phospholipid were fitted mono-exponentially, resulting in values of 180 ± 4, 19 ± 3 and 20 ± 4 ms, respectively. Coefficients of variation for the duplicate determinations of (1) H total choline (tChol) and the (31) P metabolites were calculated for the group of volunteers. The reproducibility of inorganic phosphate, the sum of phosphomonoesters and the sum of phosphodiesters with (31) P MRS imaging was superior to the reproducibility of (1) H MRS for tChol. (1) H and (31) P data were combined to calculate estimates of the absolute concentrations of PC, GPC and PE in healthy fibroglandular tissue, resulting in upper limits of 0.1, 0.1 and 0.2 mmol/kg of tissue, respectively