A silent echo-planar spectroscopic imaging readout with high spectral bandwidth MRSI using an ultrasonic gradient axis.

PURPOSE: We present a novel silent echo-planar spectroscopic imaging (EPSI) readout, which uses an ultrasonic gradient insert to accelerate MRSI while producing a high spectral bandwidth (20 kHz) and a low sound level. METHODS: The ultrasonic gradient insert consisted of a single-axis (z-direction) plug-and-play gradient coil, powered by an audio amplifier, and produced 40 mT/m at 20 kHz. The silent EPSI readout was implemented in a phase-encoded MRSI acquisition. Here, the additional spatial encoding provided by this silent EPSI readout was used to reduce the number of phase-encoding steps. Spectroscopic acquisitions using phase-encoded MRSI, a conventional EPSI-readout, and the silent EPSI readout were performed on a phantom containing metabolites with resonance frequencies in the ppm range of brain metabolites (0-4 ppm). These acquisitions were used to determine sound levels, showcase the high spectral bandwidth of the silent EPSI readout, and determine the SNR efficiency and the scan efficiency. RESULTS: The silent EPSI readout featured a 19-dB lower sound level than a conventional EPSI readout while featuring a high spectral bandwidth of 20 kHz without spectral ghosting artifacts. Compared with phase-encoded MRSI, the silent EPSI readout provided a 4.5-fold reduction in scan time. In addition, the scan efficiency of the silent EPSI readout was higher (82.5% vs. 51.5%) than the conventional EPSI readout. CONCLUSIONS: We have for the first time demonstrated a silent spectroscopic imaging readout with a high spectral bandwidth and low sound level. This sound reduction provided by the silent readout is expected to have applications in sound-sensitive patient groups, whereas the high spectral bandwidth could benefit ultrahigh-field MR systems.

Fast and silent MRI using nonlinear gradient fields at the ultrasonic gradient switching frequency of 20 kHz with a Point Spread Function framework reconstruction.

PURPOSE: To demonstrate the feasibility of using a nonlinear gradient field for spatial encoding at the ultrasonic switching frequency of 20 kHz and present a framework to reconstruct data acquired in this way. METHODS: Nonlinear encoding at 20 kHz was realized by using a single-axis silent gradient insert for imaging in the periphery, that, is the nonlinear region, of the gradient field. The gradient insert induces a rapidly oscillating gradient field in the phase-encode direction, which enables nonlinear encoding when combined with a Cartesian readout from the linear whole-body gradients. Data from a 2D gradient echo sequence were reconstructed using a point spread function (PSF) framework. Accelerated scans were also simulated via retrospective undersampling (R = 1 to R = 8) to determine the effectiveness of the PSF-framework for accelerated imaging. RESULTS: Using a nonlinear gradient field switched at 20 kHz and the PSF-framework resulted in images of comparable quality to images from conventional Cartesian linear encoding. At increased acceleration factors (R ≤ 8), the PSF-framework outperformed linear SENSE reconstructions by improved controlling of aliasing artifacts. CONCLUSION: Using the PSF-framework, images of comparable quality to conventional SENSE reconstructions are possible via combining traditional linear and ultrasonic oscillating nonlinear encoding fields. Using nonlinear gradient fields relaxes the demand for strictly linear gradient fields, enabling much higher slew rates with a reduced risk of peripheral nerve stimulation or cardiac stimulation, which could aid in extension to ultrasonic whole-body MRI. The lack of aliasing artifacts also highlights the potential of accelerated imaging using the PSF-framework.

31P multi-echo MRSI with low B1 + dual-band refocusing RF pulses.

31P magnetic resonance spectroscopy (MRS) can spectrally resolve metabolites involved in phospholipid metabolism whose levels are altered in many cancers. Ultra-high field facilitates the detection of phosphomonoesters (PMEs) and phosphodiesters (PDEs) with increased SNR and spectral resolution. Utilizing multi-echo MR spectroscopic imaging (MRSI) further enhances SNR and enables T2 information estimation per metabolite. To address the specific absorption rate (SAR) challenges associated with high-power demanding adiabatic or composite block pulses in multi-echo phosphorus imaging, we present a dual-band refocusing RF pulse designed for operation at B1 amplitudes of 14.8 µT which holds potential for integration into multi-echo sequences. Phantom and in vivo experiments conducted in the brain at 7 Tesla validated the effectiveness of this low-power dual-band RF pulse. Furthermore, we implemented the dual-band RF pulse into a multi-echo MRSI sequence where it offered the potential to increase the number of echo pulses within the same acquisition time compared to high-power adiabatic implementation, demonstrating its feasibility and practicality.

Amide proton transfer weighted imaging in pediatric neuro-oncology: initial experience.

Amide proton transfer weighted (APTw) imaging enables in vivo assessment of tissue-bound mobile proteins and peptides through the detection of chemical exchange saturation transfer. Promising applications of APTw imaging have been shown in adult brain tumors. As pediatric brain tumors differ from their adult counterparts, we investigate the radiological appearance of pediatric brain tumors on APTw imaging. APTw imaging was conducted at 3 T. APTw maps were calculated using magnetization transfer ratio asymmetry at 3.5 ppm. First, the repeatability of APTw imaging was assessed in a phantom and in five healthy volunteers by calculating the within-subject coefficient of variation (wCV). APTw images of pediatric brain tumor patients were analyzed retrospectively. APTw levels were compared between solid tumor tissue and normal-appearing white matter (NAWM) and between pediatric high-grade glioma (pHGG) and pediatric low-grade glioma (pLGG) using t-tests. APTw maps were repeatable in supratentorial and infratentorial brain regions (wCV ranged from 11% to 39%), except those from the pontine region (wCV between 39% and 50%). APTw images of 23 children with brain tumor were analyzed (mean age 12 years ± 5, 12 male). Significantly higher APTw values are present in tumor compared with NAWM for both pHGG and pLGG (p < 0.05). APTw values were higher in pLGG subtype pilocytic astrocytoma compared with other pLGG subtypes (p < 0.05). Non-invasive characterization of pediatric brain tumor biology with APTw imaging could aid the radiologist in clinical decision-making.

Indirect 1H-[13C] MRS of the human brain at 7 T using a 13C-birdcage coil and eight transmit-receive 1H-dipole antennas with a 32-channel 1H-receive array.

The neuronal tricarboxylic acid and glutamate/glutamine (Glu/Gln) cycles play important roles in brain function. These processes can be measured in vivo using dynamic 1H-[13C] MRS during administration of 13C-labeled glucose. Proton-observed carbon-edited (POCE) MRS enhances the signal-to-noise ratio (SNR) compared with direct 13C-MRS. Ultra-high field further boosts the SNR and increases spectral dispersion; however, even at 7 T, Glu and Gln 1H-resonances may overlap. Further gain can be obtained with selective POCE (selPOCE). Our aim was to create a setup for indirect dynamic 1H-[13C] MRS in the human brain at 7 T. A home-built non-shielded transmit-receive 13C-birdcage head coil with eight transmit-receive 1H-dipole antennas was used together with a 32-channel 1H-receive array. Electromagnetic simulations were carried out to ensure that acquisitions remained within local and global head SAR limits. POCE-MRS was performed using slice-selective excitation with semi-localization by adiabatic selective refocusing (sLASER) and stimulated echo acquisition mode (STEAM) localization, and selPOCE-MRS using STEAM. Sequences were tested in a phantom containing non-enriched Glu and Gln, and in three healthy volunteers during uniformly labeled 13C-glucose infusions. In one subject the voxel position was alternated between bi-frontal and bi-occipital placement within one session. [4-13C]Glu-H4 and [4-13C]Gln-H4 signals could be separately detected using both STEAM-POCE and STEAM-selPOCE in the phantom. In vivo, [4,5-13C]Glx could be detected using both sLASER-POCE and STEAM-POCE, with similar sensitivities, but [4,5-13C]Glu and [4,5-13C]Gln signals could not be completely resolved. STEAM-POCE was alternately performed bi-frontal and bi-occipital within a single session without repositioning of the subject, yielding similar results. With STEAM-selPOCE, [4,5-13C]Glu and [4,5-13C]Gln could be clearly separated. We have shown that with our setup indirect dynamic 1H-[13C] MRS at 7 T is feasible in different locations in the brain within one session, and by using STEAM-selPOCE it is possible to separate Glu from Gln in vivo while obtaining high quality spectra.

Measurement of metabolite levels and treatment-induced changes in hepatic metastases of gastro-esophageal cancer using 7-T phosphorus magnetic resonance spectroscopic imaging.

Methods for early treatment response evaluation to systemic therapy of liver metastases are lacking. Tumor tissue often exhibits an increased ratio of phosphomonoesters to phosphodiesters (PME/PDE), which can be noninvasively measured by phosphorus magnetic resonance spectroscopy (31P MRS), and may be a marker for early therapy response assessment in liver metastases. However, with commonly used 31P surface coils for liver 31P MRS, the liver is not fully covered, and metastases may be missed. The objective of this study was to demonstrate the feasibility of 31P MRS imaging (31P MRSI) with full liver coverage to assess 31P metabolite levels and chemotherapy-induced changes in liver metastases of gastro-esophageal cancer, using a 31P whole-body birdcage transmit coil in combination with a 31P body receive array at 7 T. 3D 31P MRSI data were acquired in two patients with hepatic metastases of esophageal cancer, before the start of chemotherapy and after 2 (and 9 in patient 2) weeks of chemotherapy. 3D 31P MRSI acquisitions were performed using an integrated 31P whole-body transmit coil in combination with a 16-channel body receive array at 7 T, with a field of view covering the full abdomen and a nominal voxel size of 20-mm isotropic. From the 31P MRSI data, 12 31P metabolite signals were quantified. Prior to chemotherapy initiation, both PMEs, that is, phosphocholine (PC) and phosphoethanolamine (PE), were significantly higher in all metastases compared with the levels previously determined in the liver of healthy volunteers. After 2 weeks of chemotherapy, PC and PE levels remained high or even increased further, resulting in increased PME/PDE ratios compared with healthy liver tissue, in correspondence with the clinical assessment of progressive disease after 2 months of chemotherapy. The suggested approach may present a viable tool for early therapy (non)response assessment of tumor metabolism in patients with liver metastases.

Human Brain Deuterium Metabolic Imaging at 7 T: Impact of Different [6,6'-2H2]Glucose Doses.

BACKGROUND: Deuterium metabolic imaging (DMI) is an innovative, noninvasive metabolic MR imaging method conducted after administration of 2H-labeled substrates. DMI after [6,6'-2H2]glucose consumption has been used to investigate brain metabolic processes, but the impact of different [6,6'-2H2]glucose doses on DMI brain data is not well known. PURPOSE: To investigate three different [6,6'-2H2]glucose doses for DMI in the human brain at 7 T. STUDY TYPE: Prospective. POPULATION: Six healthy participants (age: 28 ± 8 years, male/female: 3/3). FIELD STRENGTH/SEQUENCE: 7 T, 3D 2H free-induction-decay (FID)-magnetic resonance spectroscopic imaging (MRSI) sequence. ASSESSMENT: Three subjects received two different doses (0.25 g/kg, 0.50 g/kg or 0.75 g/kg body weight) of [6,6'-2H2]glucose on two occasions and underwent consecutive 2H-MRSI scans for 120 minutes. Blood was sampled every 10 minutes during the scan, to determine plasma glucose levels and plasma 2H-Glucose atom percent excess (APE) (part-1). Three subjects underwent the same protocol once after receiving 0.50 g/kg [6,6'-2H2]glucose (part-2). STATISTICAL TEST: Mean plasma 2H-Glucose APE and glucose plasma concentrations were compared using one-way ANOVA. Brain 2H-Glc and brain 2H-Glx (part-1) were analyzed with a two-level Linear Mixed Model. In part-2, a General Linear Model was used to compare brain metabolite signals. Statistical significance was set at P < 0.05. RESULTS: Between 60 and 100 minutes after ingesting [6,6'-2H2]glucose, plasma 2H-Glc APE did not differ between 0.50 g/kg and 0.75 g/kg doses (P = 0.961), but was significantly lower for 0.25 g/kg. Time and doses significantly affected brain 2H-Glucose levels (estimate ± standard error [SE]: 0.89 ± 0.01, 1.09 ± 0.01, and 1.27 ± 0.01, for 0.25 g/kg, 0.50 g/kg, and 0.75 g/kg, respectively) and brain 2H-Glutamate/Glutamine levels (estimate ± SE: 1.91 ± 0.03, 2.27 ± 0.03, and 2.46 ± 0.03, for 0.25 g/kg, 0.50 g/kg, and 0.75 g/kg, respectively). Plasma 2H-Glc APE, brain 2H-Glc, and brain 2H-Glx levels were comparable among subjects receiving 0.50 g/kg [6,6'-2H2]glucose. DATA CONCLUSION: Brain 2H-Glucose and brain 2H-Glutamate/Glutamine showed to be [6,6'-2H2]glucose dose dependent. A dose of 0.50 g/kg demonstrated comparable, and well-detectable, 2H-Glucose and 2H-Glutamate/Glutamine signals in the brain. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

31 P MR Spectroscopy in the Pancreas: Repeatability, Comparison With Liver, and Pilot Pancreatic Cancer Data.

BACKGROUND: Non-invasive evaluation of phosphomonoesters (PMEs) and phosphodiesters (PDEs) by 31-phosphorus MR spectroscopy (31 P MRS) may have potential for early therapy (non-)response assessment in cancer. However, 31 P MRS has not yet been applied to investigate the human pancreas in vivo. PURPOSE: To assess the technical feasibility and repeatability of 31 P MR spectroscopic imaging (MRSI) of the pancreas, compare 31 P metabolite levels between pancreas and liver, and determine the feasibility of 31 P MRSI in pancreatic cancer. STUDY TYPE: Prospective cohort study. POPULATION: 10 healthy subjects (age 34 ± 12 years, four females) and one patient (73-year-old female) with pancreatic ductal adenocarcinoma. FIELD STRENGTH/SEQUENCE: 7-T, 31 P FID-MRSI, 1 H gradient-echo MRI. ASSESSMENT: 31 P FID-MRSI of the abdomen (including the pancreas and liver) was performed with a nominal voxel size of 20 mm (isotropic). For repeatability measurements, healthy subjects were scanned twice on the same day. The patient was only scanned once. Test-retest 31 P MRSI data of pancreas and liver voxels (segmented on 1 H MRI) of healthy subjects were quantified by fitting in the time domain and signal amplitudes were normalized to γ-adenosine triphosphate. In addition, the PME/PDE ratio was calculated. Metabolite levels were averaged over all voxels within the pancreas, right liver lobe and left liver lobe, respectively. STATISTICAL TESTS: Repeatability of test-retest data from healthy pancreas was assessed by paired t-tests, Bland-Altman analyses, and calculation of the intrasubject coefficients of variation (CoVs). Significant differences between healthy pancreas and right and left liver lobes were assessed with a two-way analysis of variance (ANOVA) for repeated measures. A P-value <0.05 was considered statistically significant. RESULTS: The intrasubject CoVs for PME, PDE, and PME/PDE in healthy pancreas were below 20%. Furthermore, PME and PME/PDE were significantly higher in pancreas compared to liver. In the patient with pancreatic cancer, qualitatively, elevated relative PME signals were observed in comparison with healthy pancreas. DATA CONCLUSION: In vivo 31 P MRSI of the human healthy pancreas and in pancreatic cancer may be feasible at 7 T. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

An RF coil design to enable quintuple nuclear whole-brain MRI.

PURPOSE: To bring metabolic imaging based on multi-NMR toward practical use from the RF hardware perspective. METHODS: A highly integrated RF coil is designed for whole-brain MRI and MRS targeted to five nuclear species: 1 H, 19 F, 31 P, 23 Na, and 13 C. Dipole antennas and closely loaded local receiver loops are combined in this setup. RESULTS: High-quality in vivo scan results of 1 H, 31 P, 23 Na, and 13 C on healthy volunteers have been achieved. For 1 H, the transmit efficiency is 77% of a single-tuned commercial head coil (NOVA 8-transmit [Tx]/32-receive [Rx]; NOVA Medical, Wilmington, MA, USA). For 31 P, 110% SNR of a dual-tuned close-fit head-birdcage was achieved at the center of the subject, based on MR experiments on a phantom. For 31 P, 23 Na, and 13 C, bench measurements indicate SNR loss of 15%, 27%, and 30% compared with single-tuned conditions. 19 F performance has been proven to be similar to that of 1 H through bench tests and electromagnetic simulations. CONCLUSION: With this device, 1 H-based anatomic images that are expected to meet clinical requirements, as well as high-quality multi-NMR images and spectra, can be acquired within one scan session without hardware replacement or patient repositioning, enabling morphologic and metabolic MRI within acceptable scan time.

Deuterium echo-planar spectroscopic imaging (EPSI) in the human liver in vivo at 7 T.

PURPOSE: To demonstrate the feasibility of deuterium echo-planar spectroscopic imaging (EPSI) to accelerate 3D deuterium metabolic imaging in the human liver at 7 T. METHODS: A deuterium EPSI sequence, featuring a Hamming-weighted k-space acquisition pattern for the phase-encoding directions, was implemented. Three-dimensional deuterium EPSI and conventional MRSI were performed on a water/acetone phantom and in vivo in the human liver at natural abundance. Moreover, in vivo deuterium EPSI measurements were acquired after oral administration of deuterated glucose. The effect of acquisition time on SNR was evaluated by retrospectively reducing the number of averages. RESULTS: The SNR of natural abundance deuterated water signal in deuterium EPSI was 6.5% and 5.9% lower than that of MRSI in the phantom and in vivo experiments, respectively. In return, the acquisition time of in vivo EPSI data could be reduced retrospectively to 2 min, beyond the minimal acquisition time of conventional MRSI (of 20 min in this case), while still leaving sufficient SNR. Three-dimensional deuterium EPSI, after administration of deuterated glucose, enabled monitoring of hepatic glucose dynamics with full liver coverage, a spatial resolution of 20 mm isotropic, and a temporal resolution of 9 min 50 s, which could retrospectively be shortened to 2 min. CONCLUSION: In this work, we demonstrate the feasibility of accelerated 3D deuterium metabolic imaging of the human liver using deuterium EPSI. The acceleration obtained with EPSI can be used to increase temporal and/or spatial resolution, which will be valuable to study tissue metabolism of deuterated compounds over time.

Deuterium body array for the simultaneous measurement of hepatic and renal glucose metabolism and gastric emptying with dynamic 3D deuterium metabolic imaging at 7 T.

Deuterium metabolic imaging (DMI) is a novel noninvasive method to assess tissue metabolism and organ (patho)physiology in vivo using deuterated substrates, such as [6,6'-2 H2 ]-glucose. The liver and kidneys play a central role in whole-body glucose homeostasis, and in type 2 diabetes, both hepatic and renal glucose metabolism are dysregulated. Diabetes is also associated with gastric emptying abnormalities. In this study, we developed a four-channel 2 H transmit/receive body array coil for DMI in the human abdomen at 7 T and assessed its performance. In addition, the feasibility of simultaneously measuring gastric emptying, and hepatic and renal glucose uptake and metabolism with dynamic 3D DMI upon administration of deuterated glucose, was investigated. Simulated and measured B1 + patterns were in good agreement. The intrasession variability of the natural abundance deuterated water signal in the liver and right kidney, measured in nine healthy volunteers, was 5.6% ± 0.9% and 4.9% ± 0.7%, respectively. Dynamic 3D DMI scans with oral administration of [6,6'-2 H2 ]-glucose showed similar kinetics of deuterated glucose appearance and disappearance in the liver and kidney. The measured gastric emptying half time was 80 ± 10 min, which is in good agreement with scintigraphy measurements. In conclusion, DMI with oral administration of [6,6'-2 H2 ]-glucose enables simultaneous assessment of gastric emptying and liver and kidney glucose uptake and metabolism. When applied in patients with diabetes, this approach may advance our understanding of the interplay between disturbances in liver and kidney glucose uptake and metabolism and gastric emptying, at a detail that cannot be achieved by any other method.

In vivo phosphorus magnetic resonance spectroscopic imaging of the whole human liver at 7 T using a phosphorus whole-body transmit coil and 16-channel receive array: Repeatability and effects of principal component analysis-based denoising.

Quantitative three-dimensional (3D) imaging of phosphorus (31 P) metabolites is potentially a promising technique with which to assess the progression of liver disease and monitor therapy response. However, 31 P magnetic resonance spectroscopy has a low sensitivity and commonly used 31 P surface coils do not provide full coverage of the liver. This study aimed to overcome these limitations by using a 31 P whole-body transmit coil in combination with a 16-channel 31 P receive array at 7 T. Using this setup, we determined the repeatability of whole-liver 31 P magnetic resonance spectroscopic imaging (31 P MRSI) in healthy subjects and assessed the effects of principal component analysis (PCA)-based denoising on the repeatability parameters. In addition, spatial variations of 31 P metabolites within the liver were analyzed. 3D 31 P MRSI data of the liver were acquired with a nominal voxel size of 20 mm isotropic in 10 healthy volunteers twice on the same day. Data were reconstructed without denoising, and with PCA-based denoising before or after channel combination. From the test-retest data, repeatability parameters for metabolite level quantification were determined for 12 31 P metabolite signals. On average, 31 P MR spectra from 100 ± 25 voxels in the liver were analyzed. Only voxels with contamination from skeletal muscle or the gall bladder were excluded and no voxels were discarded based on (low) signal-to-noise ratio (SNR). Repeatability for most quantified 31 P metabolite levels in the liver was good to excellent, with an intrasubject variability below 10%. PCA-based denoising increased the SNR ~ 3-fold, but did not improve the repeatability for mean liver 31 P metabolite quantification with the fitting constraints used. Significant spatial heterogeneity of various 31 P metabolite levels within the liver was observed, with marked differences for the phosphomonoester and phosphodiester metabolites between the left and right lobe. In conclusion, using a 31 P whole-body transmit coil in combination with a 16-channel 31 P receive array at 7 T allowed 31 P MRSI acquisitions with full liver coverage and good to excellent repeatability.

Tier-based formalism for safety assessment of custom-built radio-frequency transmit coils.

The purpose of this work is to propose a tier-based formalism for safety assessment of custom-built radio-frequency (RF) coils that balances validation effort with the effort put in determinating the safety factor. The formalism has three tier levels. Higher tiers require increased effort when validating electromagnetic simulation results but allow for less conservative safety factors. In addition, we propose a new method to calculate modeling uncertainty between simulations and measurements and a new method to propagate uncertainties in the simulation into a safety factor that minimizes the risk of underestimating the peak specific absorption rate (SAR). The new safety assessment procedure was completed for all tier levels for an eight-channel dipole array for prostate imaging at 7 T and an eight-channel dipole array for head imaging at 10.5 T, using data from two different research sites. For the 7 T body array, the validation procedure resulted in a modeling uncertainty of 77% between measured and simulated local SAR distributions. For a situation where RF shimming is performed on the prostate, average power limits of 2.4 and 4.5 W/channel were found for tiers 2 and 3, respectively. When the worst-case peak SAR among all phase settings was calculated, power limits of 1.4 and 2.7 W/channel were found for tiers 2 and 3, respectively. For the 10.5 T head array, a modeling uncertainty of 21% was found based on B1 + mapping. For the tier 2 validation, a power limit of 2.6 W/channel was calculated. The demonstrated tier system provides a strategy for evaluating modeling inaccuracy, allowing for the rapid translation of novel coil designs with conservative safety factors and the implementation of less conservative safety factors for frequently used coil arrays at the expense of increased validation effort.

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.

Patient-derived cancer cells cultured in vitro are a cornerstone of cancer metabolism research. More recently, the introduction of organoids has provided the research community with a more versatile model system. Physiological structure and organization of the cell source tissue are maintained in organoids, representing a closer link to in vivo tumor models. High-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) is a commonly applied analytical approach for metabolic profiling of intact tissue, but its use has not been reported for organoids. The aim of the current work was to compare the performance of HR MAS MRS and extraction-based nuclear magnetic resonance (NMR) in metabolic profiling of wild-type and tumor progression organoids (TPOs) from human colon cancer, and further to investigate how the sequentially increased genetic alterations of the TPOs affect the metabolic profile. Sixteen metabolites were reliably identified and quantified both in spectra based on NMR of extracts and HR MAS MRS of intact organoids. The metabolite concentrations from the two approaches were highly correlated (r = 0.94), and both approaches were able to capture the systematic changes in metabolic features introduced by the genetic alterations characteristic of colorectal cancer progression (e.g., increased levels of lactate and decreased levels of myo-inositol and phosphocholine with an increasing number of mutations). The current work highlights that HR MAS MRS is a well-suited method for metabolic profiling of intact organoids, with the additional benefit that the nondestructive nature of HR MAS enables subsequent recovery of the organoids for further analyses based on nucleic acids or proteins.

Feasibility of clinical studies of chemical exchange saturation transfer magnetic resonance imaging of prostate cancer at 7 T.

Chemical exchange saturation transfer (CEST) has been explored for differentiation between tumour and benign tissue in prostate cancer (PCa) patients. With ultrahigh field strengths such as 7-T, the increase of spectral resolution and sensitivity could allow for selective detection of amide proton transfer (APT) at 3.5 ppm and a group of compounds that resonate at 2 ppm (i.e., [poly]amines and/or creatine). The potential of 7-T multipool CEST analysis of the prostate and the detection of PCa was studied in patients with proven localised PCa who were scheduled to undergo robot-assisted radical prostatectomy (RARP). Twelve patients were prospectively included (mean age 68.0 years, mean serum prostate-specific antigen 7.8ng/mL). A total of 24 lesions larger than 2 mm were analysed. Used were 7-T T2-weighted (T2W) imaging and 48 spectral CEST points. Patients received 1.5-T/3-T prostate magnetic resonance imaging and galium-68-prostate-specific membrane antigen-positron emission tomography/computerised tomography to determine the location of the single-slice CEST. Based on the histopathological results after RARP, three regions of interest were drawn on the T2W images from a known malignant zone and benign zone in the central and peripheral zones. These areas were transposed to the CEST data, from which the APT and 2-ppm CEST were calculated. The statistical significance of the CEST between the central zone, the peripheral zone, and tumour was calculated using a Kruskal-Wallis test. The z-spectra showed that APT and even a distinct pool that resonated at 2 ppm were detectable. This study showed a difference trend in the APT levels, but no difference in the 2-ppm levels when tested between the central zone, the peripheral zone, and tumour (H(2) = 4.8, p = 0.093 and H(2) = 0.86, p = 0.651, respectively). Thus, to conclude, we could most likely detect APT and amines and/or creatine levels noninvasively in prostate using the CEST effect. At group level, CEST showed a higher level of APT in the peripheral versus the central zone; however, no differences of APT and 2-ppm levels were observed in tumours.

Prospective of 31 P MR Spectroscopy in Hepatopancreatobiliary Cancer: A Systematic Review of the Literature.

BACKGROUND: The incidence of liver and pancreatic cancer is rising. Patients benefit from current treatments, but there are limitations in the evaluation of (early) response to treatment. Tumor metabolic alterations can be measured noninvasively with phosphorus (31 P) magnetic resonance spectroscopy (MRS). PURPOSE: To conduct a quantitative analysis of the available literature on 31 P MRS performed in hepatopancreatobiliary cancer and to provide insight into its current and potential for therapy (non-) response assessment. POPULATION: Patients with hepatopancreatobiliary cancer. FIELD STRENGTH/SEQUENCE: 31 P MRS. ASSESSMENT: The PubMed, EMBASE, and Cochrane library databases were systematically searched for studies published to 17 March 17, 2022. All 31 P MRS studies in hepatopancreatobiliary cancer reporting 31 P metabolite levels were included. STATISTICAL TESTS: Relative differences in 31 P metabolite levels/ratios between patients before therapy and healthy controls, and the relative changes in 31 P metabolite levels/ratios in patients before and after therapy were determined. RESULTS: The search yielded 10 studies, comprising 301 subjects, of whom 132 (44%) healthy volunteers and 169 (56%) patients with liver cancer of various etiology. To date, 31 P MRS has not been applied in pancreatic cancer. In liver cancer, alterations in levels of 31 P metabolites involved in cell proliferation (phosphomonoesters [PMEs] and phosphodiesters [PDEs]) and energy metabolism (ATP and inorganic phosphate [Pi]) were observed. In particular, liver tumors were associated with elevations of PME/PDE and PME/Pi compared to healthy liver tissue, although there was a broad variety among studies (elevations of 2%-267% and 21%-233%, respectively). Changes in PME/PDE in liver tumors upon therapy were substantial, yet very heterogeneous and both decreases and increases were observed, whereas PME/Pi was consistently decreased after therapy in all studies (-13% to -76%). DATA CONCLUSION: 31 P MRS has great potential for treatment monitoring in oncology. Future studies are needed to correlate the changes in 31 P metabolite levels in hepatopancreatobiliary tumors with treatment response. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Simulation-based evaluation of SAR and flip angle homogeneity for five transmit head arrays at 14 T.

INTRODUCTION: Various research sites are pursuing 14 T MRI systems. However, both local SAR and RF transmit field inhomogeneity will increase. The aim of this simulation study is to investigate the trade-offs between peak local SAR and flip angle uniformity for five transmit coil array designs at 14 T in comparison to 7 T. METHODS: Investigated coil array designs are: 8 dipole antennas (8D), 16 dipole antennas (16D), 8 loop coils (8D), 16 loop coils (16L), 8 dipoles/8 loop coils (8D8L) and for reference 8 dipoles at 7 T. Both RF shimming and kT-points were investigated by plotting L-curves of peak SAR levels vs flip angle homogeneity. RESULTS: For RF shimming, the 16L array performs best. For kT-points, superior flip angle homogeneity is achieved at the expense of more power deposition, and the dipole arrays outperform the loop coil arrays. DISCUSSION AND CONCLUSION: For most arrays and regular imaging, the constraint on head SAR is reached before constraints on peak local SAR are violated. Furthermore, the different drive vectors in kT-points alleviate strong peaks in local SAR. Flip angle inhomogeneity can be alleviated by kT-points at the expense of larger power deposition. For kT-points, the dipole arrays seem to outperform loop coil arrays.

A vision of 14 T MR for fundamental and clinical science.

OBJECTIVE: We outline our vision for a 14 Tesla MR system. This comprises a novel whole-body magnet design utilizing high temperature superconductor; a console and associated electronic equipment; an optimized radiofrequency coil setup for proton measurement in the brain, which also has a local shim capability; and a high-performance gradient set. RESEARCH FIELDS: The 14 Tesla system can be considered a 'mesocope': a device capable of measuring on biologically relevant scales. In neuroscience the increased spatial resolution will anatomically resolve all layers of the cortex, cerebellum, subcortical structures, and inner nuclei. Spectroscopic imaging will simultaneously measure excitatory and inhibitory activity, characterizing the excitation/inhibition balance of neural circuits. In medical research (including brain disorders) we will visualize fine-grained patterns of structural abnormalities and relate these changes to functional and molecular changes. The significantly increased spectral resolution will make it possible to detect (dynamic changes in) individual metabolites associated with pathological pathways including molecular interactions and dynamic disease processes. CONCLUSIONS: The 14 Tesla system will offer new perspectives in neuroscience and fundamental research. We anticipate that this initiative will usher in a new era of ultra-high-field MR.

Accelerating Brain Imaging Using a Silent Spatial Encoding Axis.

PURPOSE: To characterize the acceleration capabilities of a silent head insert gradient axis that operates at the inaudible frequency of 20 kHz and a maximum gradient amplitude of 40 mT/m without inducing peripheral nerve stimulation. METHODS: The silent gradient axis' acquisitions feature an oscillating gradient in the phase-encoding direction that is played out on top of a cartesian readout, similarly as done in Wave-CAIPI. The additional spatial encoding fills k-space in readout lanes allowing for the acquisition of fewer phase-encoding steps without increasing aliasing artifacts. Fully sampled 2D gradient echo datasets were acquired both with and without the silent readout. All scans were retrospectively undersampled (acceleration factors R = 1 to 12) to compare conventional SENSE acceleration and acceleration using the silent gradient. The silent gradient amplitude and the readout bandwidth were varied to investigate the effect on artifacts and g-factor. RESULTS: The silent readout reduced the g-factor for all acceleration factors when compared to SENSE acceleration. Increasing the silent gradient amplitude from 31.5 mT/m to 40 mT/m at an acceleration factor of 10 yielded a reduction in the average g-factor (gavg ) from 1.3 ± 0.14 (gmax  = 1.9) to 1.1 ± 0.09 (gmax  = 1.6). Furthermore, reducing the number of cycles increased the readout bandwidth and the g-factor that reached gavg  = 1.5 ± 0.16 for a readout bandwidth of 651 Hz/pixel and an acceleration factor of R = 8. CONCLUSION: A silent gradient axis enables high acceleration factors up to R = 10 while maintaining a g-factor close to unity (gavg  = 1.1 and gmax  = 1.6) and can be acquired with clinically relevant readout bandwidths.

A silent gradient axis for soundless spatial encoding to enable fast and quiet brain imaging.

PURPOSE: A novel silent imaging method is proposed that combines a gradient insert oscillating at the inaudible frequency 20 kHz with slew rate-limited gradient waveforms to form a silent gradient axis that enable quiet and fast imaging. METHODS: The gradient insert consisted of a plug-and-play (45 kg) single axis z-gradient, which operated as an additional fourth gradient axis. This insert was made resonant using capacitors and combined with an audio amplifier to allow for operation at 20 kHz. The gradient field was characterized using field measurements and the physiological effects of operating a gradient field at 20 kHz were explored using peripheral nerve stimulation experiments, tissue heating simulations and sound measurements. The imaging sequence consisted of a modified gradient-echo sequence which fills k-space in readout lanes with a width proportional to the oscillating gradient amplitude. The feasibility of the method was demonstrated in-vivo using 2D and 3D gradient echo (GRE) sequences which were reconstructed using a conjugate-gradient SENSE reconstruction. RESULTS: Field measurements yielded a maximum gradient amplitude and slew rate of 40.8 mT/m and 5178T/m/s at 20 kHz. Physiological effects such as peripheral nerve stimulation and tissue heating were found not to be limiting at this amplitude and slew rate. For a 3D GRE sequence, a maximum sound level of 85 db(A) was measured during scanning. Imaging experiments using the silent gradient axis produced artifact free images while also featuring a 5.3-fold shorter scan time than a fully sampled acquisition. CONCLUSION: A silent gradient axis provides a novel pathway to fast and quiet brain imaging.