Glucose versus fructose metabolism in the liver measured with deuterium metabolic imaging.

Chronic intake of high amounts of fructose has been linked to the development of metabolic disorders, which has been attributed to the almost complete clearance of fructose by the liver. However, direct measurement of hepatic fructose uptake is complicated by the fact that the portal vein is difficult to access. Here we present a new, non-invasive method to measure hepatic fructose uptake and metabolism with the use of deuterium metabolic imaging (DMI) upon administration of [6,6'-2H2]fructose. Using both [6,6'-2H2]glucose and [6,6'-2H2]fructose, we determined differences in the uptake and metabolism of glucose and fructose in the mouse liver with dynamic DMI. The deuterated compounds were administered either by fast intravenous (IV) bolus injection or by slow IV infusion. Directly after IV bolus injection of [6,6'-2H2]fructose, a more than two-fold higher initial uptake and subsequent 2.5-fold faster decay of fructose was observed in the mouse liver as compared to that of glucose after bolus injection of [6,6'-2H2]glucose. In contrast, after slow IV infusion of fructose, the 2H fructose/glucose signal maximum in liver spectra was lower compared to the 2H glucose signal maximum after slow infusion of glucose. With both bolus injection and slow infusion protocols, deuterium labeling of water was faster with fructose than with glucose. These observations are in line with a higher extraction and faster turnover of fructose in the liver, as compared with glucose. DMI with [6,6'-2H2]glucose and [6,6'-2H2]fructose could potentially contribute to a better understanding of healthy human liver metabolism and aberrations in metabolic diseases.

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.

Proton metabolic mapping of the brain at 7 T using a two-dimensional free induction decay-echo-planar spectroscopic imaging readout with lipid suppression.

The increased signal-to-noise ratio (SNR) and chemical shift dispersion at high magnetic fields (≥7 T) have enabled neuro-metabolic imaging at high spatial resolutions. To avoid very long acquisition times with conventional magnetic resonance spectroscopic imaging (MRSI) phase-encoding schemes, solutions such as pulse-acquire or free induction decay (FID) sequences with short repetition time and inner volume selection methods with acceleration (echo-planar spectroscopic imaging [EPSI]), have been proposed. With the inner volume selection methods, limited spatial coverage of the brain and long echo times may still impede clinical implementation. FID-MRSI sequences benefit from a short echo time and have a high SNR per time unit; however, contamination from strong extra-cranial lipid signals remains a problem that can hinder correct metabolite quantification. L2-regularization can be applied to remove lipid signals in cases with high spatial resolution and accurate prior knowledge. In this work, we developed an accelerated two-dimensional (2D) FID-MRSI sequence using an echo-planar readout and investigated the performance of lipid suppression by L2-regularization, an external crusher coil, and the combination of these two methods to compare the resulting spectral quality in three subjects. The reduction factor of lipid suppression using the crusher coil alone varies from 2 to 7 in the lipid region of the brain boundary. For the combination of the two methods, the average lipid area inside the brain was reduced by 2% to 38% compared with that of unsuppressed lipids, depending on the subject's region of interest. 2D FID-EPSI with external lipid crushing and L2-regularization provides high in-plane coverage and is suitable for investigating brain metabolite distributions at high fields.

Residual quadrupolar couplings observed in 7 Tesla deuterium MR spectra of skeletal muscle.

PURPOSE: Deuterium metabolic imaging could potentially be used to investigate metabolism in skeletal muscle noninvasively. However, skeletal muscle is a tissue with a high degree of spatial organization. In this study, we investigated the effect of incomplete motional averaging on the naturally abundant deuterated water signal in 7 Tesla deuterium spectra of the lower leg muscles and the dependence on the angle between the muscle fibers and the main magnetic field B0 , as determined by DTI. METHODS: Natural abundance deuterium MRSI measurements of the right lower leg muscles were performed at 7 Tesla. Three subjects were scanned in a supine position, with the right leg parallel with the B0 field. One subject was scanned twice; during the second scan, the subject was laying on his right side and the right knee was bent such that the angle between the right lower leg and B0 was approximately 45°. DTI was performed in the same subjects in the same positions at 3 Tesla to determine muscle fiber angles. RESULTS: We observed splittings in the natural abundance deuterated water signal. The size of the splittings varied between different muscles in the lower leg but were mostly similar among subjects for each muscle. The splittings depended on the orientation of the muscle fibers with respect to the main magnetic field B0 . CONCLUSION: Partial molecular alignment in skeletal muscle leads to residual deuteron quadrupolar couplings in deuterated water, the size of which depends on the angle between the muscle fibers and B0 .

A plug-and-play, lightweight, single-axis gradient insert design for increasing spatiotemporal resolution in echo planar imaging-based brain imaging.

The goal of this study was to introduce and evaluate the performance of a lightweight, high-performance, single-axis (z-axis) gradient insert design primarily intended for high-resolution functional magnetic resonance imaging, and aimed at providing both ease of use and a boost in spatiotemporal resolution. The optimal winding positions of the coil were obtained using a genetic algorithm with a cost function that balanced gradient performance (minimum 0.30 mT/m/A) and field linearity (≥16 cm linear region). These parameters were verified using field distribution measurements by B0 -mapping. The correction of geometrical distortions was performed using theoretical field distribution of the coil. Simulations and measurements were performed to investigate the echo planar imaging echo-spacing reduction due to the improved gradient performance. The resulting coil featured a 16-cm linear region, a weight of 45 kg, an installation time of 15 min, and a maximum gradient strength and slew rate of 200 mT/m and 1300 T/m/s, respectively, when paired with a commercially available gradient amplifier (940 V/630 A). The field distribution measurements matched the theoretically expected field. By utilizing the theoretical field distribution, geometrical distortions were corrected to within 6% of the whole-body gradient reference image in the target region. Compared with a whole-body gradient set, a maximum reduction in echo-spacing of a factor of 2.3 was found, translating to a 344 µs echo-spacing, for a field of view of 192 mm, a receiver bandwidth of 920 kHz and a gradient amplitude of 112 mT/m. We present a lightweight, single-axis gradient insert design that can provide high gradient performance and an increase in spatiotemporal resolution with correctable geometrical distortions while also offering a short installation time of less than 15 min and minimal system modifications.

Pushing functional MRI spatial and temporal resolution further: High-density receive arrays combined with shot-selective 2D CAIPIRINHA for 3D echo-planar imaging at 7 T.

To be able to examine dynamic and detailed brain functions, the spatial and temporal resolution of 7 T MRI needs to improve. In this study, it was investigated whether submillimeter multishot 3D EPI fMRI scans, acquired with high-density receive arrays, can benefit from a 2D CAIPIRINHA sampling pattern, in terms of noise amplification (g-factor), temporal SNR and fMRI sensitivity. High-density receive arrays were combined with a shot-selective 2D CAIPIRINHA implementation for multishot 3D EPI sequences at 7 T. In this implementation, in contrast to conventional inclusion of extra kz gradient blips, specific EPI shots are left out to create a CAIPIRINHA shift and reduction of scan time. First, the implementation of the CAIPIRINHA sequence was evaluated with a standard receive setup by acquiring submillimeter whole brain T2 *-weighted anatomy images. Second, the CAIPIRINHA sequence was combined with high-density receive arrays to push the temporal resolution of submillimeter 3D EPI fMRI scans of the visual cortex. Results show that the shot-selective 2D CAIPIRINHA sequence enables a reduction in scan time for 0.5 mm isotropic 3D EPI T2 *-weighted anatomy scans by a factor of 4 compared with earlier reports. The use of the 2D CAIPIRINHA implementation in combination with high-density receive arrays, enhances the image quality of submillimeter 3D EPI scans of the visual cortex at high acceleration as compared to conventional SENSE. Both the g-factor and temporal SNR improved, resulting in a method that is more sensitive to the fMRI signal. Using this method, it is possible to acquire submillimeter single volume 3D EPI scans of the visual cortex in a subsecond timeframe. Overall, high-density receive arrays in combination with shot-selective 2D CAIPIRINHA for 3D EPI scans prove to be valuable for reducing the scan time of submillimeter MRI acquisitions.

On the magnetic field dependence of deuterium metabolic imaging.

Deuterium metabolic imaging (DMI) is a novel MR-based method to spatially map metabolism of deuterated substrates such as [6,6'-2 H2 ]-glucose in vivo. Compared with traditional 13 C-MR-based metabolic studies, the MR sensitivity of DMI is high due to the larger 2 H magnetic moment and favorable T1 and T2 relaxation times. Here, the magnetic field dependence of DMI sensitivity and transmit efficiency is studied on phantoms and rat brain postmortem at 4, 9.4 and 11.7 T. The sensitivity and spectral resolution on human brain in vivo are investigated at 4 and 7 T before and after an oral dose of [6,6'-2 H2 ]-glucose. For small animal surface coils (Ø 30 mm), the experimentally measured sensitivity and transmit efficiency scale with the magnetic field to a power of +1.75 and -0.30, respectively. These are in excellent agreement with theoretical predictions made from the principle of reciprocity for a coil noise-dominant regime. For larger human surface coils (Ø 80 mm), the sensitivity scales as a +1.65 power. The spectral resolution increases linearly due to near-constant linewidths. With optimal multireceiver arrays the acquisition of DMI at a nominal 1 mL spatial resolution is feasible at 7 T.

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

Energy metabolism of the human visual cortex was investigated by performing 31 P 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 31 P-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 31 P measurements were combined. This included: a close fitting 31 P 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 31 P 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.

Potential acceleration performance of a 256-channel whole-brain receive array at 7 T.

PURPOSE: Assess the potential gain in acceleration performance of a 256-channel versus 32-channel receive coil array at 7 T in combination with a 2D CAIPIRINHA sequence for 3D data sets. METHODS: A 256-channel receive setup was simulated by placing 2 small 16-channel high-density receive arrays at 2 × 8 different locations on the head of healthy participants. Multiple consecutive measurements were performed and coil sensitivity maps were combined to form a complete 256-channel data set. This setup was compared with a standard 32-channel head coil, in terms of SNR, noise correlation, and acceleration performance (g-factor). RESULTS: In the periphery of the brain, the receive SNR was on average a factor 1.5 higher (ranging up to a factor 2.7 higher) than the 32-channel coil; in the center of the brain the SNR was comparable or lower, depending on the size of the region of interest, with a factor 1.0 on average (ranging from 0.7 up to a factor of 1.6). The average noise correlation between coil elements was 3% for the 256-channel coil, and 5% for the 32-channel coil. At acceptable g-factors (< 2), the achievable acceleration factor using SENSE and 2D CAIPIRINHA was 24 and 28, respectively, versus 9 and 12 for the 32-channel coil. CONCLUSION: The receive performance of the simulated 256 channel array was better than the 32-channel reference. Combined with 2D CAIPIRINHA, a peak acceleration factor of 28 was assessed, showing great potential for high-density receive arrays.

Maximizing sensitivity for fast GABA edited spectroscopy in the visual cortex at 7 T.

The combination of functional MRI (fMRI) and MRS is a promising approach to relate BOLD imaging to neuronal metabolism, especially at high field strength. However, typical scan times for GABA edited spectroscopy are of the order of 6-30 min, which is long compared with functional changes observed with fMRI. The aim of this study is to reduce scan time and increase GABA sensitivity for edited spectroscopy in the human visual cortex, by enlarging the volume of activated tissue in the primary visual cortex. A dedicated setup at 7 T for combined fMRI and GABA MRS is developed. This setup consists of a half volume multi-transmit coil with a large screen for visual cortex activation, two high density receive arrays and an optimized single-voxel MEGA-sLASER sequence with macromolecular suppression for signal acquisition. The coil setup performance as well as the GABA measurement speed, SNR, and stability were evaluated. A 2.2-fold gain of the average SNR for GABA detection was obtained, as compared with a conventional 7 T setup. This was achieved by increasing the viewing angle of the participant with respect to the visual stimulus, thereby activating almost the entire primary visual cortex, allowing larger spectroscopy measurement volumes and resulting in an improved GABA SNR. Fewer than 16 signal averages, lasting 1 min 23 s in total, were needed for the GABA fit method to become stable, as demonstrated in three participants. The stability of the measurement setup was sufficient to detect GABA with an accuracy of 5%, as determined with a GABA phantom. In vivo, larger variations in GABA concentration are found: 14-25%. Overall, the results bring functional GABA detections at a temporal resolution closer to the physiological time scale of BOLD cortex activation.

Quantitative first-pass perfusion MRI of the mouse myocardium.

In this article, we present a first-pass perfusion imaging protocol to determine quantitative regional perfusion values (in mL min(-1) g(-1)) of the mouse myocardium. Perfusion was quantified using a Fermi-constrained deconvolution of the myocardial tissue response with the arterial input function. A dual-bolus approach was implemented. Experimental evidence is presented for the linearity of signal intensity in the left-ventricular lumen during the prebolus (r=0.99, P<0.001) and in the myocardium during the full-bolus injection (r=0.99, P<0.01) as function of Gd(DTPA)2- injection concentration used. The prebolus was used to reconstruct a nonsaturated arterial input function. Regional perfusion values proved repeatable in a cohort of nine healthy C57BL/6 mice. The perfusion values over two measurements with a 1-week interval were 7.3±0.9 and 7.2±0.6 mL min(-1) g(-1), respectively. No effects of time (P>0.05) and myocardial region (P>0.05) were observed. The between-session coefficient of variation was only 6%, whereas the inter-animal coefficient of variation was 11 and 8% for the separate experiments. We expect that the first-pass perfusion method here presented will be useful in preclinical studies of myocardial perfusion deficits and valuable to assess the impact of pro-angiogenic therapy after myocardial infarction.