Showing papers by "Robin A. de Graaf published in 2018"

Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo

Abstract: Currently, the only widely available metabolic imaging technique in the clinic is positron emission tomography (PET) detection of the radioactive glucose analog 2-18F-fluoro-2-deoxy-d-glucose (18FDG). However, 18FDG-PET does not inform on metabolism downstream of glucose uptake and often provides ambiguous results in organs with intrinsic high glucose uptake, such as the brain. Deuterium metabolic imaging (DMI) is a novel, noninvasive approach that combines deuterium magnetic resonance spectroscopic imaging with oral intake or intravenous infusion of nonradioactive 2H-labeled substrates to generate three-dimensional metabolic maps. DMI can reveal glucose metabolism beyond mere uptake and can be used with other 2H-labeled substrates as well. We demonstrate DMI by mapping metabolism in the brain and liver of animal models and human subjects using [6,6′-2H2]glucose or [2H3]acetate. In a rat glioma model, DMI revealed pronounced metabolic differences between normal brain and tumor tissue, with high-contrast metabolic maps depicting the Warburg effect. We observed similar metabolic patterns and image contrast in two patients with a high-grade brain tumor after oral intake of 2H-labeled glucose. Further, DMI used in rat and human livers showed [6,6′-2H2]glucose stored as labeled glycogen. DMI is a versatile, robust, and easy-to-implement technique that requires minimal modifications to existing clinical magnetic resonance imaging scanners. DMI has great potential to become a widespread method for metabolic imaging in both (pre)clinical research and the clinic.

Selective proton‐observed, carbon‐edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C‐labeling in the human frontal cortex

Abstract: Purpose 13 C magnetic resonance spectroscopy (MRS) in combination with infusion of 13 C-labeled substrates has led to unique insights into human brain metabolism and neurotransmitter cycling. However, the low sensitivity of direct 13 C MRS and high radiofrequency power requirements has limited 13 C MRS studies to predominantly data acquisition in large volumes of the occipital cortex. The purpose of this study is to develop an MRS technique for localized detection of 13 C-labeling of glutamate and glutamine in the human frontal lobe. Methods We used an indirect (1 H-[13 C]), proton-observed, carbon-edited MRS sequence (selPOCE) for detection of 13 C-labeled metabolites in relatively small volumes located in the frontal lobe at 4 T. The SelPOCE method allows for selective and separate detection of glutamate and glutamine resonances, which significantly overlap at magnetic field strengths used for clinical MRI. Results Phantom data illustrate how selPOCE can be tuned to selectively detect 13 C labeling in different metabolites. Three-dimensional specific absorption rate simulations of radiofrequency power deposition show that the selPOCE method operates comfortably within the global and local Food and Drug Administration specific absorption rate guidelines. In vivo selPOCE data are presented, which were acquired from a 45-mL volume in the frontal lobe of healthy subjects. The in vivo data show the time-dependent 13 C-labeling of glutamate and glutamine during intravenous infusion of [1-13 C]-glucose. Metrics describing spectral fitting quality of the glutamate and glutamine resonances are reported. Conclusions The SelPOCE sequence allows the detection of 13 C-labeling in glutamate and glutamine from a relatively small volume in the human frontal lobe at low radiofrequency power requirements. Magn Reson Med 80:11-20, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Elliptical localization with pulsed second-order fields (ECLIPSE) for robust lipid suppression in proton MRSI.

Abstract: Proton MRSI has great clinical potential for metabolic mapping of the healthy and pathological human brain. Unfortunately, the promise has not yet been fully achieved due to numerous technical challenges related to insufficient spectral quality caused by magnetic field inhomogeneity, insufficient RF transmit power and incomplete lipid suppression. Here a robust, novel method for lipid suppression in 1 H MRSI is presented. The method is based on 2D spatial localization of an elliptical region of interest using pulsed second-order spherical harmonic (SH) magnetic fields. A dedicated, high-amplitude second-order SH gradient setup was designed and constructed, containing coils to generate Z2, X2Y2 and XY magnetic fields. Simulations and phantom MRI results are used to demonstrate the principles of the method and illustrate the manifestation of chemical shift displacement. 1 H MRSI on human brain in vivo demonstrates high quality, robust suppression of extracranial lipids. The method allows a wide range of inner or outer volume selection or suppression and should find application in MRSI, reduced-field-of-view MRI and single-volume MRS.

Measurement of lipid composition in human skeletal muscle and adipose tissue with 1 H-MRS homonuclear spectral editing.

Abstract: PURPOSE Accumulation of triglycerides in nonadipose tissue (e.g. ectopic lipids) is characteristic of metabolic derangements and is linked to insulin resistance and cardiovascular disease. Although the detrimental effects of the total amount of ectopic fat has been established, the role of composition of the ectopic lipid stores is unknown. In this study we used proton magnetic resonance spectroscopy (1 H-MRS) homonuclear spectral editing to characterize lipid stores in adipose tissue and skeletal muscle at 4 T. METHODS A MEGA-sLASER sequence was used to selectively detect lipid resonances that are scalar coupled to the methine resonance at 5.31 ppm and that can be used to estimate saturated fatty acid and mono- and polyunsaturated fatty acids. Phantom experiments were performed to empirically determine correction factors for editing efficiency of the different lipid groups. RESULTS The spectral editing approach enabled the estimation of saturated, mono-unsaturated, and polyunsaturated fatty acid contributions in phantoms and in vivo. These estimations are in the same order as reported in studies using invasive biopsies. CONCLUSIONS In this study, we have shown the feasibility of spectral editing techniques for ectopic lipid store characterization with 1 H-MRS, regardless of spectral resolution (e.g., B0- field strength). This new approach offers the opportunity to study ectopic lipid composition in relation to metabolic diseases. Magn Reson Med 79:619-627, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Minimum echo time PRESS-based proton observed carbon edited (POCE) MRS in rat brain using simultaneous editing and localization pulses.

Abstract: PURPOSE Indirect 13 C MRS by proton-observed carbon editing (POCE) is a powerful method to study brain metabolism. The sensitivity of POCE-MRS can be enhanced through the use of short TEs, which primarily minimizes homonuclear J-evolution related losses; previous POCE-MRS implementations use longer than optimal echo times due to sequence limitations, or short TE image selected in vivo spectroscopy-based multi-shot acquisitions for 3D localization. To that end, this paper presents a novel single-shot point resolved spectroscopy (PRESS)-localized POCE-MRS sequence that involves the application of simultaneous editing and localization pulses (SEAL)-PRESS, allowing the TE to be reduced to a theoretically optimal value of ∼ 1/JHC . METHODS The optimized SEAL-PRESS sequence was first evaluated in simulation and in phantom; next, the sequence was validated with dynamic in vivo POCE-MRS performed in a rat preparation during a 1,6-13 C2 -Glc infusion, and on a microwave fixed rat brain following a 2-hour [1,6-13 C2 ]-Glc infusion. POCE spectra from the SEAL-PRESS sequence were compared against a previously described 12.6-ms PRESS-POCE sequence utilizing a classical carbon editing scheme. RESULTS The SEAL-PRESS sequence provides > 95% editing efficiency, optimal sensitivity, and localization for POCE MRS with an overall sequence TE of 8.1 ms. Signal amplitude of 13 C-labeled metabolites Glu-H4, Gln-H4, Glx-H3, Glc-H6 +Glx-H2, and Asp-H2 were shown to be improved by >17% relative to a 12.6-ms PRESS-POCE sequence in vivo. CONCLUSION We report for the first time, a single-shot PRESS-localized and edited 8.1-ms TE POCE-MRS sequence with optimal sensitivity, editing efficiency, and localization.