Correlation chemical shift imaging with low-power adiabatic pulses and constant-density spiral trajectories

In this work we introduce the concept of correlation chemical shift imaging (CCSI). Novel CCSI pulse sequences are demonstrated on clinical scanners for two-dimensional Correlation Spectroscopy (COSY) and Total Correlation Spectroscopy (TOCSY) imaging experiments. To date there has been limited progress reported towards a feasible and robust multivoxel 2D COSY. Localized 2D TOCSY imaging is shown for the first time in this work. Excitation with adiabatic GOIA-W(16,4) pulses (Gradient Offset Independent Adiabaticity Wurst modulation) provides minimal chemical shift displacement error, reduced lipid contamination from subcutaneous fat, uniform optimal flip angles, and efficient mixing for coupled spins, while enabling short repetition times due to low power requirements. Constant-density spiral readout trajectories are used to acquire simultaneously two spatial dimensions and f2 frequency dimension in (kx,ky,t2) space in order to speed up data collection, while f1 frequency dimension is encoded by consecutive time increments of t1 in (kx,ky,t1,t2) space. The efficient spiral sampling of the k-space enables the acquisition of a single-slice 2D COSY dataset with an 8 × 8 matrix in 8:32 min on 3 T clinical scanners, which makes it feasible for in vivo studies on human subjects. Here we present the first results obtained on phantoms, human volunteers and patients with brain tumors. The patient data obtained by us represent the first clinical demonstration of a feasible and robust multivoxel 2D COSY. Compared to the 2D J-resolved method, 2D COSY and TOCSY provide increased spectral dispersion which scales up with increasing main magnetic field strength and may have improved ability to unambiguously identify overlapping metabolites. It is expected that the new developments presented in this work will facilitate in vivo application of 2D chemical shift correlation MRS in basic science and clinical studies.National Institutes of Health (U.S.) (NIH grant R01 1200-206456)National Institutes of Health (U.S.) (NIH grant R01 EB007942)Siemens Aktiengesellschaft (Siemens-MIT Alliance

Quantitative In Vivo Magnetic Resonance Spectroscopy Using Synthetic Signal Injection

Accurate conversion of magnetic resonance spectra to quantitative units of concentration generally requires compensation for differences in coil loading conditions, the gains of the various receiver amplifiers, and rescaling that occurs during post-processing manipulations. This can be efficiently achieved by injecting a precalibrated, artificial reference signal, or pseudo-signal into the data. We have previously demonstrated, using in vitro measurements, that robust pseudo-signal injection can be accomplished using a second coil, called the injector coil, properly designed and oriented so that it couples inductively with the receive coil used to acquire the data. In this work, we acquired nonlocalized phosphorous magnetic resonance spectroscopy measurements from resting human tibialis anterior muscles and used pseudo-signal injection to calculate the Pi, PCr, and ATP concentrations. We compared these results to parallel estimates of concentrations obtained using the more established phantom replacement method. Our results demonstrate that pseudo-signal injection using inductive coupling provides a robust calibration factor that is immune to coil loading conditions and suitable for use in human measurements. Having benefits in terms of ease of use and quantitative accuracy, this method is feasible for clinical use. The protocol we describe could be readily translated for use in patients with mitochondrial disease, where sensitive assessment of metabolite content could improve diagnosis and treatment

Quantitative 2D In-Vivo Spectroscopy Using the ERETIC Method

A fundamental requirement to use spectroscopy in a clinical setting is the ability to reliably quantify the individual metabolites. While 2D experiments like JPRESS can provide improved spectral separation by dispersing spectral information in an additional frequency dimension the artificially injected ERETIC signal can serve as a stable and well known reference signal. It is shown that the ERETIC reference signal can be readily incorporated into in-vivo 2D spectroscopic experiments, which finally provides the necessary premises for reliable quantification in in-vivo 2D MRS

ERETIC based in vivo 1H MRSI quantification

A modified ERETIC method has been developed to enable quantification of metabolite concentrations in proton spectroscopic images (MRSI). Together with the acquisition of a B1 map, an accurate quantification of absolute metabolite concentrations is achieved in vivo

ERETIC based in vivo 1H MRSI quantification

Purpose/Introduction: Proton MR spectroscopy allows the noninvasive evaluation of in vivo brain metabolites. In children, the measured metabolite concentration can be age dependent. We examined the effect of maturation on the regional distribution of brain metabolite concentrations in different brain regions during the first two decades of life with a multivoxel chemical shift imaging (CSI) technique. Subjects and Methods: 92 healthy children and young adults, aged 3.5months to 20 years, were examined by a two-dimensional 1H MRS-CSI sequence during routine MR imaging. CSI was performed on two axial slices at the level of the head of the caudate nucleus and infratentorial through the middle cerebellar peduncles. Spectra were obtained from voxels of 1,5 cm 3 in regions of the frontal and parietal white matter and the caudate head on both sides, the genu and splenium of the corpus callosum, in the midbrain as well as in the right and left cerebellar hemisphere. In each subject, spectra in these brain regions were selected and the metabolite concentrations were evaluated by LC Model. Results: The concentration of N-acetylaspartate increased in the frontal and parietal white matter and in the region of the right and left caudate head during infancy and childhood, whereas it remained constant in the region of the genu and splenium of the corpus callosum. The concentration of creatine minimally decreased during maturation in the frontal white matter, in the region of the genu and splenium and in the midbrain. It remained constant in the parietal white matter. The concentration of choline containing compounds had the tendency to decrease over time in the region of the caudate head, in the genu and splenium and in the parietal white matter. Because of the small size of the genu and splenium especially in very young children and because of artifacts in the posterior fossa, reliable concentrations in those regions were difficult to establish. Discussion/Conclusion: Using CSI it was possible to determine metabolite concentrations in different regions of the brain in an acceptable time frame as part of routine MR imaging. The obtained data about age dependency will be helpful in future pediatric CSI measurements to decide whether the concentration of one of the main metabolites in different examined areas is within the range of normal values or has to be considered as pathologic

Accurate determination of brain metabolite concentrations using ERETIC as external reference

Magnetic Resonance Spectroscopy (MRS) can provide in vivo metabolite concentrations in standard concentration units if a reliable reference signal is available. For 1H MRS in the human brain, typically the signal from the tissue water is used as the (internal) reference signal. However, a concentration determination based on the tissue water signal most often requires a reliable estimate of the water concentration present in the investigated tissue. Especially in clinically interesting cases, this estimation might be difficult. To avoid assumptions about the water in the investigated tissue, the Electric REference To access In vivo Concentrations (ERETIC) method has been proposed. In this approach, the metabolite signal is compared with a reference signal acquired in a phantom and potential coil-loading differences are corrected using a synthetic reference signal. The aim of this study, conducted with a transceiver quadrature head coil, was to increase the accuracy of the ERETIC method by correcting the influence of spatial B1 inhomogeneities and to simplify the quantification with ERETIC by incorporating an automatic phase correction for the ERETIC signal. Transmit field (B1 +) differences are minimized with a volume-selective power optimization, whereas reception sensitivity changes are corrected using contrast-minimized images of the brain and by adapting the voxel location in the phantom measurement closely to the position measured in vivo. By applying the proposed B1 correction scheme, the mean metabolite concentrations determined with ERETIC in 21 healthy subjects at three different positions agree with concentrations derived with the tissue water signal as reference. In addition, brain water concentrations determined with ERETIC were in agreement with estimations derived using tissue segmentation and literature values for relative water densities. Based on the results, the ERETIC method presented here is a valid tool to derive in vivo metabolite concentration, with potential advantages compared with internal water referencing in diseased tissue

Muscle group specific quantification of unsaturated fatty acids by localized DEPT-enhanced 13C MRS and ERETIC

The quantification of metabolite concentrations of spatially specific 13C NMR spectra is questionable due to the low sensitivity. We propose a combined SNR enhancement by proton decoupling and ISIS-localized DEPT, aiming at muscle-group specific detection of unsaturated fatty acid in the calf muscle. Comparative measurements of four localized SNR enhancement sequences were performed with a 13C/1H dual-tune volume calf coil equipped with ERETIC. ERETIC signal intensity with and without proton decoupling as determined with TDFDfit was identical. This ISIS-localized DEPT combined with proton decoupling and the ERETIC reference standard technique can be easily extended to other muscle metabolites of interest

Accurate determination of brain metabolite concentrations using ERETIC as external reference

Magnetic Resonance Spectroscopy (MRS) can provide in vivo metabolite concentrations in standard concentration units if a reliable reference signal is available. For 1H MRS in the human brain, typically the signal from the tissue water is used as the (internal) reference signal. However, a concentration determination based on the tissue water signal most often requires a reliable estimate of the water concentration present in the investigated tissue. Especially in clinically interesting cases, this estimation might be difficult. To avoid assumptions about the water in the investigated tissue, the Electric REference To access In vivo Concentrations (ERETIC) method has been proposed. In this approach, the metabolite signal is compared with a reference signal acquired in a phantom and potential coil-loading differences are corrected using a synthetic reference signal. The aim of this study, conducted with a transceiver quadrature head coil, was to increase the accuracy of the ERETIC method by correcting the influence of spatial B1 inhomogeneities and to simplify the quantification with ERETIC by incorporating an automatic phase correction for the ERETIC signal. Transmit field ( math formula) differences are minimized with a volume-selective power optimization, whereas reception sensitivity changes are corrected using contrast-minimized images of the brain and by adapting the voxel location in the phantom measurement closely to the position measured in vivo. By applying the proposed B1 correction scheme, the mean metabolite concentrations determined with ERETIC in 21 healthy subjects at three different positions agree with concentrations derived with the tissue water signal as reference. In addition, brain water concentrations determined with ERETIC were in agreement with estimations derived using tissue segmentation and literature values for relative water densities. Based on the results, the ERETIC method presented here is a valid tool to derive in vivo metabolite concentration, with potential advantages compared with internal water referencing in diseased tissue

Muscle group specific quantification of unsaturated fatty acids by localized DEPT-enhanced 13C MRS and ERETIC

The concentration of unsaturated fatty acids in human skeletal muscles can be used to assess the dietary intake with in vivo 13C MR spectroscopy. However the variety of muscle fiber groups may result in the difference of absolute concentration of the metabolites. The inherent low sensitivity and multiple structures restrict the quantification of metabolic concentrations of specific localized 13C spectra. We propose a combined SNR enhancement method by proton decoupling and ISIS-localized DEPT, aiming at muscle-group specific detection of unsaturated fatty acid in the calf muscle. With the chosen enhancement method in vivo calf muscle spectra from small volumes of interest in specific muscle fiber groups can be acquired and quantified using the ERETIC signal as a synthetic reference standard

Advanced Exercise Ergometer Setup for in Vivo MRS Studies of Skeletal Muscle Metabolism

Magnetic resonance spectroscopy (MRS) is frequently used to assess dynamic metabolic changes in skeletal muscle. To study metabolism during exercise in an MR scanner, ergometers have to be designed that are compatible with the constraints imposed by the scanner. We present an improved MRS ergometer setup for the measurement of muscular metabolism during isometric contractions of the plantarflexor muscles. Key features of the setup are a pedal with an integrated strain gauge, flexible adjustment of ankle joint angle, and real-time visual feedback for subjects on momentary contraction. Using this setup, we were able to determine metabolic parameters under standardized conditions