3D 31 P MR spectroscopic imaging of the human brain at 3 T with a 31 P receive array: An assessment of 1 H decoupling, T1 relaxation times, 1 H-31 P nuclear Overhauser effects and NAD.

31 P MR spectroscopic imaging (MRSI) is a versatile technique to study phospholipid precursors and energy metabolism in the healthy and diseased human brain. However, mainly due to its low sensitivity, 31 P MRSI is currently limited to research purposes. To obtain 3D 31 P MRSI spectra with improved signal-to-noise ratio on clinical 3 T MR systems, we used a coil combination consisting of a dual-tuned birdcage transmit coil and a 31 P eight-channel phased-array receive insert. To further increase resolution and sensitivity we applied WALTZ4 1 H decoupling and continuous wave nuclear Overhauser effect (NOE) enhancement and acquired high-quality MRSI spectra with nominal voxel volumes of ~ 17.6 cm3 (effective voxel volume ~ 51 cm3 ) in a clinically relevant measurement time of ~ 13 minutes, without exceeding SAR limits. Steady-state NOE enhancements ranged from 15 ± 9% (γ-ATP) and 33 ± 3% (phosphocreatine) to 48 ± 11% (phosphoethanolamine). Because of these improvements, we resolved and detected all 31 P signals of metabolites that have also been reported for ultrahigh field strengths, including resonances for NAD+ , NADH and extracellular inorganic phosphate. T1 times of extracellular inorganic phosphate were longer than for intracellular inorganic phosphate (3.8 ± 1.4s vs 1.8 ± 0.65 seconds). A comparison of measured T1 relaxation times and NOE enhancements at 3 T with published values between 1.5 and 9.4 T indicates that T1 relaxation of 31 P metabolite spins in the human brain is dominated by dipolar relaxation for this field strength range. Even although intrinsic sensitivity is higher at ultrahigh fields, we demonstrate that at a clinical field strength of 3 T, similar 31 P MRSI information content can be obtained using a sophisticated coil design combined with 1 H decoupling and NOE enhancement.

GABAergic changes in the thalamocortical circuit in Parkinson's disease.

Parkinson's disease is characterized by bradykinesia, rigidity, and tremor. These symptoms have been related to an increased gamma-aminobutyric acid (GABA)ergic inhibitory drive from globus pallidus onto the thalamus. However, in vivo empirical evidence for the role of GABA in Parkinson's disease is limited. Some discrepancies in the literature may be explained by the presence or absence of tremor. Specifically, recent functional magnetic resonance imaging (fMRI) findings suggest that Parkinson's tremor is associated with reduced, dopamine-dependent thalamic inhibition. Here, we tested the hypothesis that GABA in the thalamocortical motor circuit is increased in Parkinson's disease, and we explored differences between clinical phenotypes. We included 60 Parkinson patients with dopamine-resistant tremor (n = 17), dopamine-responsive tremor (n = 23), or no tremor (n = 20), and healthy controls (n = 22). Using magnetic resonance spectroscopy, we measured GABA-to-total-creatine ratio in motor cortex, thalamus, and a control region (visual cortex) on two separate days (ON and OFF dopaminergic medication). GABA levels were unaltered by Parkinson's disease, clinical phenotype, or medication. However, motor cortex GABA levels were inversely correlated with disease severity, particularly rigidity and tremor, both ON and OFF medication. We conclude that cortical GABA plays a beneficial rather than a detrimental role in Parkinson's disease, and that GABA depletion may contribute to increased motor symptom expression.

Repeatability of (31) P MRSI in the human brain at 7 T with and without the nuclear Overhauser effect.

An often-employed strategy to enhance signals in (31) P MRS is the generation of the nuclear Overhauser effect (NOE) by saturation of the water resonance. However, NOE allegedly increases the variability of the (31) P data, because variation is reported in NOE enhancements. This would negate the signal-to-noise (SNR) gain it generates. We hypothesized that the variation in NOE enhancement values is not caused by the variability in NOE itself, but is attributable to measurement uncertainties in the values used to calculate the enhancement. If true, the expected increase in SNR with NOE would improve the repeatability of (31) P MRS measurements. To verify this hypothesis, a repeatability study of native and NOE-enhanced (31) P MRSI was performed in the brains of seven healthy volunteers at 7 T. The repeatability coefficient (RC) and the coefficient of variation in repeated measurements (CoVrepeat ) were determined for each method, and the 95% limits of agreement (LoAs) between native and NOE-enhanced signals were calculated. The variation between the methods, defined by the LoA, is at least as great as that predicted by the RC of each method. The sources of variation in NOE enhancements were determined using variance component analysis. In the seven metabolites with a positive NOE enhancement (nine metabolite resonances assessed), CoVrepeat improved, on average, by 15%. The LoAs could be explained by the RCs of the individual methods for the majority of the metabolites, generally confirming our hypothesis. Variation in NOE enhancement was mainly attributable to the factor repeat, but between-voxel effects were also present for phosphoethanolamine and (glycero)phosphocholine. CoVrepeat and fitting error were strongly correlated and improved with positive NOE. Our findings generally indicate that NOE enhances the signal of metabolites, improving the repeatability of metabolite measurements. Additional variability as a result of NOE was minimal. These findings encourage the use of NOE-enhanced (31) P MRSI. Copyright © 2015 John Wiley & Sons, Ltd.

Optimized (31)P MRS in the human brain at 7 T with a dedicated RF coil setup.

The design and construction of a dedicated RF coil setup for human brain imaging ((1)H) and spectroscopy ((31)P) at ultra-high magnetic field strength (7 T) is presented. The setup is optimized for signal handling at the resonance frequencies for (1)H (297.2 MHz) and (31)P (120.3 MHz). It consists of an eight-channel (1)H transmit-receive head coil with multi-transmit capabilities, and an insertable, actively detunable (31)P birdcage (transmit-receive and transmit only), which can be combined with a seven-channel receive-only (31)P array. The setup enables anatomical imaging and (31)P studies without removal of the coil or the patient. By separating transmit and receive channels and by optimized addition of array signals with whitened singular value decomposition we can obtain a sevenfold increase in SNR of (31)P signals in the occipital lobe of the human brain compared with the birdcage alone. These signals can be further enhanced by 30 ± 9% using the nuclear Overhauser effect by B1-shimmed low-power irradiation of water protons. Together, these features enable acquisition of (31)P MRSI at high spatial resolutions (3.0 cm(3) voxel) in the occipital lobe of the human brain in clinically acceptable scan times (~15 min).

Metabolic imaging of multiple x-nucleus resonances.

This study describes a technique for fast imaging of x-nuclei metabolites. Due to increased sensitivity and larger chemical shift dispersion at high magnetic fields, images of multiple metabolites can be obtained simultaneously by selective excitation of their resonances with a multifrequency selective radiofrequency pulse at any desired flip angle. This aim is achieved by combining a three-dimensional gradient echo imaging sequence with a Shinnar-LeRoux optimized excitation pulse. A proper choice of bandwidth, imaging matrix size, and field of view allows using the chemical shift dispersion of the different resonances to completely separate their images within one large field of view. The method of fast metabolic imaging is illustrated with (13)C measurements of a phantom containing a solution of (13)C labeled glucose, lactate, and sodium octanoate and by dynamic measurements of the (31)P metabolites phosphocreatine and ß-adenosine triphosphate in human femoral muscle in vivo, both at 7T. With dynamic selective (31)P imaging of the larger part of the upper leg, phosphocreatine signal intensity changes of specific muscles can be studied simultaneously by analyzing the sum of phosphocreatine signals within arbitrarily shaped regions of interest following the muscles' contours. This concept of dynamic metabolic imaging can be applied to other organs and further expanded to other MR-detectable nuclei and metabolites.

Prostate cancer aggressiveness: in vivo assessment of MR spectroscopy and diffusion-weighted imaging at 3 T.

PURPOSE: To determine the individual and combined performance of magnetic resonance (MR) spectroscopic imaging and diffusion-weighted (DW) imaging at 3 T in the in vivo assessment of prostate cancer aggressiveness by using histopathologically defined regions of interest on radical prostatectomy specimens to define the prostate cancer regions to be investigated. MATERIALS AND METHODS: The local institutional ethics review board approved this retrospective study and waived the informed consent requirement. Fifty-four patients with biopsy-proved prostate cancer underwent clinical MR spectroscopic imaging followed by prostatectomy. Guided by the histopathologic map, all spectroscopy voxels that contained tumor tissue were selected, and metabolite ratios (choline [Cho] plus creatine [Cr]-to-citrate [Cit] and Cho/Cr ratios) were derived. For each spectroscopic voxel, 25th percentile apparent diffusion coefficient (ADC) of the region corresponding to that voxel was determined, representing the most aberrant tumor part on the ADC map, which was often smaller than spectroscopic imaging voxels. Maximum metabolic ratios and minimum 25th percentile ADC of each tumor were related to tumor aggressiveness and were used to differentiate aggressiveness classes. A logistic regression model (LRM) was used to combine data from both modalities. RESULTS: Significant correlation was found between aggressiveness classes and maximum Cho+Cr/Cit ratio (ρ=0.36), maximum Cho/Cr ratio (ρ=0.35), and minimum 25th percentile ADC (ρ=-0.63) in the peripheral zone (PZ). In the transition zone (TZ), the correlation was significant for only Cho+Cr/Cit and Cho/Cr ratios (ρ=0.58 and ρ=0.60, respectively). For differentiation between aggressiveness classes, LRM use did not result in significantly improved differentiation over any individual variables. CONCLUSION: These findings enabled confirmation that MR spectroscopic imaging and DW imaging offer potential for in vivo noninvasive assessment of prostate cancer aggressiveness, and both modalities have comparable performance. The combination did not result in better performance. Nonetheless, the better performances of metabolite ratios in the TZ and of ADCs in the PZ suggest that they have complementary value.

In vivo 31P MR spectroscopic imaging of the human prostate at 7 T: safety and feasibility.

(31)P MR spectroscopic imaging of the human prostate provides information about phosphorylated metabolites that could be used for prostate cancer characterization. The sensitivity of a magnetic field strength of 7 T might enable 3D (31)P MR spectroscopic imaging with relevant spatial resolution in a clinically acceptable measurement time. To this end, a (31)P endorectal coil was developed and combined with an eight-channel (1)H body-array coil to relate metabolic information to anatomical location. An extensive safety validation was performed to evaluate the specific absorption rate, the radiofrequency field distribution, and the temperature distribution of both coils. This validation consisted of detailed Finite Integration Technique simulations, confirmed by MR thermometry and B 1+ measurements in a phantom and in vivo temperature measurements. The safety studies demonstrated that the presence of the (31)P endorectal coil had no influence on the specific absorption rate levels and temperature distribution of the external eight-channel (1)H array coil. To stay within a 10 g averaged local specific absorption rate of 10 W/kg, a maximum time-averaged input power of 33 W for the (1)H array coil was allowed. For transmitting with the (31)P endorectal coil, our safety limit of less than 1°C temperature increase in vivo during a 15-min MR spectroscopic imaging experiment was reached at a time-averaged input power of 1.9 W. With this power setting, a second in vivo measurement was performed on a healthy volunteer. Using adiabatic excitation, 3D (31)P MR spectroscopic imaging produced spectra from the entire prostate in 18 min with a spatial resolution of 4 cm(3). The spectral resolution enabled the separate detection of phosphocholine, phosphoethanolamine, inorganic phosphate, and other metabolites that could play an important role in the characterization of prostate cancer.