Comparison of glycosaminoglycan chemical exchange saturation transfer using Gaussian-shaped and off-resonant spin-lock radiofrequency pulses in intervertebral disks.

PURPOSE: To investigate, if a train of spin-lock pulses (chemical exchange saturation transfer with spin-lock pulses = CESL) improves biochemical glycosaminoglycan imaging compared with conventional chemical exchange saturation transfer with Gaussian-shaped pulses (CEST) in lumbar intervertebral discs. METHODS: T2 , CEST, and CESL imaging was performed in lumbar intervertebral discs of 15 healthy volunteers at 3 Tesla. Mean and standard deviation of the asymmetric magnetization transfer ratio (MTRasym ), the asymmetric spin-lock ratio (SLRasym ) and T2 values were calculated for nucleus pulposus (NP) and annulus fibrosus (AF). Wilcoxon test was used to analyze differences between MTRasym and SLRasym . Pearson correlation was used to determine the relationship between MTRasym , SLRasym and T2 . RESULTS: Data showed no significant difference between MTRasym and SLRasym (NP: P = 0.35; AF: P = 0.34). MTRasym and SLRasym values differed significantly between NP and AF (MTRasym : P = 0.014, SLRasym : P = 0.005). T2 values correlated significantly with MTRasym (NP: ρ = 0.76, P < 0.001; AF: ρ = 0.60, P < 0.001) and SLRasym (NP: ρ = 0.73, P < 0.001; AF: ρ = 0.47, P < 0.001). CONCLUSION: CESL does not improve the chemical exchange asymmetry effect compared with conventional CEST, but leads to comparable results. Magn Reson Med 78:280-284, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Covert hepatic encephalopathy: elevated total glutathione and absence of brain water content changes.

Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local brain water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy ((1)H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI brain water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with brain water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE.

Quantitative liver 31P magnetic resonance spectroscopy at 3T on a clinical scanner.

PURPOSE: The aims of this study were (i) to establish a robust and fast method to quantify hepatocellular phosphorus compounds in molar concentration on a 3T clinical scanner, (ii) to evaluate its reproducibility, and (iii) to test its feasibility for a use in large cohort studies. METHOD: Proton-decoupled (31) P magnetic resonance spectroscopy of liver (31) P compounds were acquired on 85 healthy subjects employing image selected in-vivo spectroscopy localization in 13 min of acquisition at 3T. Absolute quantification was achieved using an external reference and double-matching phantoms (inorganic phosphates and adenosine triphosphate (ATP) solutions). Reproducibility of the method was also examined. RESULTS: This method showed a high intra- and interday as well as inter- and intraobserver reproducibility (r > 0.98; P < 0.001), with a high signal to noise ratio (SNR) (i.e., mean SNR of γ-ATP: 16). The mean liver concentrations of 85 healthy subjects were assessed to be 1.99 ± 0.51 and 2.74 ± 0.55 mmol/l of wet tissue volume for Pi and γ-ATP, respectively. CONCLUSION: This method reliably quantified molar concentrations of liver (31) P compounds on 85 subjects with a short total examination time (∼25 min) on a 3T clinical scanner. Thus, the current method can be readily utilized for a clinical study, such as a large cohort study.

Monounsaturated fat rapidly induces hepatic gluconeogenesis and whole-body insulin resistance.

BACKGROUNDWhile saturated fat intake leads to insulin resistance and nonalcoholic fatty liver, Mediterranean-like diets enriched in monounsaturated fatty acids (MUFA) may have beneficial effects. This study examined effects of MUFA on tissue-specific insulin sensitivity and energy metabolism.METHODSA randomized placebo-controlled cross-over study enrolled 16 glucose-tolerant volunteers to receive either oil (OIL, ~1.18 g/kg), rich in MUFA, or vehicle (VCL, water) on 2 occasions. Insulin sensitivity was assessed during preclamp and hyperinsulinemic-euglycemic clamp conditions. Ingestion of 2H2O/acetaminophen was combined with [6,6-2H2]glucose infusion and in vivo 13C/31P/1H/ex vivo 2H-magnet resonance spectroscopy to quantify hepatic glucose and energy fluxes.RESULTSOIL increased plasma triglycerides and oleic acid concentrations by 44% and 66% compared with VCL. Upon OIL intervention, preclamp hepatic and whole-body insulin sensitivity markedly decreased by 28% and 27%, respectively, along with 61% higher rates of hepatic gluconeogenesis and 32% lower rates of net glycogenolysis, while hepatic triglyceride and ATP concentrations did not differ from VCL. During insulin stimulation hepatic and whole-body insulin sensitivity were reduced by 21% and 25%, respectively, after OIL ingestion compared with that in controls.CONCLUSIONA single MUFA-load suffices to induce insulin resistance but affects neither hepatic triglycerides nor energy-rich phosphates. These data indicate that amount of ingested fat, rather than its composition, primarily determines the development of acute insulin resistance.TRIAL REGISTRATIONClinicalTrials.gov NCT01736202.FUNDINGGerman Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Diabetes Association, German Center for Diabetes Research, Portugal Foundation for Science and Technology, European Regional Development Fund, and Rede Nacional de Ressonancia Magnética Nuclear.

Differential effects of D-cycloserine and amantadine on motor behavior and D2/3 receptor binding in the nigrostriatal and mesolimbic system of the adult rat.

D-cycloserine (DCS) and amantadine (AMA) act as partial NMDA receptor (R) agonist and antagonist, respectively. In the present study, we compared the effects of DCS and AMA on dopamine D2/3R binding in the brain of adult rats in relation to motor behavior. D2/3R binding was determined with small animal SPECT in baseline and after challenge with DCS (20 mg/kg) or AMA (40 mg/kg) with [123I]IBZM as radioligand. Immediately post-challenge, motor/exploratory behavior was assessed for 30 min in an open field. The regional binding potentials (ratios of the specifically bound compartments to the cerebellar reference region) were computed in baseline and post-challenge. DCS increased D2/3R binding in nucleus accumbens, substantia nigra/ventral tegmental area, thalamus, frontal, motor and parietal cortex as well as anterodorsal and posterior hippocampus, whereas AMA decreased D2/3R binding in nucleus accumbens, caudateputamen and thalamus. After DCS, ambulation and head-shoulder motility were decreased, while sitting was increased compared to vehicle and AMA. Moreover, DCS increased rearing relative to AMA. The regional elevations of D2/3R binding after DCS reflect a reduction of available dopamine throughout the mesolimbocortical system. In contrast, the reductions of D2/3R binding after AMA indicate increased dopamine in nucleus accumbens, caudateputamen and thalamus. Findings imply that, after DCS, nigrostriatal and mesolimbic dopamine levels are directly related to motor/exploratory activity, whereas an inverse relationship may be inferred for AMA.

Amantadine enhances nigrostriatal and mesolimbic dopamine function in the rat brain in relation to motor and exploratory activity.

PURPOSE: The present study assessed the influence of the NMDA receptor (R) antagonist amantadine (AMA) on cerebral dopamine D2/3R binding in relation to motor and exploratory activity in the rat. METHODS: D2/3R binding was determined in anaesthetized animals with small animal SPECT in baseline and after challenge with AMA (10 or 40 mg/kg) using [123I]IBZM as radioligand. Immediately post-challenge and prior to radioligand administration, motor/exploratory behaviors were assessed for 30 min in an open field. Each rat underwent measurements with a dedicated small animal MRI in order to gain anatomical information. Regions of interest were defined on SPECT-MRI overlays. The regional binding potentials in baseline and post-challenge were estimated by computing ratios of the specifically bound compartments to the cerebellar reference region. RESULTS: 40 mg/kg AMA reduced D2/3R binding in nucleus accumbens, caudateputamen and thalamus, while 10 mg/kg decreased D2/3R binding in the anterodorsal hippocampus. The higher dose decreased ambulatory activity, rearing and grooming, but elevated sitting and head-shoulder motility relative to both vehicle and the lower dose in the first 15 min post-challenge. CONCLUSIONS: Results showed reductions of D2/3R binding in regions of the nigrostriatal and mesolimbic system after challenge with AMA, which reflect an increased availability of dopamine. Thereby, an inverse relationship between nigrostriatal and mesolimbic dopamine and motor/exploratory activity can be inferred. Findings may be relevant for the treatment of neurological and psychiatric conditions such as Parkinson's disease, Huntington's disease or schizophrenia, which are characterized by both dopaminergic and glutamatergic dysfunction.

Use of quantitative brain water imaging as concentration reference for J-edited MR spectroscopy of GABA.

PURPOSE: To compare two different methods of obtaining the water reference for determination of quantitative water-scaled in vivo concentration estimates of γ-aminobutyric acid (GABA). METHODS: Water-scaled GABA estimates from localized J-difference edited MR spectroscopy experiments can be computed using standard values for tissue-specific water content and relaxation times. Water content and relaxation may, however, be altered in pathology. This work re-analyzed data from a recent study in healthy controls and patients with minimal (mHE) or grade I (HE 1) hepatic encephalopathy, a disease associated with slight elevation of brain water content. J-difference edited MR spectroscopy data were combined with quantitative brain water measures, which provided individual water density references and T1 relaxation times. Resulting GABA estimates were compared to concentration values obtained using standard tissue-specific water content and relaxation values. RESULTS: Occipital GABA concentration values obtained from individual water and T1 maps were 1.64±0.35mM in controls, and significantly higher (P<0.01) than in mHE (1.15±0.28mM) and HE 1 patients (1.18±0.09mM). Results from the tissue-dependent approach (1.58±0.30mM (controls), 1.10±0.27mM (mHE) and 1.12±0.12mM (HE 1)) were slightly lower (P<0.05 in each group). CONCLUSION: Water-scaled in vivo GABA estimates can be obtained with individual water density and T1 relaxation mapping. This approach may be useful for studying GABA levels in pathologies with substantial brain water content or relaxation changes.

Improvement of water saturation shift referencing by sequence and analysis optimization to enhance chemical exchange saturation transfer imaging.

PURPOSE: To optimize B0-field inhomogeneity correction for chemical exchange saturation transfer (CEST) imaging by investigating different water saturation shift referencing (WASSR) Z-spectrum shapes and different frequency correction techniques. METHODS: WASSR Z-spectra were simulated for different B1-fields and pulse durations (PD). Two parameter settings were used for further simulations and experiments (WASSR1: B1=0.1 µT, PD=50ms; WASSR2: B1=0.3 µT, PD=40ms). Four frequency correction techniques were investigated: 1) MinW: Minimum of the spline-interpolated WASSR-spectrum; 2) MSCF: maximum symmetry center frequency algorithm; 3) PMSCF: further development of MSCF algorithm; 4) BFit: fit with Bloch equations. Performance of frequency correction was assessed with Monte-Carlo simulations and in-vivo MR examinations in the brain and intervertebral disks. RESULTS: Different shapes of WASSR-Z-spectra were obtained by changing B1 and PD including spectra with one (1-Peak) or two (2-Peak) minima. WASSR1 resulted in 1-Peak WASSR-spectrum, whereas WASSR2 resulted in 2-Peak WASSR-spectrum. Both Monte-Carlo simulations and in-vivo MR examinations revealed highest accuracy of field-inhomogeneity correction with WASSR1 combined with PMSCF or BFit. CONCLUSION: Using a WASSR sequence, which results in a Z-spectrum with a single absorption peak, in combination with advanced postprocessing algorithms enables improved B0-field inhomogeneity correction for CEST imaging.