Peak assignment in localized 1H MR spectra of human muscle based on oral creatine supplementation

¹H-MR spectra of human skeletal muscle feature peak splittings due to dipolar coupling. Quantitative difference spectroscopy in a double-blind cross-over trial testing oral creatine supplementation revealed that most of the resonances affected by dipolar coupling can be assigned to creatine and/or phosphocreatine. The assignment was performed in two different skeletal muscles and confirmed by measurements at the magic angle where dipolar splittings vanish. Numerical spectral simulations revealed that the observed spectra are consistent with partly-averaged dipolar coupling among methylene and methyl protons of (phospho)creatine. The possible nature of the molecular dynamics leading to incomplete dipolar averaging is discussed.     

Intramyocellular lipid quantification from 1H long echo time spectra at 1.5 and 3 T by means of the LCModel technique

PURPOSE: To introduce a method of independent determination of CH2 and CH3 components of intramyocellular lipids (IMCLs) by using long TE for spectra measurement and LCModel for spectra evaluation, to test this technique in controls and insulin-resistant subjects, and to compare results at 1.5 and 3 T. MATERIALS AND METHODS: Eight healthy volunteers and 11 patients with type 2 diabetes mellitus underwent measurement using a 1.5-T MR scanner; six healthy volunteers were measured using a 3-T MR scanner. Spectra from the tibialis anterior muscle were acquired by using a point resolved spectroscopy (PRESS) sequence with the following parameters: TR/TE/ACQ = 2000 msec/270 msec/256. Spectra were processed by LCModel 6.1 software with two types of adopted basis-set. RESULTS: Spectra with good separation of both CH2 and CH3 components of IMCL and extramyocellular lipids (EMCLs) were obtained and the LCModel routine was successfully applied. The reproducibility comparison (N= 7 at 1.5 T vs. N = 5 at 3 T) showed that better results can be obtained at higher B0 values. The comparison of the healthy and insulin-resistant subjects proved that both IMCL_CH2/Cr and IMCL_CH3/Cr ratios significantly differ. CONCLUSION: Long TE spectroscopy of the human muscle with IMCL quantification using the LCModel technique can detect changes in IMCL levels as well as help in the study of fatty acyl chain composition. Using a higher field strength increased the intra-individual reproducibility by approximately 150%.     

Resolution of creatine and phosphocreatine 1H signals in isolated human skeletal muscle using HR-MAS 1H NMR

Proton NMR spectra of freshly isolated human skeletal muscle samples contain creatine and phosphocreatine resonances with distinct chemical shifts that are easily visualized with magic angle spinning (MAS, spinning the sample rapidly at 54.7 degrees with respect to the magnetic field) methods. The identification of the phosphocreatine resonance was based on two findings: that (i) the possible small dipolar coupling does not contribute to line splitting under rapid MAS, and (ii) the 1H signal decreases concurrently with the phosphocreatine resonance observed in 31P NMR experiments. In the MAS 1H spectra, the phosphocreatine resonance remains a singlet with a linewidth of less than 3 Hz. The creatine resonances are split into two peaks with linewidths at half height of approximately 2 and 6 Hz, respectively. The resonance with the broader linewidth represents creatine that is significantly motion-restricted and suggests that a creatine pool in muscle tissue is highly compartmentalized.     

In vivo high‐resolution localized 1H MR spectroscopy in the awake rat brain at 7 T

In vivo localized high‐resolution ¹H MR spectroscopy was performed in multiple brain regions without the use of anesthetic or paralytic agents in awake head‐restrained rats that were previously trained in a simulated MRI environment using a 7T MR system. Spectra were obtained using a short echo time single‐voxel point‐resolved spectroscopy technique with voxel size ranging from 27 to 32.4 mm³ in the regions of anterior cingulate cortex, somatosensory cortex, hippocampus, and thalamus. Quantifiable spectra, without the need for any additional postprocessing to correct for possible motion, were reliably detected including the metabolites of interest such as γ‐aminobutyric acid, glutamine, glutamate, myo‐inositol, N‐acetylaspartate, taurine, glycerophosphorylcholine/phosphorylcholine, creatine/phosphocreatine, and N‐acetylaspartate/N‐acetylaspartylglutamate. The spectral quality was comparable to spectra from anesthetized animals with sufficient spectral dispersion to separate metabolites such as glutamine and glutamate. Results from this study suggest that reliable information on major metabolites can be obtained without the confounding effects of anesthesia or paralytic agents in rodents. Magn Reson Med 69:937–943, 2013. © 2012 Wiley Periodicals, Inc.     

1H MRS of intramyocellular lipids in soleus muscle at 7 T: Spectral simplification by using long echo times without water suppression

The popular short echo time ¹H MR spectroscopy acquisition method for detection of intramyocellular lipids suffers from spectral overlap due to the large, broad, and asymmetric extramyocellular lipid signals, the time‐consuming practice of selecting “lean” voxels for spectroscopy, and the overlap of the extramyocellular lipid signal with the creatine methyl ¹H signal at ～3 parts per million (ppm), commonly used as an internal standard. Using an alternative acquisition strategy, spectra with well‐resolved intramyocellular lipids resonances were acquired from large volumes (10 to 15 mL) of human soleus muscle in less than 5 min by single‐voxel 7‐T ¹H MR spectroscopy, using an echo time of 280 ms. From the high‐resolution spectra, an average intramyocellular lipid concentration of 7.7 ± 3.5 mmol/kg muscle was found for 25 healthy subjects (male/female 17/8; age 29.4 ± 6.6 years). Since water suppression was not required, the ¹H signals from unsaturated intracellular triglycerides at about 5.3 ppm were easily detected, which, in combination with the well‐determined ? (CH₂)_n? /CH₃ intensity ratio at long echo time, enabled assessment of the composition of triglycerides in the intramyocellular lipids compartment. Long‐echo single‐voxel spectroscopy at 7 T offers rapid and convenient acquisition of high‐resolution spectra from human soleus muscle. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

MR relaxometry and 1H MR spectroscopy for the determination of iron and metabolite concentrations in PKAN patients

The influence of iron deposits on T2 values and the content of metabolites in the brain of three patients with DNA proved pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome) was studied. An eye-of-the-tiger sign, a typical MR finding for PKAN, was observed in two patients with the same mutation. A hypointensive lesion in a whole globus pallidus was observed in the third patient with the additional mutation. T2 values in the globus pallidus of the patients were about 40% shorter than in controls (71/48 ms in controls vs. patients), which corresponds to the increase of Fe concentration based on the ferritin basis from 17 mg for controls to 48 mg (100 g wet brain weight) in PKAN patients. 1H MR spectroscopy (MRS) has mainly been used to describe neuronal damage represented by decreased NAA (6.4 mmol vs. 9 mmol) and Cr/PCr (7.0 mmol vs. 9.8 mmol) concentrations in the basal ganglia region of the patient group to controls; MRS is much more case-sensitive and describes individual development of the disease as demonstrated in the difference between the spectra of typical PKAN patients (1, 2), and the patient (3) with atypical PKAN development. Any significant changes of metabolite concentration with the exception glutamine, glutamate and GABA were found in the white matter.Part of the study was presented at the ISMRM Meeting, 2004, abstract no. 1423.     

Optimized detection of changes in glucose-6-phosphate levels in human skeletal muscle by 31P MR spectroscopy.

As glucose-6-phosphate (G6P) plays a central role in muscle energy metabolism, the possibility to observe changes in the tissue level of this compound in vivo is very relevant. G6P can be detected noninvasively by (31)P MR spectroscopy, but its visibility in vivo is severely hampered due to low tissue levels and spectral overlap with other, stronger phosphomonoester signals. To optimize the observation of changes in G6P levels in human calf muscle by (31)P MR spectroscopy at 1.5 T, we implemented an approach involving a new RF probe and a postacquisition correction method. An anatomically shaped circularly polarized (31)P coil was designed for high intrinsic sensitivity. Together with an additional (1)H coil and (1)H blocking circuits this allowed the application of NOE and (1)H decoupling to further enhance sensitivity. A hyperglycemic hyperinsulinemic clamp was used to increase G6P levels. The spectra were corrected for frequency and phase drift due to scanner instability and leg movements using an automated phase and frequency correction method. Difference (31)P spectroscopy was applied to detect changes of the G6P signal. The result, in five healthy subjects, demonstrated that the combination of sensitivity optimization with automated drift correction enabled a robust detection of G6P changes in time series experiments down to a resolution of 10 min.     

Localized MR 1H spectroscopy reveals alterations of susceptibility in bone marrow with hemosiderosis

A noninvasive investigation of the structure of hemopoietic bone marrow is based on the determination of the magnetic field distribution within small volume elements in vertebral bodies by localized ¹H MR spectroscopy. In patients with he-matological diseases the status of the bone marrow was found to considerably influence the homogeneity of the magnetic field in trabecular bone in vivo. The line widths of the ¹H signals were evaluated in follow-up studies during initial chemotherapy of eight patients with leukemia. lntraindividual comparison revealed significant broadening of the field distribution after a few weeks of cytotoxic treatment in five of the patients. Additionally, 19 patients after bone marrow transplantation showed significantly broader field distributions in the lipid signals than 13 matched healthy volunteers. These alterations of the microscopic field homogeneity were not caused by trabecular density effects. Iliac crest biopsies revealed high amounts of hemosiderin in the cases with broadened line widths. Ten of the 19 patients after bone marrow transplantation showed high amounts of hemosiderin and broad lines in the spectra. The content of hemosiderin of the other patients was not significantly increased.     

Determination of deoxymyoglobin changes during graded myocardial ischemia: An in Vivo 1H NMR spectroscopy study

¹H NMR spectroscopy was used to detect the proximal histidyl N_δ, proton signal of deoxymyoglobin from canine hearts in vivo during graded myocardial ischemia. The NMR signal intensity provided an indicator of intracellular oxygenation in myocardium. The relationship between the myocardial blood flow and the deoxymyoglobin concentration was successfully measured during resting, partial, and complete coronary artery occlusion conditions. The results demonstrate the feasibility to detect deoxymyoglobin using a ¹H NMR spectroscopy technique in living hearts for the first time and the possibility to use this technique for investigating myocardial oxidative metabolism nondestructively and repetitively.     

(1)H MR spectroscopy of human brain tumours: a practical approach

Magnetic resonance spectroscopy (MRS) is proposed in addition to magnetic resonance imaging (MRI) to help in the characterization of brain tumours by detecting metabolic alterations that may be indicative of the tumour class. MRS can be routinely performed on clinical magnets, within a reasonable acquisition time and if performed under adequate conditions, MRS is reproducible and thus can be used for longitudinal follow-up of treatment. MRS can also be performed in clinical practice to guide the neurosurgeon into the most aggressive part of the lesions or to avoid unnecessary surgery, which may furthermore decrease the risk of surgical morbidity.     

Noninvasive temperature measurement in Vivo using a temperature-sensitive lanthanide complex and 1H magnetic resonance spectroscopy

A new lanthanide complex, praseodymium-2-methoxyethyl-DO3A, was tested as a temperature indicator for ¹H magnetic resonance spectroscopy under in vivo conditions, using a 2-T imaging system. The chemical shift of the methoxy group of the compound is strongly temperature dependent. In vitro, a shift change of ?0.131 ppm/°C was found. The signal was shifted by about ?24 ppm relative to the water signal, allowing easy water suppression and signal identification in vivo. The body temperatures of eight anesthetized rats were measured in the liver after intravenous administration of 1 mmol/kg of the praseodymium complex under different heating conditions of the animal. The temperatures calculated from the spectra were in good agreement (deviation < ± 1°C) with values obtained simultaneously with a thermocouple placed in the rectum of the animals.     

1H T1 and T2 measurements of the MR imaging contrast agents Gd-DTPA and Gd-DTPA BMA at 1.5T

We report in vitro T₁ and T₂ relaxation studies for the open-chain complexes Gd-DTPA and Gd-DTPA BMA. Measurements were performed on phantoms containing aqueous and plasma solutions of different concentrations by MR imaging in a 1.5T superconducting whole-body scanner. Longitudinal relaxation times T₁ were evaluated from serial turbo-FLASH experiments for concentrations less than 1 mM, whereas for larger concentrations the values were obtained from a standard inversion recovery (IR) sequence. Transverse relaxation times T₂ were determined using multi-echo spin-echo MRI protocols. The T₁ and T₂ relaxivities of the nonionic Gd-DTPA BMA are similar to those of the Gd-DTPA. The temperature dependencies of the relaxivities were determined over a temperature interval ranging from 21 to 50 °C and were found to be slightly different for the two contrast agents. In the case of Gd-DTPA BMA a larger deviation of the expected temperature behavior of the relaxivities was observed as compared with Gd-DTPA. Deviations from a strictly linear dependence of relaxation times on temperature were found at lower concentrations in aqueous solutions. In plasma solutions a high T₁/T₂ ratio was observed for low concentrations, which decreased monotonically with increasing concentrations. Received 2 October 1995; Revision received 17 April 1996; Accepted 24 April 1996     

1.5 T磁共振兔VX2肝癌活体二维多体素1H-MRS应用初探

目的探讨应用1.5 T磁共振仪对兔VX2肝癌进行活体二维多体素氢质子磁共振波谱（1H-MRS）检查的可行性,对所得1H-MRS图作初步观察. 材料与方法采用经腹腔瘤块种植法建立兔VX2肝癌模型,利用1.5 T磁共振仪进行常规MR平扫和二维多体素1H-MRS,包括激励回波采样模式（STEAM）和点分辨波谱（PRESS）序列检查,初步比较肿瘤实质、瘤周和邻近正常肝组织的1H-MRS图的差别.扫描结束次日处死动物,取其相应位置肝脏组织块进行病理组织学分析. 结果建立兔VX2肝癌模型共计16只,均按照计划进行了MR平扫和二维多体素1H-MRS检查,共24瘤次,其中22瘤次获得令人满意的1H-MRS图,技术成功率达到92.0%.1H-MRS图上可见4个主要的波峰,包括脂质（Lip）、谷氨酰胺和谷氨酸复合物（Glx）、胆碱（Cho）、糖原和葡萄糖复合物（Glyu）.发现瘤周和邻近正常肝组织内Cho峰和Glyu峰较肿瘤实质内的要高,Lip峰稍降低.其他参数相同的情况下,STEAM和PRESS序列在本研究1H-MRS扫描中所得波谱谱图无明显区别. 结论应用1.5 T磁共振仪对兔VX2肝癌进行活体二维多体素1H-MRS检查是可行的.     

In vivo localized 1H MR spectroscopy of rat testes: stimulated echo acquisition mode (STEAM) combined with short TI inversion recovery (STIR) improves the detection of metabolite signals.

A noninvasive NMR technique for evaluating testicular function was explored in this study. Localized in vivo 1H NMR spectroscopy was performed on rat testes using a stimulated echo acquisition mode (STEAM) sequence with a short echo time (TE). In the 1H spectra, large lipid signals dominated the chemical shift range of 0.89-2.78 ppm, which prevented the observation of metabolite signals in this region. To suppress these lipid signals, short inversion time (TI) inversion recovery (STIR) was combined with STEAM (STIR-STEAM). The optimal TI was typically 320 ms. STIR-STEAM with a TE of 15 ms allowed successful suppression of the lipid signals and the sensitive detection of several new metabolite signals. In normal testes, choline, creatine, glutamate, and glycine signals were identified. In addition to these metabolites, a lactate signal was observed in ischemic testes. To our knowledge, the signals of glutamate, glycine, and lactate have not been previously assigned in 1H MR spectra of testes in vivo. Lipid suppression by STIR aided in the detection of these metabolites, which would otherwise have been masked by the lipid signals.     

1H NMR Determination of lactate 13C-enrichment in skeletal muscle: Using a double quantum filter for the simultaneous editing of 13C-coupled and 13C-uncoupled methyl protons resonance

¹H NMR simultaneous editing of ¹³C-coupled and ¹³C-uncoupled methyl protons resonance, using the selection of double quantum coherences by a gradient pulse, was analyzed in vitro and demonstrated in situ on the hindlimb of an exercised rat model postmortem. In vitro calibration showed agreement with theoretical analysis. High-resolution NMR of muscle extract confirmed the accuracy of the lactate ¹³C-enrichment calculated using the in situ NMR data and the calibration factor obtained in vitro.     

Correlation of the apparent diffusion coefficient and the creatine level in early ischemic stroke: a comparison of different patterns by magnetic resonance

It has been reported that reduction of the apparent diffusion coefficient (ADC) after stroke can persist for several days, after which the ADC increases gradually to an abnormally high level. We evaluated ADC values of stroke lesions and compared the results to the cellular density of the lesion by means of the creatine (Cre) level. This two-parameter estimation is of particular relevance in ascertaining the underlying cellular status. Lesion-to-contralateral ADC ratios (ADCn) were obtained based on diffusion-weighted echo-planar and fast spin-echo imaging. Single-voxel localized spectroscopy was used for quantification of cerebral metabolites in infarcted regions. Their levels were also compared to that in homotopic contralateral regions. Fifteen patients with ischemic stroke were examined at times ranging from 18-88 hours following the onset of symptoms. In the stroke lesion, there was a significant correlation between the ADC and the Cre level showing that the higher the cell density the lower the ADC value. For ADCn vs. the lesion Cre concentration and the lesion-to-contralateral Cre ratio (Cre(n)), the strengths of relationship were R2 = 0.70 and 0.58, respectively. It is concluded that ADC is a good reflection of cell density. Greatly lowered ADC values occur within the context of a stable cellularity. ADC and the Cre level have complementary roles in the characterization of stroke lesion with regard to the sequential stage.     

1H mrs of human brain abscesses in vivo and in vitro

Five patients, each with a brain abscess, were examined by means of ¹H MR spectroscopic imaging in vivo. The aspirated pus was analyzed in vitro by means of 1D and 2D COSY ¹H MRS. In addition to resonance lines from compounds (lactate, alanine and lipids) often found in the spectra from intracranial tumors, resonance lines were detected from a number of markers of infectious involvement (acetate, succinate, and various amino acids). These results suggest that ¹H MRS in vivo might contribute in establishing noninvasively a differential diagnosis between brain abscess and tumor.     

New method for the simultaneous detection of metabolites and water in localized in vivo 1H nuclear magnetic resonance spectroscopy.

A new two-scan method for localized 1H in vivo NMR spectroscopy (MRS) without water suppression (WS) is described. In one of the scans, two chemical shift selective 180 degrees pulses are applied prior to a standard localization sequence to invert all metabolite signals upfield and downfield from water, which remains unaffected. The difference spectrum records the metabolites whereas water and accompanying gradient induced artifacts are widely suppressed. The method was implemented on a 4.7-T system using point resolved spectroscopy with a short echo time of 18 ms. Phantom measurements proved the feasibility of absolute quantification using water as an internal reference. Measurements on healthy rat brain yielded comparable spectrum quality as measurements with water presaturation. The method does not require additional adjustments or sophisticated data postprocessing and scales favorably with increasing B(0) field. Therefore, the method should be useful for 1H MRS without WS. Although the two-step method doubles the minimum total measurement time, it may also be of interest for spectroscopic imaging (SI) without WS, in particular if fast SI techniques are applied.     

Detection of an intense resonance at 2.4 ppm in 1H MR spectra of patients with severe late-delayed, radiation-induced brain injuries.

Proton MRS and MRI were used to monitor the progression of severe cerebral radiation injuries in 10 patients over a period of 18 months. An unknown resonance (Px) in the 2.37-2.40 ppm region was consistently detected in the affected temporal lobes of four patients. The detection of Px was only confined to spectra with lactate (Lac) and in patients with the highest severity grading of radiation injury. The incidence of Px in Lac-positive spectra was 42.8% (15/35) and in lesions with highest injury grading was 46.8% (15/32). Lesions with Px had significantly higher Lac/creatine (Cr) ratios and more extensive mass effect changes when compared to lesions without Px. The probable identity of Px was examined in the context of anaerobic glycolysis producing pyruvate (2.37 ppm) and the model of metabolic changes in brain abscess formation implicating succinate (2.40 ppm).