Reproducibility of whole‐brain temperature mapping and metabolite quantification using proton magnetic resonance spectroscopy

Assessing brain temperature can provide important information about disease processes (e.g., stroke, trauma) and therapeutic effects (e.g., cerebral hypothermia treatment). Whole‐brain magnetic resonance spectroscopic imaging (WB‐MRSI) is increasingly used to quantify brain metabolites across the entire brain. However, its feasibility and reliability for estimating brain temperature needs further validation. Therefore, the present study evaluates the reproducibility of WB‐MRSI for temperature mapping as well as metabolite quantification across the whole brain in healthy volunteers. Ten healthy adults were scanned on three occasions 1 week apart. Brain temperature, along with four commonly assessed brain metabolites—total N‐acetyl‐aspartate (tNAA), total creatine (tCr), total choline (tCho) and myo‐inositol (mI)—were measured from WB‐MRSI data. Reproducibility was evaluated using the coefficient of variation (CV). The measured mean (range) of the intra‐subject CVs was 0.9% (0.6%‐1.6%) for brain temperature mapping, and 4.7% (2.5%‐15.7%), 6.4% (2.4%‐18.9%) and 14.2% (4.4%‐52.6%) for tNAA, tCho and mI, respectively, with reference to tCr. Consistently larger variability was found when using H₂O as the reference for metabolite quantifications: 7.8% (3.3%‐17.8%), 7.8% (3.1%‐18.0%), 9.8% (3.7%‐31.0%) and 17.0% (5.9%‐54.0%) for tNAA, tCr, tCho and mI, respectively. Further, the larger the brain region (indicated by a greater number of voxels within that region), the better the reproducibility for both temperature and metabolite estimates. Our results demonstrate good reproducibility of whole‐brain temperature and metabolite measurements using the WB‐MRSI technique.     

Reproducibility of 31P cardiac magnetic resonance spectroscopy at 3 T

The purpose of this work was to take advantage of the new clinical field strength of 3 T to implement and optimize a chemical shift imaging (CSI) acquisition protocol to produce spectra of high quality with high specificity to the myocardium within a clinically feasible scan time. Further, an analysis method was implemented dependent purely on anatomical location of spectra, and as such free from any potential user bias caused by inference from spectral information. Twenty healthy male subjects were scanned on two separate occasions using the optimized CSI protocol at 3 T. Data were analyzed for intra‐ and inter‐subject variability, as well as intra‐ and inter‐observer variability. The average phosphocreatine (PCr)/adenosine triphosphate (ATP) value for scan 1 was 2.07 ± 0.38 and for scan 2 was 2.14 ± 0.46, showing no significant difference between scans. Intra‐subject variability was 0.43 ± 0.35 (percentage difference 20%) and the inter‐subject coefficient of variation was 18%. The intra‐observer variability, assessed as the absolute difference between analyses of the data by a single observer, was 0.14 ± 0.24 with no significant difference between analyses. The inter‐observer variability showed no significant differences between the PCr/ATP value measured by four different observers as demonstrated by an intra‐class correlation coefficient of 0.763. The increased signal available at 3 T has improved spatial resolution and thereby increased myocardial specificity without any significant decrease in reproducibility over previous studies at 1.5 T. We present an acquisition protocol that routinely provides high quality spectra and a robust analysis method that is free from potential user bias. Copyright © 2008 John Wiley & Sons, Ltd.     

Assessing the effect of hypoxia on cardiac metabolism using hyperpolarized 13C magnetic resonance spectroscopy

Hypoxia plays a role in many diseases and can have a wide range of effects on cardiac metabolism depending on the extent of the hypoxic insult. Noninvasive imaging methods could shed valuable light on the metabolic effects of hypoxia on the heart in vivo. Hyperpolarized carbon‐13 magnetic resonance spectroscopy (HP ¹³C MRS) in particular is an exciting technique for imaging metabolism that could provide such information. The aim of our work was, therefore, to establish whether hyperpolarized ¹³C MRS can be used to assess the in vivo heart's metabolism of pyruvate in response to systemic acute and chronic hypoxic exposure. Groups of healthy male Wistar rats were exposed to either acute (30 minutes), 1 week or 3 weeks of hypoxia. In vivo MRS of hyperpolarized [1‐¹³C] pyruvate was carried out along with assessments of physiological parameters and ejection fraction. Hematocrit was elevated after 1 week and 3 weeks of hypoxia. 30 minutes of hypoxia resulted in a significant reduction in pyruvate dehydrogenase (PDH) flux, whereas 1 or 3 weeks of hypoxia resulted in a PDH flux that was not different to normoxic animals. Conversion of hyperpolarized [1‐¹³C] pyruvate into [1‐¹³C] lactate was elevated following acute hypoxia, suggestive of enhanced anaerobic glycolysis. Elevated HP pyruvate to lactate conversion was also seen at the one week timepoint, in concert with an increase in lactate dehydrogenase (LDH) expression. Following three weeks of hypoxic exposure, cardiac metabolism of pyruvate was comparable with that observed in normoxia. We have successfully visualized the effects of systemic hypoxia on cardiac metabolism of pyruvate using hyperpolarized ¹³C MRS, with differences observed following 30 minutes and 1 week of hypoxia. This demonstrates the potential of in vivo hyperpolarized ¹³C MRS data for assessing the cardiometabolic effects of hypoxia in disease.     

放射性脑病发生的高危因素及MRI影像学改变研究

目的探讨放射性脑病（REP）发生的高危因素和MRI在REP早期诊断中的价值。方法回顾性分析我院近年106例REP患者的临床资料,将发病时间、照射疗程和剂量与MRI影像学检查相结合进行分析。结果 REP发病时间多集中在首次放疗后1～5年,射野上界在OM线上〉2.5cm者及生物效应剂量（BED）〉139Gy者易发生REP;15.09%的患者尚未出现明显神经系统损害表现时,MRI检查提示为T1WI等或低信号、T2WI高信号。结论对病人采取合理配比照射区域和次数可减少REP的发生,MRI检查有助于早期发现和诊断REP。     

1H magnetic resonance spectroscopy at 3 T in cryptogenic and mesial temporal lobe epilepsy

The objectives of this work were to compare concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), Glx (=Glu + Gln), myo-inositol (mI), total creatine (Cre) and other metabolites in the temporal lobes of patients with mesial temporal lobe epilepsy (mTLE), cryptogenic TLE (cTLE), who show no abnormalities in high-resolution MRI, and healthy controls using single voxel (1)H MRS at 3 T. Twelve patients with mTLE, nine with cTLE and 22 controls were investigated using a short echo time STEAM protocol. Voxels were positioned bilaterally in the medial and lateral temporal lobes. Spectra were processed with LCModel. Significantly lower mean NAA were detected in mTLE patients (P < 0.001) and a trend towards lower NAA in cTLE patients compared to controls (P = 0.053). Glx was not different between groups. Estimates of Glu showed a different metabolic pattern in mTLE with elevated Glu in lateral compared with medial voxels on the ipsilateral side to seizure onset (P = 0.019). MI concentrations were significantly lower in cTLE (P < 0.001) and in mTLE patients (P = 0.005) compared with healthy controls. MI/Cre was significantly reduced in cTLE patients only (P = 0.004). The results confirm low NAA in mTLE and to a lesser extent in cTLE patients. MI and mI/Cre were identified as potential metabolic indicators of the epileptogenic area in cTLE.     

局灶性皮质发育不良患者的磁共振波谱分析与临床相关性研究

目的:应用多体素氢质子磁共振波谱(MRS)研究局灶性皮质发育不良(FCD)患者脑代谢特点,并进一步探讨(癎)性发作的机制.方法:收集来自贵阳医学院附属医院和重庆医科大学临床学院神经科门诊及住院明确诊断的20例大脑FCD伴有(癎)性发作患者和20名健康受试者进行多体素MRS扫描,测量患者病灶区、病灶比邻区和远离病灶区皮质氮-乙酰门冬氨酸(NAA)与肌酸(Cr)的比值(NAA/Cr),并与对照组受试者相对应皮质区NAA/Cr值比较.结果:FCD患者病灶区、病灶比邻区较对照组皮质区NAA/Cr比值显著降低(P＜0.01),远侧病灶区皮质区与对照组皮质区NAA/Cr比值之间比较差异无统计学意义(P＞0.05);病灶区皮质NAA/Cr比值与临床(癎)性发作次数之间未见相关性.结论:多体素MRS可无创观察FCD患者脑代谢改变,为手术治疗FCD伴有难治性癫(癎)患者提供了一个重要的参考指标.     

Detecting colorectal cancer by 1H magnetic resonance spectroscopy of fecal extracts

Colorectal cancer is one of the most common cancers in the western world. Its early detection has been found to improve the prognosis of the patient, providing a wide window of opportunity for successful therapeutic interventions. However, current diagnostic techniques all have some limitations; there is a need to develop a better technique for routine screening purposes. We present a new methodology based on magnetic resonance spectroscopy of fecal extracts for the non‐invasive detection of colorectal cancer. Five hundred twenty‐three human subjects (412 with no colonic neoplasia and 111 with colorectal cancer, who were scheduled for colonoscopy or surgery) were recruited to donate a single sample of stool. One‐dimensional ¹H magnetic resonance spectroscopy (MRS) experiments were performed on the supernatant of aqueous dispersions of the stool samples. Using a statistical classification strategy, several multivariate classifiers were developed. Applying the preprocessing, feature selection and classifier development stages of the Statistical Classification Strategy led to ～87% average balanced sensitivity and specificity for both training and monitoring sets, improving to ～92% when only crisp results, i.e. class assignment probabilities ≥75%, are considered. These results indicate that ¹H magnetic resonance spectroscopy of human fecal extracts, combined with appropriate data analysis methodology, has the potential to detect colorectal neoplasia accurately and reliably, and could be a useful addition to the current screening tools. Copyright © 2009 John Wiley & Sons, Ltd.     

Biochemical analysis of cervical mucus by nuclear magnetic resonance spectroscopy.

Biochemical evaluation of cervical mucus is difficult due to the characteristic rheological properties of this hydrogel. The application of high resolution nuclear magnetic resonance spectroscopy proved to be a valuable new method for differentiated biochemical analyses of human cervical mucus. A particular advantage is that it is non-destructive, that it can be applied to specimens of small volume and that no sample preparation, such as solubilization, is necessary.     

Diagnosing testicular function using 31P magnetic resonance spectroscopy: a current review

Patients with low sperm counts combined with normal concentrationsof gonadotrophins, and in whom physical examination and post-ejaculatoryurine analysis are normal, present a diagnostic dilemma. Thissituation can be caused by testicular failure or by ductal obstruction,which have very different clinical prognoses. Ductal obstructionmight be correctable by microsurgical vasovaso/vasoepididymostomy,whereas this approach is of no use in primary testicular failure.A possible diagnostic step for these patients is a testicularbiopsy to differentiate between hyposper-matogenesis and a normalgonad. However, to date testicular biopsy is seldom performedbecause of its invasive character. An alternative accurate,non-invasive method to assess testicular function could be veryhelpful in the evaluation of idiopathic azoosper-mia or idiopathicoligozoospermia. During the past decade, magnetic resonance(MR) spectroscopy has been developed from a scientific toolinto a non-invasive clinical diagnostic tool and has also beenused to study testicular function. Recent studies have shownthat ³¹P-MR spectroscopy, based upon differences in the ratioof peaks of phosphomonoester to P-adenos-inetriphosphate, isa non-invasive technique able to differentiate between groupsof patients with testicular failure and ductal obstruction,and it correlates reasonably well with the averaged mean Johnsenscore of testicular biopsy. The role for a non-invasive techniquein the diagnosis of male infertility, such as 31P-MR spectroscopy,can be manifold. It serves not only as an alternative for biopsybut can also be used to assess obstruction as the cause of infertilityin patients with subnormal sperm counts, and to predict thechances of pregnancy in patients planned for vaso-vasostomyto correct a prior vasectomy. However, the main limitation toMR spectroscopy becoming a universal clinical diagnostic techniqueis the limited availability of 1.5 Tesla MR scanners.     

Quantitative magnetic resonance spectroscopy at 3T based on the principle of reciprocity

Quantification of magnetic resonance spectroscopy signals using the phantom replacement method requires an adequate correction of differences between the acquisition of the reference signal in the phantom and the measurement in vivo. Applying the principle of reciprocity, sensitivity differences can be corrected at low field strength by measuring the RF transmitter gain needed to obtain a certain flip angle in the measured volume. However, at higher field strength the transmit sensitivity may vary from the reception sensitivity, which leads to wrongly estimated concentrations. To address this issue, a quantification approach based on the principle of reciprocity for use at 3T is proposed and validated thoroughly. In this approach, the RF transmitter gain is determined automatically using a volume‐selective power optimization and complemented with information from relative reception sensitivity maps derived from contrast‐minimized images to correct differences in transmission and reception sensitivity. In this way, a reliable measure of the local sensitivity was obtained. The proposed method is used to derive in vivo concentrations of brain metabolites and tissue water in two studies with different coil sets in a total of 40 healthy volunteers. Resulting molar concentrations are compared with results using internal water referencing (IWR) and Electric REference To access In vivo Concentrations (ERETIC). With the proposed method, changes in coil loading and regional sensitivity due to B₁ inhomogeneities are successfully corrected, as demonstrated in phantom and in vivo measurements. For the tissue water content, coefficients of variation between 2% and 3.5% were obtained (0.6–1.4% in a single subject). The coefficients of variation of the three major metabolites ranged from 3.4–14.5%. In general, the derived concentrations agree well with values estimated with IWR. Hence, the presented method is a valuable alternative for IWR, without the need for additional hardware such as ERETIC and with potential advantages in diseased tissue.     

1H magnetic resonance spectroscopy of invasive cervical cancer: an in vivo study with ex vivo corroboration

The objective of this study was to establish in vivo (1)H-magnetic resonance (MR) spectroscopic appearances of cervical cancer using an endovaginal receiver coil and corroborate findings with magic angle spinning (MAS) MR spectroscopy of tissue samples. Fifty-three women (14 controls and 39 with cervical cancer) underwent endovaginal coil MR imaging at 1.5 T with T(1)- and T(2)-weighted scans sagittal and transverse to the cervix. Localized (1)H MR spectra (PRESS technique, TR 1600 ms, TE 135 ms) were accumulated in all controls and 29 cancer patients whose tumour filled > 50% of a single 3.4 cm(3) voxel. Peaks from triglyceride-CH(2) and -CH(3) were defined as present and in-phase (with the choline resonance), present but out-of-phase, or not present. Peak areas of choline-containing compounds were standardized to the area of unsuppressed tissue water resonance. Comparisons in observed resonances between groups were made using Fisher's exact test (qualitative data) and a t-test (quantitative data). Biopsies from these women analysed using MAS-MR spectroscopy and normalized to the intensity of an external standard of silicone rubber were similarly compared. Adequate water suppression permitted spectral analysis in 11 controls and 27 cancer patients. In-phase triglyceride-CH(2) resonances (1.3 ppm) were observed in 74% of tumours but in no control women (p < 0.001). No differences were observed in the presence of a 2 ppm resonance, choline-containing compounds or creatine in cancer compared with control women. However, ex vivo analysis showed significant differences not only in -CH(2), but also in -CH(3), a 2 ppm resonance, choline-containing compounds and creatine between tissues from control women and cancer tissue (p < 0.001, = 0.001, = 0.036, < 0.001 and = 0.004 respectively). On in vivo (1)H-MR spectroscopy, the presence of positive triglyceride-CH(2) resonances can be used to detect and confirm the presence of cervical cancer. However, technical improvements are required before routine clinical use.     

Towards a neurochemical profile of the amygdala using short‐TE 1H magnetic resonance spectroscopy at 3 T

The amygdala plays a key role in emotional learning and in the processing of emotions. As disturbed amygdala function has been linked to several psychiatric conditions, a knowledge of its biochemistry, especially neurotransmitter levels, is highly desirable. The spin echo full intensity acquired localized (SPECIAL) sequence, together with a transmit/receive coil, was used to perform very short‐TE magnetic resonance spectroscopy at 3 T to determine the neurochemical profile in a spectroscopic voxel containing the amygdala in 21 healthy adult subjects. For spectral analysis, advanced data processing was applied in combination with a macromolecule baseline measured in the anterior cingulate for spectral fitting. The concentrations of total N‐acetylaspartate, total creatine, total choline, myo‐inositol and, for the first time, glutamate were quantified with high reliability (uncertainties far below 10%). For these metabolites, the inter‐individual variability, reflected by the relative standard deviations for the cohort studied, varied between 12% (glutamate) and 22% (myo‐inositol). Glutamine and glutathione could also be determined, albeit with lower precision. Retest on four subjects showed good reproducibility. The devised method allows the determination of metabolite concentrations in the amygdala voxel, including glutamate, provides an estimation of glutamine and glutathione, and may help in the study of disturbed amygdala metabolism in pathologies such as anxiety disorder, autism and major depression.     

Proton magnetic resonance spectroscopy assessment of neonatal brain metabolism during cardiopulmonary bypass surgery

Here, we report on the development and performance of a robust 3-T single-voxel proton magnetic resonance spectroscopy (¹H MRS) experimental protocol and data analysis pipeline for quantifying brain metabolism during cardiopulmonary bypass (CPB) surgery in a neonatal porcine model, with the overall goal of elucidating primary mechanisms of brain injury associated with these procedures. The specific aims were to assess which metabolic processes can be reliably interrogated by ¹H MRS on a 3-T clinical scanner and to provide an initial assessment of brain metabolism during deep hypothermia cardiac arrest (DHCA) surgery and recovery. Fourteen neonatal pigs underwent CPB surgery while placed in a 3-T MRI scanner for 18, 28, and 37°C DHCA studies under hyperglycemic, euglycemic, and hypoglycemic conditions. Total imaging times, including baseline measurements, circulatory arrest (CA), and recovery averaged 3 h/animal, during which 30–40 single-voxel ¹H MRS spectra (sLASER pulse sequence, TR/TE = 2000/30 ms, 64 or 128 averages) were acquired from a 2.2-cc right midbrain voxel. ¹H MRS at 3 T was able to reliably quantify (1) anaerobic metabolism via depletion of brain glucose and the associated build-up of lactate during CA, (2) phosphocreatine (PCr) to creatine (Cr) conversion during CA and subsequent recovery upon reperfusion, (3) a robust increase in the glutamine-to-glutamate (Gln/Glu) ratio during the post-CA recovery period, and (4) a broadening of the water peak during CA. In vivo ¹H MRS at 3 T can reliably quantify subtle metabolic brain changes previously deemed challenging to interrogate, including brain glucose concentrations even under hypoglycemic conditions, ATP usage via the conversion of PCr to Cr, and differential changes in Glu and Gln. Observed metabolic changes during CPB surgery of a neonatal porcine model provide new insights into possible mechanisms for prevention of neuronal injury.     

31P-Nuclear magnetic resonance spectroscopy study of the time course of energy metabolism during exercise and recovery

Summary This study evaluated the time courses of intracellular pH and the metabolism of phosphocreatine (PCr) and inorganic phosphate (P) at the onset of four exercise intensities and recoveries. Non-invasive evaluation of continuous changes in phosphorus metabolites has become possible using³¹P-nuclear magnetic resonance spectroscopy (³¹P-MRS). After measurements at rest, six healthy male subjects performed 4 min of femoral flexion exercise at intensities of 0 (loadless), 10, 20 and 30 kg · m · min^–1 in a 2.1 T superconducting magnet with a 67-cm bore. Measurements were continuously made during 5 min of recovery. During a series of rest-exercise-recovery procedures,³¹P-MRS were accumulated using 32 scans · spectrum^–1 requiring 12.8 s each. At the onset of exercise, PCr decreased exponentially with a time constant of 27–32 s regardless of the exercise intensity. The time constant PCr resynthesis during recovery was about 27–40 s. The PCr kinetics were independent of exercise intensity. There were similar Pi kinetics at the onset of all types of exercise, while those of Pi recovery became significantly longer at the higher exercise intensities (P < 0.05). Furthermore, the intracellular pH indicated temporary alkalosis just at the onset of exercise, probably due to absorption of hydrogen ions by PCr hydrolysis, and then decrease at a point about 40%–50% of the preexercise PCr. The pH recovery time was longer than that for the P_i or PCr kinetics. By using a more efficient resolution system it was possible to obtain the phosphorus kinetics during exercise and to follow PCr resynthesis within the first few minutes of recovery. From our results it was concluded that in general the time course of PCr and Pi metabolism were unaffected by the exercise intensity, both at the onset of exercise and during recovery, with the exception of P_i recovery.     

Imaging central neurochemical alterations in chronic pain with proton magnetic resonance spectroscopy

Proton magnetic resonance spectroscopy has been used extensively in the study of various neurobiological disorders: depression, schizophrenia, autism, etc. But its application to chronic pain is relatively new. Not many studies in chronic pain have used (1)H-MRS. The unique ability of (1)H-MRS to assess both static and dynamic levels of glutamate and γ-aminobutyric acid (GABA) gives this method a unique position in neuroscience. Emerging evidence in chronic pain suggests an elevated excitatory/inhibitory neurotransmitter ratio is present within brain regions involved in pain processing. The combination of (1)H-MRS imaging with pharmacologic interventions holds significant promise as a direct one-to-one matching of disease pathology with drug mechanism of action can be made. As such (1)H-MRS may be useful in discovery of novel compounds for chronic pain. Research in these areas may lead to improved diagnosis and treatment of these complex patients.     

正常成年人椎体氢质子磁共振波谱与个体因素的初步研究

目的应用氢质子磁共振波谱(1H-MRS)技术,探讨正常成年人腰椎(L1~L4)椎体的脂水比(LWR)和脂肪含量(FF%)与性别、年龄及体质量指数(BMI)之间的关系。方法选择100例MRI检查正常的成年人,其中男性52例(52%),女性48例(48%);年龄18~79岁,平均年龄46.77岁;平均BMI为22.85。按性别、年龄及BMI进行分组:男性组52例,女性组48例:青年组(≤44岁)44例,中年组(45~59岁)33例,老年组(≥60岁)22例;正常组(18.5BMI24.0)69例,超质量肥胖组(BMI≥24)31例。所有纳入对象行MRI常规扫描及L1~L4椎体的1H-MRS扫描,测量并记录椎体的LWR及FF%,采用SPSS13.0对所有数据按组别进行统计学分析。结果 L1~L4椎体的平均LWR及FF%分别为1.20±0.75、1.41±0.93、1.57±1.05、1.58±1.09和0.50±0.15、0.53±0.15、0.56±0.15、0.56±0.15,LWR及FF%在性别及年龄组间的差异具有统计学意义(P0.05),而BMI组间差异不具有统计学意义(P0.05);相关性分析结果显示,L1~L4椎体的LWR和FF%与年龄呈正相关(P0.05,相关系数为0.47~0.54),但与BMI没有相关性(P0.05)。结论 L1~L4各椎体的LWR和FF%均存在性别差异(男性高于女性),并随着年龄的增加而增大。     

H magnetic resonance spectroscopy study of thalamus in treatment resistant depressive patients

Treatment-resistant depression (TRD) is a common clinical problem, and represents a considerable challenge to treatment, however, the pathogenesis of this disease is poorly understood. Thalamus is generally believed to have a role in the pathophysiology of depression. In this study, we adopted 1.5 T ¹H magnetic resonance spectroscopy (¹H MRS) to examine possible alterations of thalamus metabolism in 20 adult TRD patients. Our results suggested there might be damage and loss of neurons, as well as membrane phospholipids associated metabolism abnormality in the TRD thalamus.