Proton MR spectroscopy in a child with pyruvate dehydrogenase complex deficiency.

The purpose of this study was the non-invasive quantitative determination by proton MR Spectroscopy (1H MRS) of alterations in cerebral metabolism in a 19-month-old male infant with severe global developmental delay caused by a Pyruvate Dehydrogenase Complex (PDHC) deficiency due to a mutation at the thiamine binding site. Two investigations were performed at different CSF thiamine concentrations to assess the effect of thiamine supplementation. 1H MR spectra were collected at different echo times (20-270 ms) from a voxel located in the striatum; spectroscopic imaging was done on a larger region including occipital white matter. The tissue levels of N-acetylaspartate and choline were in the normal range, while creatine appeared elevated. Abnormally high lactate and alanine signals were observed both in and outside the striatum; the levels of these metabolites were higher during the second measurement at a lower thiamine concentration. Abnormal cerebral levels of alanine have only been described once before in PDHC deficiency. The 1H MRS profile of this patient reflects the diversity of brain metabolite alterations in patients with this genetically heterogeneous disease.     

Cystic intracranial mass lesions: Possible role of in vivo MR spectroscopy in its differential diagnosis

Thirty-four patients showing cystic intracranial mass lesions on MR imaging were evaluated by in vivo proton MR spectroscopy (MRS) with the aim of detecting lesion-specific spectral patterns that may assist imaging in better tissue characterization. In vivo spectroscopy was performed using stimulated echo acquisition mode with echo times 20 m and 270 m in all, and spin echo with echo time 135 m in 11 patients. All primary neoplasms (intra-as well as extra-axial) showed choline (3.22 ppm) resonance along with lipid and/or lactate (1.3 ppm). It was not possible to grade cystic gliomas based on N-acetyl asparate-to-choline ratio. High-grade gliomas (n = 8) showed lipid/lactate and low-grade gliomas (n = 6) showed only lactate. Seven patients with brain abscess showed resonances only from acetate (1.92 ppm), lactate (1.3 ppm) and alanine (1.5 ppm). Two cases of metastatic adenocarcinoma showed only lipid/lactate. In 7 patients with epidermoid cyst, lactate along with an unassigned resonance at 1.8 ppm was observed and could be easily differentiated from arachnoid cyst (n = 2), which showed only minimal lactate. A case of cystic meningioma could be differentiated from cystic schowannoma by the presence of alanine in the former. It is concluded that MR imaging, when combined with in vivo MRS, may help to better characterize intracranial cystic mass lesions.     

Reproducibility of GABA measurements using 2D J-resolved magnetic resonance spectroscopy

We determined the reproducibility of GABA (gamma-aminobutyric acid) measurements using 2D J-resolved magnetic resonance spectroscopy (MRS) on a clinical 1.5-T MR imaging scanner. Two-dimensional J-resolved spectra were acquired in vitro across five GABA concentrations using a volume head coil and a 5-in. surface coil. Additional spectra using a sixth GABA phantom with a very low concentration and from a healthy volunteer were recorded in the 5-in. surface coil only. In each case, the 3.01-ppm GABA resonance was quantified; for comparison, the peak integrals of choline (3.2 ppm) and creatine (3.03 ppm) were recorded. At a physiological concentration (1.2 mM), in vitro GABA measurement was significantly more reproducible in the surface coil than in the volume coil (P=.005), with coefficients of variation (CVs) being less than 16% with the surface coil and up to 68% with the volume head coil. At the smallest concentration of in vivo GABA reported using other spectroscopy techniques (0.8 mM) and detected only using the surface coil, the CV for GABA was 23% and was less than 10% for choline and creatine, which compare favorably with results from published studies. In vivo, the CV for GABA measurement was 26%, suggesting that 2D J-resolved MRS would be suitable for detecting physiological changes in GABA, similar to those reported using other methods.     

In vivo quantification of the metabolites in normal brain and brain tumors by proton MR spectroscopy using water as an internal standard

Metabolite concentrations in normal adult brains and in gliomas were quantitatively analyzed by in vivo proton magnetic resonance spectroscopy (MRS) using the fully relaxed water signal as an internal standard. Between January 1998 and October 2001, 28 healthy volunteers and 18 patients with gliomas were examined by in vivo proton MRS. Single voxel spectra were acquired using the point-resolved spectroscopic pulse sequence with a 1.5-T scanner (TR/TE/Ave = 3000 ms/30 ms/64). The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre), choline (Cho), and water (H2O) in the normal hemispheric white matter were 23.59 +/- 2.62 mM (mean +/- SD), 13.06 +/- 1.8 mM, 4.28 +/- 0.8 mM, and 47280.96 +/- 5414.85 mM, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). The NAA/Cho and NAA/H2O ratios can distinguish the normal brain from gliomas, and low-grade astrocytoma from high-grade group (p < 0.001). The concentration of taurine (Tau) in medulloblastomas was 29.64 +/- 5.76 mM. This is the first quantitative analysis of Tau in medulloblastoma in vivo and confirms earlier in vitro findings.     

In vivo C magnetic resonance spectroscopy of a human brain tumor after application of C-1-enriched glucose

Objectives

As a unique tool to assess metabolic fluxes noninvasively, ¹³C magnetic resonance spectroscopy (MRS) could help to characterize and understand malignancy in human tumors. However, its low sensitivity has hampered applications in patients. The aim of this study was to demonstrate that with sensitivity-optimized localized ¹³C MRS and intravenous infusion of [1-¹³C]glucose under euglycemia, it is possible to assess the dynamic conversion of glucose into its metabolic products in vivo in human glioma tissue.

Materials and Methods

Measurements were done at 3 T with a broadband single RF channel and a quadrature ¹³C surface coil inserted in a ¹H volume coil. A ¹H/¹³C polarization transfer sequence was applied, modified for localized acquisition, alternatively in two (50 ml) voxels, one encompassing the tumor and the other normal brain tissue.

Results

After about 20 min of [1-¹³C]glucose infusion, a [3-¹³C]lactate signal appeared among several resonances of metabolic products of glucose in MR spectra of the tumor voxel. The resonance of [3-¹³C]lactate was absent in MR spectra from contralateral tissue. In addition, the intensity of [1-¹³C]glucose signals in the tumor area was about 50% higher than that in normal tissue, likely reflecting more glucose in extracellular space due to a defective blood–brain barrier. The signal intensity for metabolites produced in or via the tricarboxylic acid (TCA) cycle was lower in the tumor than in the contralateral area, albeit that the ratios of isotopomer signals were comparable.

Conclusion

With an improved ¹³C MRS approach, the uptake of glucose and its conversion into metabolites such as lactate can be monitored noninvasively in vivo in human brain tumors. This opens the way to assessing metabolic activity in human tumor tissue.     

Central neurocytoma: typical magnetic resonance spectroscopy findings and atypical ventricular dissemination

PURPOSE: Central neurocytomas (CNCs) are rare neuronal tumors that have a favorable prognosis and lower rate of recurrence compared with other intraventricular neoplasms. Although it may be difficult to distinguish CNC on conventional neuroimaging, typical MR spectroscopy (MRS) features have been reported. We describe the MRI and MRS features of CNC. MATERIALS AND METHODS: Eight patients with CNC were reviewed. Three patients underwent presurgical in vivo single-voxel MRS at short echo time (TE, 35 ms) and multi-voxel MR spectroscopic imaging at long TE (144 ms). The surgically resected tumor specimen of one of these patients was also studied ex vivo using high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance. RESULTS: All eight tumors were located in the lateral ventricles. In six patients, CNC extended into the third ventricle, and in two patients the tumor showed further contiguous intraventricular dissemination into the fourth ventricle. In all three patients who underwent MRS, a characteristic metabolite peak was detected at 3.55 parts per million (ppm) at both long and short TE. HRMAS confirmed the presence of elevated glycine (Gly) at 3.55 ppm, without increase in the concentration of myo-inositol found at the same chemical shift. Elevated choline (at 3.2 ppm) was also seen in all three patients. CONCLUSION: On MRS, CNCs have a typical appearance with a metabolite peak at 3.55 ppm due to increased Gly, and this feature may be helpful in presurgical diagnosis. Although they are rare benign intraventricular tumors, in atypical cases, CNCs can show extensive intraventricular dissemination into the fourth ventricle.     

一种脑代谢研究的有效方法——高分辨率磁共振波谱分析

介绍了一种脑代谢研究的有效方法.成年大鼠脑经漏斗法液氮冷冻,制备脑组织高氯酸提取物并冷冻干燥,所得固体溶于D2O后用¹H和³¹P磁共振波谱(MRS)检测.结果表明：脑高氯酸提取物的磁共振波谱有着极好的分辨率,³¹P MRS可以分辨出ATP、ADP、磷酸肌酸(PCr)、无机磷以及多种磷酯和糖磷;¹H MRS可以分辨出乳酸(Lac)、N-乙酰天冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)、GABA、肌醇(Ino)、琥珀酸(Suc)以及多种氨基酸.各波峰积分后得到各种物质的相对含量,而这些代谢中间产物的相对含量变化可以反应脑内的代谢状况和脑受损伤情况.     

Comparative evaluation of magnetization transfer MR imaging and in-vivo proton MR spectroscopy in brain tuberculomas

We have compared and analyzed the value of in vivo proton MR spectroscopy (PMRS) and T1 weighted magnetization transfer (MT) MR imaging in tissue characterization of brain tuberculomas. We studied 33 cases of proven intracranial tuberculomas with in vivo PMRS and T1 weighted MT MR imaging. MT ratios from the rim and core of the tuberculomas were calculated and compared with metabolites seen on PMRS. Final diagnosis of tuberculoma was based on histopathology (n = 26) and/or associated tuberculous meningitis (n = 7) in all the cases. Out of the 33 patients who underwent both PMRS and T1 weighted MT MR imaging, spectroscopy showed only lipids at 0.9 ppm, 1.3 ppm, 2.0 ppm, and 2.80 ppm in 26 cases while lipids at 0.9 ppm, 1.3 ppm, 2.0 ppm and 2.80 ppm along with choline at 3.22 ppm was seen in remaining 7 patients. MT ratios from the core or solid necrosis varied from 21-29% while from the rim or cellular region varied from 16-24%. MT ratios from all the 33 lesions were consistent with tuberculomas while PMRS showed choline along with lipids in 7 predominantly cellular lesions simulating a neoplasm. We conclude that T1 weighted MT MR imaging appears to be more consistent in the tissue characterization of brain tuberculomas.     

Detection of rectal cancer and response to concurrent chemoradiotherapy by proton magnetic resonance spectroscopy

Introduction

To diagnose rectal cancer and monitor treatment response after preoperative concurrent chemoradiotherapy (CCRT) in rectal cancer patients using proton-1 magnetic resonance spectroscopy (¹H-MRS).

Materials and Methods

We enrolled 134 rectal cancer patients before treatment, of whom 34 underwent preoperative CCRT and follow-up MR spectroscopy before surgery. ¹H-MRS was performed using a six-channel phased-array coil at 3.0 T. We evaluated the presence of a choline peak at 3.2 ppm, and lipid peaks at 0.9 and 1.3 ppm, and glutamine and glutamate peaks at 2.1-2.3 and 2.7 ppm seen at two TEs (40 and 135 ms). We divided MR spectra patterns into two groups (A and B).

Results

A choline peak at 3.2 ppm seen in both TEs was characteristic for rectal cancer before treatment. Of 103 patients, 55 (53%) showed an elevated choline peak before treatment (type A). Type A spectra were seen in 68% of patients (23/34) before preoperative CCRT. After CCRT, the choline peak disappeared, resulting in only the lipid peak at 1.3 ppm (type B) in 97% of patients (33/34).

Discussion

We optimized a localized in vivo¹H-MRS method for detection of rectal adenocarcinoma and monitoring treatment response after preoperative CCRT. The method appears to be a promising and feasible noninvasive modality.     

Alzheimer''s disease histologically proven studied by MRI and MRS: Two cases

Two patients affected by severe Alzheimer's disease (AD) were investigated by MRI and image-guided ³¹P MRS. In one case, ¹H MRS was additionally performed. In both cases the diagnosis of AD was confirmed, post mortem, by the pathologist. The spectral parameters of the ³¹P MR spectra were estimated by fitting the ³¹P MR signals in the time domain. Our ³¹P MRS results suggest that it is possible to detect the membrane catabolism, as indexed with the level of PDE resonances visible in in vivo ³¹P MRS, at least in severe AD cases. The ¹H spectrum from AD brain showed a marked decrease of NAA signal respect to choline.     

In vivo magnetic resonance microscopy of brain structure in unanesthetized flies

We present near-cellular-resolution magnetic resonance (MR) images of an unanesthetized animal, the blowfly Sarcophaga bullata. Immobilized flies were inserted into a home-built gradient probe in a 14.1-T magnet, and images of voxel size (20-40 microm)(3)--comparable to the diameter of many neuronal cell bodies in the fly's brain--were obtained in several hours. Use of applied field gradients on the order of 60 G/cm allowed minimally distorted images to be produced, despite significant susceptibility differences across the specimen. The images we obtained have exceptional contrast-to-noise levels; comparison with histology-based anatomical information shows that the MR microscopy faithfully represents patterns of nervous tissue and allows distinct brain regions to be clearly identified. Even at the highest resolutions we explored, morphological detail was pronounced in the apparent absence of instabilities or movement-related artifacts frequently observed during imaging of live animal specimens. This work demonstrates that the challenges of noninvasive in vivo MR microscopy can be overcome in a system amenable to studies of brain structure and physiology.     

Fast detection of choline-containing metabolites in liver using 2D ¹H-¹⁴N three-bond correlation (HN3BC) spectroscopy

Detection and quantification of total choline-containing metabolites (CCMs) in tissues by magnetic resonance spectroscopy (MRS) has received considerable attention as a biomarker of cancer. Tissue CCMs are mainly choline (Cho), phosphocholine (PCho), and glycerophosphocholine (GPCho). Because the methyl (1)H resonances of tissue CCMs exhibit small chemical shift differences and overlap significantly in 1D (1)H MRS, quantification of individual components is precluded. Development of a MRS method capably of resolving individual components of tissue CCMs would be a significant advance. Herein, a modification of the 2D (1)H-(14)N HSQC technique is targeted on the two methylene (1)H in the CH(2)O group ((3)J(1H14N)=2.7 Hz) and applied to ex vivo mouse and human liver samples at physiological temperature (37°C). Specifically, the (1)H-(14)N HSQC technique is modified into a 2D (1)H-(14)N three-bond correlation (HN3BC) experiment, which selectively detects the (1)H of CH(2)O coupled to (14)N in CCMs. Separate signals from Cho, PCho, and GPCho components are resolved with high detection sensitivity. A 2D HN3BC spectrum can be recorded from mouse liver in only 1.5 min and from human carcinoma liver tissue in less than 3 min with effective sample volume of 0.2 ml at 14.1T.     

Development of a 1.0 T MR microscope using a Nd-Fe-B permanent magnet

A compact 1.0 T MR microscope was developed using a permanent magnet made of high performance Nd-Fe-B magnetic material and a compact MRI console (54 cm (W) x 77 cm (H) x 60 cm (D), 80 kg weight). Since the magnetic field of the permanent magnet had a large temperature coefficient (-1200 ppm/deg), an internal NMR locking technique was developed for the imaging sequences. The performance of the system was evaluated using several biological specimens. As a result, good SNR 3D images at (50 microm)(3)-(200 microm)(3) voxel dimensions were obtained in practical imaging times (0.5-7.5 hours). Thus we have concluded that the permanent-magnet compact MR microscope has great promise as a research or analytical tool.     

Feasibility of in-vivo semi-LASER renal magnetic resonance spectroscopy (MRS): Pilot study in healthy volunteers

PurposeTo evaluate the feasibility of semi-LASER renal magnetic resonance spectroscopy (MRS) in healthy volunteers and establish signature chemical composition of normal renal tissue towards future application for renal carcinoma characterization and grading.Materials and methods14 healthy volunteers were recruited after informed consent. Single voxel ¹H spectra were acquired on a 3 T MRI system using a semi-LASER sequence, employing outer-volume suppression and VAPOR water suppression with multiple averages in multiple breath-holds. Off-line processing and automatic correction for zero-order phase and frequency using the water resonance or residual water resonance for water-suppressed acquisitions was performed.Results11 volunteers successfully completed the entire examination. Phase and frequency correction was necessary to obtain optimal data quality prior to signal summation in few datasets. No lipid resonance was observed in any spectra from the unsuppressed water acquisitions, either in individual transients or in corrected summed spectra opposed to previously reported studies. No signal from other metabolites, such as choline-containing compounds, was observed in any dataset.ConclusionSemi-LASER renal MRS is technically feasible. Normal renal parenchyma does not demonstrate detectable levels of lipid or choline. This may provide a reference point for future application of this technique for noninvasive renal carcinoma histologic subtype characterization and grade.     

High-field localized 1H NMR spectroscopy in the anesthetized and in the awake monkey

Localized cerebral in vivo ¹H NMR spectroscopy (MRS) was performed in the anesthetized as well as the awake monkey using a novel vertical 7 T/60 cm MR system. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 16 metabolites in 0.1- to 1-ml volumes. Quantification was accomplished by using simulations of 18 metabolite spectra and a macromolecule (MM) background spectrum consisting of 12 components. Major cerebral metabolites (concentrations >3 mM) such as glutamate (Glu), N-acetylaspartate (NAA), creatine (Cr)/phosphocreatine (PCr) and myo-inositol (Ins) were identified with an error below 3%; most other metabolites were quantified with errors in the order of 10%. Metabolite ratios were 1.39:1 for total NAA, 1.38:1 for glutamate (Glu)/glutamine (Gln) and 0.09:1 for cholines (Cho) relative to total Cr. Taurine (Tau) was detectable at concentrations lower than 1 mM, while lactate (Lac) remained below the detection limit. The spectral dispersion was sufficient to separate metabolites of similar spectral patterns, such as Gln and Glu, N-acetylaspartylglutamate (NAAG) and NAA, and PCr–Cr. MRS in the awake monkey required the development and refinement of acquisition and correction strategies to minimize magnetic susceptibility artifacts induced by respiration and movement of the mouth or body. Periods with major motion artifacts were rejected, while a frequency/phase correction was performed on the remaining single spectra before averaging. In resting periods, both spectral amplitude and line width, that is, the voxel shim, were unaffected permitting reliable measurements. The corrected spectra obtained from the awake monkey afforded the reliable detection of 6–10 cerebral metabolites of 1-ml volumes.     

Spectral analysis of multichannel MRS data

The use of phased-array receive coils is a well-known technique to improve the image quality in magnetic resonance imaging studies of, e.g., the human brain. It is common to incorporate proton (1H) magnetic resonance spectroscopy (MRS) experiments in these studies to quantify key metabolites in a region of interest. Detecting metabolites in vivo is often difficult, requiring extensive scans to achieve signal-to-noise ratios (SNR) that provide suitable diagnostic results. Combining the MR absorption spectra obtained from several receive coils is one possible approach to increase the SNR. Previous literature does not give a clear overview of the wide range of possible approaches that can be used to combine MRS data from multiple detector coils. In this paper, we consider the multicoil MRS approach and introduce several signal processing tools to address the problem from different nonparametric, semiparametric, and parametric perspectives, depending on the amount of available prior knowledge about the data. We present a numerical study of these tools using both simulated 1H MRS data and experimental MRS data acquired from a 3T MR scanner.     

Ethanol-induced fatty liver in the rat examined by in vivo 1H chemical shift selective magnetic resonance imaging and localized spectroscopic methods.

In vivo 1H magnetic resonance imaging (MRI), chemical shift selective imaging (CSI), and localized (VOSY) 1H magnetic resonance spectroscopy (MRS) were used to study fatty infiltration in the livers of rats chronically fed an ethanol-containing all-liquid DeCarli-Lieber diet. Conventional total proton MRI showed a somewhat hyperintense liver for ethanol-fed rats, compared with pair-fed controls. CSI showed a dramatic increase in the fat signal intensity for ethanol-treated rats that was fairly homogeneous throughout the liver. However, CSI also showed a substantial decrease in the water signal intensity for the ethanol-treated rats compared to pair-fed control rats. 1H VOSY MR spectra also showed a 5.5-fold increase in the methylene resonance (1.3 ppm) of fat and a 50-70% decrease in the water resonance (4.8 ppm). Relative in vivo proton T1 and T2 relaxation times for the water resonance separate from the fat resonance, determined from modified VOSY experiments, were found to tend to increase and decrease, respectively, for ethanol-treated rat livers compared with controls. The decrease in hepatic water signal intensity could be accounted for by the decrease in T2 and decrease in water density due to the presence of accumulated hepatic fat (approximately 25 mg/g wet weight of liver). When ethanol was withdrawn from the chronically treated rats, fatty infiltration was observed by both CSI and VOSY spectra to revert toward control values with a half-life of 2-4 days. By day 16, however, the signal intensity for hepatic fat was still significantly higher than control levels. In vitro 1H MRS studies of chloroform-methanol extracts confirmed the 5.5-fold increase in total hepatic fat induced by the chronic ethanol treatment, and showed further that triacylglycerols were increased 7.7-fold, cholesterol was increased fourfold, and phospholipids were increased 3.3-fold, compared with liver extracts from pair-fed control rats.     

Novel peak assignments of in vivo (13)C MRS in human brain at 1.5 T

(13)C MRS studies at natural abundance and after intravenous 1-(13)C glucose infusion were performed on a 1.5-T clinical scanner in four subjects. Localization to the occipital cortex was achieved by a surface coil. In natural abundance spectra glucose C(3beta,5beta), myo-inositol, glutamate C(1,2,5), glutamine C(1,2,5), N-acetyl-aspartate C(1-4,C=O), creatine CH(2), CH(3), and C(C=N), taurine C(2,3), bicarbonate HCO(-)(3) were identified. After glucose infusion (13)C enrichment of glucose C(1alpha,1beta), glutamate C(1-4), glutamine C(1-4), aspartate C(2,3), N-acetyl-aspartate C(2,3), lactate C(3), alanine C(3), and HCO(-)(3) were observed. The observation of (13)C enrichment of resonances resonating at >150 ppm is an extension of previously published studies and will provide a more precise determination of metabolic rates and substrate decarboxylation in human brain.     

1H magnetic resonance spectroscopy of the normal testis: preliminary findings

PURPOSE: The purpose of this study was to determine the pre- and postpubertal 1H magnetic resonance spectroscopic characteristics of the normal testis to establish baseline values for further clinical studies. MATERIALS AND METHODS: The subjects consisted of male volunteers, of whom 19 were prepubertal with ages between 7 and 13 years and 24 were postpubertal with ages between 19 and 39 years. Their testes were evaluated at 1.5 T with magnetic resonance spectroscopy; in addition, testis volumes were measured. Major metabolite peaks were identified and their ratios were calculated. Metabolite differences of testis between pre- and postpubertal age were analyzed. RESULTS: Major constituents of spectra were 3.21 ppm choline and 0.9-1.3 ppm lipid peaks. At the echo time (TE) spectrum of 31 ms, choline/lipid ratios ranged from 0.35 to 8.30 (mean=1.87) in postpubertal males and from 0.06 to 5.45 (mean=0.88) in prepubertal males (P<.013). At the TE spectrum of 136 ms, choline/lipid ratios ranged from 0.66 to 15.42 (mean=4.09) in postpubertal males and from 0.05 to 4.91 (mean=0.9) in prepubertal males (P<.016). CONCLUSIONS: Choline/lipid ratio was higher in the postpubertal period. The existence of higher choline peak in that age group should be due to the initiation of spermatogenesis. The decrease in the lipid peak may represent the effect of testosterone on testicular tissue or may be due to histochemical changes initiated by puberty. The significant decrease in choline/lipid ratio noted after puberty could represent the presence of spermatogenesis. This hypothesis should be evaluated by further studies on postpubertal subjects with impaired spermatogenesis.