Noninvasive differentiation of tumors with use of localized H-1 MR spectroscopy in vivo: initial experience in patients with cerebral tumors

A recently developed method for image-selected localized hydrogen-1 magnetic resonance (MR) spectroscopy was assessed in the differential diagnosis of nine primary and secondary cerebral tumors, including four gliomas, two meningiomas, one neurilemoma, one arachnoid cyst, and one metastasis of breast cancer. Well-resolved H-1 MR spectra of these tumors were obtained in vivo with a conventional 1.5-T whole-body MR imaging system. All tumor spectra were remarkably different from spectra from normal brain tissue. Spectra obtained from different tumors exhibited reproducible differences, while histologically similar tumors yielded characteristic spectra with only minor differences. The observed spectral alterations reflect variations in concentrations and relaxation times of the H-1 MR sensitive pool of free (mobile) metabolites within the tissues. In most cases, the concentrations of N-acetyl-aspartate and creatine/phosphocreatine are reduced below detectability, whereas choline-containing compounds are generally enhanced. The spectral differences between the tumors are mainly due to the differing concentrations of lipids, lactic acid, and carbohydrates. Localized H-1 MR spectroscopy may become an important clinical tool for the differentiation of tumors as well as for therapeutic control.     

Characterization of CNS lesions by using high-resolution 1H MR spectroscopy of CSF: preliminary results

Sixty-six samples of CSF from 66 patients with a variety of diseases, including tumors, arteriovenous malformations, aneurysms, brain infarctions, and lumbar back pain, were studied with 1H MR spectroscopy at 360 MHz. 1H MR spectroscopy offers a simple means to obtain fast information about different metabolites simultaneously. As compared with the control group, which consisted of 19 CSF samples from the same group of 66 patients, but from individuals who had no abnormal findings on neurologic examination, common clinicochemical tests, or neuroradiologic studies, our preliminary results suggest that tumors and hemorrhages may be differentiated by 1H MR spectroscopy. MR peak intensities relative to lactate peak intensity were used as variables in a statistical analysis to determine the significance of individual resonance intensities in predicting CNS abnormalities. The most important factors for diagnosis were analyzed by means of a multivariate general linear hypothesis and a principal component method. The most important factors for predicting CNS abnormalities in the studied diseases were creatinine, glucose, creatine, citrate, protein content, glutamine, amount of cells, and valine. By using this model for discriminant analysis, we could predict hemorrhages correctly in 88% of cases and tumors in 75% of cases. All samples of controls were determined correctly. In cases of brain infarctions, different signals were observed, which may lead to further characterization of such lesions. 1H MR spectroscopy may offer a simple means for further characterizing CNS lesions. However, this needs confirmation by a prospective study, which would include a larger patient population with different diseases.     

Characterization of neoplastic and normal human breast tissues with in vivo (1)H MR spectroscopy.

The purpose of this study was to evaluate whether the detection of choline-containing compounds in in vivo (1)H magnetic resonance spectroscopy (MRS) of breast lesions is specific for carcinomas, whether a choline peak in in vivo (1)H MRS can be detected under physiological conditions of increased metabolism in breast parenchyma, and whether analysis of lipid signals can differentiate between various breast lesions and tissues. Forty patients and volunteers were examined with in vivo (1)H MR spectroscopy. Three spectra with identical localization but increasing echo times were obtained. Choline-containing compounds were detected in 9 of 11 carcinomas and in 2 of 11 benign lesions. A choline signal was also detected in five of seven volunteers who were breast-feeding at the time of examination, demonstrating that choline compounds can be detected by in vivo (1)H MRS in breast tissue under physiological conditions. Analysis of lipid signals did not contribute to differentiation between various breast lesions and tissues. J. Magn. Reson. Imaging 1999;10:159-164.     

In vivo 1H MR spectroscopy of thyroid carcinoma

To determine if proton magnetic resonance spectroscopy (1H MRS) of thyroid carcinoma is feasible and to determine if 1H MRS spectra of malignant tumors differ from that of normal thyroid tissue. We performed 1H MRS at 1.5 T at echo-times (TE) 136 and 272 ms to examine eight patients with thyroid cancer (primary tumour or nodal metastasis) larger than 1 cm3 in size and five volunteers with normal thyroids. Spectra acquired from six primary tumors (three anaplastic carcinomas, two papillary carcinomas and one follicular carcinoma) and two nodes (two papillary carcinoma metastases) were analyzed in the time-domain using a non-linear least squares fitting algorithm with incorporation of prior knowledge. Choline (3.2 ppm) was identified in all solid carcinomas with a mean choline/creatine of 4.3 at TE 136 ms and 5.4 at TE 272 ms. Ratios for malignant tumors at TE 136 ms ranged from 1.6 in well differentiated follicular carcinoma to 9.4 in anaplastic carcinoma. No choline was detected in normal thyroid tissues. Our results showed that 1H MRS is a feasible technique for the evaluation of malignant thyroid tumors larger than 1 cm3 and that proton spectra of malignant tumors differ from that of normal thyroid tissue.     

Human gallbladder bile: noninvasive investigation in vivo with single-voxel 1H MR spectroscopy

Proton (hydrogen 1) magnetic resonance (MR) spectroscopy was used to study model and porcine bile in vitro. The method was subsequently developed to facilitate the acquisition of in vivo 1H MR spectra from the gallbladder bile of 10 human volunteers. Signals attributable to phosphotidylcholine and conjugated bile acid protons were observed in eight of the 10 volunteers. Phosphotidylcholine concentrations were estimated, and five values (mean = 35.8 mmol/L, SD = 9.8) were within the expected range of levels in human bile. Findings in this preliminary investigation indicate that human gallbladder bile can be qualitatively and quantitatively studied noninvasively with 1H MR spectroscopy.     

Localized 2D J-resolved H MR spectroscopy of human brain tumors in vivo

Application of two-dimensional (2D) J-resolved MR spectroscopy, fully localized in three dimensions to monitor the metabolites in human brain tumors in vivo on a whole body MR scanner is presented. A modified PRESS sequence with [90° – 180° – t₁/2 – 180° – t₁/2-acquisition] was used for voxel localization (2D J point-resolved spectroscopy [PRESS]); chemical shift selective (CHESS) sequence was used for suppression of water. The incremental delay (t₁/2) added to the intervals before and after the last slice-selective 180° RF pulse allowed the monitoring of the J-evolution in a localized 2D NMR spectrum. The addition of the second frequency dimension in 2D J-resolved spectroscopy to encode the indirect spin-spin coupling allowed the visualization of lactate peaks not observed in the 1D MR spectrum because of severe overlap with lipid peaks. 2D spectra of a two-layer phantom with 100 mM alanine and corn oil and also from three patients with tumors are presented here. The 2D spectra show that the J-coupled lactate peaks could be separated even when the lipids peaks severely overlap.     

Reproducibility of MR perfusion and 1H spectroscopy of bone marrow

Purpose

To determine the reproducibility of proton (¹H) magnetic resonance (MR) spectroscopy and dynamic contrast‐enhanced MR imaging in a clinical setting for the assessment of marrow fat fraction and marrow perfusion in longitudinal studies.

Materials and Methods

In all, 36 subjects (17 females, 19 males, mean age 72.9 ± 2.9 years) who underwent MR spectroscopy and/or dynamic contrast‐enhanced perfusion imaging of the proximal femur were asked to return after 1 week for a repeat MR examination.

Results

Reproducibility of ¹H MR spectroscopy in all bone areas tested was high, ranging from 0.78–0.85, with the highest reproducibility being in the femoral head and lowest in the femoral neck. Reproducibility of paired perfusion measurements ranged from 0.59 (enhancement slope femoral head) to 0.98 (enhancement maximum acetabulum). Overall reproducibility of ¹H MR spectroscopy and dynamic contrast‐enhanced imaging tended to be best in areas with the highest inherent fat fraction or perfusion.

Conclusion

Reproducibility of ¹H MR spectroscopy or perfusion imaging is sufficiently high to warrant these techniques being applied to the longitudinal study of bone diseases. J. Magn. Reson. Imaging 2009;29:1438–1442. © 2009 Wiley‐Liss, Inc.     

Bone and soft-tissue lesions: diagnosis with combined H-1 MR imaging and P-31 MR spectroscopy

The feasibility of combined magnetic resonance (MR) imaging and surface coil phosphorus-31 MR spectroscopy at 1.5 T was examined in a clinical study of 34 patients before biopsy of bone or soft-tissue lesions of the extremity and trunk. The results confirmed the inability of MR imaging alone to distinguish most benign lesions from malignant ones. Malignant lesions were distinguished from benign lesions on the basis of significantly higher mean peak ratios of phosphomonoester (PME) to beta-nucleoside triphosphate (NTP) and of phosphodiester to NTP, a significantly lower mean peak area ratio of phosphocreatine to NTP, and a higher mean pH. The diagnostic performance of the PME/NTP peak area ratio is characterized by a sensitivity (true-positive fraction) of 1.00 and a specificity (true-negative fraction) of 0.93. This study provided preliminary evidence that P-31 MR spectroscopy may be used to improve diagnostic specificity in bone and soft-tissue lesions.     

Metabolite detection of pancreatic carcinoma by in vivo proton MR spectroscopy at 3T: initial results

Purpose

The authors sought to identify metabolic features of pancreatic carcinoma by in vivo proton magnetic resonance (MR) spectroscopy at 3 Tesla.

Materials and methods

Forty healthy volunteers and 40 patients with pancreatic carcinoma confirmed by histopathology underwent T2-weighted imaging for localisation of the single voxel. Respiration-triggered ¹H MR spectroscopy was used to detect metabolites in normal pancreas and cancerous tissue. All spectral data were processed with SAGE software. Unsuppressed water at 4.7 ppm was used as an internal reference to determine metabolite concentrations. Each ratio among the different peak areas was statistically evaluated between normal pancreas and pancreatic carcinoma.

Results

The following five groups of spectra were detected: unsaturated fatty acids (-CH = CH-) at 5.4 ppm; residual water at 4.7 ppm; choline metabolites at 3.2 ppm; unsaturated fatty acids (-CH2-CH = CH-) or a combination of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), glutamine, glutamate, macromolecules and unsaturated fatty acids (-CH2-CH = CH-) at 2.0 ppm and lipids at 1.3 ppm. Ratio of lipids to unsuppressed water in normal pancreas was statistically greater than that in pancreatic cancer (p=0.004). Ratio of choline to unsuppressed water in normal pancreas was statistically greater than that in pancreatic cancer (p=0.0001). Ratio of fatty acids (-CH = CH-) to lipids in normal pancreas was statistically lower than that in pancreatic cancer (p=0.006).

Conclusions

Compared with normal pancreas, pancreatic carcinoma has a higher ratio of fatty acids (-CH = CH-) to lipids and lower ratios of lipids to unsuppressed water and choline to unsuppressed water at 3T.     

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.     

Volume-selective 1H MR spectroscopy for in vivo detection of valproate in patients with epilepsy

We performed volume-selective 1H MR spectroscopy (1H-MRS) on 12 patients on valproate monotherapy to detect valproate in vivo in the brain. We also acquired reference valproate spectra in vitro in subphysiological 15 g/l albumin solution in saline, in which valproate showed two resonance peaks at 0.7 and 1.2 ppm and a minimum detection threshold of 240 mg/l. In vivo 1H-MRS spectra in brain showed peaks between 0.6 and 1.6 ppm. Simultaneous serum valproate concentrations did not correlate with these integrated MRS peaks. On follow-up, changes in these signals also did not correlate with increasing serum valproate levels. The inconsistency of in vivo 1H-MRS signals at varying serum levels and the high detection levels in vitro suggest that valproate signals are missed in vivo because valproate is metabolised or strongly bound, presumably to brain macromolecules.     

Salivary gland tumors at in vivo proton MR spectroscopy

PURPOSE: To prospectively evaluate whether proton magnetic resonance (MR) spectroscopy can be used to characterize salivary gland tumors (SGTs). MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Hydrogen 1 ((1)H) MR spectroscopy was performed with echo times of 136 and 272 msec at 1.5 T in both SGTs and normal parotid glands. Spectra were analyzed in the time domain by using prior knowledge in the fitting procedure to obtain peak amplitudes of choline (Cho), creatine (Cr), and unsuppressed water. Mean Cho/Cr and Cho/water ratios for each subgroup of SGTs were obtained, and results were compared by using a nonparametric t test. RESULTS: Successful spectra were acquired in 56 patients (35 men, 21 women; mean age, 56 years) with a total of nine malignant tumors and 47 benign SGTs (24 Warthin tumors, 22 pleomorphic adenomas, one oncocytoma). At an echo time of 136 msec, Cho/Cr ratios were obtained in 26 (47%) of 55 spectra, with a mean value (+/- standard deviation) of 1.73 +/- 0.47, 5.49 +/- 1.86, 3.46 +/- 0.84, and 2.45 for malignant tumors, Warthin tumors, pleomorphic adenomas, and oncocytoma, respectively. Differences were significant between Warthin tumors and pleomorphic adenomas (P = .028) and between benign SGTs and malignant tumors (P < .001). At an echo time of 272 msec, Cho/Cr ratios were obtained in 16 (30%) of 53 spectra, with a mean value of 2.27 +/- 0.69, 6.92 +/- 1.47, and 3.67 +/- 1.23 for malignant tumors, Warthin tumors, and pleomorphic adenomas, respectively. Differences were also significant between Warthin tumors and pleomorphic adenomas (P = .041) and benign SGTs and malignant tumors (P = .004). There was a significant difference in mean Cho/water ratio for Warthin tumors versus pleomorphic adenomas at echo times of 136 msec (P = .003) and 272 msec (P = .002) but not for benign SGTs versus malignant tumors. CONCLUSION: (1)H MR spectroscopy may be used to characterize SGTs, but a larger study is required to validate these initial results.     

Extremity bone tumors: evaluation by P-31 MR spectroscopy

High-resolution P-31 MR spectra were obtained in four patients with bone tumors of their distal extremities. In one case the tumor, a Ewing sarcoma of the tibia, was investigated during clinical remission after radiation therapy and chemotherapy. The other three cases - one low-grade chondrosarcoma of the tibial head, one malignant fibrous histiocytoma of the tibia, and one chondroblastoma of the medial femoral condyle - showed clinically active tumor growth, with corresponding increased metabolism as demonstrated by bone scintigraphy. The spectra of the three active tumors indicated a comparably high adenosine triphosphate content, similar to previously published spectra from animal tumors or human tumors implanted into animals. There were also high resonances of inorganic phosphate and low resonances of phosphocreatine; there were definite peaks in the phosphodiester and phosphomonoester regions, indicating the existence of these metabolites in the tumors. Slight but definite changes in the metabolite content were observed in one tumor after chemotherapy. The spectra of the unaffected leg did not show any well-resolved P-31 signals, which is typical for healthy bone. These are the first P-31 MR spectra of human bone tumors measured in patients to our knowledge.     

弥漫性星形细胞肿瘤的活体1H MR波谱及灌注成像和扩散成像分级

目的 探讨活体^1HMR波谱（MRS）、脑灌注成像（PI）及扩散成像（DWI）对弥漫性星形细胞肿瘤的分级价值。方法 搜集经手术病理证实的弥漫性星形细胞肿瘤154例。按世界卫生组织分级：星形细胞瘤（Ⅱ级），间变型星形细胞瘤（Ⅲ级）以及胶质母细胞瘤（Ⅳ级）。35例行^1HMRS检查，其中Ⅱ级8例，Ⅲ级13例，Ⅳ级14例，比较各级肿瘤之间胆碱／肌酸（Cho／Cr）、N-乙酰天冬氨酸（NAA）／Cr及乳酸（Lac）／Cr值；76例应用MR平面回波成像技术（EPI）行对比剂增强灌注成像（CEPI），包括Ⅱ级36例，Ⅲ级20例，Ⅳ级20例，比较各级别星形细胞瘤内最大相对局部脑血容量（rrCBV）；43例行DWI，其中Ⅱ级26例，Ⅲ级6例，Ⅳ级11例，比较各级别肿瘤间的表观扩散系数比率（ADCR）。结果 ^1HMRS组中Ⅱ、Ⅲ、Ⅳ级星形细胞瘤的Cho／Cr分别为2．709±1．228，5．812±2．374及5．289±1．462，3组之间差异有统计学意义（P〈0．05）。Ⅱ、Ⅲ、Ⅳ级星形细胞瘤的Lac／Cr分别为0．100±0．083、1．879±1．595及3．656±2．195，3组之间差异均有统计学意义（P〈0．01）。Ⅱ、Ⅲ、Ⅳ级星形细胞肿瘤的NAA／Cr之间差异无统计学意义（P〉0．05）；动态CE PI Ⅱ级与Ⅲ、Ⅳ级的rrCBV分别为1．379±0．739、2．654±1．072、3．218±1．565，3组差异有统计学意义（P〈0．01）。rrCBV与弥漫性星形细胞肿瘤的分级呈正相关（rs=0．601，P〈0．01）。rrCBV区分Ⅰ～Ⅱ级与Ⅲ～Ⅳ级的界值点为1．898（敏感性85．0％，特异性88．9％）；DWI组中Ⅱ级与Ⅲ＋Ⅳ级的ADCR差异无统计学意义（t=1．846，P=0．072）。结论 活体^1HMRS能反映不同级别星形细胞肿瘤的代谢差别；动态CEMRI可以揭示肿瘤内血管分布状况，量化病变的血管生成，为临床提供病生理学信息。依此可对弥漫性星形细胞肿瘤进行分级。     

In vivo quantification of choline compounds in the breast with 1H MR spectroscopy.

This work describes a methodology for quantifying levels of total choline-containing compounds (tCho) in the breast using in vivo (1)H MR spectroscopy (MRS) at high field (4 Tesla). Water is used as an internal reference compound to account for the partial volume of adipose tissue. Peak amplitudes are estimated by fitting one peak at a time over a narrow frequency band to allow measurement of small metabolite resonances in spectra with large lipid peaks. This quantitative method significantly improves previously reported analysis methods by accounting for the variable sensitivity of breast (1)H MRS measurements. Using this technique, we detected and quantified a tCho peak in 214 of 500 in vivo spectra. tCho levels were found to be significantly higher in malignancies than in benign abnormalities and normal breast tissues, which suggests that this technique could be used to diagnose suspicious lesions and monitor response to cancer treatments.     

Characterization of intracranial mass lesions with in vivo proton MR spectroscopy.

PURPOSETo assess the use of in vivo proton MR spectroscopy for characterization of intracranial mass lesions and to ascertain its reliability in grading of gliomas.METHODSOne hundred twenty patients with intracranial masses were subjected to volume selective spectroscopy using stimulated echo acquisition mode (echo time, 20 and 270 milliseconds) and spin echo (echo time, 135 milliseconds) sequences. The intracranial lesions were grouped into intraaxial and extraaxial, as judged with MR imaging. Assignment of resonances was confirmed in two samples each of brain abscess, epidermoid cyst, and tuberculoma using ex vivo high-resolution MR spectroscopy.RESULTSThe in vivo spectra appeared distinct compared with normal brain in all the cases. All high-grade gliomas (n = 37) showed high choline and low or absent N-acetyl-L-aspartate and creatine along with lipid and/or lactate, whereas low-grade gliomas (n = 23) were characterized by low N-acetyl-aspartate and creatine and high choline and presence of only lactate. N-acetyl-aspartate/choline ratio was significantly lower and choline/creatine ratio was significantly higher in high-grade gliomas than in low-grade gliomas. Presence of lipids suggested a higher grade of malignancy. All metastases (n = 7) showed lipid and lactate, whereas choline was visible in only four cases. Epidermoids showed resonances from lactate and an unassigned resonance at 1.8 ppm. Meningiomas could be differentiated from schwannomas by the presence of alanine in the former. Among the infective masses, pyogenic abscesses (n = 6) showed resonances only from cytosolic amino acids, lactate, alanine, and acetate; and tuberculomas (n = 11) showed only lipid resonances.CONCLUSIONSIn vivo proton MR spectroscopy, helps in tissue characterization of intracranial mass lesions. Spectroscopy is a reliable technique for grading of gliomas when N-acetyl-aspartate/choline and choline/creatine ratios and presence of lipids are used in combination.