Noninvasive evaluation of cerebral glioma grade by using multivoxel 3D proton MR spectroscopy

Objective

To determine whether metabolite ratios in multivoxel 3D proton MR spectroscopy (¹H MRS) is different between low-grade and high-grade gliomas and may be useful for glioma grading.

Materials and Methods

Thirty-nine patients (23 male and 16 female; 22-75 years old; mean age, 44.92±12.65 years) suspected of having gliomas underwent 3D ¹H MRS examinations. Metabolite ratios [choline (Cho)/creatine (Cr), N-acetylaspartate (NAA)/Cr and Cho/NAA] were measured. Tumor grade was determined by using the histopathologic grading. Receiver operating characteristic analysis of metabolite ratios was performed, and optimum thresholds for tumor grading were determined. The resulting sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for identifying high-grade gliomas were calculated.

Results

Diagnostic-quality 3D ¹H MRS with readily quantifiable Cho, Cr and NAA peaks was obtained in 94.87% of the cases. The Cho/Cr and Cho/NAA ratios were significantly higher in high-grade than in low-grade glioma (P<.001), whereas the NAA/Cr ratios were significantly lower in high-grade than in low-grade glioma (P<.001). Receiver operating characteristic analysis demonstrated a threshold value of 2.04 for Cho/Cr ratio to provide sensitivity, specificity, PPV and NPV of 84.00%, 83.33%, 91.30% and 71.43%, respectively. Threshold value of 2.20 for Cho/NAA ratio resulted in sensitivity, specificity, PPV and NPV of 88.00%, 66.67%, 84.62% and 72.73%, respectively. Overall diagnostic accuracy was not statistically significantly different between Cho/Cr and Cho/NAA ratios (χ²=0.093, P=.76).

Conclusion

Metabolite ratios of low-grade gliomas were significantly different from high-grade gliomas. Cho/Cr and Cho/NAA ratios could have the superior diagnostic performance in predicting the glioma grade.     

Localized in vivo proton spectroscopy of the bone marrow in patients with leukemia

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate the haemopoietic (iliac bone) and fatty bone marrow (tibia) in patients with leukemia and polycythaemia vera. Selective measurements of the relaxation times T₁ and T₂ for the “water” and “fat” resonances in the bone marrow spectra were performed. Nine patients with acute leukemia and three patients with chronic leukemia were examined at diagnosis. Three patients with acute leukemia in remission were also examined. Five of the leukemic patients had follow-up examinations performed in relation to chemotherapeutic treatment. Nine patients with polycythaemia vera and 21 normal control subjects were examined with identical methods for comparison. All patients had bone marrow biopsies performed prior to every MR examination. Significant differences could be detected in the spectral patterns from iliac bone marrow in patients with leukemia at diagnosis compared to the healthy normal controls. The “relative water content” was increased in the iliac bone marrow spectra of the leukemic patients compared to the normal subjects, which indicates an increase in the amount of haemopoietic tissue and a corresponding decrease in marrow fat content. The T₁ relaxation times of the “water” resonance in the spectra from the iliac bone marrow of the leukemic patients were significantly prolonged at diagnosis, compared to the normal controls and the patients with polycythaemia vera. After chemotherapeutic induction of remission, the spectra from the iliac bone marrow in the patients with leukemia resembled normal spectra. Four leukemic patients had abnormal spectra from the tibial bone marrow and one patients showed early changes in tibial marrow during chemotherapeutic treatment, before any major changes could be detected in the iliac bone marrow.     

Proton magnetic resonance spectroscopy and biochemical investigation of type 2 diabetes mellitus in Asian Indians: observation of high muscle lipids and C-reactive protein levels

We report the determination of intramyocellular lipids (IMCLs) of the soleus muscle of patients with type 2 diabetes mellitus (T2DM) using proton magnetic resonance spectroscopy. In addition, the various anthropometric and biochemical profiles of these patients were determined, including estimation of C-reactive protein (CRP), an inflammatory marker of coronary heart disease, and insulin resistance [Homeostasis Model Assessment (HOMA-IR)]. The estimated CRP level and the IMCL content in these patients were correlated with body mass index, percentage of body fat, other measures of abdominal obesity, serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. The IMCL content (P=.04), CRP (P=.008) and insulin resistance (P=.0007) were significantly higher in T2DM patients compared to healthy controls. However, IMCL content did not correlate with values of fasting insulin, HOMA-IR or CRP in either group. These findings have strong implications of increased cardiovascular risk in Asian Indians with T2DM. The absence of relationship between CRP and IMCL needs to be explored further in a study using a large sample size.     

H MR spectroscopy monitoring of changes in choline peak area and line shape after Gd-contrast administration

Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in ¹H MR spectra of contrast-enhancing tumor at 5–10 min after Gd-contrast administration [Magn. Reson. Med. 37:222–225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0–5, 5–10, and/or 10–15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 ± 3, 12 ± 2, and 14 ± 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.     

In vivo proton magnetic resonance spectroscopy of alcohol in rhesus monkey brain

Brain alcohol was measured in rhesus monkeys (Macaca mulatta) by proton magnetic resonance spectroscopy (MRS) following acute nasogastric alcohol administration (0.8 g/kg). Monkeys were anesthetized with ketamine and xylazine. A 1.5 T whole body imager and a 3-inch surface coil were used to acquire TE 30 and 270 ms spectra from a 7.5 cc voxel localized with a stimulated echo (STEAM) sequence. Venous blood samples were collected during spectral acquisitions for gas chromatographic determination of temporally concordant blood alcohol levels (BALs). Acute alcohol administration did not alter the resonance areas of N-acetylaspartate/N-acetyl containing compounds (NAA), choline containing compounds, or total creatine. The NAA resonance was used as an internal standard to calculate approximate brain alcohol concentrations, which averaged 27 ± 3% and 27 ± 8% of temporally concordant BALs (T₂-corrected TE 30 and TE 270 ms spectra, respectively). In addition to reconfirming results from prior studies finding incomplete detection of brain alcohol with MRS, these results demonstrate the feasibility of measuring brain alcohol in anesthetized nonhuman primates to examine relationships between alcohol exposure history and MRS-visibility of brain alcohol.     

Similarity in the metabolic profile in macroscopically involved and un-involved colonic mucosa in patients with inflammatory bowel disease: an in vitro proton (H) MR spectroscopy study

Background

The histological extent of inflammatory bowel disease (IBD) is greater than that evident by colonoscopic evaluation. We hypothesized that metabolic profile in macroscopically un-involved colonic mucosa in IBD is similar to that of controls with healthy colon. We thus assessed the differences in metabolic profile in macroscopically involved and un-involved colonic mucosa of IBD patients to further substantiate the extent of disease.

Patients and Methods

Colonic mucosal biopsies were obtained and snap frozen from both the macroscopically un-involved and involved colonic mucosa of IBD patients and macroscopically normal colonic mucosa of controls and were subjected to in-vitro high-resolution proton (¹H) magnetic resonance (MR) spectroscopy and the concentrations of metabolites were determined.

Results

Thirty-two metabolites were assigned in the proton MR spectrum of colonic mucosa of IBD patients. The concentrations of amino acids (isoleucine, leucine, valine, arginine, lysine, glutamine/glutamate, alanine), membrane metabolites (choline, glycerophosphorylcholine/phosphorylcholine), glycolytic product (lactate) and short chain fatty acid (formate) were significantly lower while significantly high level of glucose were observed in the macroscopically un-involved colonic mucosa of IBD patients compared to the macroscopically normal mucosa of controls. There was no significant difference in the concentrations of metabolites in macroscopically involved and un-involved colonic mucosa of IBD patients.

Conclusions

The metabolic profile in macroscopically un-involved colonic mucosa of IBD patients is similar to that of macroscopically involved mucosa but different from colonic mucosa of controls. This suggests that even macroscopically un-involved colonic mucosa is metabolically abnormal and may explain the increase in extent of disease with time.     

Central neurocytoma: proton MR spectroscopy and diffusion weighted MR imaging findings

Purpose

To present proton magnetic resonance spectroscopy and diffusion-weighted imaging (DWI) findings of central neurocytoma (CN).

Methods and Materials

Imaging findings of seven patients with the histopathological diagnosis of CN (five male and two female; age range, 21–28 years of age) were evaluated retrospectively. In addition to conventional magnetic resonance imaging features, we also assessed the metabolite ratios and tumor normalized apparent diffusion coefficient (NADC), which was calculated by dividing the tumor apparent diffusion coefficient (ADC) values by normal ADC. Approval from our institutional review board was obtained for this review.

Results

The tumor choline/creatine ratios were 5.17±2.38, while N-acetyl aspartate/choline and N-acetyl aspartate/creatine ratios were 0.33±0.15 and 1.84±1.38, respectively. On DWI, tumors had heterogeneous hyperintense appearances when compared with the contralateral parietal lobe white matter and tumor NADC values were 0.63±0.05.

Conclusion

Significantly increased choline/creatine and decreased N-acetyl aspartate/choline ratios with lower NADC values in CN resemble high-grade gliomas and complicate the diagnosis. Familarity its physiologic features would help to presurgical diagnosis of ventricular and exraventricular CNs.     

Quantitative multivoxel proton chemical shift imaging of the breast

The study of focal pathology by single-voxel magnetic resonance spectroscopy (MRS) is hampered by the impossibility to study tissue heterogeneity or compare the metabolite signals in breast lesion directly to those in unaffected tissue. Multivoxel MRS studies, while potentially allowing for truly quantitative tissue characterization, have up to now also been far from quantitative with, for example, the signal-to-noise ratio of the choline (Cho) signal serving as measure of tumor activity. Shown in this study is that in a standard clinical setting with a regular 1.5-T magnetic resonance scanner, it is possible to perform quantitative multivoxel MRS. With the use of literature values for the T1 and T2 relaxation times of Cho and water in fibroglandular breast tissue and tumors, one can determine the concentrations of Cho in different tumor compartments and surrounding tissues in two brief multivoxel MRS measurements. This opens excellent perspectives to quantitative diagnostic and follow-up studies of focal pathology such as lesions suspected of breast cancer.     

Accuracy and stability of measuring GABA, glutamate, and glutamine by proton magnetic resonance spectroscopy: a phantom study at 4 Tesla

Proton magnetic resonance spectroscopy has the potential to provide valuable information about alterations in gamma-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln) in psychiatric and neurological disorders. In order to use this technique effectively, it is important to establish the accuracy and reproducibility of the methodology. In this study, phantoms with known metabolite concentrations were used to compare the accuracy of 2D J-resolved MRS, single-echo 30 ms PRESS, and GABA-edited MEGA-PRESS for measuring all three aforementioned neurochemicals simultaneously. The phantoms included metabolite concentrations above and below the physiological range and scans were performed at baseline, 1 week, and 1 month time-points. For GABA measurement, MEGA-PRESS proved optimal with a measured-to-target correlation of R(2)=0.999, with J-resolved providing R(2)=0.973 for GABA. All three methods proved effective in measuring Glu with R(2)=0.987 (30 ms PRESS), R(2)=0.996 (J-resolved) and R(2)=0.910 (MEGA-PRESS). J-resolved and MEGA-PRESS yielded good results for Gln measures with respective R(2)=0.855 (J-resolved) and R(2)=0.815 (MEGA-PRESS). The 30 ms PRESS method proved ineffective in measuring GABA and Gln. When measurement stability at in vivo concentration was assessed as a function of varying spectral quality, J-resolved proved the most stable and immune to signal-to-noise and linewidth fluctuation compared to MEGA-PRESS and 30 ms PRESS.     

Cerebellar metabolite alterations detected in vivo by proton MR spectroscopy

The aim of our work was to evaluate the feasibility of in vivo single-voxel quantitative proton MR spectroscopy in order to identify possible alterations in the main metabolite concentrations due to some metabolic dysfunctions in the cerebellum of patients suffering from a particular form of migraine called “with aura.” Measurements of metabolite levels in the cerebellum disclosed reduced choline values (normalized both to N-acetyl-aspartate and creatine) in the patient group with respect to the age-matched control group. Our interest in this pathology is motivated by the fact that there are no available specific biochemical markers for migraine characterization, and the current diagnostic only takes advantage of the medical history and the clinical examination.     

The combined effect of hypertension and type 2 diabetes mellitus on aortic stiffness and endothelial dysfunction: An integrated study with high-resolution MRI

Purpose

The purpose of this study was to investigate the combined effect of hypertension and type 2 diabetes mellitus (DM2) on aortic stiffness and endothelial dysfunction by using an integrated MRI approach.

Materials and Methods

A total of 31 non-hypertensive DM2 patients and 31 hypertensive DM2 patients underwent 3.0-T MRI. Aortic distensibility (AD), pulse wave velocity (PWV) and brachial artery flow-mediated dilation (FMD) were assessed. Student's t-test, Mann–Whitney U test, chi-squared test, Pearson correlation analysis, and univariable and multiple linear regression analyses were used for statistical analyses.

Results

The hypertensive patients showed lower AD at multiple levels (ascending aorta [AA]: 2.07 ± 0.98 × 10^− 3 mm Hg^− 1 vs. 3.21 ± 1.70 × 10^− 3 mm Hg^− 1, p < 0.01; proximal thoracic descending aorta [PDA]: 2.58 ± 0.72 × 10^− 3 mm Hg^− 1 vs. 3.58 ± 1.47 × 10^− 3 mm Hg^− 1, p < 0.01; distal descending aorta [DDA]: 3.11 ± 1.84 × 10^− 3 mm Hg^− 1 vs. 4.27 ± 1.75 × 10^− 3 mm Hg^− 1, p < 0.01); faster PWV (7.46 ± 2.28 m/s vs. 5.82 ± 1.12 m/s, p < 0.05) and lower FMD (12.67% ± 6.49% vs. 20.66% ± 9.7%; p < 0.01). Systolic blood pressure was an independent predictor of PWV, AA-AD, DDA-AD and FMD. FMD was statistically significantly associated with PWV (r = − 0.37, p < 0.01) and AD (p < 0.01).

Conclusions

Hypertension has a contributive effect on aortic stiffness and endothelial dysfunction in DM2 patients.     

Quantification of low fat contents: a comparison of MR imaging and spectroscopy methods at 1.5 and 3 T

Magnetic resonance spectroscopy (MRS) has long been considered the golden standard for non-invasive measurement of tissue fat content. With improved techniques for fat/water separation, imaging has become an alternative to MRS for fat quantification. Several imaging models have been proposed, but their performance relative to MRS at very low fat contents is yet not fully established. In this work, imaging and spectroscopy were compared at 1.5 T and 3 T in phantoms with 0-3% fat fraction (FF). We propose a multispectral model with individual a priori R₂ relaxation rates for water and fat, and a common unknown R₂′ relaxation. Magnitude and complex image reconstructions were also compared. Best accuracy was obtained with the imaging method at 1.5 T. At 3 T, the FFs were underestimated due to larger fat-water phase shifts. Agreement between measured and true FF was excellent for the imaging method at 1.5 T (imaging: FF_meas= 0.98 FF_true− 0.01%, spectroscopy: FF_meas= 0.77 FF_true+ 0.08%), and fair at 3 T (imaging: FF_meas= 0.91 FF_true− 0.19%, spectroscopy: FF_meas= 0.79 FF_true+ 0.02%). The imaging method was able to quantify FFs down to approx. 0.5%. We conclude that the suggested imaging model is capable of fat quantification with accuracy and precision similar to or better than spectroscopy and offers an improvement vs. a model with a common R₂* relaxation only.     

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling

Objective

To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis.

Methods

Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis.

Results

Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity.

Conclusion

Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.     

The use of multivariate MR imaging intensities versus metabolic data from MR spectroscopic imaging for brain tumour classification

This study investigated the value of information from both magnetic resonance imaging and magnetic resonance spectroscopic imaging (MRSI) to automated discrimination of brain tumours. The influence of imaging intensities and metabolic data was tested by comparing the use of MR spectra from MRSI, MR imaging intensities, peak integration values obtained from the MR spectra and a combination of the latter two. Three classification techniques were objectively compared: linear discriminant analysis, least squares support vector machines (LS-SVM) with a linear kernel as linear techniques and LS-SVM with radial basis function kernel as a nonlinear technique. Classifiers were evaluated over 100 stratified random splittings of the dataset into training and test sets. The area under the receiver operating characteristic (ROC) curve (AUC) was used as a global performance measure on test data. In general, all techniques obtained a high performance when using peak integration values with or without MR imaging intensities. For example for low- versus high-grade tumours, low- versus high-grade gliomas and gliomas versus meningiomas, the mean test AUC was higher than 0.91, 0.94, and 0.99, respectively, when both MR imaging intensities and peak integration values were used. The use of metabolic data from MRSI significantly improved automated classification of brain tumour types compared to the use of MR imaging intensities solely.     

Proton spectroscopy of human stroke: Assessment of transverse relaxation times and partial volume effects in single volume STEAM MRS

Proton T₂ relaxation times were measured in 13 stroke patients and 13 aged-matched normal subjects at 2.1 T. Spectra were acquired from an 8-cc volume using the STEAM sequence with echo times (TE) of 30.4 ms and 270.0 ms and repetition time of 2.8 s. Transverse relaxation times were estimated using two-point calculations. Percentage volume of infarct in the STEAM voxel was measured on spin-echo MRI encompassing the infarct and correlated with the peak amplitude of N-acetylated compounds (NA). T₂ values of NA, creatine, and choline resonances showed no significant difference between patients and controls. T₂ for lactate in patients was 780 ± 257 ms, respectively (mean ± SE, n = 7). In stroke patients, high inverse correlation was found between the absolute NA signal and partial volume of normal brain contributing to each spectrum (p < .001, r = 0.97). Together with unchanged T₂, this suggests that NAA largely disappears from infarcted tissue within 24 hr postinfarct.     

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.