Magnetic Resonance Spectroscopic Imaging Measurements Research Articles

Magnetic resonance spectroscopy outperforms perfusion in distinguishing between pseudoprogression and disease progression in patients with glioblastoma.

BackgroundThere is a need to establish biomarkers that distinguish between pseudoprogression (PsP) and true tumor progression in patients with glioblastoma (GBM) treated with chemoradiation.MethodsWe analyzed magnetic resonance spectroscopic imaging (MRSI) and dynamic susceptibility contrast (DSC) MR perfusion data in patients with GBM with PsP or disease progression after chemoradiation. MRSI metabolites of interest included intratumoral choline (Cho), myo-inositol (mI), glutamate + glutamine (Glx), lactate (Lac), and creatine on the contralateral hemisphere (c-Cr). Student T-tests and area under the ROC curve analyses were used to detect group differences in metabolic ratios and their ability to predict clinical status, respectively.Results28 subjects (63 ± 9 years, 19 men) were evaluated. Subjects with true progression (n = 20) had decreased enhancing region mI/c-Cr (P = .011), a marker for more aggressive tumors, compared to those with PsP, which predicted tumor progression (AUC: 0.84 [0.76, 0.92]). Those with true progression had elevated Lac/Glx (P = .0009), a proxy of the Warburg effect, compared to those with PsP which predicted tumor progression (AUC: 0.84 [0.75, 0.92]). Cho/c-Cr did not distinguish between PsP and true tumor progression. Despite rCBV (AUC: 0.70 [0.60, 0.80]) and rCBF (AUC: 0.75 [0.65, 0.84]) being individually predictive of tumor response, they added no additional predictive value when combined with MRSI metabolic markers.ConclusionsIncorporating enhancing lesion MRSI measures of mI/c-Cr and Lac/Glx into brain tumor imaging protocols can distinguish between PsP and true progression and inform patient management decisions.

Advanced magnetic resonance spectroscopic neuroimaging: Experts' consensus recommendations.

Magnetic resonance spectroscopic imaging (MRSI) offers considerable promise for monitoring metabolic alterations associated with disease or injury; however, to date, these methods have not had a significant impact on clinical care, and their use remains largely confined to the research community and a limited number of clinical sites. The MRSI methods currently implemented on clinical MRI instruments have remained essentially unchanged for two decades, with only incremental improvements in sequence implementation. During this time, a number of technological developments have taken place that have already greatly benefited the quality of MRSI measurements within the research community and which promise to bring advanced MRSI studies to the point where the technique becomes a true imaging modality, while making the traditional review of individual spectra a secondary requirement. Furthermore, the increasing use of biomedical MR spectroscopy studies has indicated clinical areas where advanced MRSI methods can provide valuable information for clinical care. In light of this rapidly changing technological environment and growing understanding of the value of MRSI studies for biomedical studies, this article presents a consensus from a group of experts in the field that reviews the state-of-the-art for clinical proton MRSI studies of the human brain, recommends minimal standards for further development of vendor-provided MRSI implementations, and identifies areas which need further technical development.

Variance components associated with long-echo-time MR spectroscopic imaging in human brain at 1.5T and 3T.

ObjectMagnetic resonance spectroscopic imaging (MRSI) is increasingly used in medicine and clinical research. Previous reliability studies have used small samples and focussed on limited aspects of variability; information regarding 1.5T versus 3T performance is lacking. The aim of the present work was to measure the inter-session, intra-session, inter-subject, within-brain and residual variance components using both 1.5T and 3T MR scanners.Materials and methodsEleven healthy volunteers were invited for MRSI scanning on three occasions at both 1.5T and 3T, with four scans acquired at each visit. We measured variance components, correcting for grey matter and white matter content of voxels, of metabolite peak areas and peak area ratios.ResultsResidual variance was in general the largest component at 1.5T (8.6–24.6%), while within-brain variation was the largest component at 3T (12.0–24.7%). Inter-subject variation was around 5%, while inter- and intra-session variance were both generally small.ConclusionMultiple variance contributions associated with MRSI measurements were quantified and the performance of 1.5T and 3T MRI scanners compared using data from the same group of subjects. Residual error is much lower at 3T, but other variance components remain important.

3D characterization of gas phase reactors with regularly and irregularly structured monolithic catalysts by NMR imaging and modeling

A heterogeneously catalyzed gas phase reaction process was characterized regarding temperature and concentration profiles by means of three dimensional (3D) 1H magnetic resonance spectroscopic imaging (MRSI), using the exothermal ethylene hydrogenation as an example. Here, temperature mapping was achieved by using specifically designed thermometers filled with ethylene glycol.The impact of heat and mass transfer on the process performance was investigated by using two different monolithic catalysts with completely different heat and mass transfer characteristics: a regularly structured honeycomb monolith and a irregularly structured open-cell foam packing. The influence of these characteristics on the reaction zones within the monolithic catalysts was demonstrated by simulations that were based on 2D reactor models.To evaluate the applicability of temperature and concentration mapping by 1H MRSI for model validation, a predictive two dimensional model of the process was applied. The resulting simulations of temperature profiles and concentration distributions were in very good agreement with the experimental data with deviations below 9%. Conventional mass spectroscopic measurements provided further evidence of the accuracy of 3D MRSI measurements as well as the 2D reactor model.

Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial

Milnacipran, a serotonin/norepinephrine reuptake inhibitor, has been approved by the US Food and Drug Administration for the treatment of fibromyalgia (FM). This report presents the results of a randomized, double-blind, placebo-controlled trial of milnacipran conducted to test the hypotheses that a) similar to patients with chronic fatigue syndrome, patients with FM have increased ventricular lactate levels at baseline; b) 8 weeks of treatment with milnacipran will lower ventricular lactate levels compared with baseline levels and with ventricular lactate levels after placebo; and c) treatment with milnacipran will improve attention and executive function in the Attention Network Test compared with placebo. In addition, we examined the results for potential associations between ventricular lactate and pain. Baseline ventricular lactate measured by proton magnetic resonance spectroscopic imaging was found to be higher in patients with FM than in healthy controls (F1,37 = 22.11, P < .0001, partial η2 = .37). Milnacipran reduced pain in patients with FM relative to placebo but had no effect on cognitive processing. At the end of the study, ventricular lactate levels in the milnacipran-treated group had decreased significantly compared with baseline and after placebo (F1,18 = 8.18, P = .01, partial η2 = .31). A significantly larger proportion of patients treated with milnacipran showed decreases in both ventricular lactate and pain than those treated with placebo (P = .03). These results suggest that proton magnetic resonance spectroscopic imaging measurements of lactate may serve as a potential biomarker for a therapeutic response in FM and that milnacipran may act, at least in part, by targeting the brain response to glial activation and neuroinflammation. PerspectivePatients treated with milnacipran showed decreases in both pain and ventricular lactate levels compared with those treated with placebo, but, even after treatment, levels of ventricular lactate remained higher than in controls. The hypothesized mechanism for these decreases is via drug-induced reductions of a central inflammatory state.

Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS.

To demonstrate the sensitivity of a recently developed whole-brain magnetic resonance spectroscopic imaging (MRSI) sequence to cerebral pathology and disability in amyotrophic lateral sclerosis (ALS), and compare with measures derived from diffusion tensor imaging. Whole-brain MRSI and diffusion tensor imaging were undertaken in 13 patients and 14 age-similar healthy controls. Mean N-acetylaspartate (NAA), fractional anisotropy, and mean diffusivity were extracted from the corticospinal tract, compared between groups, and then in relation to disability in the patient group. Significant reductions in NAA were found along the course of the corticospinal tracts on whole-brain MRSI. There were also significant changes in fractional anisotropy (decreased) and mean diffusivity (increased) in the patient group, but only NAA showed a significant relationship with disability (r = 0.65, p = 0.01). Whole-brain MRSI has potential as a quantifiable neuroimaging marker of disability in ALS. It offers renewed hope for a neuroimaging outcome measure with the potential for harmonization across multiple sites in the context of a therapeutic trial.

111 Magnetic Resonance Spectroscopic Imaging Measurement of Early Response to Vorinostat Treatment in Recurrent Glioblastoma

111 Magnetic Resonance Spectroscopic Imaging Measurement of Early Response to Vorinostat Treatment in Recurrent Glioblastoma

Three-dimensional magnetic resonance spectroscopic imaging in the substantia nigra of healthy controls and patients with Parkinson’s disease

To investigate the substantia nigra in patients with Parkinson's disease three-dimensional magnetic resonance spectroscopic imaging with high spatial resolution at 3 Tesla was performed. Regional variations of spectroscopic data between the rostral and caudal regions of the substantia nigra as well as the midbrain tegmentum areas were evaluated in healthy controls and patients with Parkinson's disease. Nine patients with Parkinson's disease and eight age- and gender-matched healthy controls were included in this study. Data were acquired by using three-dimensional magnetic resonance spectroscopic imaging measurements. The ratios between rostral and caudal voxels of the substantia nigra as well as the midbrain tegmentum areas were calculated for the main-metabolites N-acetyl aspartate, creatine, choline, and myo-inositol. Additionally, the metabolite/creatine ratios were calculated. In all subjects spectra of acceptable quality could be obtained with a nominal voxel size of 0.252ml. The calculated rostral-to-caudal ratios of the metabolites as well as of the metabolite/creatine ratios showed with exception of choline/creatine ratio significant differences between healthy controls and patients with Parkinson's disease. The findings from this study indicate that regional variations in N-acetyl aspartate/creatine ratios in the regions of the substantia nigra may differentiate patients with Parkinson's disease and healthy controls.

Quantitative Proton Magnetic Resonance Spectroscopy and Spectroscopic Imaging of the Brain

This article presents background information related to methodology for estimating brain metabolite concentration from magnetic resonance spectroscopy (MRS) and magnetic resonance spectroscopic imaging measurements of living human brain tissue. It reviews progress related to this methodology, with emphasis placed on progress reported during the past 10 years. It is written for a target audience composed of radiologists and magnetic resonance imaging technologists. It describes in general terms the relationship between MRS signal amplitude and concentration. It then presents an overview of the many practical problems associated with deriving concentration solely from absolute measured signal amplitudes and demonstrates how a various signal calibration approaches can be successfully used. The concept of integrated signal amplitude is presented with examples that are helpful for qualitative reading of MRS data as well as for understanding the methodology used for quantitative measurements. The problems associated with the accurate measurement of individual signal amplitudes in brain spectra having overlapping signals from other metabolites and overlapping nuisance signals from water and lipid are presented. Current approaches to obtaining accurate amplitude estimates with least-squares fitting software are summarized.

Whole-Brain Proton MR Spectroscopic Imaging of Mild-to-Moderate Traumatic Brain Injury and Correlation with Neuropsychological Deficits

Changes in the distribution of the magnetic resonance (MR)-observable brain metabolites N-acetyl aspartate (NAA), total choline (Cho), and total creatine (Cre), following mild-to-moderate closed-head traumatic brain injury (mTBI) were evaluated using volumetric proton MR spectroscopic imaging (MRSI). Studies were carried out during the subacute time period following injury, and associations of metabolite indices with neuropsychological test (NPT) results were evaluated. Twenty-nine subjects with mTBI and Glasgow Coma Scale (GCS) scores of 10-15 were included. Differences in individual metabolite and metabolite ratio distributions relative to those of age-matched control subjects were evaluated, as well as analyses by hemispheric lobes and tissue types. Primary findings included a widespread decrease of NAA and NAA/Cre, and increases of Cho and Cho/NAA, within all lobes of the TBI subject group, and with the largest differences seen in white matter. Examination of the association between all of the metabolite measures and the NPT scores found the strongest negative correlations to occur in the frontal lobe and for Cho/NAA. No significant correlations were found between any of the MRSI or NPT measures and the GCS. These results demonstrate that significant and widespread alterations of brain metabolites occur as a result of mild-to-moderate TBI, and that these measures correlate with measures of cognitive performance.

Improved Reconstruction for MR Spectroscopic Imaging

Sensitivity limitations of in vivo magnetic resonance spectroscopic imaging (MRSI) require that the extent of spatial-frequency (k-space) sampling be limited, thereby reducing spatial resolution and increasing the effects of Gibbs ringing that is associated with the use of Fourier transform reconstruction. Additional problems occur in the spectral dimension, where quantitation of individual spectral components is made more difficult by the typically low signal-to-noise ratios, variable lineshapes, and baseline distortions, particularly in areas of significant magnetic field inhomogeneity. Given the potential of in vivo MRSI measurements for a number of clinical and biomedical research applications, there is considerable interest in improving the quality of the metabolite image reconstructions. In this report, a reconstruction method is described that makes use of parametric modeling and MRI-derived tissue distribution functions to enhance the MRSI spatial reconstruction. Additional preprocessing steps are also proposed to avoid difficulties associated with image regions containing spectra of inadequate quality, which are commonly present in the in vivo MRSI data.

Image‐fusion of MR spectroscopic images for treatment planning of gliomas

1H magnetic resonance spectroscopic imaging (MRSI) can improve the accuracy of target delineation for gliomas, but it lacks the anatomic resolution needed for image fusion. This paper presents a simple protocol for fusing simulation computer tomography (CT) and MRSI images for glioma intensity-modulated radiotherapy (IMRT), including a retrospective study of 12 patients. Each patient first underwent whole-brain axial fluid-attenuated-inversion-recovery (FLAIR) MRI (3 mm slice thickness, no spacing), followed by three-dimensional (3D) MRSI measurements (TE/TR: 144/1000 ms) of a user-specified volume encompassing the extent of the tumor. The nominal voxel size of MRSI ranged from 8 x 8 x 10 mm3 to 12 x 12 x 10 mm3. A system was developed to grade the tumor using the choline-to-creatine (Cho/Cr) ratios from each MRSI voxel. The merged MRSI images were then generated by replacing the Cho/Cr value of each MRSI voxel with intensities according to the Cho/Cr grades, and resampling the poorer-resolution Cho/Cr map into the higher-resolution FLAIR image space. The FUNCTOOL processing software was also used to create the screen-dumped MRSI images in which these data were overlaid with each FLAIR MRI image. The screen-dumped MRSI images were manually translated and fused with the FLAIR MRI images. Since the merged MRSI images were intrinsically fused with the FLAIR MRI images, they were also registered with the screen-dumped MRSI images. The position of the MRSI volume on the merged MRSI images was compared with that of the screen-dumped MRSI images and was shifted until agreement was within a predetermined tolerance. Three clinical target volumes (CTVs) were then contoured on the FLAIR MRI images corresponding to the Cho/Cr grades. Finally, the FLAIR MRI images were fused with the simulation CT images using a mutual-information algorithm, yielding an IMRT plan that simultaneously delivers three different dose levels to the three CTVs. The image-fusion protocol was tested on 12 (six high-grade and six low-grade) glioma patients. The average agreement of the MRSI volume position on the screen-dumped MRSI images and the merged MRSI images was 0.29 mm with a standard deviation of 0.07 mm. Of all the voxels with Cho/Cr grade one or above, the distribution of Cho/Cr grade was found to correlate with the glioma grade from pathologic finding and is consistent with literature results indicating Cho/Cr elevation as a marker for malignancy. In conclusion, an image-fusion protocol was developed that successfully incorporates MRSI information into the IMRT treatment plan for glioma.

Comparison of Magnetic Resonance Spectroscopy and Perfusion-weighted Imaging in Presurgical Grading of Oligodendroglial Tumors

Oligodendroglial tumors form an uncommon, but distinct, subgroup of gliomas with longer survival, better treatment response, and characteristic genetic alterations. Noninvasive grading of oligodendroglial tumors using functional and metabolic magnetic resonance imaging may be helpful in guiding the treatment approach and predicting malignant transformation of these tumors. We used perfusion-weighted magnetic resonance imaging and proton magnetic resonance spectroscopic imaging (MRSI) to predict the oligodendroglioma grade. Twenty-four patients with pathologically confirmed oligodendrogliomas underwent dynamic contrast-enhanced perfusion-weighted magnetic resonance imaging and/or proton MRSI before surgery. We assessed the ability of tumor contrast enhancement, normalized cerebral blood volume, normalized choline, and the presence of either lactate or lipid metabolites to correctly predict the World Health Organization tumor grade. The accuracy of tumor grading using each method was also compared. Tumor contrast enhancement (P = 0.069) and normalized cerebral blood volume (P = 0.181) were not significantly different between low and high-grade oligodendrogliomas. The MRSI measurement of normalized choline was significantly higher in high-grade (2.82 +/- 0.64) than in low-grade (1.62 +/- 0.46) oligodendrogliomas (P < 0.001), and the presence of lactate or lipid metabolites also correctly predicted high-grade tumors (P = 0.014). The maximum accuracy of contrast enhancement, normalized cerebral blood volume, normalized choline, and lactate or lipid metabolites in grading oligodendroglioma was 71, 83, 90, and 85%, respectively. MRSI measurements are more accurate than perfusion-weighted magnetic resonance imaging or conventional contrast enhancement in differentiating oligodendroglial tumor grade. In these inherently vascular tumors, metabolic measurements of mitosis and necrosis may be better than measures of neovascularity in presurgical grading.

Longitudinal multivoxel MR spectroscopy study of pediatric diffuse pontine gliomas treated by radiotherapy

Longitudinal multivoxel MR spectroscopy study of pediatric diffuse pontine gliomas treated by radiotherapy

Simplified methods for calculating cerebral metabolic rate of oxygen based on 17O magnetic resonance spectroscopic imaging measurement during a short 17O2 inhalation.

It has recently been shown that 17O magnetic resonance (MR) spectroscopic imaging at ultrahigh fields provides a reliable method for measuring CMRO2 during a short period of 17O2 gas inhalation. The mathematical (or complete) model used in the 17O MR method for calculating CMRO2 requires simultaneous measurements of multiple parameters including the concentration of H2 17O produced in the brain tissue from inhaled 17O2 gas (Cb), CBF, and the input function for the H2 17O concentration in the feeding artery (Ca). Both invasive and noninvasive measurements are involved in determining all of these parameters. In this article, two simplified methods are proposed and validated for calculating CMRO2 based on 17O MR measurement(s); the first method requires the measurements of Cb and CBF, but not Ca, and the second method only requires a single noninvasive measurement of Cb. The simplified methods were used to calculate CMRO2 in anesthetized rat brain, and the results were compared with those obtained using the complete model. The results from this work show (1) the validity of the simplified methods for quantifying CMRO2, and (2) the feasibility for establishing a completely noninvasive 17O MR approach for imaging CMRO2 in vivo.

Proton magnetic resonance spectroscopic imaging of human breast cancer: a preliminary study.

To investigate the diagnostic value of proton magnetic resonance spectroscopic imaging (MRSI) in patients with breast lesions. Eighteen patients underwent breast MRSI and MRI at 1.5 T. Contrast-enhanced MR was used to identify the lesion, after which single-slice MRSI (TR/TE = 2000/272 msec, 10-mm slice thickness) was performed. Water, lipid, and choline (Cho) images were reconstructed from MRSI data. The area of the Cho was measured in the lesion and expressed relative to the background noise level (signal-to-noise ratio (SNR)), measured between 7.0 and 9.0 ppm. Cho SNRs were compared between benign and malignant lesions as determined by histopathology. Three cases were considered technical failures on MRSI. Of the remaining 15 cases, on histopathology, eight were classified as malignant carcinoma and seven were benign. The Cho SNR from malignant tissue was significantly elevated compared to benign tissue (6.2 +/- 2.1 vs. 2.4 +/- 0.7, P < 0.0008). MRSI measurements of Cho are feasible in the human breast, and the SNR for Cho was significantly different between benign and malignant lesions. The potential advantages of MRSI over SV spectroscopy include the ability to assess multiple lesions as well as tissue with normal MRI appearance, as well as to perhaps gauge lesion borders and infiltration into surrounding tissue.

A magnetic resonance spectroscopic imaging study of adult nonhuman primates exposed to early-life stressors

Background Long-term behavioral, immunologic, and neurochemical alterations have been found in primates exposed to adverse early rearing. Methods Bonnet macaque ( Macaca radiata) mother–infant dyads were exposed to uncertain requirements for food procurement (variable foraging demand, VFD) for a few months. Ten years later, these offspring and age- and gender-matched control subjects were studied using proton magnetic resonance spectroscopic imaging (MRSI). Results In anterior cingulate, VFD-reared subjects displayed significantly decreased N-acetylaspartate (NAA) resonance and significantly increased glutamate–glutamine–γ-aminobutyric acid (Glx) resonance relative to the stable neurometabolite creatine (Cr). Across all subjects, NAA/Cr and Glx/Cr ratios in the anterior cingulate were negatively correlated ( r = −.638, p = .014). In the medial temporal lobe, the ratio of choline-containing compounds to Cr was significantly increased in VFD subjects. Conclusions These findings indicate that adverse early rearing in primates has an enduring impact on adult MRSI measures considered reflective of neuronal integrity and metabolism, membrane structure and glial function, and cerebral glutamate content, and that these alterations occur in the same brain regions implicated in trauma-related psychiatric disorders.

Choline, myo‐inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex

Alterations in choline and myo-inositol metabolism have been noted in bipolar disorder, and the therapeutic efficacy of lithium in mania may be related to these effects. We wished to determine the relationship between anterior cingulate cortex choline and myo-inositol levels, assessed using proton magnetic resonance spectroscopic imaging (MRSI), and mood state in subjects with bipolar disorder. Serial assessments of anterior cingulate cortex choline and myo-inositol metabolism were performed in nine subjects with bipolar disorder, taking either lithium or valproate, and 14 controls. Each bipolar subject was examined between one and four times (3.1 +/- 1.3). On the occasion of each examination, standardized ratings of both depression and mania were recorded. In the left cingulate cortex, the bipolar subjects' depression ratings correlated positively with MRSI measures of Cho/Cr-PCr. In the right cingulate cortex, the Cho/Cr-PCr ratio was significantly higher in subjects with bipolar disorder compared with control subjects. In addition, bipolar subjects not taking antidepressants had a significantly higher right cingulate cortex Cho/Cr-PCr ratio compared with patients taking antidepressants or controls. No clinical or drug-related changes were observed for the Ino/Cr-PCr ratio. The results of this study suggest that bipolar disorder is associated with alterations in the metabolism of cytosolic, choline-containing compounds in the anterior cingulate cortex. As this resonance arises primarily from phosphocholine and glycerophosphocholine, both of which are metabolites of phosphatidylcholine, these results are consistent with impaired intraneuronal signaling mechanisms.

Magnetic resonance spectroscopy of N‐acetylaspartate in hypoxic–ischemic encephalopathy

Magnetic resonance imaging and water-suppressed proton magnetic resonance spectroscopic imaging were used to study N-acetylaspartate and other metabolites in a patient with severe hypoxic-ischemic encephalopathy. The N-acetylaspartate signal, a putative marker of neuronal density, was markedly reduced in the forebrain. The relative signal intensity of choline-containing metabolites, which are more abundant in astrocytes than neurons, was increased. These results support the hypothesis that water-suppressed proton magnetic resonance spectroscopic imaging measurements of N-acetylaspartate may be useful for noninvasive detection of selective neuronal loss in a variety of disease states in the human brain.