Magnetic Resonance Spectroscopic Imaging Data Research Articles

Novel methodology for the archiving and interactive reading of clinical magnetic resonance spectroscopic imaging.

Archiving clinical magnetic resonance spectroscopic imaging (MRSI) data and presenting the data to specialists (e.g., neuroradiologists, neurosurgeons, neurologists, neuro-oncologists, and MR scientists) who work in different physical locations is a practical problem of significance. This communication describes a novel solution. The study hypothesis was that it is possible to use widely available distributed computing techniques to create a clinical MRSI user interface addressable from any personal computer with a suitable network connection. A worldwide web MRSI archive and interface system was created that permits the user to interactively view individual MRSI voxel spectra with correlation to MR images and to parametric spectroscopic images. Web browser software (i.e., Netscape and Internet Explorer) permits users in various physical locations to access centrally archived MRSI data using a variety of operating systems and client workstations. The system was used for archiving and displaying more than 1000 clinical MRSI studies performed at the authors' institution. The system also permits MRSI data to be viewed via the Internet from distant locations worldwide. The study illustrates that widely available software operating within highly distributed electronic networks can be used for archiving and interactive reading of large amounts of clinical MRSI data.

Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem.

Quantitative, multislice proton MR spectroscopic imaging (MRSI) was used to investigate regional metabolite levels and ratios in the normal adult human posterior fossa. Six normal volunteers (36 +/- 3 years, five male, one female) were scanned on a 1.5 T scanner using multislice MRSI at long echo time (TE 280 msec). The entire cerebellum was covered using three oblique-axial slice locations, which also included the pons, mid-brain, insular cortex, and parieto-occipital lobe. Concentrations of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were estimated using the phantom replacement technique. Regional variations of the concentrations were assessed using ANOVA (P < 0.05). High-resolution MRSI data was obtained in all subjects and brain regions examined. Metabolite concentrations (mM) (mean +/- SD) were as follows: cerebellar vermis: 2.3 +/- 0.4, 8.8 +/- 1.7 and 7.6 +/- 1.0 for Cho, Cr, and NAA respectively; cerebellar hemisphere: 2.2 +/- 0.6, 8.9 +/- 2.1, 7.5 +/- 0.8; pons 2.2 +/- 0.5, 4.3 +/- 1.1, 8.3 +/- 0.9; insular cortex, 1.8 +/- 0.5, 7.8 +/- 2, 8.0 +/- 1.1, parieto-occipital gray matter, 1.3 +/- 0.3, 5.7 +/- 1.1, 7.2 +/- 0.9, and occipital white matter, 1.4 +/- 0.3, 5.3 +/- 1.3, 7.5 +/- 0.8. Consistent with previous reports, significantly higher levels of Cr were found in the cerebellum compared to parieto-occipital gray and occipital white matter, and pons (P < 0.0001). NAA was essentially uniformly distributed within the regions chosen for analysis, with the highest level in the pons (P < 0.04). Cho was significantly higher in the cerebellum and pons than parieto-occipital gray and occipital white matter (P < 0.002) and was also higher in the pons than in the insular cortex (P < 0.05). Quantitative multislice MRSI of the posterior fossa is feasible and significant regional differences in metabolite concentrations were found.

Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem

Quantitative, multislice proton MR spectroscopic imaging (MRSI) was used to investigate regional metabolite levels and ratios in the normal adult human posterior fossa. Six normal volunteers (36 ± 3 years, five male, one female) were scanned on a 1.5 T scanner using multislice MRSI at long echo time (TE 280 msec). The entire cerebellum was covered using three oblique-axial slice locations, which also included the pons, mid-brain, insular cortex, and parieto-occipital lobe. Concentrations of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were estimated using the phantom replacement technique. Regional variations of the concentrations were assessed using ANOVA (P < 0.05). High-resolution MRSI data was obtained in all subjects and brain regions examined. Metabolite concentrations (mM) (mean ± SD) were as follows: cerebellar vermis: 2.3 ± 0.4, 8.8 ± 1.7 and 7.6 ± 1.0 for Cho, Cr, and NAA respectively; cerebellar hemisphere: 2.2 ± 0.6, 8.9 ± 2.1, 7.5 ± 0.8; pons 2.2 ± 0.5, 4.3 ± 1.1, 8.3 ± 0.9; insular cortex, 1.8 ± 0.5, 7.8 ± 2, 8.0 ± 1.1, parieto-occipital gray matter, 1.3 ± 0.3, 5.7 ± 1.1, 7.2 ± 0.9, and occipital white matter, 1.4 ± 0.3, 5.3 ± 1.3, 7.5 ± 0.8. Consistent with previous reports, significantly higher levels of Cr were found in the cerebellum compared to parieto-occipital gray and occipital white matter, and pons (P < 0.0001). NAA was essentially uniformly distributed within the regions chosen for analysis, with the highest level in the pons (P < 0.04). Cho was significantly higher in the cerebellum and pons than parieto-occipital gray and occipital white matter (P < 0.002) and was also higher in the pons than in the insular cortex (P < 0.05). Quantitative multislice MRSI of the posterior fossa is feasible and significant regional differences in metabolite concentrations were found. Magn Reson Med 46:699–705, 2001. © 2001 Wiley-Liss, Inc.

In Vivo Short Echo Time 1H-Magnetic Resonance Spectroscopic Imaging (MRSI) of the Temporal Lobes

Two different methodologies for obtaining PRESS-localized magnetic resonance spectroscopic imaging (MRSI) data from the mesial and lateral temporal lobes were investigated. The study used short echo times (30 ms) and long repetition times (3000 ms) to minimize relaxation effects. Inhomogeneity and spectral distortions from the proximity of the temporal bones precluded the attainment of consistently good-quality data from both temporal lobes at once. Even when the right and left temporal lobes were studied separately, distortions often disturbed spectra from the anterior lateral temporal lobe. Quantitative analysis using LCModel was therefore performed only on the posterior lateral temporal lobe, and the posterior, middle, and anterior mesial temporal lobe. No significant left-right differences in metabolite content were found in a series of 10 controls. Significantly higher concentrations of myoinositol and choline were found in the anterior mesial temporal lobe, even when grey matter content was included as a covariate. The concentration of N-acetyl aspartate plus N-acetyl aspartyl glutamate (NAc) was not found to vary significantly along the length of the hippocampus. The previously observed lower anterior ratios of NAA to creatine plus choline (NAA/(Cr + Cho) may instead have been due to higher anterior choline. Large differences in metabolite concentrations were seen between posterior lateral temporal lobe (predominantly subcortical white matter) and the posterior mesial temporal lobe, most notably lower creatine, glutamate/glutamine, and myo-inositol, and higher NAA/(Cr + Cho) in the lateral than mesial temporal lobe. This pattern was similar to that previously seen for grey/white matter differences in the frontal, parietal and occipital regions.

Analysis of volume MRI and MR spectroscopic imaging data for the evaluation of patients with brain tumors.

The combination of volumetric MRI and multivoxel localized MR spectroscopic imaging (MRSI) data provides the potential for quantifying variations in tissue morphology and function. These techniques have numerous applications for the evaluation of neurological diseases. While state-of-the-art whole-body MR scanners are able to acquire both types of data, there have been relatively few reports which have presented clinical applications of the technology. One of the reasons for this has been the need to develop software for reconstruction and reliable interpretation of 3D imaging and spectral data. In this article, we describe the strategy developed for quantitative analysis of combined MRI and MRSI examinations from patients with brain tumors and evaluate the key components of this procedure using both simulations and empirical data from phantoms, normal volunteers, and patients. Important factors are the use of volume or interleaved multislice anatomic images as a reference, the reconstruction and correction of the spectral data for frequency, phase, and baseline distortions and consideration of the characteristics of the coil, RF pulses used for spatial selection, and phase encoding procedures. These studies show that the metabolic parameters most critical for distinguishing tumor from normal and necrotic tissue were relative levels of choline and NAA. Levels of creatine and lactate were found to be variable, both in terms of their spatial distribution within individual lesions and between different patients.

Reanalysis of multislice (1)H MRSI in amyotrophic lateral sclerosis.

The goal of this work was to reexamine previously published (1) brain spectroscopy data of abnormal metabolite ratios in amyotrophic lateral sclerosis (ALS). Toward this goal, (1)H MR spectroscopic imaging data from 10 ALS and nine control subjects were reanalyzed using improved data analysis techniques, including automated curve fitting and tissue-volume correction. In the motor cortex of ALS, N-acetyl aspartate (NAA) was 23% (P = 0.004) lower than in controls, and in the posterior internal capsule of ALS choline compounds (Cho) were 20% (P = 0.02) higher. This demonstrates that the metabolite ratio changes in ALS were due to NAA loss in the motor cortex (as expected) and Cho increase in the posterior internal capsule (not expected). Magn Reson Med 45:513-516, 2001.

Short TE in vivo 1H MR spectroscopic imaging at 1.5 T: acquisition and automated spectral analysis

Spectral analysis of short TE in vivo proton magnetic resonance spectroscopic imaging (MRSI) data are complicated by the presence of spectral overlap, low signal to noise and uncharacterized signal contributions. In this study, it is shown that an automated data analysis method can be used to generate metabolite images from MRSI data obtained from human brain at TE = 25 ms and 1.5 T when optimized pulse sequences and a priori metabolite knowledge are used. The analysis approach made use of computer simulation methods to obtain a priori spectral information of the metabolites of interest and utilized a combination of parametric spectral modeling and non-parametric signal characterization for baseline fitting. This approach was applied to data from optimized PRESS-SI and multi-slice spin-echo SI acquisitions, for which sample spectra and metabolite images are shown.

Implications of respiratory motion for the quantification of2D MR spectroscopic imaging data in the abdomen

Magnetic resonance spectroscopic imaging (MRSI) studies in the abdomenor breast are acquired in the presence of respiratory motion. Thismodifies the point spread function (PSF) and hence the reconstructedspectra. We evaluated the quantitative effects of both periodic andaperiodic motion on spectra localized by MRSI. Artefactual signalchanges, both the modification of native to a voxel and spurioussignals arising elsewhere, depend primarily upon the motion amplituderelative to the voxel dimension. A similar dependence on motionamplitude was observed for simple harmonic motion (SHM), quasi-periodicmotion and random displacements. No systematic dependence upon theperiod or initial phase of SHM or on the array size was found.There was also no significant variation with motion direction relativeto the internal and external phase-encoding directions. In measuredexcursion ranges of 20 breast and abdominal tumours, 70% moved ⩽ 5 mm, while 30% moved 6-23 mm. The diaphragm and fatty tissuesin the gut typically moved ~ 15-20 mm. While tumour/organexcursions less than half the voxel dimension do not substantiallyaffect native signals, the bleeding in of strong lipid signals will beproblematic in 1H studies. MRSI studies in the abdomen, even ofrelatively well-anchored tumours, are thus likely to benefit from theaddition of respiratory triggering or other motion compensationstrategies.

Lateralization of temporal lobe epilepsy (TLE) and discrimination of TLE from extra-TLE using pattern analysis of magnetic resonance spectroscopic and volumetric data.

To examine whether or not pattern analysis of magnetic resonance volumetric (MRVol) and proton magnetic resonance spectroscopic imaging (1H-MRSI) data would enable (a) the accurate lateralization of temporal lobe epilepsy (TLE) and (b) the discrimination of TLE from extratemporal epilepsy (E-TLE). For lateralization analysis, we used data from 150 nonforeign tissue lesional TLE patients [88 left-sided (L-TLE), 46 right-sided (R-TLE), and 16 bilateral (Bi-TLE)]. For the discrimination of TLE from E-TLE, we used data from 174 patients (145 with unilateral TLE, 14 with unilateral E-TLE, and 15 with widespread epileptogenic zones involving both the TL and extra-TL regions-multilobar epilepsy). A series of "leave-one-out" cross-validated linear discriminant analyses were performed using the MRVol and 1H-MRSI data sets to lateralize TLE and discriminate it from E-TLE. Lateralization: The leave-one-out linear discriminant analyses were able to correctly lateralize (with a posterior probability >0.50) 120 (90%) of the 134 L-TLE and R-TLE patients. Imposing higher posterior probability (>0.95) increased accuracy of lateralization to 98%, with only two discordant cases who underwent surgery on the side of electroencephalogram, and both had bad outcome. Discrimination: the leave-one-out linear discriminant analyses were able to correctly classify (with a posterior probability >0.50) 142 (89%) of the 159 TLE and E-TLE patients. Accuracy increased slightly as higher posterior probability cutoffs were imposed, with fewer patients being classified. Pattern analysis of 1H-MRSI and MRVol data can accurately lateralize TLE. Discriminating TLE from E-TLE was less accurate, probably due to the presence of temporal lobe damage in some patients with E-TLE reflecting dual pathology.

Treatment planning for prostate implants using magnetic-resonance spectroscopy imaging

Purpose: Recent studies have demonstrated that magnetic-resonance spectroscopic imaging (MRSI) of the prostate may effectively distinguish between regions of cancer and normal prostatic epithelium. This diagnostic imaging tool takes advantage of the increased choline plus creatine versus citrate ratio found in malignant compared to normal prostate tissue. The purpose of this study is to describe a novel brachytherapy treatment-planning optimization module using an integer programming technique that will utilize biologic-based optimization. A method is described that registers MRSI to intraoperative-obtained ultrasound images and incorporates this information into a treatment-planning system to achieve dose escalation to intraprostatic tumor deposits. Methods: MRSI was obtained for a patient with Gleason 7 clinically localized prostate cancer. The ratios of choline plus creatine to citrate for the prostate were analyzed, and regions of high risk for malignant cells were identified. The ratios representing peaks on the MR spectrum were calculated on a spatial grid covering the prostate tissue. A procedure for mapping points of interest from the MRSI to the ultrasound images is described. An integer-programming technique is described as an optimization module to determine optimal seed distribution for permanent interstitial implantation. MRSI data are incorporated into the treatment-planning system to test the feasibility of dose escalation to positive voxels with relative sparing of surrounding normal tissues. The resultant tumor control probability (TCP) is estimated and compared to TCP for standard brachytherapy-planned implantation. Results: The proposed brachytherapy treatment-planning system is able to achieve a minimum dose of 120% of the 144 Gy prescription to the MRS positive voxels using 125I seeds. The preset dose bounds of 100–150% to the prostate and 100–120% to the urethra were maintained. When compared to a standard plan without MRS-guided optimization, the estimated TCP for the MRS-optimized plan is superior. The enhanced TCP was more pronounced for smaller volumes of intraprostatic tumor deposits compared to estimated TCP values for larger lesions. Conclusions: Using this brachytherapy-optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for 125I permanent prostate implants. Based on probability estimates of anticipated improved TCP, this approach may have an impact on the ability to safely escalate dose and potentially improve outcome for patients with organ-confined but aggressive prostatic cancers. The magnitude of the TCP enhancement, and therefore the risks of ignoring the MR data, appear to be more substantial when the tumor is well localized; however, the gain achievable in TCP may depend quite considerably on the MRS tumor-detection efficiency.

A multiscale approach for analyzing in vivo spectroscopic imaging data.

A multiscale approach for analyzing in vivo magnetic resonance spectroscopic imaging (SI) data is described in this paper. With this method, fitting is performed at multiple spatial scales in a coarse-to-fine order. Results obtained at one scale are used as prior knowledge in fitting spectra at the next scale. The multiscale approach was validated with simulated data and demonstrated with proton SI datasets of the human brains. The results showed that this method improved the robustness and efficiency of the fitting and facilitated the automatic analysis of in vivo SI data.

Automated spectral analysis III: application to in vivo proton MR spectroscopy and spectroscopic imaging.

An automated method for analysis of in vivo proton magnetic resonance (MR) spectra and reconstruction of metabolite distributions from MR spectroscopic imaging (MRSI) data is described. A parametric spectral model using acquisition specific, a priori information is combined with a wavelet-based, nonparametric characterization of baseline signals. For image reconstruction, the initial fit estimates were additionally modified according to a priori spatial constraints. The automated fitting procedure was applied to four different examples of MRS data obtained at 1.5 T and 4.1 T. For analysis of major metabolites at medium TE values, the method was shown to perform reliably even in the presence of large baseline signals and relatively poor signal-to-noise ratios typical of in vivo proton MRSI. Identification of additional metabolites was also demonstrated for short TE data. Automated formation of metabolite images will greatly facilitate and expand the clinical applications of MR spectroscopic imaging.

Using pattern analysis of in vivo proton MRSI data to improve the diagnosis and surgical management of patients with brain tumors.

We have used pattern analysis of proton magnetic resonance spectroscopic imaging (1H MRSI) data in a variety of situations related to the clinical management of patients with brain tumors and other cerebral space-occupying lesions (SOLs). Here, we review how 'leave-one-out' linear discriminant analyses (LDAs) of in vivo 1H MRSI spectral patterns have enabled us to quickly, accurately, and non-invasively: (1) discriminate amongst tissue arising from the five most common types of supratentorial tumors found in adults, and (2) use the metabolic heterogeneity of cerebral SOLs to predict certain pathological characteristics that are useful in guiding stereotaxic biopsy and selective tumor resection. These findings suggest that pattern analysis of 1H MRSI data can significantly improve the diagnostic specificity and surgical management of patients with certain cerebral SOLs.

Proton magnetic resonance spectroscopic imaging in patients with extratemporal epilepsy.

Reduced levels of N-acetylaspartate (NAA) in temporal lobes responsible for temporal lobe epilepsy have been observed consistently in proton magnetic resonance spectroscopy (MRS) studies. We investigated the potential of proton MRS to detect low NAA outside of the temporal lobes in patients with non-lesional partial extratemporal epilepsy. Proton MR spectroscopic imaging (MRSI) data of both frontal lobes and central/postcentral regions were obtained in 20 such patients and 16 normal control subjects. The epileptogenic region was determined by an extensive clinical-EEG investigation, including the recording of habitual seizures in each patient, and intracranial EEG recordings in 10 patients. The relative NAA resonance intensities (i.e., NAA/phosphocreatine plus creatine (CR(t)), NAA/choline-containing metabolites (Cho(t)) and NAA/Cr(t) + Cho(t)), were all significantly reduced throughout the spectroscopic image as compared with that of the controls. Furthermore, reduction of the NAA ratios was greater in the epileptogenic region as compared with the nonepileptogenic regions, on EEG investigation. In vivo proton MRSI of patients with nonlesional partial extratemporal epilepsy detected evidence of widespread neuronal damage or dysfunction that was greatest in the region of seizure focus.

Imaging axonal damage of normal-appearing white matter in multiple sclerosis.

The current study was designed to determine the relative distribution of decreases of N-acetylasparate (NAA), a marker of axonal damage, between lesions and normal-appearing white matter of patients with established multiple sclerosis and to test for associations between changes in the ratio of NAA to creatine/phosphocreatine (NAA:Cr) in those compartments and changes in disability. Data were collected from a 30-month longitudinal study of 28 patients with either a relapsing course with partial remissons and no progression between attacks (relapsing/remitting) (11 patients) or a course of progressively increasing disability, following a period of relapsing/remitting disease (secondary progressive) (17 patients). Proton magnetic resonance spectroscopic imaging (MRSI) and conventional MRI examinations were performed at 6-8-month intervals with concurrent clinical assessments of disability. General linear models were used to test associations between MRSI, MRI, lesion volume and clinical data. Analysis confirmed that the NAA:Cr ratio is lower in lesions than in the normal-appearing white matter (-15.3% in relapsing/remitting multiple sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower NAA:Cr ratio per unit lesion volume previously observed for secondary progressive relative to relapsing/remitting patients was found to result from a lower ratio (8.2%, P < 0.01) in the normal-appearing white matter rather than from any differences within lesions. The importance of changes in the normal-appearing white matter was emphasized further with the observation that the NAA:Cr ratio in the normal-appearing white matter accounted for most of the observed 15.6% (P < 0.001) decrease in the NAA:Cr ratio in the brains of relapsing/remitting patients over the period of study. The decrease in the NAA:Cr ratio in normal-appearing white matter correlated strongly (P < 0.001) with changes in disability in the relapsing/remitting subgroup. These results add to data suggesting that axonal damage or loss may be responsible for functional impairments in multiple sclerosis. The accumulation of secondary axonal damage in the normal-appearing white matter may be of particular significance for understanding chronic disability in this disease.

High spatial resolution and speed in MRSI.

The in vivo applications of magnetic resonance spectroscopic imaging (MRSI) have expanded significantly over the past 10 years and have reached the point where clinical trials are underway for a number of different diseases. One of the limiting factors in the widespread use of this technology has been the lack of widely available tools for obtaining data which are localized to sufficiently small tissue volumes to make an impact upon diagnosis and treatment planning. This is especially difficult within the timeframe of a clinical MR examination, which requires that both anatomic and metabolic data are acquired and processed. Recent advances in the hardware and software associated with clinical scanners have provided the potential for improvements in the spatial and time resolution of imaging and spectral data. The two areas which hold the most promise in terms of MRSI data are the use of phased array coils and the implementation of echo planar k-space sampling techniques. These could have immediate impact for 1H MRSI and may prove valuable for future applications of 31P MRSI.

Alzheimer disease and subcortical ischemic vascular dementia: evaluation by combining MR imaging segmentation and H-1 MR spectroscopic imaging.

To determine the association between H-1 magnetic resonance (MR) spectroscopic imaging and MR imaging differences in subjects with Alzheimer disease (AD) or subcortical ischemic vascular dementia (SIVD) versus control subjects and if both studies combined enable discrimination of AD from control subjects better than either study alone. Measures were obtained in nine AD, eight SIVD, and 11 control subjects with MR imaging segmentation software. Statistically significantly lower N-acetylaspartate/choline-containing metabolites (Cho) and higher Cho/creatine-containing metabolites in posterior mesial gray matter in AD versus control subjects were independent of MR imagining differences. Combined measures allowed correct classification of AD and control subjects, but none of the MR measures allowed accurate discrimination between AD and SIVD subjects. Between-group differences in tissue-type contributions to H-1 MR spectroscopic imaging voxels must be accounted for when reporting H-1 MR spectroscopic imaging data in AD, SIVD, and control subjects. Combined studies allowed more accurate discrimination between AD and control subjects than either study alone.

In vivo detection of myelin phospholipids in multiple sclerosis with phosphorus magnetic resonance spectroscopic imaging.

The goal of this study was to investigate myelin phospholipids in vivo in multiple sclerosis lesions and normal-appearing white matter by evaluating the spectral broad component from phosphorus 31 magnetic resonance spectroscopic imaging data. The phospholipid broad component was reduced nearly 35% (p < 0.001) in both lesions and in normal-appearing white matter in multiple sclerosis subjects compared to control subjects, suggesting reduced myelin phospholipid concentration or altered relaxation times.

Spectroscopic imaging display and analysis

A system for display of magnetic resonance (MR) spectroscopic imaging (SI) data is described which provides for efficient review and analysis of the multidimensional spectroscopic and spatial data format of this technique. Features include the rapid display of spectra from selected image voxels, formation of spectroscopic images, spectral and image data processing operations, methods for correlating spectroscopic image data with high resolution 1H MR images, and hardcopy facilities. Examples are shown for 31P and 1H spectroscopic imaging studies obtained in human and rat brain.