Magnetic Resonance Spectroscopic Imaging Technique Research Articles

0089 Feasibility of Rapid Measurement of Brain Metabolites in Obstructive Sleep Apnea

Abstract Introduction Obstructive Sleep Apnea (OSA) affects over 15% of the adult population and is associated with brain dysfunction. Although the dysfunction is well-identified and presents brain morphological changes as shown with structural imaging, it is unclear what pathology underlies these neural alterations. Magnetic resonance spectroscopic imaging (MRSI) can non-invasively measure several metabolites from multiple brain regions in vivo. However, the clinical practicality of the standard MRSI techniques (Cartesian phase-encoding or echo-planar [EP]) is hindered by long scan times. In order to assess clinical populations, our group developed an alternative MRSI technique, “radial” EP-MRSI. To assess the feasibility and calculate effect sizes we did a pilot study of brain metabolites in OSA using radial EP-MRSI. Methods Radial EP-MRSI data with a speed-up (undersampling) factor of 2.5 (compared to a fully-sampled Cartesian MRSI scan) were acquired in 5 OSA patients (3 males, 37±11 yrs., Apnea Hypopnea Index (AHI): 8.2±5.5) and 10 healthy controls (5 males, 28±7 yrs.). Spectra from twelve brain regions were selected from each subject and five metabolites–total choline, myo-inositol (mI), total N-acetylaspartate, glutamine+glutamate (Glx) and lactate (Lac)–were quantified as ratios with respect to creatine (Cr), using “LC Model” software. The brain regions include left/right of: basal ganglia, insula, and gray/white of the frontal and occipital regions. Mean group differences were calculated and compared with independent samples t-tests. Results Glx/Cr was significantly decreased (27%; p<0.05) in OSA vs. control in the left posterior insula. Other metabolites did not show significant differences. mI/Cr trends were consistent with previous findings (higher in OSA) and Lac/Cr trended higher OSA. Conclusion This feasibility study showed that it is possible to measure multiple metabolites in multiple regions and detect effects of OSA. The accelerated technique enabled measurements to be completed in under 4 minutes. Support (If Any)

Fast data acquisition techniques in magnetic resonance spectroscopic imaging.

Magnetic resonance spectroscopic imaging (MRSI) is an important technique for assessing the spatial variation of metabolites in vivo. The long scan times in MRSI limit clinical applicability due to patient discomfort, increased costs, motion artifacts, and limited protocol flexibility. Faster acquisition strategies can address these limitations and could potentially facilitate increased adoption of MRSI into routine clinical protocols with minimal addition to the current anatomical and functional acquisition protocols in terms of imaging time. Not surprisingly, a lot of effort has been devoted to the development of faster MRSI techniques that aim to capture the same underlying metabolic information (relative metabolite peak areas and spatial distribution) as obtained by conventional MRSI, in greatly reduced time. The gain in imaging time results, in some cases, in a loss of signal-to-noise ratio and/or in spatial and spectral blurring. This review examines the current techniques and advances in fast MRSI in two and three spatial dimensions and their applications. This review categorizes the acceleration techniques according to their strategy for acquisition of the k-space. Techniques such as fast/turbo-spin echo MRSI, echo-planar spectroscopic imaging, and non-Cartesian MRSI effectively cover the full k-space in a more efficient manner per TR . On the other hand, techniques such as parallel imaging and compressed sensing acquire fewer k-space points and employ advanced reconstruction algorithms to recreate the spatial-spectral information, which maintains statistical fidelity in test conditions (ie no statistically significant differences on voxel-wise comparisions) with the fully sampled data. The advantages and limitations of each state-of-the-art technique are reviewed in detail, concluding with a note on future directions and challenges in the field of fast spectroscopic imaging.

Gamma-aminobutyric acid edited echo-planar spectroscopic imaging (EPSI) with MEGA-sLASER at 7T.

PurposeFor rapid spatial mapping of gamma‐aminobutyric acid (GABA) at the increased sensitivity and spectral separation for ultra‐high magnetic field strength (7 tesla [T]), an accelerated edited magnetic resonance spectroscopic imaging technique was developed and optimized for the human brain at 7 T.MethodsA MEGA‐sLASER sequence was used for GABA editing and volume selection to maximize editing efficiency and minimize chemical shift displacement errors. To accommodate the high bandwidth requirements at 7 T, a single‐shot echo planar readout was used for rapid simultaneous encoding of the temporal dimension and 1 spatial. B 0 and B 1 field aspects specific for 7 T were studied together with correction procedures, and feasibility of the EPSI MEGA‐sLASER technique was tested in vivo in 5 healthy subjects.ResultsLocalized edited spectra could be measured in all subjects giving spatial GABA signal distributions over a central brain region, having 45‐ to 50‐Hz spatial intervoxel B 0 field variations and up to 30% B 1 field deviations. MEGA editing was found unaffected by the B 0 inhomogeneities for the optimized sequence. The correction procedures reduced effects of intervoxel B0 inhomogeneities, corrected for spatial editing efficiency variations, and compensated for GABA resonance phase and frequency shifts from subtle motion and acquisition instabilities. The optimized oscillating echo‐planar gradient scheme permitted full spectral acquisition at 7 T and exhibited minimal spectral‐spatial ghosting effects for the selected brain region.ConclusionThe EPSI MEGA‐sLASER technique was shown to provide time‐efficient mapping of regional variations in cerebral GABA in a central volume of interest with spatial B 1 and B 0 field variations typical for 7 T.

Density-weighted concentric rings k-space trajectory for 1 H magnetic resonance spectroscopic imaging at 7T.

It has been shown that density‐weighted (DW) k‐space sampling with spiral and conventional phase encoding trajectories reduces spatial side lobes in magnetic resonance spectroscopic imaging (MRSI). In this study, we propose a new concentric ring trajectory (CRT) for DW‐MRSI that samples k‐space with a density that is proportional to a spatial, isotropic Hanning window. The properties of two different DW‐CRTs were compared against a radially equidistant (RE) CRT and an echo‐planar spectroscopic imaging (EPSI) trajectory in simulations, phantoms and in vivo experiments. These experiments, conducted at 7 T with a fixed nominal voxel size and matched acquisition times, revealed that the two DW‐CRT designs improved the shape of the spatial response function by suppressing side lobes, also resulting in improved signal‐to‐noise ratio (SNR). High‐quality spectra were acquired for all trajectories from a specific region of interest in the motor cortex with an in‐plane resolution of 7.5 × 7.5 mm2 in 8 min 3 s. Due to hardware limitations, high‐spatial‐resolution spectra with an in‐plane resolution of 5 × 5 mm2 and an acquisition time of 12 min 48 s were acquired only for the RE and one of the DW‐CRT trajectories and not for EPSI. For all phantom and in vivo experiments, DW‐CRTs resulted in the highest SNR. The achieved in vivo spectral quality of the DW‐CRT method allowed for reliable metabolic mapping of eight metabolites including N‐acetylaspartylglutamate, γ‐aminobutyric acid and glutathione with Cramér‐Rao lower bounds below 50%, using an LCModel analysis. Finally, high‐quality metabolic mapping of a whole brain slice using DW‐CRT was achieved with a high in‐plane resolution of 5 × 5 mm2 in a healthy subject. These findings demonstrate that our DW‐CRT MRSI technique can perform robustly on MRI systems and within a clinically feasible acquisition time.

Whole Brain ¹H-Spectroscopy: A Developing Technique for Advanced Analysis of Cerebral Metabolism.

Accompanying the advance of neuroscientific research and modern therapeutic methods, efforts have been made to develop more practical and effective advanced magnetic resonance (MR) spectroscopic techniques. We present a brief overview on (1)H-MRS techniques in neuroradiological diagnosis and several application examples of recently reported whole brain MR spectroscopic imaging technique (wbMRSI). Despite the benefits of using established (1)H-MRS techniques both single voxel MR spectroscopy (SVS) and chemical shift imaging (CSI) techniques suffer from limited spatial coverage. It is always necessary to define prior to the MRS examination which brain structure is physiologically or pathologically involved and thus should be targeted with (1)H-MRS. In contrast, the advanced wbMRSI allows estimating metabolite changes within a much larger brain region and at multiple brain structures simultaneously. As a developing technique for advanced analysis of cerebral metabolism a wide application of the wbMRSI in both clinical diagnostics and neuroscience could be expected.

Phase-difference and spectroscopic imaging for monitoring of human brain temperature during cooling

Decrease of the human brain temperature was induced by intranasal cooling. The main purpose of this study was to compare the two magnetic resonance methods for monitoring brain temperature changes during cooling: phase-difference and magnetic resonance spectroscopic imaging (MRSI) with high spatial resolution. Ten healthy volunteers were measured. Selective brain cooling was performed through nasal cavities using saline-cooled balloon catheters. MRSI was based on a radiofrequency spoiled gradient echo sequence. The spectral information was encoded by incrementing the echo time of the subsequent eight image records. Reconstructed voxel size was 1×1×5 mm3. Relative brain temperature was computed from the positions of water spectral lines. Phase maps were obtained from the first image record of the MRSI sequence. Mild hypothermia was achieved in 15–20 min. Mean brain temperature reduction varied in the interval <−3.0; −0.6>°C and <−2.7; −0.7>°C as measured by the MRSI and phase-difference methods, respectively. Very good correlation was found in all locations between the temperatures measured by both techniques except in the frontal lobe. Measurements in the transversal slices were more robust to the movement artifacts than those in the sagittal planes. Good agreement was found between the MRSI and phase-difference techniques.

Wavelet Encoding Spectroscopic Imaging in Small FOV Regime: Comparison to Chemical Shift Imaging at 3 Tesla

We have recently proposed a new magnetic resonance spectroscopic imaging (MRSI) technique called wavelet encoding spectroscopic imaging (WE-SI), and described its implementation on a clinical 1.5 T scanner. This technique is proposed as an alternative to chemical shift imaging (CSI), to decrease acquisition time, and voxel contamination. The proposed method is implemented here on a clinical 3 T scanner. Phantom and in vivo studies are chosen to validate the technique at higher field, as well as to fully explore the usefulness of this technique, and find its niche of application in the chain of existing MRSI techniques. In wavelet encoding, a set of dilated and translated wavelets are used to span a localized space by dividing it into a set of sub-spaces with pre-determined sizes and locations. Due to their simple shapes, Haar wavelets are chosen. They are represented in the modified PRESS sequence by the selective excitation and refocusing radio-frequency (RF) pulses. The wavelets dilation and translation are achieved by changing the strength of the localization gradients and frequency shift of the RF pulses, respectively. Data acquisition time is reduced using the minimum recovery time when successive MR signals from adjacent sub-spaces are collected. The results obtained at 3 T confirm those obtained at 1.5 T, and demonstrate that despite the low signal-to-noise ratio, the proposed WE-SI provides accurate results and reduces both voxel contamination and acquisition time as compared to CSI. This applies especially in the small field-of-view regime where only a small number of voxels is required.

31P Magnetic resonance spectroscopic imaging with polarisation transfer of phosphomono‐ and diesters at 3 T in the human brain: relation with age and spatial differences

Tissue levels of the compounds phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) can be studied by in vivo 31P MRS. However, the detection of the signals of these compounds suffers from low sensitivity and contamination by underlying broad resonances of other phosphorylated compounds. Improved sensitivity without this contamination can be achieved with a method for optimal polarisation transfer of 1H to 31P spins in these molecules, called selective refocused insensitive nuclei-enhanced polarisation transfer (sRINEPT). The aim of this study was to implement a three-dimensional magnetic resonance spectroscopic imaging (MRSI) version of sRINEPT on a clinical 3 T magnetic resonance system to obtain spatially resolved relative levels of PC, PE, GPC and GPE in the human brain as a function of age, which could be used as a reference dataset for clinical applications. Good signal-to-noise ratios were obtained from voxels of 17 cm(3) of the parietal and occipital lobes of the brain within a clinically acceptable measurement time of 17 min. Eighteen healthy subjects of different ages (16-70 years) were examined with this method. A strong inverse relation of the PE/GPE and PC/GPC ratios with age was found. Spatial resolution was sufficient to detect differences in metabolite ratios between white and grey matter. Moreover, we showed the feasibility of this method for clinical use in a pilot study of patients with brain tumours. The sRINEPT MRSI technique enables the exploration of phospholipid metabolism in brain diseases with a better sensitivity than was possible with earlier 31P MRS methods.

Quantification of lipids in human lower limbs using yellow bone marrow as the internal reference: gender-related effects

The main purpose of this study was to determine and compare extra- and intramyocellular (IMCL) lipids content in the calf and thigh muscles of normal male and female volunteers using high-spatial-resolution magnetic resonance spectroscopic imaging (MRSI). The study groups consisted of 10 females and 10 males. The subjects were healthy and normal-weight. Fat (yellow bone marrow) was used as the internal concentration reference. Total fat and IMCL content were computed for all muscles in the slice and for three muscle compartments in the thigh, whereas three muscles and three muscle compartments were evaluated in the calf. To avoid the confounding effects of physical activity and diet, measurements were performed in the same session. A common feature for both genders was that thigh muscles had approximately 2.5 times greater total fat content as compared to muscles of the calf. The mean IMCL level was, however, more than 3 times higher in the calf muscles compared with the thigh. No significant differences in lipid concentrations of correspondent regions of interest were found between genders. The high-spatial-resolution MRSI technique enables a more detailed study of muscle lipid distribution and can therefore improve understanding of muscle lipid metabolism in healthy volunteers and in studies of patients with metabolic disorders.

A high spatial resolution in vivo 1H magnetic resonance spectroscopic imaging technique for the human breast at

The technical challenges that have prevented routine proton magnetic resonance spectroscopic imaging (1H MRSI) examinations of the breast include insufficient spatial resolution, increased difficulties in shimming compared to the brain, and strong lipid contamination at short echo time (TE) at 1.5 T. The authors investigated the feasibility of high spatial resolution 1H MRSI of human breast cancer in a clinical setting at 3 T. Ten patient studies (eight cancers and two benign lesions) were performed in a 3 T whole-body clinical imager using a pulse sequence consisting of optional outer volume presaturation, optional CHESS pulse for lipid suppression, CHESS pulse for water suppression, and standard 2D/3D PRESS pulse sequence with an elliptical weighted k-space sampling scheme. All ten studies were technically successful. The spectral quality was acceptable for all cases even the one with a 65 Hz width of water peak at half height. Choline (Cho) signals were clearly visible in malignant lesion areas, while there was no detectable Cho in normal appearing breast or in benign lesions. It was also observed that the distribution of Cho signal can be nonuniform across MRI demonstrated lesions. To the author's knowledge, this is the first 2D/3D MRSI study of human breast cancer with short TE (less than 135 ms) at 3 T and the highest spatial resolution (up to 0.25 cm3) to date. In conclusion, the authors have presented a robust technique for high spatial resolution in vivo 1H MRSI of human breast cancer that uses the combined advantages of high field, short TE, multivoxel, and high spatial resolution itself to overcome the major technical challenges and illustrated its potential for routine clinical examination as well as advantages over single-voxel techniques in studying metabolite heterogeneity.

1H spectroscopic imaging of human brain at 3 Tesla: Comparison of fast three‐dimensional magnetic resonance spectroscopic imaging techniques

To investigate the signal-to-noise-ratio (SNR) and data quality of time-reduced three-dimensional (3D) proton magnetic resonance spectroscopic imaging ((1)H MRSI) techniques in the human brain at 3 Tesla. Techniques that were investigated included ellipsoidal k-space sampling, parallel imaging, and echo-planar spectroscopic imaging (EPSI). The SNR values for N-acetyl aspartate, choline, creatine, and lactate or lipid peaks were compared after correcting for effective spatial resolution and acquisition time in a phantom and in the brains of human volunteers. Other factors considered were linewidths, metabolite ratios, partial volume effects, and subcutaneous lipid contamination. In volunteers, the median normalized SNR for parallel imaging data decreased by 34-42%, but could be significantly improved using regularization. The normalized signal to noise loss in flyback EPSI data was 11-18%. The effective spatial resolutions of the traditional, ellipsoidal, sensitivity encoding (SENSE) sampling scheme, and EPSI data were 1.02, 2.43, 1.03, and 1.01 cm(3), respectively. As expected, lipid contamination was variable between subjects but was highest for the SENSE data. Patient data obtained using the flyback EPSI method were of excellent quality. Data from all (1)H 3D-MRSI techniques were qualitatively acceptable, based upon SNR, linewidths, and metabolite ratios. The larger field of view obtained with the EPSI methods showed negligible lipid aliasing with acceptable SNR values in less than 9.5 min without compromising the point-spread function.

Elliptical magnetic resonance spectroscopic imaging with GRAPPA for imaging brain tumors at 3 T

Magnetic Resonance Spectroscopic Imaging (MRSI) is a technique for imaging spatial variation of metabolites and has been very useful in characterizing biochemical changes associated with disease as well as response to therapy in malignant pathologies. This work presents a self-calibrated undersampling to accelerate 3D elliptical MRSI and an extrapolation-reconstruction algorithm based on the GRAPPA method. The accelerated MRSI technique was tested in three volunteers and five brain tumor patients. Acceleration allowed larger spatial coverage and consequently, less lipid contamination in spectra, compared to fully sampled acquisition within the same scantime. Metabolite concentrations measured from the accelerated acquisitions were in good agreement with measurements obtained from fully sampled MRSI scans.

A high spatial resolution 1H magnetic resonance spectroscopic imaging technique for breast cancer with a short echo time

The high sensitivity but low specificity of breast MRI has prompted exploration of breast (1)H MRS for breast cancer detection. However, several obstacles still prevent the routine application of in vivo breast (1)H MRS, including poor spatial resolution, long acquisition time associated with conventional multi-voxel MRS imaging (MRSI) techniques, and the difficulty of "extra" lipid suppression in a magnetic field with relatively poor achievable homogeneity compared to the brain. Using a combination of a recently developed echo-filter (EF) suppression technique and an elliptical sampling scheme, we demonstrate the feasibility of overcoming these difficulties. It is robust (the suppression technique is insensitive to magnetic field inhomogeneity), fast (acquisition time of about 12 min) and offers high spatial resolution (up to 0.6 cm(3) per voxel at 1.5 T with a TE of only 60 ms). This approach should be even better at 3 T with higher resolution and/or shorter TE.

TH‐D‐M100J‐08: A Fast and High Spatial Resolution 1H Magnetic Resonance Spectroscopic Imaging Technique for Breast Cancer

Purpose: We present our initial experience with in vivo high spatial resolution 1H MRSI of human breast lesions at a short echo time, by using recently developed echo‐filter suppression technique and the elliptical sampling scheme Method and Materials: The technique consists of three parts: optional inversion recovery, optional outer volume pre‐saturation (OVP), and an echo‐filter MRSI with a weighted k‐space sampling scheme. The simplest echo‐filter pulse sequence consists of a 900 RF pulse (or a series of pulses) to define the volume of interest (VOI), a delay TE/2, a frequency‐selective (FS) 1800 pulse, and another delay TE/2 with equally strong crusher gradients (G) on each side of the FS pulse. To improve sampling efficiency, a weighted k‐space sampling scheme is used to acquire the MRSI data set. Siemens whole‐body 1.5T Sonata is used, TR=1600 ms, TE=60 ms, Ave=8, acquisition time= 12.1 min, and a 60 Hz Gaussian FS pulse setting at Cho resonance (3.2 ppm). Results: To date, six studies from five patients with DCE‐MRI, 5 succeed, the spectra are well differentiated between biopsy proven tumor and control voxels. The spatial resolution here is only 0.59 cm3, the highest spatial resolution for in vivo 1H breast MRS at 1.5T to date. Excellent lipid and water suppression for in vivo 1H MRS was achieved. Aside from 8 Hz filter in the time domain and fast Fourier transform (FFT), no other processing was used to generate the spectra. Conclusion: As demonstrated, the proposed technique has the potential to overcome the difficulties for routine breast 1H MRS. It is robust (suppression technique is insensitive to magnetic field inhomogeneity), high spatial resolution (0.59 cc at 1.5T with a TE of only 60 ms), fast (acquisition time of 12 minutes), and even better at 3T (higher resolution and/or shorter TE).

An improved 1H magnetic resonance spectroscopic imaging technique for the human breast: preliminary results

The high sensitivity but poor specificity of magnetic resonance imaging for detecting breast cancer has stimulated interest in magnetic resonance spectroscopic imaging (MRSI) as a tool to improve specificity and reduce the number of benign biopsies. The challenge of applying 1H MRSI to the diagnosis of cancer in the human breast is the need for robust lipid suppression and a clinically acceptable acquisition time. We present an improved 1H MRSI technique that uses an independently optimized chemical-shift-selective for lipid suppression and weighted elliptical k-space sampling combined with a Hamming filter for improved sampling efficiency.

Molecular mechanisms of axonal damage in inflammatory central nervous system diseases.

Axonal dysfunction and damage is an early pathological sign of autoimmune central nervous system disease, viral and bacterial infections, and brain trauma. Axonal injury has attracted considerable interest during the past few years because the degree of axonal damage appears to determine long-term clinical outcome. Advanced magnetic resonance spectroscopic imaging techniques have suggested that axonal loss and dysfunction is responsible for the persistent neurological deficits that occur in patients with multiple sclerosis. Histopathological methods have shown that axonal damage is defined primarily by dysfunction of axonal transport, and finally by complete transection and degeneration of axons. Recent studies have demonstrated that the extent of axonal damage in the primary demyelinating lesion of multiple sclerosis patients is associated with the number of activated microglia/macrophages and cytotoxic CD8+ T lymphocytes. In addition, diffuse axonal dysfunction independent of demyelination develops in normal appearing white matter, possibly due to indirect effects of inflammation. The fact that axonal damage in response to overt inflammatory reactions may occur gradually, leaving a window for therapeutical intervention, has important clinical implications. Determination of the exact molecular mechanism might help in finding new therapies for inflammatory axonal damage.

Scan time reduction in proton magnetic resonance spectroscopic imaging of the human brain

A simple technique is described for scan time reductions in proton magnetic resonance spectroscopic imaging (MRSI) of the human brain. Scan time is reduced by approximately 35% while preserving spatial resolution by reducing the field of view (FOV) and number of phase-encoding steps in the transverse direction of the brain. A multislice MRSI of the brain is demonstrated which takes approximately 20 min with a square FOV, and 13 min with a reduced FOV. The signal-to-noise ratio (SNR) in the reduced FOV scan was measured to be 15% lower than that of the full FOV scan, which is close to the expected theoretical value of 19% based on the square root of the scan time. The method can be applied with any sequence, and requires minimal software and no hardware modifications. Scan time in MRSI is minimized in this method by using FOVs no larger than the dimensions of the object to be imaged. The method may also be combined with other fast MRSI techniques to provide further scan time reductions.

Spatial Assessment of the Dynamics of Lactate Formation in Focal Ischemic Rat Brain

Early identification of the potentially salvageable penumbra is critical for the determination of therapeutic intervention strategies in acute focal cerebral ischemia. This study differentiates the ischemic penumbra from the core on the basis of the dynamics of lactate formation. This was tested in a rat model of focal cerebral ischemia by infusion of [1-13C]-glucose, using lactate-edited magnetic resonance spectroscopic imaging techniques. The authors detected essentially no enrichment of lactate with 13C-label from the infused 13C-glucose in the ischemic core. However, in borderzone areas, 13C was incorporated into lactate, which could point toward compromised but potentially viable tissue. The authors' findings suggest that this combination of 13C-glucose infusion with the proposed magnetic resonance methods may aid in differentiating the penumbra from the core in cerebral ischemia.

1H-spectroscopic imaging with read gradient during acquisition in inhomogeneous fields: analysis, measurement strategy, and data processing.

The proton magnetic resonance spectroscopic imaging techniques that use read gradient during acquisition produce proton spectra with high spatial and moderately high spectroscopic resolution in a reasonable time for in vivo applications. These techniques suffer mainly from the spatial and spectral distortions caused by the convolution of spectral/spatial information (chemical-shift artifacts) and from the spectral shifts caused by static magnetic field inhomogeneities. The investigators analyze the chemical-shift artifacts in the presence of nonnegligible static magnetic field inhomogeneities and propose a postdetection processing scheme to correct for such effects. Spectral artifacts caused by chemical shifts, spectral line overlapping, streak broadening, and magnetic field inhomogeneities are discussed. The postdetection data processing scheme is demonstrated on measurements of a phantom as well as a human leg.

Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging.

The goals of the current study were threefold: first, to confirm previous single volume proton (1H) magnetic resonance spectroscopy results of reduced N-acetyl aspartate (NAA, a putative marker of neurons) in multiple sclerosis (MS) white matter lesions using multiple volume 1H magnetic resonance spectroscopic imaging (MRSI); second, to measure the phospholipid metabolites phosphomonoesters and phosphodiesters in such lesions using phosphorus (31P) MRSI; and third, to test the hypothesis that biochemical changes occur in the normal-appearing (on spin echo T2-weighted magnetic resonance images) white matter in patients with MS. Thirteen subjects with clinically definite MS were studied with both 1H and 31P MRSI, and 19 controls were studied with either 1H MRSI, 31P MRSI, or both. MS lesion, MS normal-appearing white matter, and region-matched control spectra from the centrum semiovale were analyzed. The major findings of this study were that in both white matter lesions and normal-appearing white matter in patients with MS, the metabolite ratio NAA/creatine and the total 31P peak integrals were significantly reduced compared with controls. In addition, in MS lesions NAA/choline and phosphodiesters/total 31P were significantly reduced compared with controls, and in MS normal-appearing white matter there was a trend for NAA/choline to be reduced compared with controls. In normal-appearing white matter in patients with MS, total creatine and phosphocreatine were significantly increased compared to controls, as detected with both 1H (total creatine peak integrals) and 31P (phosphocreatine/total 31P) MRSI techniques. These results suggest reduced neuronal density and altered phospholipid metabolites in white matter lesions in patients with MS.(ABSTRACT TRUNCATED AT 250 WORDS)