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Introduction

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

Neuropsychiatric (NP) systemic lupus erythematosus (SLE) is characterized by a large spectrum of physical and behavioral manifestations. One major difficulty is the absence of diagnostic tools for assessing disease activity and severity of NP manifestation. The neurologic symptoms can be of new onset, chronic, or of a former or resolved nature (1). Although several studies have used different neuroimaging tools, including computed tomography, magnetic resonance imaging (MRI), and single-photon–emission computed tomography, no single technique has proven to be definitive for diagnosis of NP manifestations in persons with SLE (1).

Magnetic resonance spectroscopy (MRS) permits chemically specific, noninvasive measurements of some compounds of biologic importance in living tissues. MRS was discovered in 1946, but was only first used in living animal brain in 1980 (2), followed by use in human brains in several pathologies. In the human brain, phosphate energy stores, intracellular pH, lactate concentrations, and the neuronal marker N-acetylaspartate are examples of MRS-measurable variables (3).

The purpose of this article is to review studies using MRS in SLE and to discuss the clinical utility of this technique in determining central nervous system (CNS) involvement in individuals with SLE. We will also discuss future applications of MRS in the evaluation and treatment of NP manifestations in patients with SLE.

History

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

The nuclear magnetic resonance (NMR) phenomenon was discovered independently in 2 laboratories in 1946 by Bloch and Purcell, which led them to receive the Nobel Prize for physics in 1952. When imaging methods using the NMR signal were first developed, the term NMR imaging had been applied. But because of increasing danger of nuclear energy in the 1980s and because MR techniques do not use ionizing radiation, the term nuclear was dropped in clinical use, being maintained only to describe the physical phenomenon itself (3).

MRS physics

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

Spectroscopy deals with the interaction of electromagnetic radiation with matter; therefore, because the structure of atomic nuclei have magnetic properties, they respond to strong magnetic fields. During relaxation from the excitation of a magnetic field, atomic nuclei emit oscillating signals at a frequency that perturbs the nuclei. These signals may be detected by coils and then converted into spectra or images. The position of peaks in the spectrum is determined by its molecular characteristics. Information about their metabolites can be extracted based upon the amplitude or area under a given peak (3).

Advantages of MRS

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

There are several advantages to performing MRS in vivo. Metabolic studies of organs in their normal environment can increase understanding of the function of complex organisms and enable researchers to evaluate changes during diseases. The noninvasive nature of MRS allows repeated measurements in order to evaluate kinetic and longitudinal studies and to study human tissues that are inaccessible by invasive techniques. At the strength of the magnetic field needed for human studies in vivo, no deleterious effect on living tissue has been noted (3). Precautions such as excluding magnetic objects from the magnet are the main recommendation.

Disadvantages of MRS

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

The major disadvantage of MRS is its lack of sensitivity, which depends on a wide range of factors, including the nucleus investigated, the volume of the region of interest, and the magnetic field strength, among others. In general, only small molecules that tumble rapidly in solution create an MRS signal strong enough to be detected in vivo (3). MRS findings are specific to the area analyzed in the study. Therefore, MRS studies can only be compared if the same anatomic area is analyzed.

Proton spectra of the human brain

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

The brain tissue consists of the cortex, a layer of gray matter 1.5–4 mm thick that covers the white matter of the cerebral hemispheres. The gray matter consists of neuronal cell bodies and neuroglial cells, such as astrocytes and oligodendroglia cells. The white matter consists of neuronal axons involved by myelin sheets and neuroglial cells. The water concentration in these tissues varies due to different concentrations and properties of lipids and proteins (4). Water-suppressed, localized MRS of normal human brain at echo times (TEs) between 136 msec and 272 msec reveals 4 major resonances (Figure 1) (3).

thumbnail image

Figure 1. Water-suppressed, localized magnetic resonance spectroscopy of normal human brain. Cho = choline; Cr = creatine; NAA = N-acetylaspartate.

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N-acetyl groups.

Several studies suggest that the peak of N-acetyl groups, at 2.0 parts per million, which originates largely from N-acetylaspartate (NAA), can be used as a neuronal marker because NAA is found exclusively in neurons and their processes in the mature brain (3). In human brain spectra, NAA is reduced in conditions known to be associated with neuronal loss, such as in neuronal degenerative disorders, stroke, and glial tumors (4). When a decrease in the relative NAA signal arises from neuronal or axonal degeneration, irreversible changes are expected. However, several studies have shown reversible decreases in NAA in a number of conditions, emphasizing that neuronal dysfunction or transient relative volume change can also lead to a decrease in NAA (4). The ability to quantify specifically neuronal loss or damage is one of the interesting applications of MRS in vivo.

Several studies observed that CNS manifestations in patients with SLE are associated with reduction in NAA over creatine ratios and NAA over choline ratios not only in lesions, but also in normal-appearing white matter when compared with controls. Reduced NAA over creatine ratios were observed in SLE patients with severe atrophy when compared with SLE patients with mild atrophy and controls (5), suggesting that atrophy in patients with SLE is caused by neuronal and axonal dropout or damage. Brooks et al (1) demonstrated that patients with white matter lesions also had a more pronounced reduction in these metabolites, when compared with patients without lesions, suggesting that NP manifestations are associated with a complex multifocal and diffuse neurotoxic process. We further demonstrated that the reduction in NAA over creatine ratios correlated with disease activity, independently of CNS manifestations, and that NAA over creatine ratios in normal-appearing white matter returned to normal range after remission (6).

Some studies suggest that the amount of reduction in relative and absolute concentrations of NAA is associated with the severity of clinical manifestations (6, 7) and CNS manifestations (7–10), although no distinction between acute and chronic disease has been demonstrated (7, 11, 12). The NAA reduction reflects both neuronal loss and dysfunction and has been correlated with cognitive dysfunction and extent of brain damage (7, 13), suggesting that it could be used as a disease outcome measurement.

Tetramethyl-amines (mainly from choline-containing phospholipids).

Changes in the resonance intensity of choline probably result from an increase in the steady state levels of phosphocholine and glycerol phosphocholine. These choline-containing membrane phospholipids are released during active myelin breakdown. Therefore, the resonance of choline increases in acute demyelinating lesions in humans. Chronic, slowly progressive leukodystrophies are associated with normal choline over creatine ratios, presumably because the loss of myelin is so slow that significant increases in released membrane phospholipids do not accumulate.

Increased choline over creatine ratios were also observed in patients with SLE, especially in those with major NP events, although this increase did not enable the distinction between acute and chronic CNS manifestations. Choline metabolites have been shown to increase in CNS involvement in SLE, which can be due to the inflammatory process (14) or the increased amount of lipids secondary to myelin breakdown. Increased choline was associated with the presence of cognitive dysfunction in patients with SLE (9, 12, 13). Furthermore, one study (10) demonstrated that increased choline over creatine ratios in normal-appearing white matter may predict the appearance of white matter lesions. Smaller fixed focal lesions evident on T2-weighted MR images may represent small infarcts in subcortical or deep white matter. Similar findings are observed in healthy adults, often associated with older age. However, if neurometabolic changes are observed within these lesions, it could be inferred that these white matter lesions represent a serious pathologic process resulting in focal neuronal death or injury (14). Furthermore, if the presence of increased choline over creatine ratios in normal-appearing white matter may predict the appearance of fixed white matter lesions, new treatment strategies could be introduced.

Creatine and phosphocreatine.

Total creatine concentration is relatively constant throughout the brain and tends to be relatively resistant to changes; however, variations in creatine levels do occur, as in the gradual loss of creatine together with other major metabolites in tissue death or necrosis (4). Creatine may increase as a hyperosmolar response to craniocerebral trauma, or may be absent as in the case of creatine deficiency, a rare congenital disease (3, 6). It is reasonable to use creatine as an internal standard to normalize NAA and choline resonances to correct for artifactual variations in signal intensities due to magnetic fields and radiofrequency inhomogeneity (7). However, some studies suggest the loss of information by using this approach. An alternative is the use of external concentration reference, but factors such as radiofrequency field inhomogeneity and coil tuning and coupling have to be controlled (3).

In a large study, we observed constant creatine values in 50 patients with SLE followed for 19 months (6). Similar findings were observed by Axford et al (8).

Lactate.

Lactic acid is the end product of glycolysis and accumulates when oxidative metabolism cannot meet energy requirements. Elevation of lactic acid in cerebral neoplasms correlates approximately with relative rates of glucose uptake. However, because lactic acid is present in the intracellular and extracellular compartments, a large amount can be accumulated outside actively anaerobic tissue (4). In inflammation, lactate accumulation may also reflect metabolism of inflammatory cells rather than brain parenchyma itself. The lactate peak is above the baseline when the TE is low (20–35 msec) or high (270–288 msec). At an intermediate TE (135–144 msec), the lactate peak inverts to project below the baseline, a feature that enables its distinction from lipids and some macromolecules seen at a similar location on the spectrum (15).

Only a few studies have analyzed the presence of lactate in patients with SLE. Brooks et al (14) did not find an increased lactate over creatine in patients with normal-appearing white matter or white matter lesions when compared with controls.

Other metabolites.

Myo-inositol (mI) is an osmolyte and astrocyte marker. Its resonance at 3.56 ppm is visualized when performing MRS using a short TE (15, 16). Only in one study was mI measured, where all patients with major CNS involvement had higher values of mI than patients with minor manifestations (8).

Normal variations

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

There are age-related and regional variations in the concentrations of various metabolites in the brain, especially a constant reduction of NAA over creatine ratios in the elderly. Regional variations of metabolite concentrations in the brain are seen between gray and white matter (NAA is higher in white matter, and creatine and choline are higher in gray matter) and within different parts of the brain (1, 15, 16).

MRS techniques

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

Commonly used spectroscopic techniques include the single-voxel spectroscopy, with a spatial resolution in the order of 1–8 cm3 (16), and the multivoxel technique, allowing the derivation of metabolite maps (16). Although single-voxel spectroscopy allows evaluation of only small volumes of tissue, it is time efficient and allows the acquisition of quantitative data. Multivoxel MRS allows examination of different areas of the brain at the same time (15, 16). Most SLE studies have used single-voxel MRS, especially because patients with SLE included in the studies were severely ill and needed a shorter time for examinations (Table 1). %The selection of appropriate MRS techniques, including measurement parameters such as repetition time (TR) and TE, depends on the clinical question. Short TE (20–35 msec) evaluations are required when there is a need for detection of metabolites with short relaxation times, such as glutamine, glutamate, mI, and certain amino acids (15, 16), whereas long TE studies (135–270 msec) are sufficient for the detection of the major metabolites such as NAA, choline, creatine, and lactate/lipids (16). Different TR and TE used in patients with SLE are shown in Table 1.

Table 1. MRS findings in systemic lupus erythematosus: literature review*
Author (reference)Localization MRSNo. of patientsVoxel sizeMRS parametersMRS findingsClinical associationsOthers
  • *

    MRS = magnetic resonance spectroscopy; TR = repetition time; TE = echo time; [DOWNWARDS ARROW] = decreased; [UPWARDS ARROW] = increased; NAA = N-acetylaspartate; Cr = creatine; NAWM = normal-appearing white matter; Cho = choline; NP = neuropsychiatric manifestations; SAAF = antiphospholipid syndrome; SLICC = Systemic Lupus International Collaborating Clinics; MRI = magnetic resonance imaging; mI = myo-inositol; SPECT = single-photon–emission computed tomography.

Sibbitt et al (5)White matter, superior to the ventricles, extending through both hemispheres212 × 2 × 2 cm3TR = 1,500; TE = 19[DOWNWARDS ARROW]NAA/Cr More pronounced in severe atrophy
Davie et al (11)White matter lesions (5 patients) or NAWM in frontal region (7 patients)133.5–6 mlTR = 2,000 msec; TE = 10 and 135 msec[DOWNWARDS ARROW]NAA/CrNo correlation with neurologic and psychiatric involvement[DOWNWARDS ARROW]NAA/Cr in lesions
Brooks et al (14)Lesions and NAWM in periventricular white, occipital white, and occipital gray matter141 mlTE = 270 msec; TR = 2,300 msec[DOWNWARDS ARROW]NAA/CrIn all regions of the brainMore pronounced in lesions
Chinn et al (19)Frontal white matter and the parieto-occipital white matter478 mlTR = 1,600 msec; TE = 135 msec[DOWNWARDS ARROW]NAA/Cr; [DOWNWARDS ARROW]Cho/Cr Corticosteroids
Sibbitt et al (7)NAWM parietal lobe368 cm3TE = 26 and 136 msec; TR = 2,000 msec[DOWNWARDS ARROW]NAA/CrMajor NP; disease activity 
Sabet et al (18)Deep occipitoparietal white matter; multislice4310 cm3TE = 19 msec; TR = 2,000 msec; TE = 270 msec; TR = 2,300 msec[DOWNWARDS ARROW]NAA/Cr [UPWARDS ARROW]Cho/Cr in SAAF
Friedman et al (12)NAWM in occipitoparietal region424 cm3TE = 19 msec; TR = 2,000 msec[DOWNWARDS ARROW]NAA/Cr; [UPWARDS ARROW]Cho/Cr [DOWNWARDS ARROW]NAA/Cr associated with small focal lesions [UPWARDS ARROW]Cho/Cr associated with cerebral infarct
Brooks et al (1)Lesions and NAWM in periventricular white, occipital white, and occipital gray matter121 mlTE = 270 msec; TR = 2,300 msec[UPWARDS ARROW]Cho/CrCognitive impairment; SLICC 
Lim et al (13)Basal ganglia and left peritrigonal periventricular white matter268 cm3TE = 30 msec; TR = 3,000 msec[DOWNWARDS ARROW]NAA/Cr in basal ganglia [UPWARDS ARROW]Cho/Cr in periventricular white matterMajor NP manifestationsNo correlation with MRI findings
Axford et al (8)Parietal NAWM98 cm3TE = 30 msec; TR = 2,020 msec[DOWNWARDS ARROW]NAA,[UPWARDS ARROW]mI; [UPWARDS ARROW]ChoMajor NP manifestations; Minor NP manifestations[UPWARDS ARROW]mI in NAWM
Handa et al (9)Frontal and parieto-occipital NAWM201–8 mlTE = 135 msec, 270 msec; TR = 3,000 msec[DOWNWARDS ARROW]NAA/CrNP manifestations 
Castellino et al (10)Hypoperfused or normoperfused frontal areas by SPECT88 cm3TE = 135 msec; TR = 2,000 msec[DOWNWARDS ARROW]NAA/Cho in hypoperfused [UPWARDS ARROW]Cho/Cr in normoperfused areaWhite matter lesionsNew white matter lesions on previous areas of hypoperfusion and [DOWNWARDS ARROW]NAA/Cho
Appenzeller et al (6)NAWM superior to posterior region of corpus callosum9010 cm3TE = 135 msec; TR = 1,500 msec[DOWNWARDS ARROW]NAA/CrActive disease, reversible with inactivity 
Kozora et al (17)NAWM frontal periventricular72 × 2 × 2 cmTE = 135 msec; TR = 1,500 msec[UPWARDS ARROW]Cho/Cr[UPWARDS ARROW] in cognitive impairment 

Proton MRS studies in specific NP manifestations

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

Most studies using MRS in patients with SLE have included patients with or without CNS involvement. No study has used MRS for investigating specific manifestations. Brooks et al (1) and Kozora et al (17) observed increased choline over creatine ratios in patients with cognitive impairment.

Laboratory and treatment features

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

The use of corticosteroids and the presence of antiphospholipid antibodies may also influence neurometabolic markers. One study (18) demonstrated that patients receiving corticosteroids had lower NAA over creatine ratios than patients not receiving corticosteroids.

The presence of antiphospholipid antibodies is associated with epilepsy and stroke in patients with SLE. We did not observe a difference in NAA over creatine ratios between patients with and those without antiphospholipid antibodies (6), although one previous study showed a correlation between the presence of IgG antiphospholipid antibodies and NAA over creatine ratios (19).

Conclusion

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

MRS allows the quantification of changes in neuronal markers and the monitoring of disease progression. MRS seems to be more sensitive than MRI in detecting neuronal damage or dysfunction in patients with SLE. Although different MRS techniques and different localization of the MRS volume of interest were used in SLE studies, we observed that most authors report a significant decrease in NAA over creatine ratios in patients with SLE when compared with controls. Although some studies correlate the NAA decrease with NP manifestations, global disease activity is often not mentioned. Increased choline over creatine ratios were observed, especially in white matter lesions and NP manifestations.

Further directions

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES

Active SLE is characterized by reduced NAA over creatine values that may be reversible after disease control (6). Further studies are necessary to determine the potential role of NAA as a surrogate marker of disease activity in patients with SLE, which will allow for an early aggressive treatment, perhaps avoiding chronic neurologic impairment.

The increase in choline over creatine ratios in normal-appearing white matter and the possibility that this change may predict the appearance of white matter lesions in SLE is another important finding that needs to be investigated further. Specific treatment features could be used to prevent the appearance of these lesions, which, in the light of current research, could be considered specific CNS damage. Therefore, MRS may be used as a marker for disease activity and CNS damage.

Other MRS metabolites have to be studied in larger longitudinal studies to determine their clinical significance. The use of multivoxel MRS may be helpful to determine if these changes are uniform in the entire brain or localized to some specific area, especially if gray and white matter have the same pattern of neurometabolic abnormalities.

The specificity of MRS for individual CNS manifestations has to be determined in further studies. However, due to the low frequency of some manifestations, multicenter studies may be necessary.

REFERENCES

  1. Top of page
  2. Introduction
  3. History
  4. MRS physics
  5. Advantages of MRS
  6. Disadvantages of MRS
  7. Proton spectra of the human brain
  8. Normal variations
  9. MRS techniques
  10. Proton MRS studies in specific NP manifestations
  11. Laboratory and treatment features
  12. Conclusion
  13. Further directions
  14. REFERENCES
  • 1
    Brooks WM, Jung RE, Ford CC, Greinel EJ, Sibbitt WL Jr. Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus. J Rheumatol 1999; 26: 815.
  • 2
    Ackerman JJ, Grove TH, Wong GG, Gadian DG, Radda GK. Mapping of metabolites in whole animals by 31P NMR using surface coils. Nature 1980; 283: 16770.
  • 3
    De Certaines JD, Bovee WM, Podo F. Magnetic resonance spectroscopy in biology and medicine: functional and pathological tissue characterization. New York: Pergamon Press; 1992.
  • 4
    Rudkin TM, Arnold DL. Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders. Arch Neurol 1999; 56: 91926.
  • 5
    Sibbitt WL Jr, Haseler LJ, Griffey RH, Hart BL, Sibbitt RR, Matwiyoff NA. Analysis of cerebral structural changes in systemic lupus erythematosus by proton MR spectroscopy. AJNR Am J Neuroradiol 1994; 15: 9238.
  • 6
    Appenzeller S, Li LM, Costallat LT, Cendes F. Evidence of reversible axonal dysfunction in systemic lupus erythematosus: a proton MRS study. Brain 2005; 128: 293340.
  • 7
    Sibbitt WL Jr, Haseler LJ, Griffey RR, Friedman SD, Brooks WM. Neurometabolism of active neuropsychiatric lupus determined with proton MR spectroscopy. AJNR Am J Neuroradiol 1997; 18: 12717.
  • 8
    Axford JS, Howe FA, Heron C, Griffiths JR. Sensitivity of quantitative (1)H magnetic resonance spectroscopy of the brain in detecting early neuronal damage in systemic lupus erythematosus. Ann Rheum Dis 2001; 60: 10611.
  • 9
    Handa R, Sahota P, Kumar M, Jagannathan NR, Bal CS, Gulati M, et al. In vivo proton magnetic resonance spectroscopy (MRS) and single photon emission computerized tomography (SPECT) in systemic lupus erythematosus (SLE). Magn Reson Imaging 2003; 21: 10337.
  • 10
    Castellino G, Govoni M, Padovan M, Colamussi P, Borrelli M, Trotta F. Proton magnetic resonance spectroscopy may predict future brain lesions in SLE patients: a functional multi-imaging approach and follow up. Ann Rheum Dis 2005; 64: 10227.
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    Davie CA, Feinstein A, Kartsounis LD, Barker GJ, McHugh NJ, Walport MJ, et al. Proton magnetic resonance spectroscopy of systemic lupus erythematosus involving the central nervous system. J Neurol 1995; 242: 5228.
  • 12
    Friedman SD, Stidley CA, Brooks WM, Hart BL, Sibbitt WL Jr. Brain injury and neurometabolic abnormalities in systemic lupus erythematosus. Radiology 1998; 209: 7984.
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    Lim MK, Suh CH, Kim HJ, Cho YK, Choi SH, Kang JH, et al. Systemic lupus erythematosus: brain MR imaging and single-voxel hydrogen 1 MR spectroscopy. Radiology 2000; 217: 439.
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    Brooks WM, Sabet A, Sibbitt WL Jr, Barker PB, van Zijl PC, Duyn JH, et al. Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus. J Rheumatol 1997; 24: 23239.
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    Gujar SK, Maheshwari S, Bjorkman-Burtscher I, Sundgren PC. Magnetic resonance spectroscopy. J Neuroophthalmol 2005; 25: 21726.
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    Sundgren PC, Jennings J, Attwood JT, Nan B, Gebarski S, McCune WJ, et al. MRI and 2D-CSI MR spectroscopy of the brain in the evaluation of patients with acute onset of neuropsychiatric systemic lupus erythematosus. Neuroradiology 2005; 47: 57685.
  • 17
    Kozora E, Arciniegas DB, Filley CM, Ellison MC, West SG, Brown MS, et al. Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data. Cogn Behav Neurol 2005; 18: 15962.
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    Sabet A, Sibbitt WL Jr, Stidley CA, Danska J, Brooks WM. Neurometabolite markers of cerebral injury in the antiphospholipid antibody syndrome of systemic lupus erythematosus. Stroke 1998; 29: 225460.
  • 19
    Chinn RJ, Wilkinson ID, Hall-Craggs MA, Paley MN, Shortall E, Carter S, et al. Magnetic resonance imaging of the brain and cerebral proton spectroscopy in patients with systemic lupus erythematosus. Arthritis Rheum 1997; 40: 3646.