Original article
Quantitative proton magnetic resonance spectroscopy of focal brain lesions

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Abstract

The diagnostic value of single-voxel proton magnetic resonance spectroscopy (2 T, stimulated echo acquisition mode, TR = 6,000 ms, TE = 20 ms, 4-5 mL volumes-of-interest) was assessed for a differentiation of focal brain lesions of unknown etiology in 17 patients 1-14 years of age. Absolute metabolite concentrations were compared with age-matched control subjects and an individual control region. Most of the brain tumors were characterized by strongly reduced total N-acetylaspartyl compounds and marked increases of myo-inositol and choline-containing compounds, consistent with a lack of neuroaxonal tissue and a proliferation of glial cells. Lactate was elevated in only four patients. When using this pattern for a metabolic discrimination of brain tumors from other focal lesions, proton spectroscopy correctly identified 14 of 17 abnormalities, as confirmed by histologic examination after neurosurgical intervention. One false-positive tumor diagnosis was a severe reactive gliosis mimicking a typical tumor spectrum. Two inconclusive cases comprised an astrocytoma with moderately elevated myo-inositol but reduced choline-containing compounds and a patient with an abscess leading to a marked reduction of all metabolites but strong contributions from mobile lipids. In summary, quantitative proton spectroscopy has considerable clinical value for preoperative characterization of focal brain lesions.

Introduction

Tumors of the central nervous system are the most common form of childhood solid neoplasms and the leading cause of death from cancer in children younger than 15 years of age [1]. Consistent etiologic factors are not known, and neurobiologic alterations are not understood. Because the clinical presentation of these tumors varies largely depending on type, localization, and growth rate, the differential diagnosis of malignant brain tumors and focal lesions of other origin often poses a problem when based on clinical and neuroradiologic findings alone.

Localized proton magnetic resonance spectroscopy (MRS) provides noninvasive insights into the neurochemistry of normal and pathologic states of the central nervous system. It has technically matured during the past decade and been successfully applied to a large range of cerebral abnormalities in children and adults [2], [3]. Although a specific histologic classification or grading of tumors by proton MRS faces complications from a variety of sources [4], [5], numerous studies reported consistent differences between neoplastic and normal brain tissue since early descriptions [6]. For recent studies of brain tumors in children see Girard et al. [7] and Norfray et al. [8].

The purpose of this study was to confirm the utility of quantitative single-voxel proton MRS in the differential diagnosis of brain tumors and other focal abnormalities. In particular, we studied 17 children with suspect magnetic resonance imaging (MRI) findings and exploited the characteristic alterations of brain metabolites that are associated with the occurrence of a primary brain tumor (i.e., reduced content or even lack of neuroaxonal tissue and proliferation of glial cells). The prospective value of proton MRS was determined by a comparison with results from histopathologic examinations after neurosurgical intervention.

Section snippets

Material and methods

Seventeen patients (mean age = 7.3 years, range = 1-14, nine female, eight male) with suspect focal cerebral lesions and an uncertain diagnosis underwent MRS as part of the diagnostic evaluation. Subsequent neurosurgical intervention ranging from stereotactic biopsy to tumor removal was performed in all children and yielded a histopathologically confirmed diagnosis in all cases. Before each proton MRS examination, informed written consent was obtained from the parents. Proton MRS studies of

Results

The spectroscopic results for all patients are summarized in Table 2, in which metabolite alterations are given as the percentage of deviation from control subjects. Most of the intracranial tumors were characterized by low neuroaxonal and high glial tissue components relative to normal brain. Accordingly, their proton MR spectra comprise low tNAA levels and elevated Ins or Cho concentrations. Lac was detected in only a few patients with brain tumors. In contrast, gliosis mostly resulted in

Patient 9

This 2-year-old female had a normal neurologic development. After a head injury caused by falling down three steps of a staircase, she was continuously sleepy. The neurologic examination was normal. Cranial computed tomography revealed a hyperdense area in the right cerebellar hemisphere but no signs of hemorrhage. This lesion was subsequently confirmed by MRI (Fig 3A). The differential diagnosis included an ischemic lesion, a low-grade tumor, or hamartoma.

The proton MR spectra in Figures 3B

Discussion

In agreement with previous studies of various brain disorders, the two most prominent pathologic processes in brain tissue that give rise to MRS-detectable alterations are a loss or damage of neuroaxonal tissue and the occurrence of glial proliferation [2], [3]. Using tNAA and Ins as respective key markers, any reduction of neuroaxonal cells manifests itself as reduced tNAA (and glutamate) in proton MR spectra; however, growth of glial cells (mainly astrocytes) leads to increased Ins (and

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