Child's Nerv Syst (1996) 12:626-629 9 Springer-Verlag 1996

B. Wilken G. Helms H. J. Christen J. Behnke J. Frahm E Hanefeld

Received: 4 October 1995 B. Wilken 9H. J. Christen - F. Hanefeld (~) Department of Pediatrics and Pediatric Neurology, Georg August University, Robert-Koch-Strasse 40, D-37075 G/3ttingen, Germany Tel.: (49) 551-39 80 35 Fax: (49) 551-39 62 52 G. Helms 9J. Frahm Biomedizinische NMR Forschungs GmbH am Max-Planck Institut ftir biophysikalische Chemie, Am Fassberg 11, D-37077 G6ttingen, Germany J. Behnke Department of Neurosurgery, Georg August University, Robert-Koch-Strasse 40, D-37075 G6ttingen, Germany

Localized proton magnetic resonance spectroscopy of a cerebeUar tumor in a two.year.old child

Abstract N o n i n v a s i v e l o c a l i z e d proton m a g n e t i c r e s o n a n c e spectrosc o p y ( M R S ) was used for differential d i a g n o s i s o f a focal b r a i n lesion in a 2 . 5 - y e a r - o l d girl. T h e c l i n i c a l signs were a m i l d h e a d tilt and n e c k pain. M a g n e t i c r e s o n a n c e i m a g i n g (MRI) r e v e a l e d a l e s i o n in the right h e m i sphere o f the c e r e b e l l u m , but its nature r e m a i n e d obscure. In this lesion quantitative d e t e r m i n a t i o n s o f cerebral m e t a b o l i t e s b y fully relaxed, s h o r t - e c h o - t i m e p r o t o n M R S revealed markedly lowered N-acetylaspartate ( N A A ) and p r o n o u n c e d elevations o f c h o l i n e - c o n t a i n i n g c o m p o u n d s (Cho) and m y o - i n o s i t o l (Ins), w h e r e a s m e t a b o l i t e c o n c e n t r a t i o n s in cortical gray m a t t e r and white m a t t e r

were within n o r m a l ranges. T h e m e tabolite pattern of the lesion indic a t e d loss o f vital n e u r o a x o n a l tissue (low N A A ) and e n h a n c e d glial proliferation (high C h o and Ins), which, together with the M R I m o r p h o l o g y , s u g g e s t e d a brain tumor. The d i a g n o sis was e s t a b l i s h e d b y n e u r o s u r g i c a l e x p l o r a t i o n and total extirpation o f the tumor. H i s t o l o g y c o n f i r m e d an a s t r o c y t o m a ( W H O II). A f t e r 2 w e e k s ' r e c o v e r y the child was disc h a r g e d with no n e u r o l o g i c a l signs.

Key words M a g n e t i c r e s o n a n c e i m a g i n g 9M a g n e t i c r e s o n a n c e spectroscopy 9Children. B r a i n t u m o r 9A s t r o c y t o m a

Introduction

Case report

D e s p i t e c o n s i d e r a b l e i m p r o v e m e n t s in i m a g i n g m e t h o d o l o g y [4], u n a m b i g u o u s d i a g n o s i s o f i n t r a c r a n i a l t u m o r s in c h i l d r e n often r e m a i n s a challenge. H o w e v e r , a clear diagnosis is n e c e s s a r y b e f o r e a n e u r o s u r g i c a l i n t e r v e n t i o n can b e planned. A d d i t i o n a l i n f o r m a t i o n on the m e t a b o l i c status o f a s u s p e c t e d n e o p l a s m m a y be o b t a i n e d b y l o c a l i z e d p r o ton M R S in v i v o (see e.g., [2, 6]). This a p p r o a c h allows a n o n i n v a s i v e and quantitative a s s e s s m e n t o f c e r e b r a l m e tabolites in i m a g e - s e l e c t e d b r a i n areas as small as 1 m l [5, 9, 10] and, therefore, can p o t e n t i a l l y i m p r o v e d i a g n o s t i c s p e c i f i c i t y c o n s i d e r a b l y b y a d d i t i o n a l m e t a b o l i c characterization of the tissue. Here w e p r e s e n t the h i s t o r y o f a 2.5y e a r - o l d girl with a focal l e s i o n o f an u n k n o w n nature (mal i g n a n t / b e n i g n ) in the c e r e b e l l u m . Proton M R S was f o u n d h e l p f u l in e s t a b l i s h i n g the correct d i a g n o s i s and for g u i d ing the n e u r o s u r g i c a l intervention.

After a normal pregnancy, the patient had been delivered by cesarean section. The Apgar score after 5 rain was 10, and the pH of the arterial cord blood was 7.41. Body weight and length at birth were within normal ranges; head circumference was 35.5 cm (90th percentile). The neonatal period of the girl was uneventful. At the age of 15 months the first symptoms were neck pain and a mild head tilt to the left, leading to difficulties in running. Cranial CT at the age of 21 months gave a normal result. At 26 months Tl-weighted MRI showed an obscure hypointense signal in the right hemisphere of the cerebellum, with no signs that the surrounding tissue was affected. The clinical course was not progressive. The differential diagnosis took into account vasculitis, followed by edema, gliotic tissue changes, infectious disease, and glioma. On the child's admission to hospital at the age of 30 months, we found a mild head tilt to the left side. The girl's physical state was normal, and she had no enlarged organs. She was intellectually normal and there were no neurological deficits. Head circumference was now 1 cm above the 97th percentile. All laboratory investigations, including cerebrospinal fluid, were normal. No signs of inflammatory disease were found. Neurophysiolog-

627

Cho

ical examinations, including BAER (brainstem auditory evoked response), VEP (visually evoked potential), and EEG, showed normal results. Ins Methods

Localized proton MRS was performed at 2.0 T (Siemens Magnetom, Erlangen, Germany), with use of the standard imaging head coil. To simplify quantification of cerebral metabolite concentrations, spectra were obtained at short echo times (TE=20 ms) and long repetition times (TR=6000 ms, 64 accumulations for data averaging). Spectral analysis was fully automated to preclude user bias in spectral phasing, baseline estimation, and peak area integration. Technical details of data acquisition and spectral evaluation have been described elsewhere [5, 12]. Metabolite concentrations were compared with those of young adult controls because no age-matched data were available. However, low concentrations of N-acetylaspartate (NAA) and concentrations of choline-containing compounds (cho) and myoinositol (Ins) during early infancy have been demonstrated to reach adult levels at (NAA) or even before (Cho, Ins) the age of 2-3 years, largely in parallel with brain myelination [7, 11].

Cr NAA

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315

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Cr C ~ ~ I ~ Cho

Results

F i g u r e 1 shows a c o r o n a l T l - w e i g h t e d M R i m a g e o f the suspected lesion in the right h e m i s p h e r e o f the cerebellum. A l o c a l i z e d p r o t o n M R s p e c t r u m from a c o r r e s p o n d i n g volu m e o f interest ( V O I ) is d e p i c t e d in Fig. 2 (top), c o m p a r e d with proton M R spectra from a p p a r e n t l y n o r m a l parietal white (middle) and gray matter (bottom). Visual i n s p e c tion reveals c o n s i d e r a b l e alterations o f N A A , Cho, and Ins r e s o n a n c e s contrasting with the n o r m a l m e t a b o l i t e patterns in both g r a y and white cortical matter. Quantitative analy-

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2'.5

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112

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1'.o

o12

NAA

Cr

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alo

215

2'.0

Chemical shift (ppm)

Fig. 1 Tl-weighted MR image of the patient (3D FLASH, TR/ TE= 15/6 ms, flip angle 20 ~ 4-ram coronal section) demonstrating a hypointense area in the right hemisphere of the cerebellum. The box (16• 16 mm 2) indicates the 4.1-ml volume of interest (VOI) selected for MRS

Fig. 2 Localized proton MR spectra (STEAM, TR/TE/TM=6000/ 20/30 ms, 64 accumulations) of the cerebellar lesion (top: 4.1-ml VOI as in Fig. 1), parietal white matter (middle 5.l-ml VOI), and paramedian parietal gray matter (bottom 18-ml VOI). The tumor is characterized by markedly lowered N-acetylaspartate (NAA) and prominent elevations of choline-containing compounds (Cho) and myo-inositol (Ins), while the combined creatine and phosphocreatine (Cr) level is within normal ranges. White and gray matter spectra are not suggestive of any lesions. All spectra are scaled in proportion to volume, and processed and plotted using identical parameters

628

Table 1 Absolute concentrations (raM) of N-acetylaspartate (NAA), creatine and phosphocreatine (Cr), choline-containing compounds (Cho), and myo-inositol (Ins) in apparently healthy parietal white and gray matter and a cerebellar lesion of a 2.5-year-old girl. Control specimens (n=8) are from hemispheric cerebellar of young adults (mean age 27 years)

White matter Gray matter Cerebellar lesion Controls

NAA

Cr

Cho

Ins

6.9 6.4 4.1 8.8+1.6

4.7 4,9 5,7 7.4•

1.5 0.9 2.9 2.1•

2.6 3.7 7.4 6.3•

sis, as summarized in Table l, showed markedly lowered NAA concentrations and prounounced elevations of Cho and Ins levels in the lesion compared with either cerebellar control values (young adults) or the values recorded in apparently normal gray and white matter in the patient. Since these findings suggested a cerebellar tumor, neurosurgical exploration was planned and total extirpation of the tumor was possible. On histopathological investigation an astrocytoma (WHO II) was diagnosed. The patient made an excellent recovery: the head tilt disappeared and after 2 weeks the child was discharged with no signs of neurological or mental impairment. The spectral pattern of metabolite concentrations obtained from the lesion differed markedly from that of unaffected gray and white matter or of normal cerebellum. When correlated to total creatine (Cr) to exclude potential partial volume effects, the corresponding concentration ratios of NAA/Cr (0.73, normal: 1.21+_0.17), Cho/Cr (0.52 vs 0.28_+0.08), and Ins/Cr (1.30 vs 0.86+-0.41) showed statistically significant deviations (1-3 SD) from those in young adult controls. Taking the concentration ratio of Cho/NAA as a highly sensitive index of pathology, the current lesion (0.71) differs from normal cerebellum (0.24) by a factor of 3.

Discussion Owing to its neuronal origin, a decrease of N A A is commonly understood as an (irreversible) loss of or damage to neuroaxonal integrity, while increased levels of Cho and Ins are consistent with proliferative glial cell growth. In particular, Ins has only been found in glial cell preparations, and not in cultured neurons [1]. On the other hand, owing to spectroscopic overlap, the analysis cannot entirely exclude potential contributions of elevated glycine to the Ins resonance. It is noteworthy that proton MRS did not reveal enhanced concentrations of lactate in the lesion. Thus, an intact oxidative energy metabolism could be assumed, which suggested slow tissue growth and/or adequate vascularization. Together with the MRI appearance, the metabolic findings therefore suggested a low-grade glioma, in agreement with previous proton MRS studies of gliomas in adults [2, 3, 6]. This was confirmed by histology of the surgical specimen. Although the cellular heterogeneity of tumors represents an unsurmountable problem for in vivo assessments, in vitro proton MRS studies of brain tumors have shown metabolic differences between tumor cell lines [8, 13]. If optimized experimental strategies are backed up by careful interpretation of in vivo proton MRS data [3], then its diagnostic specificity at least allows discrimination between normal brain and neoplasms, and also other pathologies, such as cerebral cysts, edema, necrosis, infectious disease, and inborn errors of metabolism. The present case demonstrates the successful clinical utilization of a new and not yet fully explored modality that represents a noninvasive tool for use not only in differential diagnosis, but also in studying the clinical course after neurosurgical intervention.

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