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Magnetic Resonance Imaging 28 (2010) 1390–1394

Case report

N-Acetyl peak in MR spectra of intracranial metastaticmucinous adenocarcinomas

Xiang Liua,⁎, Barbara I. Germinb, Jianhui Zhonga, Sven Ekholma

aDepartment of Imaging Sciences, University of Rochester School of Medicine and Dentistry, PO Box 648, Rochester, NY 14642, USAbDepartment of Pathology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA

Received 10 June 2009; revised 16 April 2010; accepted 25 June 2010

Abstract

Absence of N-acetylaspartate (NAA) is one important diagnostic criterion of MR spectroscopy (MRS) that may suggest that anintracranial mass lesion is a metastasis. We report two cases of histopathology-confirmed intracranial metastatic mucinous adenocarcinoma,which predominantly showed a large metabolite peak at 2.0 ppm, mimicking an NAA peak of normal brain tissue. This finding could be ofhelp in the interpretation of MRS in cases of intracranial enhancing mass lesions, metastases or gliomas.© 2010 Elsevier Inc. All rights reserved.

Keywords: Metastatic mucinous adenocarcinoma; MR spectroscopy; N-Acetylaspartate; Glycoprotein

1. Introduction

MR spectroscopy (MRS) is widely used clinically to helpdifferentiate between intracranial metastases and intra-axialhigh-grade gliomas. Absence of N-acetylaspartate (NAA) isone diagnostic feature that can indicate an intracranialmetastasis [1–4]. We report two cases with histopatholog-ically confirmed intracranial metastatic mucinous adenocar-cinomas, which presented on MRS with a predominant, largemetabolite peak at 2.0 ppm that mimics the NAA peak ofnormal brain tissue.

2. Materials and methods

Two cases of biopsy-confirmed intracranial metastaticmucinous adenocarcinomas were examined on a clinicalMRI scanner (3T Signa HDX, GE Healthcare, Milwaukee,WI) prior to surgery. Besides the conventional routineclinical imaging protocol with and without contrast en-hancement, two-dimensional multivoxel chemical shiftimaging (CSI) proton MRS using a point resolvedspectroscopy sequence was performed. The parameters

⁎ Corresponding author. Tel.: +1 585 275 6363; fax: +1 585 473 4861E-mail address: xiang_liu@urmc.rochester.edu (X. Liu).

0730-725X/$ – see front matter © 2010 Elsevier Inc. All rights reserved.doi:10.1016/j.mri.2010.06.015

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included a field of view of 24×24 cm, a slice thickness of 1.5cm and a CSI matrix of 16×16, resulting in voxels of1.5×1.5×1.5 cm in size. One NEX (number of excitation)was used, with an echo time (TE) of 35 and 144 ms and arepetition time of 1000 ms. The volume of interest (VOI) forMRSI was positioned within the brain based on images inthree orthogonal planes (sagittal, coronal and axial planes) toprevent the subcutaneous fat signals from contributing to thespectra. The VOI covered the lesion and an area ofcontralateral hemisphere. Six presaturation bands wereplaced around the VOI to minimize contamination by thesurrounding tissue. The total duration of CSI acquisition wasabout 4 1/2 min.

Spectral apodization and spatial filters were applied to theraw spectra using the vendor predefined parameters (spectralGauss filter of 2.4 Hz, spatial Fermi filter of diameter 0.85and transition width 0.25) before Fourier transform. TheFourier-transformed data set was phase and baselinecorrected. Metabolite peaks including N-acetyl compound(“NAA”) at 2.0 ppm, choline-containing compounds (Cho) at3.22 ppm and creatine+phosphocreatine (Cr) at 3.01 ppmwere analyzed with Functool software (version 3.1.22)provided by the scanner vendor. For quantitative compar-isons of tumor and normal metabolic ratios, an ROI of 4voxels (with total area of 900 mm2) was placed within thetumor in both patients. Another ROI of the same size was

Fig. 1. Patient Case 1. (A) Post-contrast T1-weighted image for proton MRS localization displays a ring-enhancing lesion involving the right thalamus and themidbrain. A voxel within the lesion is identified with a green square. (B) MR spectrum of this voxel and an “N-acetyl compound”/Cr ratio of 2.45 detected byFunctool. (C) LCModel fit of the MR spectrum in the ROI shows a remarkable and dominant peak at 2.0 ppm.

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placed on the contralateral side of the brain for reference.The ratios of Cho/Cr and “NAA”/Cr as presented in thefollowing were calculated based on the MRS data withTE=144 ms only.

In addition to the Functool analysis, for Case 1, thespectral fit program LCModel (version 6.1) was subsequent-ly used. Peaks of reliably detected metabolites wereidentified with S.D. b20%, as suggested by LCModel [5,6].

2.1. Case 1

A 48-year-old female presented with left-sided weak-ness; she had no history of previous cancer. Post-contrastT1-weighted images showed a ring-enhanced lesion on theright side within the thalamus and midbrain. The Cho/Crand “NAA”/Cr ratios from a voxel within the lesion were1.12 and 2.45 (Fig. 1), respectively. The Cho/Cr and“NAA”/Cr ratios from the ROI in the contralateral, normalbrain tissue were 0.896 and 1.63, respectively (Fig. 2).

Fig. 2. Patient Case 1. (A) Localizing image with a voxel in the contralateral, normal brain tissue. (B) MR spectrum shows an NAA/Cr ratio of 1.63 by Functool

The LCModel fit revealed a remarkable and dominantNAA-like peak (Fig. 1C).

2.2. Case 2

A 77-year-old female presented with progressive confu-sion; she also had no prior history of cancer. Her MRI examrevealed a left thalamic ring-enhancing lesion on the T1-weighted images. The Cho/Cr and “NAA”/Cr ratios from avoxel within the lesion were 0.633 and 3.41, respectively.The Cho/Cr and “NAA”/Cr ratios from a voxel in thecontralateral, normal brain tissue were 0.465 and 1.56,respectively (Fig. 3).

3. Pathology findings

The cytopathology of the cerebral spinal fluid in Case 1revealed malignant tumor cells derived from mucinousadenocarcinoma (Fig. 4A). An immunocytochemical stain

.

Fig. 3. Patient Case 2. (A) Post-contrast T1-weighted image for protonMRS localization displays a ring-enhancing lesion involving the left thalamus. A voxel withinthe lesion is identified with a green square. (B)MR spectrum of this voxel shows an “N-acetyl compound”/Cr ratio of 3.41 detected by Functool. (C) Localizing imageshows a voxel in the contralateral, normal brain tissue, (D) MR spectrum of the voxel in Panel C shows NAA/Cr ratio of 1.56 detected by Functool.

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for CK7 was positive. Stains for CK20 and TTF-1 werenegative, which was consistent with a pancreatic/biliaryprimary cancer. Her brain tissue biopsy showed gliosis.

Fig. 4. Pathology images. (A) Hematoxylin and eosin, ×40 in Case 1: Metastatic neoplastic cells with the cytoplasm completely filled with “soap bubble”-likemucin vacuoles. (B) Diff Quick stain, ×40 in Case 2: Metastatic neoplastic cells with cytoplasm displaying mucin vacuoles. The cells are also suspended in amucinous background.

Case 2 (Fig. 4B) revealed metastatic mucinous adenocar-cinoma with signet ring cell features consistent with agastric cancer primary.

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4. Discussion

NAA is one of the main in vivo detectable metabolites innormal brain tissues. As NAA is an amino acid that is uniquefor the brain and is present in high concentrations in normalneurons and axons, it is commonly described as a marker ofneuronal integrity. Intracranial metastases most oftenoriginate from tissues outside the central nervous systemand subsequently consist of cells of non-neuronal origin. Theabsence of NAA in these lesions will thus make it animportant and typical feature of MRS spectra in anintracranial metastasis (Fig. 5). It has been noted that thesingle-voxel spectroscopy samples a smaller volume oftissue, and 2D CSI technique obtains spectroscopic infor-mation from multiple adjacent volumes over a large VOI in asingle measurement [2]. The presence of an NAA peak inintracranial lesions has usually been interpreted as contam-ination of the voxel from the surrounding normal braintissue, an effect of partial volume averaging [7–9].

However, the N-acetyl compound peak at 2 ppm consistsof primarily NAA and N-acetyl aspartylglutamate. Andre etal. [10] and Periakaruppan et al. [11] reported an N-acetyl(NAA-like) metabolite peak in the center of intracranialsinus mucocele and colloid-like cyst, respectively. Hascaliket al. [12] described an “NAA” peak in both the cystic andthe solid portion of an ovarian mucinous cystadenoma. Thelarge dominant NAA-like peak at 2.0 ppm in the center ofthese pathology-confirmed cases suggests that this resonanceis not related to NAA. This was further supported by an invitro proton nuclear magnetic resonance spectroscopicanalysis of surgical mucocele samples by Andre et al. [10]that indicated that an N-acetyl compound with the samemethyl group and chemical bonds may be responsible forthis peak. Andre et al. [10] and Periakaruppan et al. [11]hypothesized that the peak found in the intracranial sinusmucocele as well as the colloid-like cyst was probably

Fig. 5. An MRS sample intracranial, non-mucinous metastatic adenocarcinoma. (Aenhancing lesion, and a white square identifies a voxel within the lesion. (B) Single-is the typical MRS finding of intracranial metastases.

related to glycoproteins in mucin. Both these cases, the sinusmucocele and the colloid-like cyst, are clearly extra-axiallesions identified on conventional MR imaging.

The two cases presented in this article are intra-axial, ring-enhancing lesions that look like other intra-axial brainlesions, including high-grade gliomas and abscesses. Asring-enhancing brain metastases sometimes are difficult todistinguish from high-grade gliomas, even with the help ofMR perfusion-weighted imaging and diffusion imaging[3,4,13], the absence of NAA in MRS is an importantdiagnostic criterion to establish the diagnosis [1–4]. In bothour cases, the commercial MRS post-processing software(Functool) recognized the large, dominant 2.0-ppm peak asNAA. In addition, off-line processing with the LCMODELanalysis in one of the cases defined the peak as NAA. Theabnormal increased ratios of N-acetyl compound/Cr betweenthe lesion and the contralateral normal brain tissue (1.50 and2.19, respectively) in the present two cases indicate that thelarge and dominant 2.0-ppm peak may be induced by theintrinsic characteristics of the tumors rather than partialvolume effect from the contamination by the normal braintissue. The mechanism of this peak is unclear from thecurrent study, and in vitro chromatography or high-resolution NMR may be needed in the future to explorethe chemical origin of this peak. It may be related with aglycoprotein of N-acetyl glucosamine or galactosamine inmucin, and its appearance may cause confusion in tumordiagnosis. Björkman-Burtscher et al. [14] presented apreliminary report of a similar finding of an NAA-likepeak in a histologically confirmed cystic metastasis from amucinous adenocarcinoma. Opstad et al. [15] also describeda similar peak in MRS of brain metastasis, but none of theirintracranial lesions were histologically proven. It should,however, be noted that Guruprasad et al. [16] did not detectsuch an NAA-like peak in their case of an intracranialmetastatic mucinous adenocarcinoma.

) Localizing image post-contrast T1-weighted image shows the right frontalvoxel spectrum within this voxel shows no NAA-like peak at 2.0 ppm, which

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The cases reported in this article and what has been shownin literature previously suggest that intracranial metastaticmucinous adenocarcinomas may present with an NAA-likepeak that is not due to the effect of contamination fromnormal brain tissue. It is thus important to rule out a possiblecontamination from outside the lesion to avoid misinterpre-tation. However, the marked increase in the “NAA”/Cr ratio,which was much higher than normal brain tissue, may behelpful in the differentiation between intracranial metastatictumors with a high mucinous content and high-gradegliomas, as well as other metastatic lesions.

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