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Research ArticlePEDIATRICS

Citrate in Pediatric CNS Tumors?

Z.A. Seymour, A. Panigrahy, J.L. Finlay, M.D. Nelson and S. Blüml
American Journal of Neuroradiology May 2008, 29 (5) 1006-1011; DOI: https://doi.org/10.3174/ajnr.A1018
Z.A. Seymour
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A. Panigrahy
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J.L. Finlay
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M.D. Nelson Jr
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S. Blüml
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    Fig 1.

    Short TE PRESS 1H-MR spectroscopy of pediatric brain tumors. Shown are spectra of DIBSG (A), ependymoma (B), and anaplastic astrocytoma (C) with a complex signal centered at 2.6 ppm consistent with citrate (D).

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    Fig 2.

    Signal modulation of in vivo PRESS spectra of anaplastic astrocytoma (i) and DIBSG (ii + iii) acquired with different TE. In vivo spectra acquired at TE of 35 ms (A), 144 ms (B), and 316 ms (C) from the same ROI are compared with spectra obtained from a citrate model solution at the same conditions. The complex signal centered at 2.6 ppm in tumor spectra shows the same J-modulation as citrate. At a TE of 316 ms, the center peaks of citrate are inverted.

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    Fig 3.

    Time course of citrate in DIBSG. A, Nonrandom residual signal, not accounted for by standard metabolites included in the LCModel basis set and consistent with citrate, can be detected in the MR spectrum obtained from a representative patient at the time of initial diagnosis. This signal is less readily detected in follow-up studies of this patient at 7 and 11 months when there was clinical progression of disease. Spectra are scaled to measured absolute concentrations to allow direct comparison of peak areas. Shown are unfiltered raw data (thin line) and the LCModel fit to the data (thick line). B, Plotted are tumor citrate concentrations versus time after initial diagnoses obtained from 6 patients in whom studies were performed repeatedly. Concentrations of citrate decrease significantly with time.

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    Fig 4.

    MR spectroscopy of age-matched controls. There is no evidence for citrate in spectra of age-matched control subjects as illustrated in a representative PRESS (TE, 35 ms) spectrum of occipital gray matter (A). Spectra from model solutions of citrate and NAA are shown for comparison (B). Note that the NAA peak at approximately 2.7 ppm does not co-resonate with citrate.

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    Fig 5.

    MR spectroscopy of premature brain. A, An MR spectrum of a premature baby (gestational age, 33 weeks; 7 weeks premature) who underwent an MR examination to rule out white matter injury is shown. The MR images were interpreted as normal, and neurologic sequelae are not reported at this stage. A small signal at 2.6 ppm consistent with citrate is detected. Note that the low levels of NAA are normal for premature brain.24 B, T2-weighted MR image indicating the ROI.

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    Fig 6.

    Citrate metabolism. Citrate is an intermediate in the TCA cycle. Citrate is also used to transport acetyl-CoA carbons to the cytoplasm for the biosynthesis of fatty acids to store energy and for membrane generation.

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    Table 1:

    “Apparent” citrate concentrations (mmol/kg) and prevalence in common pediatric brain tumors

    AllDIBSGA/AAE/AEMBLPA
    Subjects851214142223
    Mean Cit2.3 ± 1.74.0 ± 1.12.6 ± 1.82.9 ± 2.21.9 ± 1.2*1.4 ± 1.1**
    Cit CRLB49 ± 41%22 ± 7%37 ± 25%46 ± 67%56 ± 37%*64 ± 37%**
    #CRLB < 25%26 (31%)8 (67%)5 (36%)5 (36%)5 (23%)3 (13%)
    • Note:—Cit indicates citrate; DIBSG, diffuse intrinsic brain stem glioma; A/AA, low-grade and anaplastic astrocytoma; E/AE, low-grade and anaplastic ependymoma; MBL, medulloblastoma; PA, pilocytic astrocytoma; CRLB, Cramer-Rao lower bounds; #CLRB < 25%, number of subjects in whom CRLB for Cit was less than 25%.

    • Represents significance compared with DIBSG.

    • * P < .001.

    • ** P < .0001. Mean CRLB were computed from all spectra.

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    Table 2:

    Summary of the prevalence of low and high Cramer-Rao lower bounds (CRLB) for citrate detection in spectra acquired in controls with negative MR imaging results and unremarkable clinical follow-up

    AllAge > 6 Months (Group A)Age < 6 Months (Group B)
    Subjects (Spectra)Subjects (Spectra)Subjects (Spectra)
    #CRLB < 25%39 (43)0 (0)39 (43)
    #CRLB ≥ 25%430 (572)275 (359)155 (213)
    Total469 (615)275 (359)194 (256)
    Mean Cit CRLB240% ± 348%357% ± 394%80% ± 173%*
    • Note:—CRLB indicates Cramer-Rao lower bounds; #CLRB < 25%, number of subjects in whom CRLB for Cit was less than 25%; #CRLB ≥ 25%, number of subjects in whom CRLB for Cit was equal to or greater than 25%.

    • * P < .0001 (2-sided Student ttest) group A vs. group B.

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American Journal of Neuroradiology: 29 (5)
American Journal of Neuroradiology
Vol. 29, Issue 5
May 2008
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Cite this article
Z.A. Seymour, A. Panigrahy, J.L. Finlay, M.D. Nelson, S. Blüml
Citrate in Pediatric CNS Tumors?
American Journal of Neuroradiology May 2008, 29 (5) 1006-1011; DOI: 10.3174/ajnr.A1018

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Citrate in Pediatric CNS Tumors?
Z.A. Seymour, A. Panigrahy, J.L. Finlay, M.D. Nelson, S. Blüml
American Journal of Neuroradiology May 2008, 29 (5) 1006-1011; DOI: 10.3174/ajnr.A1018
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