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Research ArticlePediatric Neuroimaging
Open Access

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers

A.W. Autry, I. Park, C. Kline, H.-Y. Chen, J.W. Gordon, S. Raber, C. Hoffman, Y. Kim, K. Okamoto, D.B. Vigneron, J.M. Lupo, M. Prados, Y. Li, D. Xu and S. Mueller
American Journal of Neuroradiology January 2021, 42 (1) 178-184; DOI: https://doi.org/10.3174/ajnr.A6937
A.W. Autry
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
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I. Park
gDepartment of Radiology (I.P.), Chonnam National University College of Medicine and Hospital, Gwangju, Korea
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C. Kline
bDivision of Hematology/Oncology (C.K., S.R., C.H., M.P., S.M.), Department of Pediatrics
cDepartment of Neurology (C.K., S.M.)
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H.-Y. Chen
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
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J.W. Gordon
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
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S. Raber
bDivision of Hematology/Oncology (C.K., S.R., C.H., M.P., S.M.), Department of Pediatrics
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C. Hoffman
bDivision of Hematology/Oncology (C.K., S.R., C.H., M.P., S.M.), Department of Pediatrics
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Y. Kim
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
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K. Okamoto
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
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D.B. Vigneron
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
dBioengineering and Therapeutic Sciences (D.B.V.)
eNeurological Surgery (D.B.V., M.P., S.M.)
fUCSF/UC Berkeley Joint Graduate Group in Bioengineering (D.B.V., J.M.L., D.X.), University of California, San Francisco, San Francisco, California
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J.M. Lupo
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
fUCSF/UC Berkeley Joint Graduate Group in Bioengineering (D.B.V., J.M.L., D.X.), University of California, San Francisco, San Francisco, California
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M. Prados
bDivision of Hematology/Oncology (C.K., S.R., C.H., M.P., S.M.), Department of Pediatrics
eNeurological Surgery (D.B.V., M.P., S.M.)
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Y. Li
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
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D. Xu
aFrom the Departments of Radiology and Biomedical Imaging (A.W.A., H.-Y.C., J.W.G., Y.K., K.O., D.B.V., J.M.L., Y.L., D.X.)
fUCSF/UC Berkeley Joint Graduate Group in Bioengineering (D.B.V., J.M.L., D.X.), University of California, San Francisco, San Francisco, California
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S. Mueller
bDivision of Hematology/Oncology (C.K., S.R., C.H., M.P., S.M.), Department of Pediatrics
cDepartment of Neurology (C.K., S.M.)
eNeurological Surgery (D.B.V., M.P., S.M.)
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    FIG 1.

    HP-13C imaging of DIPG. HP-13C EPI of a 9-year-old male participant (P-01) with DIPG following injection of HP [1-13C]pyruvate. Maps of the temporally summed signal from HP [1-13C]pyruvate and downstream metabolites [1-13C]lactate and [13C]bicarbonate are overlaid on 1H FLAIR images, along with the ratio of [1-13C]lactate to [1-13C]pyruvate, which removes the shading of 13C hardware sensitivity. Within the hyper- and hypointense T2 lesion indicated by the yellow arrows, there is a subtle increase in [1-13C]lactate signal relative to the normal-appearing contralateral brain stem. The ratio of [1-13C]lactate to [1-13C]pyruvate also demonstrates a local maximum in this anatomic lesion (yellow arrow). Pyr indicates pyruvate; Lac, lactate; Bicarb, bicarbonate; AU, arbitrary units.

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    FIG 2.

    HP-13C spectroscopy of DIPG. HP-13C EPSI of a 12-year-old male participant (P-02) with DIPG following injection of HP [1-13C]pyruvate. Temporally summed 13C spectra are shown together with their spatial correspondence to a 1H FLAIR image from the center of the 2-cm-thick 13C volume (A). Spectra from normal-appearing tissue (B) and the lesion (C) illustrate individual HP metabolite resonances. The [13C]bicarbonate resonance is aliased from 160.8 ppm. Pyr indicates [1-13C]pyruvate; Pyr-H2O, [1-13C]pyruvate-hydrate; Lac, [1-13C]lactate; Bic, [13C]bicarbonate; Ala, [1-13C]alanine exclusively from outside the brain.

Tables

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    Table 1:

    Participant demographics

    Demographics
    Consented (n = 12)
     Age (median) (range) (yr)14 (8–17)
     Males (No.) (%)10 (83)
    Treatment (No. of patients)
     Completed protocol therapy6
     Eligible, withdrawna6
    Completed 13C injection (n = 6)
     Age (median) (range) (yr)14 (10–17)
     Males (No.) (%)5 (83)
    Diagnosis (anatomic location) (No.) (%)
     Diffuse intrinsic pontine glioma (pons)3 (50)
     Craniopharyngioma (suprasellar)1 (17)
     Medulloblastoma (posterior fossa)1 (17)
     Pineoblastoma (pineal gland)1 (17)
    Dose level (No. of patients)
     Dose level 13
     Dose level 23
    Safety (No. of events)
     Dose level toxicity0
     Adverse events0
    • ↵a Withdrawn due to the following: technical issue with MR imaging scanner (n = 1) or generating HP [1-13C]pyruvate (n = 3); change in participant choice to participate (n = 1); or disease progression before participation and participant did not return to University of California, San Francisco for follow-up treatment (n = 1).

    • View popup
    Table 2:

    Quality control for HP-13C injections

    Participant IDEPA Conc. (µM)[1-13C] Pyruvate Conc. (mM)Volume Injected (mL)Polarization (%)Temp. (oC)pHTime to Injection (sec)
    P-011.623023.044.034.67.756
    P-020.623221.842.531.97.675
    P-030.523516.038.831.07.766
    P-040.323036.038.130.77.753
    P-050.523120.843.932.17.655
    P-061.424222.233.630.97.570
    • Note:—EPA indicates electron paramagnetic agent; Conc., concentration; Temp, temperature.

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American Journal of Neuroradiology: 42 (1)
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A.W. Autry, I. Park, C. Kline, H.-Y. Chen, J.W. Gordon, S. Raber, C. Hoffman, Y. Kim, K. Okamoto, D.B. Vigneron, J.M. Lupo, M. Prados, Y. Li, D. Xu, S. Mueller
Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers
American Journal of Neuroradiology Jan 2021, 42 (1) 178-184; DOI: 10.3174/ajnr.A6937

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Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers
A.W. Autry, I. Park, C. Kline, H.-Y. Chen, J.W. Gordon, S. Raber, C. Hoffman, Y. Kim, K. Okamoto, D.B. Vigneron, J.M. Lupo, M. Prados, Y. Li, D. Xu, S. Mueller
American Journal of Neuroradiology Jan 2021, 42 (1) 178-184; DOI: 10.3174/ajnr.A6937
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