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Research ArticleADULT BRAIN
Open Access

Performance of Standardized Relative CBV for Quantifying Regional Histologic Tumor Burden in Recurrent High-Grade Glioma: Comparison against Normalized Relative CBV Using Image-Localized Stereotactic Biopsies

J.M. Hoxworth, J.M. Eschbacher, A.C. Gonzales, K.W. Singleton, G.D. Leon, K.A. Smith, A.M. Stokes, Y. Zhou, G.L. Mazza, A.B. Porter, M.M. Mrugala, R.S. Zimmerman, B.R. Bendok, D.P. Patra, C. Krishna, J.L. Boxerman, L.C. Baxter, K.R. Swanson, C.C. Quarles, K.M. Schmainda and L.S. Hu
American Journal of Neuroradiology March 2020, DOI: https://doi.org/10.3174/ajnr.A6486
J.M. Hoxworth
aFrom the Departments of Radiology (J.M.H., Y.Z., L.S.H.)
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  • ORCID record for J.M. Hoxworth
J.M. Eschbacher
fDepartments of Pathology (J.M.E.)
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A.C. Gonzales
bPsychiatry and Psychology (A.C.G.)
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K.W. Singleton
ePrecision Neurotherapeutics Lab (K.W.S., G.D.L., B.R.B., K.R.S.), Mayo Clinic in Arizona, Phoenix, Arizona
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G.D. Leon
ePrecision Neurotherapeutics Lab (K.W.S., G.D.L., B.R.B., K.R.S.), Mayo Clinic in Arizona, Phoenix, Arizona
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K.A. Smith
gNeurosurgery (K.A.S.)
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A.M. Stokes
iKeller Center for Imaging Innovation (A.M.S.), Barrow Neurological Institute, Phoenix, Arizona
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  • ORCID record for A.M. Stokes
Y. Zhou
aFrom the Departments of Radiology (J.M.H., Y.Z., L.S.H.)
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  • ORCID record for Y. Zhou
G.L. Mazza
jDepartment of Health Sciences Research (G.L.M.), Division of Biomedical Statistics and Informatics, Mayo Clinic Scottsdale, Scottsdale, Arizona
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  • ORCID record for G.L. Mazza
A.B. Porter
cNeuro-Oncology (A.B.P., M.M.M.)
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M.M. Mrugala
cNeuro-Oncology (A.B.P., M.M.M.)
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R.S. Zimmerman
dNeurosurgery (R.S.Z., C.K.)
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B.R. Bendok
ePrecision Neurotherapeutics Lab (K.W.S., G.D.L., B.R.B., K.R.S.), Mayo Clinic in Arizona, Phoenix, Arizona
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D.P. Patra
kDepartments of Neurosurgery (D.P.P.)
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C. Krishna
dNeurosurgery (R.S.Z., C.K.)
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J.L. Boxerman
mDepartment of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island
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L.C. Baxter
lNeuropsychology (L.C.B.), Mayo Clinic Hospital, Phoenix, Arizona
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K.R. Swanson
ePrecision Neurotherapeutics Lab (K.W.S., G.D.L., B.R.B., K.R.S.), Mayo Clinic in Arizona, Phoenix, Arizona
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C.C. Quarles
hNeurobiology (C.C.Q.)
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K.M. Schmainda
nDepartment of Radiology (K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin.
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L.S. Hu
aFrom the Departments of Radiology (J.M.H., Y.Z., L.S.H.)
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Abstract

BACKGROUND AND PURPOSE: Perfusion MR imaging measures of relative CBV can distinguish recurrent tumor from posttreatment radiation effects in high-grade gliomas. Currently, relative CBV measurement requires normalization based on user-defined reference tissues. A recently proposed method of relative CBV standardization eliminates the need for user input. This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects.

MATERIALS AND METHODS: We recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for new contrast-enhancing lesions concerning for recurrent tumor versus posttreatment radiation effects. We recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. We measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. We compared relative CBV performance to predict tumor content, including the Pearson correlation (r), against histologic tumor content (0%–100%) and the receiver operating characteristic area under the curve for predicting high-versus-low tumor content using binary histologic cutoffs (≥50%; ≥80% tumor).

RESULTS: Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%–100%) for normalized (r = 0.63, P < .001) and standardized (r = 0.66, P < .001) values. With binary cutoffs (ie, ≥50%; ≥80% tumor), predictive accuracies were similar for both standardized and normalized metrics and across relative CBV metrics. Median relative CBV achieved the highest area under the curve (normalized = 0.87, standardized = 0.86) for predicting ≥50% tumor, while fractional tumor burden achieved the highest area under the curve (normalized = 0.77, standardized = 0.80) for predicting ≥80% tumor.

CONCLUSIONS: Standardization of relative CBV achieves similar performance compared with normalized relative CBV and offers an important step toward workflow optimization and consensus methodology.

ABBREVIATIONS:

AUC
area under the curve
FTB
fractional tumor burden
GBM
glioblastoma multiforme
NAWM
normal-appearing white matter
PTRE
posttreatment radiation effects
rCBV
relative CBV
ROC
receiver operating characteristic

Footnotes

  • This work was supported by grants NS082609 (NIH), CA221938 (NIH), CA220378 (NIH), CA158079 (NIH), Mayo Clinic Foundation, James S. McDonnell Foundation, Ben and Catherine Ivy Foundation, and the Arizona Biomedical Research Commission (ABRC).

  • Disclosures: Kris A. Smith—UNRELATED: Payment for Lectures Including Service on Speakers Bureaus: Metabolic Health; Patents (Planned, Pending or Issued): OsteoMed. Richard S. Zimmerman—UNRELATED: Consultancy: NeuroPage, Medtronic. Leslie C. Baxter—RELATED: Grant: National Cancer Institute, Comments: My institution received funding as part of the grant under which this work was performed*; UNRELATED: Employment: Barrow Neurological Institute. Kristin R. Swanson—RELATED: Grant: NS082609, CA221938, CA220378, Mayo Clinic Foundation, James S. McDonnell Foundation, Ivy Foundation, Arizona Biomedical Research Commission*; UNRELATED: Board Membership: James S McDonnell Foundation Scientific Board; Payment for Development of Educational Presentations: multiple patents and applications but no funds. Christopher C. Quarles—RELATED: Grant: National Institutes of Health.* Kathleen M. Schmainda—RELATED: Grant: National Institutes of Health*; UNRELATED: Stock/Stock Options: IQ-AI Ltd, Comments: ownership interest; Other: Imaging Biometrics LLC, Comments: spouse’s salary. Leland S. Hu—RELATED: Grant: U01 CA220378, R01 CA221938, R21 NS082609, Mayo Clinic Foundation, Arizona Biomedical Research Commission*; UNRELATED: Patents (Planned, Pending or Issued): multiple patents but no money paid. *Money paid to the institution.

  • © 2020 by American Journal of Neuroradiology

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Performance of Standardized Relative CBV for Quantifying Regional Histologic Tumor Burden in Recurrent High-Grade Glioma: Comparison against Normalized Relative CBV Using Image-Localized Stereotactic Biopsies
J.M. Hoxworth, J.M. Eschbacher, A.C. Gonzales, K.W. Singleton, G.D. Leon, K.A. Smith, A.M. Stokes, Y. Zhou, G.L. Mazza, A.B. Porter, M.M. Mrugala, R.S. Zimmerman, B.R. Bendok, D.P. Patra, C. Krishna, J.L. Boxerman, L.C. Baxter, K.R. Swanson, C.C. Quarles, K.M. Schmainda, L.S. Hu
American Journal of Neuroradiology Mar 2020, DOI: 10.3174/ajnr.A6486

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Performance of Standardized Relative CBV for Quantifying Regional Histologic Tumor Burden in Recurrent High-Grade Glioma: Comparison against Normalized Relative CBV Using Image-Localized Stereotactic Biopsies
J.M. Hoxworth, J.M. Eschbacher, A.C. Gonzales, K.W. Singleton, G.D. Leon, K.A. Smith, A.M. Stokes, Y. Zhou, G.L. Mazza, A.B. Porter, M.M. Mrugala, R.S. Zimmerman, B.R. Bendok, D.P. Patra, C. Krishna, J.L. Boxerman, L.C. Baxter, K.R. Swanson, C.C. Quarles, K.M. Schmainda, L.S. Hu
American Journal of Neuroradiology Mar 2020, DOI: 10.3174/ajnr.A6486
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