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Improved Turnaround Times | Median time to first decision: 12 days

Research ArticleORIGINAL RESEARCH

Identification of a single-dose, low flip angle based CBV threshold for fractional tumor burden (FTB) mapping in recurrent glioblastoma

Aliya Anil, Ashley M. Stokes, John P. Karis, Laura C. Bell, Jennifer Eschbacher, Kristofer Jennings, Melissa A. Prah, Leland S. Hu, Jerrold L. Boxerman, Kathleen M. Schmainda and C. Chad Quarles
American Journal of Neuroradiology May 2024, ajnr.A8357; DOI: https://doi.org/10.3174/ajnr.A8357
Aliya Anil
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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Ashley M. Stokes
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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John P. Karis
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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Laura C. Bell
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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Jennifer Eschbacher
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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Kristofer Jennings
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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Melissa A. Prah
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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Leland S. Hu
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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Jerrold L. Boxerman
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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Kathleen M. Schmainda
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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C. Chad Quarles
From the Department of Cancer Systems Imaging (A.A., C.C.Q.), and Department of Biostatistics (K.J.), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center (A.M.S.), Department of Neuroradiology (J.P.K.), and Department of Neuropathology (J.E.), Barrow Neurological Institute, Phoenix, Arizona, United States; Clinical Imaging Group (L.C.B.), Genentech Inc., South San Francisco, California, United States; Department of Biophysics (M.A.P., K.M.S.), Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Radiology (L.S.H.), Mayo Clinic, Phoenix, Arizona, United States; Department of Diagnostic Imaging (J.L.B.), Rhode Island Hospital, Providence, Rhode Island, United States. Laura C Bell is employed by Genentech Inc. Kathleen M. Schmainda has ownership interest in IQ-AI Ltd and Prism Clinical Imaging. Kathleen M. Schmainda has financial interest in Imaging Biometrics LLC. Kathleen M. Schmainda is a board member for Prism Clinical Imaging
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ABSTRACT

BACKGROUND AND PURPOSE: DSC-MRI can be used to generate fractional tumor burden (FTB) maps, via application of relative CBV thresholds, to spatially differentiate glioblastoma recurrence from post treatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MRI protocol using preload, a moderate flip angle (MFA, 60°) and post-processing leakage correction. Recently, a DSC-MRI protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected RCBV equivalent to the reference protocol. This study aims to identify the RCBV thresholds for the LFA protocol that generate the most accurate FTB maps, concordant with those obtained from the reference MFA protocol.

MATERIALS AND METHODS: Fifty-two patients with grade IV GBM who had prior surgical resection and received chemotherapy and radiotherapy were included in the study. Two sets of DSC-MRI data were collected sequentially first using LFA protocol with no preload, which served as the preload for the subsequent MFA protocol. Standardized relative CBV maps (sRCBV) were obtained for each patient and co-registered with the anatomical post-contrast T1-weighted images. The reference MFA-based FTB maps were computed using previously published sRCBV thresholds (1.0 and 1.56). An ROC analysis was conducted to identify the optimal, voxelwise LFA sRCBV thresholds, and the sensitivity, specificity, and accuracy of the LFA-based FTB maps were computed with respect to the MFA-based reference.

RESULTS: The mean sRCBV values of tumors across patients exhibited strong agreement (CCC = 0.99) between the two protocols. Using the ROC analysis, the optimal lower LFA threshold that accurately distinguishes PTRE from tumor recurrence was found to be 1.0 (sensitivity: 87.77%; specificity: 90.22%), equivalent to the ground truth. To identify aggressive tumor regions, the ROC analysis identified an upper LFA threshold of 1.37 (sensitivity: 90.87%; specificity: 91.10%) for the reference MFA threshold of 1.56.

CONCLUSION: For LFA-based FTB maps, a sRCBV threshold of 1.0 and 1.37 can differentiate PTRE from recurrent tumor. FTB maps aids in surgical planning, guiding pathological diagnosis and treatment strategies in the recurrent setting. This study further confirms the reliability of single-dose LFA-based DSC-MRI.

ABBREVIATIONS: LFA = low flip angle; MFA = moderate flip angle; sRCBV = standardized relative cerebral blood volume; FTB = fractional tumor burden; PTRE = post treatment radiation effects; ROC = receiver operating characteristics; CCC = concordance correlation coefficient.

Footnotes

  • The remaining authors declare no conflicts of interest related to the content of this article.

  • © 2024 by American Journal of Neuroradiology
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Accepted Manuscript
Identification of a single-dose, low flip angle based CBV threshold for fractional tumor burden (FTB) mapping in recurrent glioblastoma
Aliya Anil, Ashley M. Stokes, John P. Karis, Laura C. Bell, Jennifer Eschbacher, Kristofer Jennings, Melissa A. Prah, Leland S. Hu, Jerrold L. Boxerman, Kathleen M. Schmainda, C. Chad Quarles
American Journal of Neuroradiology May 2024, ajnr.A8357; DOI: 10.3174/ajnr.A8357
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Cite this article
Accepted Manuscript
Aliya Anil, Ashley M. Stokes, John P. Karis, Laura C. Bell, Jennifer Eschbacher, Kristofer Jennings, Melissa A. Prah, Leland S. Hu, Jerrold L. Boxerman, Kathleen M. Schmainda, C. Chad Quarles
Identification of a single-dose, low flip angle based CBV threshold for fractional tumor burden (FTB) mapping in recurrent glioblastoma
American Journal of Neuroradiology May 2024, ajnr.A8357; DOI: 10.3174/ajnr.A8357

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