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PLoS One. 2019 Nov 14;14(11):e0225093. doi: 10.1371/journal.pone.0225093. eCollection 2019.

Heterogeneity Diffusion Imaging of gliomas: Initial experience and validation.

Author information

1
Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, United States of America.
2
Department of Medical Imaging, Neuroradiology Section, University of Arizona, Tucson, Arizona, United States of America.
3
Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, Missouri, United States of America.
4
Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, United States of America.
5
Department of Biostatistics, Washington University in St. Louis, St. Louis, Missouri, United States of America.
6
Department of Neurosurgery, Washington University in St. Louis, St. Louis, Missouri, United States of America.
7
Department of Radiology, Division of Molecular Imaging and Therapeutics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
8
Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri, United States of America.

Abstract

OBJECTIVES:

Primary brain tumors are composed of tumor cells, neural/glial tissues, edema, and vasculature tissue. Conventional MRI has a limited ability to evaluate heterogeneous tumor pathologies. We developed a novel diffusion MRI-based method-Heterogeneity Diffusion Imaging (HDI)-to simultaneously detect and characterize multiple tumor pathologies and capillary blood perfusion using a single diffusion MRI scan.

METHODS:

Seven adult patients with primary brain tumors underwent standard-of-care MRI protocols and HDI protocol before planned surgical resection and/or stereotactic biopsy. Twelve tumor sampling sites were identified using a neuronavigational system and recorded for imaging data quantification. Metrics from both protocols were compared between World Health Organization (WHO) II and III tumor groups. Cerebral blood volume (CBV) derived from dynamic susceptibility contrast (DSC) perfusion imaging was also compared with the HDI-derived perfusion fraction.

RESULTS:

The conventional apparent diffusion coefficient did not identify differences between WHO II and III tumor groups. HDI-derived slow hindered diffusion fraction was significantly elevated in the WHO III group as compared with the WHO II group. There was a non-significantly increasing trend of HDI-derived tumor cellularity fraction in the WHO III group, and both HDI-derived perfusion fraction and DSC-derived CBV were found to be significantly higher in the WHO III group. Both HDI-derived perfusion fraction and slow hindered diffusion fraction strongly correlated with DSC-derived CBV. Neither HDI-derived cellularity fraction nor HDI-derived fast hindered diffusion fraction correlated with DSC-derived CBV.

CONCLUSIONS:

Conventional apparent diffusion coefficient, which measures averaged pathology properties of brain tumors, has compromised accuracy and specificity. HDI holds great promise to accurately separate and quantify the tumor cell fraction, the tumor cell packing density, edema, and capillary blood perfusion, thereby leading to an improved microenvironment characterization of primary brain tumors. Larger studies will further establish HDI's clinical value and use for facilitating biopsy planning, treatment evaluation, and noninvasive tumor grading.

Conflict of interest statement

Drs. Yong Wang and Qing Wang are the founders of InnoVoxel LLC, a startup company aiming to validate and clinically translate the diffusion basis spectrum imaging technique. A USA patent related to this technology has been filed (PCT/US2017/049440). Outside of this work, Dr. Tammie Benzinger discloses her relationships with Biogen, Roche, Jaansen, Eli Lilly and Avid Radiopharmaceuticals. Dr. Yong Wang discloses his relationship with Medtronic. The other authors report no conflicts of interest concerning the materials or methods used in this study or the findings specified in this paper. The financial disclosure does not alter our adherence to PLOS ONE policies on sharing data and materials.

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