Multi-modal imaging of tumor cellularity and Tryptophan metabolism in human Gliomas.

Jeong-Won Jeong,Diane C Chugani,Natasha L Robinette,Geoffrey R Barger,Csaba Juhász,Edit Bosnyák,Sandeep Mittal,William J Kupsky,David O Kamson

doi:10.1186/s40644-015-0045-1

Jeong-Won Jeong, Diane C Chugani + Show 7 more

Open Access

https://doi.org/10.1186/s40644-015-0045-1

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Abstract

BackgroundTo assess gliomas using image-based estimation of cellularity, we utilized isotropic diffusion spectrum imaging (IDSI) on clinically feasible diffusion tensor imaging (DTI) and compared it with amino acid uptake measured by α[11C]methyl-L-tryptophan positron emission tomography (AMT-PET).MethodsIn 10 patients with a newly-diagnosed glioma, metabolically active tumor regions were defined in both FLAIR hyperintense areas and based on increased uptake on AMT-PET. A recently developed independent component analysis with a ball and stick model was extended to perform IDSI in clinical DTI data. In tumor regions, IDSI was used to define tumor cellularity which was compared between low and high grade glioma and correlated with the glioma proliferative index.ResultsThe IDSI-derived cellularity values were elevated in both FLAIR and AMT-PET-derived regions of high-grade gliomas. ROC curve analysis found that the IDSI-derived cellularity can provide good differentiation of low-grade from high-grade gliomas (accuracy/sensitivity/specificity of 0.80/0.80/0.80). . Both apparent diffusion coefficient (ADC) and IDSI-derived cellularity showed a significant correlation with the glioma proliferative index (based on Ki-67 labeling; R = 0.95, p < 0.001), which was particularly strong when the tumor regions were confined to areas with high tryptophan uptake excluding areas with peritumoral edema.ConclusionIDSI-MRI combined with AMT-PET may provide a multi-modal imaging tool to enhance pretreatment assessment of human gliomas by evaluating tumor cellularity and differentiate low-grade form high-grade gliomas.Electronic supplementary materialThe online version of this article (doi:10.1186/s40644-015-0045-1) contains supplementary material, which is available to authorized users.

Highlights

To assess gliomas using image-based estimation of cellularity, we utilized isotropic diffusion spectrum imaging (IDSI) on clinically feasible diffusion tensor imaging (DTI) and compared it with amino acid uptake measured by α[11C]methyl-L-tryptophan positron emission tomography (AMT-PET)
The present study investigates whether the diffusion basis spectrum imaging (DBSI) technique can be implemented for clinically feasible diffusion tensor imaging (DTI) studies which have been widely used for axonal tractography analysis to guide presurgical planning of tumor resection
As marked by white arrows, the IDSI-derived cellularity detected a cluster of voxels in the region showing increased AMT-standardized uptake value (SUV) and decreased apparent diffusion coefficient (ADC) values in both grade IV gliomas

Summary

Introduction

To assess gliomas using image-based estimation of cellularity, we utilized isotropic diffusion spectrum imaging (IDSI) on clinically feasible diffusion tensor imaging (DTI) and compared it with amino acid uptake measured by α[11C]methyl-L-tryptophan positron emission tomography (AMT-PET). Current clinical neuroimaging techniques, including T1-weighted images with gadolinium (GAD) and fluidattenuated inversion recovery (FLAIR), do not accurately differentiate regions with proliferating tumor cells from vasogenic edema and necrosis, and they are inaccurate in predicting glioma grade and proliferative. Several different amino acid PET radiotracers, including [11C]methionine, 18F-fluoroethyl-tyrosine (FET), 18F-fluoro-Ldihydroxy-phenylalanine (FDOP A), and α[11C]methyl-L-tryptophan (AMT) have been tested for glioma imaging, and each of them has their unique advantages and limitations [6]. In clinical studies, increased AMT uptake was found to be useful to: (i) detect both low- and high-grade gliomas and identify gliomainfiltrated brain in non-enhancing brain regions (verified by histology) [5,6,7]; (ii) accurately differentiate recurrent gliomas from radiation injury [9]; and (iii) predict post-treatment survival in malignant gliomas [11]. PET has limitations, including relatively low spatial resolution and limited clinical availability and high cost as compared to MRI techniques

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