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Published in: Cancer Imaging 1/2015

Open Access 01-12-2015 | Research article

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

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

Published in: Cancer Imaging | Issue 1/2015

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Abstract

Background

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).

Methods

In 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.

Results

The 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.

Conclusion

IDSI-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.
Appendix
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Literature
1.
go back to reference Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013;310:1842–50.PubMedCrossRef Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013;310:1842–50.PubMedCrossRef
2.
go back to reference Xie Q, Mittal S, Berens ME. Targeting adaptive glioblastoma: an overview of proliferation and invasion. Neuro Oncol. 2014;16:1575–84.PubMedCrossRef Xie Q, Mittal S, Berens ME. Targeting adaptive glioblastoma: an overview of proliferation and invasion. Neuro Oncol. 2014;16:1575–84.PubMedCrossRef
3.
go back to reference Dhermain FG, Hau P, Lanfermann H, Jacobs AH, van den Bent MJ. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol. 2010;9:906–20.PubMedCrossRef Dhermain FG, Hau P, Lanfermann H, Jacobs AH, van den Bent MJ. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol. 2010;9:906–20.PubMedCrossRef
4.
go back to reference la Fougere C, Suchorska B, Bartenstein P, Kreth FW, Tonn JC. Molecular imaging of gliomas with PET: opportunities and limitations. Neuro Oncol. 2011;13:806–19.PubMedCentralPubMedCrossRef la Fougere C, Suchorska B, Bartenstein P, Kreth FW, Tonn JC. Molecular imaging of gliomas with PET: opportunities and limitations. Neuro Oncol. 2011;13:806–19.PubMedCentralPubMedCrossRef
5.
go back to reference Kamson DO, Juhász C, Buth A, Kupsky WJ, Barger GR, Chakraborty PK, et al. Tryptophan PET in pretreatment delineation of newly-diagnosed gliomas: MRI and histological correlates. J Neurooncol. 2013;112:121–32.PubMedCentralPubMedCrossRef Kamson DO, Juhász C, Buth A, Kupsky WJ, Barger GR, Chakraborty PK, et al. Tryptophan PET in pretreatment delineation of newly-diagnosed gliomas: MRI and histological correlates. J Neurooncol. 2013;112:121–32.PubMedCentralPubMedCrossRef
6.
go back to reference Juhász C, Dwivedi S, Kamson DO, Michelhaugh SK, Mittal S. Comparison of amino acid positron emission tomography radiotracers for molecular imaging of primary and metastatic brain tumors. Mol Imaging. 2014; Epub ahead of print; doi: 10.2310/7290.2014.00015.6. Juhász C, Dwivedi S, Kamson DO, Michelhaugh SK, Mittal S. Comparison of amino acid positron emission tomography radiotracers for molecular imaging of primary and metastatic brain tumors. Mol Imaging. 2014; Epub ahead of print; doi: 10.​2310/​7290.​2014.​00015.​6.
7.
go back to reference Juhász C, Chugani DC, Muzik O, Wu D, Sloan AE, Barger G, et al. In vivo uptake and metabolism of alpha-[11C]methyl-L-tryptophan in human brain tumors. J Cereb Blood Flow Metab. 2006;26(3):345–57.PubMedCrossRef Juhász C, Chugani DC, Muzik O, Wu D, Sloan AE, Barger G, et al. In vivo uptake and metabolism of alpha-[11C]methyl-L-tryptophan in human brain tumors. J Cereb Blood Flow Metab. 2006;26(3):345–57.PubMedCrossRef
8.
go back to reference Batista CE, Juhász C, Muzik O, Kupsky WJ, Barger G, Chugani HT, et al. Imaging correlates of differential expression of indoleamine 2,3-dioxygenase in human brain tumors. Mol Imaging Biol. 2009;11:460–6.PubMedCentralPubMedCrossRef Batista CE, Juhász C, Muzik O, Kupsky WJ, Barger G, Chugani HT, et al. Imaging correlates of differential expression of indoleamine 2,3-dioxygenase in human brain tumors. Mol Imaging Biol. 2009;11:460–6.PubMedCentralPubMedCrossRef
9.
go back to reference Alkonyi B, Barger GR, Mittal S, Muzik O, Chugani DC, Bahl G, et al. Accurate differentiation of recurrent gliomas from radiation injury by kinetic analysis of α-11C-methyl-L-tryptophan PET. J Nucl Med. 2012;53:1058–64.PubMedCentralPubMedCrossRef Alkonyi B, Barger GR, Mittal S, Muzik O, Chugani DC, Bahl G, et al. Accurate differentiation of recurrent gliomas from radiation injury by kinetic analysis of α-11C-methyl-L-tryptophan PET. J Nucl Med. 2012;53:1058–64.PubMedCentralPubMedCrossRef
10.
go back to reference Juhász C, Chugani DC, Barger GR, Kupsky WJ, Charkraborty PK, Muzik O, et al. Quantitative PET imaging of tryptophan accumulation in glioma and remote cortex: correlation with tumor proliferative activity. Clin Nucl Med. 2012;37:838–42.PubMedCentralPubMedCrossRef Juhász C, Chugani DC, Barger GR, Kupsky WJ, Charkraborty PK, Muzik O, et al. Quantitative PET imaging of tryptophan accumulation in glioma and remote cortex: correlation with tumor proliferative activity. Clin Nucl Med. 2012;37:838–42.PubMedCentralPubMedCrossRef
11.
go back to reference Kamson DO, Mittal S, Robinette NL, Muzik O, Kupsky WJ, Barger GR, et al. Increased tryptophan uptake on PET has strong independent prognostic value in patients with a previously treated high-grade glioma. Neuro Oncol. 2014;16:1373–83.PubMedCrossRef Kamson DO, Mittal S, Robinette NL, Muzik O, Kupsky WJ, Barger GR, et al. Increased tryptophan uptake on PET has strong independent prognostic value in patients with a previously treated high-grade glioma. Neuro Oncol. 2014;16:1373–83.PubMedCrossRef
12.
go back to reference Chugani DC, Muzik O. Alpha[C-11]methyl-L-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism. J Cereb Blood Flow Metab. 2000;20:2–9.PubMedCrossRef Chugani DC, Muzik O. Alpha[C-11]methyl-L-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism. J Cereb Blood Flow Metab. 2000;20:2–9.PubMedCrossRef
13.
go back to reference Adams S, Braidy N, Bessede A, Brew BJ, Grant R, Teo C, et al. The kynurenine pathway in brain tumor pathogenesis. Cancer Res. 2012;72(22):5649–57.PubMedCrossRef Adams S, Braidy N, Bessede A, Brew BJ, Grant R, Teo C, et al. The kynurenine pathway in brain tumor pathogenesis. Cancer Res. 2012;72(22):5649–57.PubMedCrossRef
14.
go back to reference LaViolette PS, Mickevicius NJ, Cochran EJ, Rand SD, Connelly J, Bovi JA, et al. Precise ex vivo histological validation of heightened cellularity and diffusion-restricted necrosis in regions of dark apparent diffusion coefficient in 7 cases of high-grade glioma. Neuro Oncol. 2014;16:1599–606.PubMedCrossRef LaViolette PS, Mickevicius NJ, Cochran EJ, Rand SD, Connelly J, Bovi JA, et al. Precise ex vivo histological validation of heightened cellularity and diffusion-restricted necrosis in regions of dark apparent diffusion coefficient in 7 cases of high-grade glioma. Neuro Oncol. 2014;16:1599–606.PubMedCrossRef
15.
go back to reference Rose S, Fay M, Thomas P, Bourgeat P, Dowson N, Salvado O, et al. Correlation of MRI-derived apparent diffusion coefficients in newly diagnosed gliomas with [18F]-fluoro-L-dopa PET: what are we really measuring with minimum ADC? AJNR Am J Neuroradiol. 2013;34(4):758–64. doi:10.3174/ajnr.A3315. Epub 2012 Oct 18.PubMedCrossRef Rose S, Fay M, Thomas P, Bourgeat P, Dowson N, Salvado O, et al. Correlation of MRI-derived apparent diffusion coefficients in newly diagnosed gliomas with [18F]-fluoro-L-dopa PET: what are we really measuring with minimum ADC? AJNR Am J Neuroradiol. 2013;34(4):758–64. doi:10.​3174/​ajnr.​A3315. Epub 2012 Oct 18.PubMedCrossRef
17.
go back to reference Rahm V, Boxheimer L, Bruehlmeier M, Berberat J, Nitzsche EU, Remonda L, et al. Focal changes in diffusivity on apparent diffusion coefficient MR imaging and amino acid uptake on PET do not colocalize in nonenhancing low-grade gliomas. J Nucl Med. 2014;55(4):546–50. doi:10.2967/jnumed.113.130732. Epub 2014 Feb 24.PubMedCrossRef Rahm V, Boxheimer L, Bruehlmeier M, Berberat J, Nitzsche EU, Remonda L, et al. Focal changes in diffusivity on apparent diffusion coefficient MR imaging and amino acid uptake on PET do not colocalize in nonenhancing low-grade gliomas. J Nucl Med. 2014;55(4):546–50. doi:10.​2967/​jnumed.​113.​130732. Epub 2014 Feb 24.PubMedCrossRef
19.
go back to reference Panagiotaki E, Schneider T, Siow B, Hall MG, Lythgoe MF, Alexander DC. Compartment models of the diffusion MR signal in brain white matter: a taxonomy and comparision. Neuroimage. 2012;59(3):2241–54.PubMedCrossRef Panagiotaki E, Schneider T, Siow B, Hall MG, Lythgoe MF, Alexander DC. Compartment models of the diffusion MR signal in brain white matter: a taxonomy and comparision. Neuroimage. 2012;59(3):2241–54.PubMedCrossRef
20.
go back to reference Jeong JW, Asano E, Yeh FC, Chugani DC, Chugani HT. Independent component analysis tractography combined with a ball-stick model to isolate intravoxel crossing fibers of the corticospinal tracts in clinical diffusion MRI. Magn Reson Med. 2013;70:441–3.PubMedCentralPubMedCrossRef Jeong JW, Asano E, Yeh FC, Chugani DC, Chugani HT. Independent component analysis tractography combined with a ball-stick model to isolate intravoxel crossing fibers of the corticospinal tracts in clinical diffusion MRI. Magn Reson Med. 2013;70:441–3.PubMedCentralPubMedCrossRef
21.
go back to reference Gauvain KM, McKinstry RC, Mukherjee P, Perry A, Neil JJ, Kaufman BA, et al. Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging. AJR Am J Roentgenol. 2001;177:449–54.PubMedCrossRef Gauvain KM, McKinstry RC, Mukherjee P, Perry A, Neil JJ, Kaufman BA, et al. Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging. AJR Am J Roentgenol. 2001;177:449–54.PubMedCrossRef
22.
go back to reference Hayashida Y, Hirai T, Morishita S, Kitajima M, Murakami R, Korogi Y, et al. Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic type and tumor celluarity. AJNR Am J Neuroradiol. 2006;27:1419–25.PubMed Hayashida Y, Hirai T, Morishita S, Kitajima M, Murakami R, Korogi Y, et al. Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic type and tumor celluarity. AJNR Am J Neuroradiol. 2006;27:1419–25.PubMed
23.
go back to reference Kinoshita M, Hashimoto N, Goto T, Kagawa N, Kishima H, Izumoto S, et al. Fractional anisotropy and tumor cell density of the tumor core show positive correlation in diffusion tensor magnetic resonance imaging of malignant brain tumors. Neuroimage. 2008;43:1081–8.CrossRef Kinoshita M, Hashimoto N, Goto T, Kagawa N, Kishima H, Izumoto S, et al. Fractional anisotropy and tumor cell density of the tumor core show positive correlation in diffusion tensor magnetic resonance imaging of malignant brain tumors. Neuroimage. 2008;43:1081–8.CrossRef
24.
go back to reference Gerstner ER, Frosch MP, Batchelor TT. Diffusion magnetic resonance imaging detects pathologically confirmed, nonenhancing tumor progression in a patient with recurrent glioblastoma receiving bevacizumab. J Clin Oncol. 2009;28:e91–3.PubMedCrossRef Gerstner ER, Frosch MP, Batchelor TT. Diffusion magnetic resonance imaging detects pathologically confirmed, nonenhancing tumor progression in a patient with recurrent glioblastoma receiving bevacizumab. J Clin Oncol. 2009;28:e91–3.PubMedCrossRef
25.
go back to reference Ellingson BM, Balkin MG, Rand SD, Connelly JM, Quinsey C, LaViolette PS, et al. Validation of functional diffusion maps (fDMs) as a biomarker for human glioma celluarity. J Magn Reson Imaging. 2010;31:538–48.PubMedCentralPubMedCrossRef Ellingson BM, Balkin MG, Rand SD, Connelly JM, Quinsey C, LaViolette PS, et al. Validation of functional diffusion maps (fDMs) as a biomarker for human glioma celluarity. J Magn Reson Imaging. 2010;31:538–48.PubMedCentralPubMedCrossRef
26.
go back to reference Onishi N, Kanao S, Kataoka M, Iima M, Sakaguchi R, Kawai M, et al. Apparent diffusion coefficient as a potential surrogate marker for Ki-67 index in mucinous breast carcinoma. J Magn Reson Imaging. 2014;41:610–5.PubMedCrossRef Onishi N, Kanao S, Kataoka M, Iima M, Sakaguchi R, Kawai M, et al. Apparent diffusion coefficient as a potential surrogate marker for Ki-67 index in mucinous breast carcinoma. J Magn Reson Imaging. 2014;41:610–5.PubMedCrossRef
27.
go back to reference Mong S, Ellingson BM, Nghiemphu PL, Kim HJ, Mirsadraei L, Lai A, et al. Persistent diffusion-restricted lesions in bevacizumab-treated malignant gliomas are associated with improved survival compared with matched controls. AJNR Am J Neuroradiol. 2012;33:1763–70.PubMedCrossRef Mong S, Ellingson BM, Nghiemphu PL, Kim HJ, Mirsadraei L, Lai A, et al. Persistent diffusion-restricted lesions in bevacizumab-treated malignant gliomas are associated with improved survival compared with matched controls. AJNR Am J Neuroradiol. 2012;33:1763–70.PubMedCrossRef
28.
go back to reference Rieger J, Bahr O, Muller K, Franz K, Steinbach J, Hattingen E. Bavacizumab-induced diffusion restricted lesions in malignant glioma patients. J Neurooncol. 2010;99:49–56.PubMedCrossRef Rieger J, Bahr O, Muller K, Franz K, Steinbach J, Hattingen E. Bavacizumab-induced diffusion restricted lesions in malignant glioma patients. J Neurooncol. 2010;99:49–56.PubMedCrossRef
29.
go back to reference Yang I, Tihan T, Han SJ, Wrensch MR, Wiencke J, Sughrue ME, et al. CD8+ T-cell infiltrate in newly diagnosed glioblastoma is associated with long-term survival. J Clin Neurosci. 2010;17:1381–5.PubMedCentralPubMedCrossRef Yang I, Tihan T, Han SJ, Wrensch MR, Wiencke J, Sughrue ME, et al. CD8+ T-cell infiltrate in newly diagnosed glioblastoma is associated with long-term survival. J Clin Neurosci. 2010;17:1381–5.PubMedCentralPubMedCrossRef
30.
go back to reference Müller A, Brandenburg S, Turkowski K, Müller S, Vajkoczy P. Resident microglia, and not peripheral macrophages, are the main source of brain tumor mononuclear cells. Int J Cancer. 2014. doi: 10.1002/ijc.29379. Müller A, Brandenburg S, Turkowski K, Müller S, Vajkoczy P. Resident microglia, and not peripheral macrophages, are the main source of brain tumor mononuclear cells. Int J Cancer. 2014. doi: 10.1002/ijc.29379.
31.
Metadata
Title
Multi-modal imaging of tumor cellularity and Tryptophan metabolism in human Gliomas
Authors
Jeong-Won Jeong
Csaba Juhász
Sandeep Mittal
Edit Bosnyák
David O. Kamson
Geoffrey R. Barger
Natasha L. Robinette
William J. Kupsky
Diane C. Chugani
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cancer Imaging / Issue 1/2015
Electronic ISSN: 1470-7330
DOI
https://doi.org/10.1186/s40644-015-0045-1

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