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Published in: EJNMMI Research 1/2019

Open Access 01-12-2019 | Original research

Radiomic detection of microscopic tumorous lesions in small animal liver SPECT imaging

Authors: Dániel S. Veres, Domokos Máthé, Nikolett Hegedűs, Ildikó Horváth, Fanni J. Kiss, Gabriella Taba, Edit Tóth-Bodrogi, Tibor Kovács, Krisztián Szigeti

Published in: EJNMMI Research | Issue 1/2019

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Abstract

Background

Our aim was to present a new data analysis technique for the early detection of tumorous lesions using single-photon emission computed tomography (SPECT) imaging. Beyond standardized uptake value (SUV) and standardized uptake concentration (SUC), the skewness and kurtosis parameters of whole liver activity distribution histograms were examined in SPECT images to reveal the presence of tumorous cells.

Methods

Four groups of mice were used in our experiment: a healthy control group, a group of obese mice with high body mass index, and two tumorous groups (primary liver cancer group with chemically induced hepatocellular carcinoma (HCC); metastatic liver tumor group—xenograft of human melanoma (HM)). For the SPECT measurements, 99mTc-labeled aggregated albumin nanoparticles were administered intravenously 2 h before the liver SPECT scans (NanoSPECT/CT, Silver Upgrade, Mediso Ltd., Hungary) to image liver macrophages. Finally, SUV, SUC, skewness, and kurtosis of activity distributions were calculated from segmented whole liver volumes.

Results

HCC animals showed moderate 99mTc-albumin particle uptake with some visually identified cold spots indicating the presence of tumors. The visual detection of cold spots however was not a reliable marker of tumorous tissue in the metastatic group. The calculated SUV, SUC, and kurtosis parameters were not able to differentiate between the healthy and the tumorous groups. However, healthy and tumorous groups could be distinguished by comparing the skewness of the activity distribution.

Conclusion

Based on our results, 99mTc-albumin nanoparticle injection followed by liver SPECT activity distribution skewness calculation is a suitable image analysis tool. This makes possible to effectively and quantitatively investigate liver macrophage inhomogeneity and identify invisible but present liver cold spot lesions. Skewness as a direct image-derived parameter is able to show altered tissue function even before the visual manifestation of liver tumor foci. The skewness of activity distribution might be related to an inhomogeneous distribution of macrophage cells as a consequence of microscopic tumor burden in the liver.
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Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008, Cancer incidence and mortality worldwide: IARC CancerBased No 10 [Internet]. Lyon: International Agency for Research on Cancer; 2010. Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008, Cancer incidence and mortality worldwide: IARC CancerBased No 10 [Internet]. Lyon: International Agency for Research on Cancer; 2010.
2.
go back to reference Sørensen M, Frisch K, Bender D, et al. The potential use of 2-[18 F] fluoro-2-deoxy-D-galactose as a PET/CT tracer for detection of hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2011;38(9):1723–31.PubMedPubMedCentralCrossRef Sørensen M, Frisch K, Bender D, et al. The potential use of 2-[18 F] fluoro-2-deoxy-D-galactose as a PET/CT tracer for detection of hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2011;38(9):1723–31.PubMedPubMedCentralCrossRef
3.
go back to reference Sørensen M, Mikkelsen KS, Frisch K, et al. Hepatic galactose metabolism quantified in humans using 2-18F-fluoro-2-deoxy-D-galactose PET/CT. J Nucl Med. 2011;52(10):1566–72.PubMedCrossRef Sørensen M, Mikkelsen KS, Frisch K, et al. Hepatic galactose metabolism quantified in humans using 2-18F-fluoro-2-deoxy-D-galactose PET/CT. J Nucl Med. 2011;52(10):1566–72.PubMedCrossRef
4.
go back to reference Cao Y, Wang H, Johnson TD, et al. Prediction of liver function by using magnetic resonance-based portal venous perfusion imaging. Int J Radiat Oncol Biol Phys. 2013;85(1):258–63.PubMedCrossRef Cao Y, Wang H, Johnson TD, et al. Prediction of liver function by using magnetic resonance-based portal venous perfusion imaging. Int J Radiat Oncol Biol Phys. 2013;85(1):258–63.PubMedCrossRef
5.
go back to reference Sirlin CB, Hussain HK, Jonas E, et al. Consensus report from the 6th international forum for liver MRI using gadoxetic acid. J Magn Reson Imaging. 2014;40(3):516–29.PubMedCrossRef Sirlin CB, Hussain HK, Jonas E, et al. Consensus report from the 6th international forum for liver MRI using gadoxetic acid. J Magn Reson Imaging. 2014;40(3):516–29.PubMedCrossRef
6.
go back to reference Ringe KI, et al. Gadoxetate disodium–enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. Am J Roentgenol. 2010;195(1):13–28.CrossRef Ringe KI, et al. Gadoxetate disodium–enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. Am J Roentgenol. 2010;195(1):13–28.CrossRef
7.
go back to reference Cruite I, Schroeder M, Merkle EM, et al. Gadoxetate disodium–enhanced MRI of the liver: part 2, protocol optimization and lesion appearance in the cirrhotic liver. Am J Roentgenol. 2010;195(1):29–41.CrossRef Cruite I, Schroeder M, Merkle EM, et al. Gadoxetate disodium–enhanced MRI of the liver: part 2, protocol optimization and lesion appearance in the cirrhotic liver. Am J Roentgenol. 2010;195(1):29–41.CrossRef
8.
go back to reference Beppu T, Hayashi H, Okabe H, et al. Liver functional volumetry for portal vein embolization using a newly developed 99m Tc-galactosyl human serum albumin scintigraphy SPECT–computed tomography fusion system. J Gastroenterol. 2011;46(7):938–43.PubMedCrossRef Beppu T, Hayashi H, Okabe H, et al. Liver functional volumetry for portal vein embolization using a newly developed 99m Tc-galactosyl human serum albumin scintigraphy SPECT–computed tomography fusion system. J Gastroenterol. 2011;46(7):938–43.PubMedCrossRef
10.
go back to reference Young H, Baum R, Cremerius U, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. Eur J Cancer. 1999;35(13):1773–82.PubMedCrossRef Young H, Baum R, Cremerius U, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. Eur J Cancer. 1999;35(13):1773–82.PubMedCrossRef
11.
go back to reference Wahl RL, Jacene H, Kasamon Y, et al. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–50S.PubMedCrossRef Wahl RL, Jacene H, Kasamon Y, et al. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–50S.PubMedCrossRef
12.
go back to reference Boellaard R, O’Doherty MJ, Weber WA, et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37(1):181.PubMedCrossRef Boellaard R, O’Doherty MJ, Weber WA, et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37(1):181.PubMedCrossRef
13.
go back to reference Ryu IS, Kim JS, Roh JL, et al. Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by 18 F-FDG PET/CT in squamous cell carcinoma of the oral cavity. Eur J Nucl Med Mol Imaging. 2014;41(3):452–61.PubMedCrossRef Ryu IS, Kim JS, Roh JL, et al. Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by 18 F-FDG PET/CT in squamous cell carcinoma of the oral cavity. Eur J Nucl Med Mol Imaging. 2014;41(3):452–61.PubMedCrossRef
14.
go back to reference Klabatsa A, Chicklore S, Barrington SF, et al. The association of 18 F-FDG PET/CT parameters with survival in malignant pleural mesothelioma. Eur J Nucl Med Mol Imaging. 2014;41(2):276–82.PubMedCrossRef Klabatsa A, Chicklore S, Barrington SF, et al. The association of 18 F-FDG PET/CT parameters with survival in malignant pleural mesothelioma. Eur J Nucl Med Mol Imaging. 2014;41(2):276–82.PubMedCrossRef
15.
go back to reference Hyun SH, Ahn HK, Kim H, et al. Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2014;41(1):50–8.PubMedCrossRef Hyun SH, Ahn HK, Kim H, et al. Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2014;41(1):50–8.PubMedCrossRef
16.
go back to reference Choi E, Ha S, Kim H, et al. Total lesion glycolysis by 18 F-FDG PET/CT is a reliable predictor of prognosis in soft-tissue sarcoma. Eur J Nucl Med Mol Imaging. 2013;40(12):1836–42.PubMedCrossRef Choi E, Ha S, Kim H, et al. Total lesion glycolysis by 18 F-FDG PET/CT is a reliable predictor of prognosis in soft-tissue sarcoma. Eur J Nucl Med Mol Imaging. 2013;40(12):1836–42.PubMedCrossRef
17.
go back to reference Maffione AM, Ferretti A, Grassetto G, et al. Fifteen different 18 F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy. Eur J Nucl Med Mol Imaging. 2013;40(6):853–64.PubMedCrossRef Maffione AM, Ferretti A, Grassetto G, et al. Fifteen different 18 F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy. Eur J Nucl Med Mol Imaging. 2013;40(6):853–64.PubMedCrossRef
18.
go back to reference Bowen SR, Chapman TR, Borgman J, et al. Measuring total liver function on sulfur colloid SPECT/CT for improved risk stratification and outcome prediction of hepatocellular carcinoma patients. EJNMMI Res. 2016;6(1):57.PubMedPubMedCentralCrossRef Bowen SR, Chapman TR, Borgman J, et al. Measuring total liver function on sulfur colloid SPECT/CT for improved risk stratification and outcome prediction of hepatocellular carcinoma patients. EJNMMI Res. 2016;6(1):57.PubMedPubMedCentralCrossRef
19.
go back to reference Jennings M, Marcu LG, Bezak E. PET-specific parameters and radiotracers in theoretical tumour modelling. In: Computational and Mathematical Methods in Medicine vol. 2015, Article ID 415923, 11 pages; 2015. Jennings M, Marcu LG, Bezak E. PET-specific parameters and radiotracers in theoretical tumour modelling. In: Computational and Mathematical Methods in Medicine vol. 2015, Article ID 415923, 11 pages; 2015.
20.
go back to reference Ganeshan B, Goh V, Mandeville HC, et al. Non–small cell lung cancer: histopathologic correlates for texture parameters at CT. Radiology. 2013;266(1):326–36.PubMedCrossRef Ganeshan B, Goh V, Mandeville HC, et al. Non–small cell lung cancer: histopathologic correlates for texture parameters at CT. Radiology. 2013;266(1):326–36.PubMedCrossRef
21.
go back to reference Rutman AM, Kuo MD. Radiogenomics: creating a link between molecular diagnostics and diagnostic imaging. Eur J Radiol. 2009;70(2):232–41.PubMedCrossRef Rutman AM, Kuo MD. Radiogenomics: creating a link between molecular diagnostics and diagnostic imaging. Eur J Radiol. 2009;70(2):232–41.PubMedCrossRef
22.
go back to reference Lambin P, Rios-Velazquez E, Leijenaar R, et al. Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer. 2012;48(4):441–6.PubMedPubMedCentralCrossRef Lambin P, Rios-Velazquez E, Leijenaar R, et al. Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer. 2012;48(4):441–6.PubMedPubMedCentralCrossRef
23.
go back to reference Asselin M, O’Connor JPB, Boellaard R, et al. Quantifying heterogeneity in human tumours using MRI and PET. Eur J Cancer. 2012;48(4):447–55.PubMedCrossRef Asselin M, O’Connor JPB, Boellaard R, et al. Quantifying heterogeneity in human tumours using MRI and PET. Eur J Cancer. 2012;48(4):447–55.PubMedCrossRef
24.
go back to reference Hainc N, Stipppich C, Stieltjes B, et al. Experimental texture analysis in glioblastoma: a methodological study. Investig Radiol. 2017;52(6):367–73.CrossRef Hainc N, Stipppich C, Stieltjes B, et al. Experimental texture analysis in glioblastoma: a methodological study. Investig Radiol. 2017;52(6):367–73.CrossRef
25.
go back to reference Bundschuh RA, Dinges J, Neumann L, et al. Textural parameters of tumor heterogeneity in 18F-FDG PET/CT for therapy response assessment and prognosis in patients with locally advanced rectal cancer. J Nucl Med. 2014;55(6):891–7.PubMedCrossRef Bundschuh RA, Dinges J, Neumann L, et al. Textural parameters of tumor heterogeneity in 18F-FDG PET/CT for therapy response assessment and prognosis in patients with locally advanced rectal cancer. J Nucl Med. 2014;55(6):891–7.PubMedCrossRef
26.
go back to reference Wagner F, Hakami YA, Warnock G, et al. Comparison of contrast-enhanced CT and [18F]DG PET/CT analysis using kurtosis and skewness in patients with primary colorectal cancer. Mol Imaging Biol. 2017;19(5):795–803.PubMedCrossRef Wagner F, Hakami YA, Warnock G, et al. Comparison of contrast-enhanced CT and [18F]DG PET/CT analysis using kurtosis and skewness in patients with primary colorectal cancer. Mol Imaging Biol. 2017;19(5):795–803.PubMedCrossRef
27.
go back to reference Veres DS, Máthé D, Futó I, et al. Quantitative liver lesion volume determination by nanoparticle-based SPECT. Mol Imaging Biol. 2014;16(2):167–72.PubMedCrossRef Veres DS, Máthé D, Futó I, et al. Quantitative liver lesion volume determination by nanoparticle-based SPECT. Mol Imaging Biol. 2014;16(2):167–72.PubMedCrossRef
28.
go back to reference Fullár A, Baghy K, Deák F, et al. Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3b pathways in vivo. PLoS One. 2014;9(4):e93469.PubMedPubMedCentralCrossRef Fullár A, Baghy K, Deák F, et al. Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3b pathways in vivo. PLoS One. 2014;9(4):e93469.PubMedPubMedCentralCrossRef
29.
go back to reference Ladányi A, Tímár J, Paku S, et al. Selection and characterization of human melanoma lines with different liver-colonizing capacity. Int J Cancer. 1990;46(3):456–61.PubMedCrossRef Ladányi A, Tímár J, Paku S, et al. Selection and characterization of human melanoma lines with different liver-colonizing capacity. Int J Cancer. 1990;46(3):456–61.PubMedCrossRef
30.
go back to reference Otsu N. A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern. 1979;9(1):62–6.CrossRef Otsu N. A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern. 1979;9(1):62–6.CrossRef
31.
go back to reference Zasadny KR, Wahl RL. Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with body weight and a method for correction. Radiology. 1993;189(3):847–50.PubMedCrossRef Zasadny KR, Wahl RL. Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with body weight and a method for correction. Radiology. 1993;189(3):847–50.PubMedCrossRef
32.
go back to reference Chaddad A, Tanougast C. High-throughput quantification of phenotype heterogeneity using statistical features. Adv Bioinforma. 2015;2015:e728164.CrossRef Chaddad A, Tanougast C. High-throughput quantification of phenotype heterogeneity using statistical features. Adv Bioinforma. 2015;2015:e728164.CrossRef
33.
go back to reference Ditmer A, Zhang B, Shujaat T, et al. Diagnostic accuracy of MRI texture analysis for grading gliomas. J Neurooncol. 2018;140(3):583–9 Epub ahead of print.PubMedCrossRef Ditmer A, Zhang B, Shujaat T, et al. Diagnostic accuracy of MRI texture analysis for grading gliomas. J Neurooncol. 2018;140(3):583–9 Epub ahead of print.PubMedCrossRef
Metadata
Title
Radiomic detection of microscopic tumorous lesions in small animal liver SPECT imaging
Authors
Dániel S. Veres
Domokos Máthé
Nikolett Hegedűs
Ildikó Horváth
Fanni J. Kiss
Gabriella Taba
Edit Tóth-Bodrogi
Tibor Kovács
Krisztián Szigeti
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2019
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-019-0532-7

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