Abstract
BackgroundOur 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.MethodsFour 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.ResultsHCC 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.ConclusionBased 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.
Highlights
The liver is one of the most affected organs for metastatic disease because of its dense vascular network
The results of whole-body 99mTc-protein nanoparticle single-photon emission computed tomography (SPECT) measurements are illustrated in Fig. 1a, while Fig. 1b–e illustrates the segmented livers of control, obese, metastatic, and primary tumor mice, respectively
The Spearman correlation test resulted in p values of 0.1083, 0.5576, 0.9271, and 0.3596 (SUV, standardized uptake concentration (SUC), skewness, kurtosis, respectively)
Summary
The liver is one of the most affected organs for metastatic disease because of its dense vascular network. It is supplied with oxygenated blood via the hepatic artery (25%) and the portal vein (75%) [1]. At an early well-treatable stage, liver metastasis may not show any specific symptoms. The symptoms often appear only in later stages when the tumorous cells have already infiltrated parts of the liver too large for curative intent therapy. The survival of liver metastatic patients varies only between several months and a few years depending on the type of the primary cancer, the size and number of metastases, and the applicable treatment based on disease stage. 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
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