Voxel-wise ratios of amide proton transfer (APT) signals and standardized uptake values (SUVs) of fluorodeoxyglucose (FDG) in the differentiation of myxoid-rich soft-tissue tumors with FDG-PET/MR imaging
Koji Sagiyama1, Yuji Watanabe2, Keisuke Ishimatsu1, Takeshi Kamitani1, Yuzo Yamasaki2, Takuya Hino1, Sungtak Hong3, Jochen Keupp4, Yoshihiro Matsumoto5, and Hiroshi Honda1

1Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 2Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 3Healthcare, Philips Electronics Japan, Tokyo, Japan, 4Philips Research, Hamburg, Germany, 5Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan


It is often difficult to differentiate myxoid-rich soft-tissue tumors on conventional imaging. In this study, we performed a direct voxel-wise comparison of amide proton transfer (APT) signals and standardized uptake values (SUVs) obtained on FDG-PET/MR imaging. Among myxoid-rich tumors including myxoid liposarcomas, myxofibrosarcomas, myxoid chondrosarcomas, and schwannomas, the mean APT/SUV was significantly higher in liposarcomas than in the other myxoid-rich tumors while a single parameter such as APT, SUV or apparent diffusion coefficient (ADC) did not show any significant differences between the two groups. The APT/SUV could be a reliable bio-imaging marker for differentiating soft-tissue tumors.


Soft-tissue tumors consist of a variety of interstitial tissues in addition to tumor cells1,2. The myxoid tissue is one of the most common interstitium observed on soft-tissue tumors, including a wide range of tumors such as myxoid liposarcomas, myxofibrosarcomas, myxoid chondrosarcomas, and schwannomas. It is usually difficult to differentiate these tumors with conventional imaging techniques when the interstitial tissue is predominant. The PET/MR system can simultaneously acquire functional MR and fluorodeoxyglucose (FDG)-PET images with precise image co-registration. Further, this system enables direct voxel-by-voxel comparison of standardized uptake values (SUV) from PET and other functional MR parameters such as the apparent diffusion coefficient (ADC)3 and amide proton transfer (APT) signal. APT imaging involves the visualization of the exchange of protons between free tissue water and the amide groups (-NH) of endogenous mobile proteins and peptides.4 Although APT imaging is useful for evaluating the degree of tumor malignancy such as gliomas or other cancers5-7, the usefulness has remained to be explored for differentiating soft-tissue tumors. The purpose of the present study was to investigate whether the direct voxel-wise combination of SUVs of FDG-uptake and APT signals on a PET/MR system was useful for differentiating myxoid-rich soft-tissue tumors.


<Image Acquisition> Fifteen patients with known soft-tissue tumors with high signals on T2WI (six liposarcomas, three myxofibrosarcomas, three chondrosarcomas and three schwannomas) were included in this study and scanned using an Ingenuity TF PET/MR scanner (Philips Healthcare, Cleveland, OH). After the scout image and a 3D-T1WI for attenuation correction were acquired, the participants underwent FDG-PET imaging with 3D-ordered subset expectation maximization and time of flight. The sampling time was 5 minutes per bed, and the images were reconstructed with 23 mm voxels. After PET imaging, transverse 2D-T2WI and T1WI were obtained to cover the entire tumor volume. A DWI with a spatially selective RF pulse8 (zoomed DWI, b = 0 and 800) was obtained, and an ADC map was generated. Finally, APT imaging with the 3D fast spin-echo Dixon method9 was performed. Briefly, a saturation pulse (duration: 2.0s, power: 2.0μT) was applied to obtain Z-spectra at seven different frequency offsets: ±2.7 ppm, ± 3.5 ppm, ± 4.3 ppm, and -1560 ppm. The scan was repeated three times at +3.5 ppm with echo shifts (ΔTE = 0.4 ms) for Dixon B0 mapping. The APT image corrected by a three-point Dixon-type B0 map was generated. Other parameters were: TR/TE = 3500/5.7 ms, voxel size = 1.8 × 1.8 mm, slice thickness = 4.4 mm, slices = 9, and scan duration = 3 m 52 s – 5 m 12 s. <Image Processing> Image registration with rigid transformation was performed between the T2WI, ADC map, APT, and PET image on an IntelliSpace Portal workstation (version 6.0, Philips Healthcare). The T2WI, ADC map, and FDG-PET image were then resliced in accordance with the APT image (4.4 mm). The APT image was divided by PET image, and APT/SUV maps were generated. On T2WI, regions of interest (ROIs) were manually drawn along the border of the tumor in all slices. The ROIs were then copied onto the other images. After extracting the tumor area, in-plane image resolution was interpolated to 22 mm. The APT signals, SUVs, ADCs, APT/SUVs were recorded on a voxel-by-voxel basis for all slices. The voxels with ADC < 0.5 ×10-3 mm2/s were excluded from analysis. The mean of APT, ADC and APT/SUV and the maximum of SUV were compared between liposarcomas and other tumors by Mann-Whitney U test.

Results and Discussion

Two representative cases of liposarcoma (top) and chondrosarcoma (bottom) are shown in Figure 1. Both tumors showed bright signals on T2WI and low uptake on FDG-PET. The liposarcoma showed higher APT signals and APT/SUV than chondrosarcoma. Only APT/SUV showed a significant difference between liposarcomas and other tumors (3.89 ± 1.31 vs. 1.62 ± 1.29, P < 0.05, Fig. 2). SUVmax (2.63 ± 0.78 vs. 4.55 ± 4.01, P = 0.07), APTmean (5.36 ± 2.32 vs. 3.00 ± 2.04, P = 0.11), and ADCmean (1.80 ± 0.47 vs. 1.73 ± 0.50, P = 0.78) did not show significant differences between liposarcomas and other tumors. APT signals indicate the concentration of mobile protein/peptide in the tissue, while SUVs of FDG-PET reflect glucose uptake of tumor cells. Therefore, the APT/SUV means the ratio of the accumulated protein/peptide to the glucose metabolism in tumors. The liposarcomas might produce and store protein/peptide more efficiently per glucose assumption than other tumors.


Voxel-wise ratios of APTWI and FDG-PET in soft-tissue tumors could differentiate liposarcomas and other myxoid-rich tumors while single parameters could not distinguish the two groups.


No acknowledgement found.


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Two representative cases of myxoid liposarcoma (top) and extraskeletal myxoid chondrosarcoma (bottom). Both tumors showed bright signals on T2WI and low uptake on FDG-PET. The liposarcoma showed very high APT signal (5.12) and APT/SUV (3.90) while the chondrosarcoma showed lower APT signal (0.53) and APT/SUV (0.31).

Comparison of (a) SUVmax, (b) APT mean, (c) ADC mean, and (d) APT/SUV between liposarcomas and other myxoid soft-tissue tumors. Only APT/SUV showed a significant difference between the two groups.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)