Detection of Myocardial Metabolic Abnormalities by 18F-FDG PET/CT and Corresponding Pathological Changes in Beagles with Local Heart Irradiation

Abstract

Objective: To determine the efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of radiation-induced myocardial damage in beagles by comparing two pre-scan preparation protocols as well as to determine the correlation between abnormal myocardial FDG uptake and pathological findings.

Materials and methods: The anterior myocardium of 12 beagles received radiotherapy locally with a single X-ray dose of 20 Gy. 18F-FDG cardiac PET/CT was performed at baseline and 3 months after radiation. Twelve beagles underwent two protocols before PET/CT: 12 hours of fasting (12H-F), 12H-F followed by a high-fat diet (F-HFD). Regions of interest were drawn on the irradiation and the non-irradiation fields to obtain their maximal standardized uptake values (SUVmax). Then the ratio of the SUV of the irradiation to the non-irradiation fields (INR) was computed. Histopathological changes were identified by light and electron microscopy.

Results: Using the 12H-F protocol, the average INRs were 1.18 ± 0.10 and 1.41 ± 0.18 before and after irradiation, respectively (p = 0.021). Using the F-HFD protocol, the average INRs were 0.99 ± 0.15 and 2.54 ± 0.43, respectively (p < 0.001). High FDG uptake in irradiation field was detected in 33.3% (4/12) of 12H-F protocol and 83.3% (10/12) of F-HFD protocol in visual analysis, respectively (p = 0.031). The pathology of the irradiated myocardium showed obvious perivascular fibrosis and changes in mitochondrial vacuoles.

Conclusion: High FDG uptake in an irradiated field may be related with radiation-induced myocardial damage resulting from microvascular damage and mitochondrial injury. An F-HFD preparation protocol used before obtaining PET/CT can improve the sensitivity of the detection of cardiotoxicity associated with radiotherapy.

Keywords: 18F-FDG PET/CT; Pathology; Radiation-induced heart disease; Radiotherapy.

Fig. 1. Description of two preparation protocols.

12H-F = 12 hours of fasting, FDG = fluorodeoxyglucose, F-HFD = fasting followed by a high-fat diet, HFD = high-fat diet, PET/CT = positron emission tomography/computed tomography

Fig. 2. 18F-FDG cardiac PET/CT images before RT from beagles treated with two pre-scan preparations.

Grade 0 image from M4 using F-HFD protocol shows homogeneously minimal myocardial FDG uptake; Grade 1 image from M3 using F-HFD protocol shows mostly minimal or mild myocardial FDG uptake; Grade 2 image from M10 using 12H-F protocol shows mostly intense or moderate myocardial FDG uptake; Grade 3 image from M2 using 12H-F protocol shows homogeneously intense myocardial FDG uptake. 12H-F = 12 hours of fasting, 18F-FDG = 18F-fluorodeoxyglucose, F-HFD = fasting followed by a high-fat diet, PET/CT = positron emission tomography/computed tomography, RT = radiotherapy

Fig. 3. Images of male beagle (M2) at baseline and 3 months after RT using F-HFD protocol.

A. Dose-distribution axial image. B. Cardiac FDG-PET/CT axial images before RT. C. Cardiac FDG-PET/CT axial images 3 months after RT. D. Myovation images of FDG at 3 months after RT. B shows suppression of myocardial FDG uptake before RT. C and D show high FDG uptake (arrows) corresponding to irradiated field 3 months after RT. FDG = fluorodeoxyglucose, F-HFD = fasting followed by a high-fat diet, PET/CT = positron emission tomography/computed tomography, RT = radiotherapy

Fig. 4. Images of bealge (M2) 3 months after RT under 12H-F protocol.

A. Cardiac FDG-PET/CT axial images 3 months after RT. B. Myovation images of FDG at 3 months after RT. No abnormal FDG uptake could be detected 3 months after RT. Physiological myocardial FDG uptake might interfere detecting pathological changes. 12H-F = 12 hours of fasting, FDG = fluorodeoxyglucose, PET/CT = positron emission tomography/computed tomography, RT = radiotherapy

Fig. 5. Hematoxylin and esoin staining of non-irradiated myocardium (A) and irradiated myocardium (B, C).

Cytoplasmic vacuolization of myocytes (black arrows) (× 400) and perivascular fibrosis (green arrow) (× 200) were visible in irradiated field of myocardium.

Fig. 6. Electron transmission micrographs of myocardium.

A. Abundant mitochondria packed around normal nuclei are shown in non-irradiated field (× 10000). B. Slightly dilated cristae in some mitochondria scattered around nucleus (black arrows), as well as enlarged nuclei (green arrows) were observed in irradiated myocardium (× 10000).