A prospective investigation into the clinical impact of 4D-PET/CT in the characterisation of solitary pulmonary nodules

Background: While the effects of respiratory motion on measuring metabolic signal in PET/CT scanning are well known, it is still standard practice in most centres to scan patients while breathing freely with no correction for the effects of respiratory motion. The aim of this study was to investigate the impact of 4D-PET/CT in classifying lesions in patients with a radiologically-indeterminate solitary pulmonary nodule. Methods: Twenty consecutive patients with a solitary pulmonary nodule for investigation were prospectively recruited and completed a whole-body (WB)-PET/CT and 4D-PET/CT in the same session. The reporting physician initially classified the nodule using a 5-point scale (Definitely Malignant, Probably Malignant, Indeterminate, Probably benign, Definitely Benign) on the WB-PET/CT. The physician was then shown the 4D-PET/CT and asked if they would re-classify the lesion. Frequency, sensitivity, specificity and accuracy values were calculated for WB-PET/CT alone and then with the addition of the 4D-PET/CT. Results: There were no changes in the classification for nodules initially classed as either benign or malignant with the addition of a 4D-PET/CT. However changes were observed between WB and 4D-PET/CT scans in lesions initially classified as indeterminate. When indeterminate lesions were defined as malignant there was a minor increase in sensitivity (from 73% to 75%), in specificity (56%-63%) and in accuracy (65%-70%) but these results do not reach statistical significance. When the Indeterminate lesions were defined as benign there was an increase in sensitivity (from 55% to 67%) but there was a reduction in the specificity (100%-75%) and accuracy (75%-70%) with the addition of the 4D-PET/CT but again the results did not reach statistical significance. Conclusion: The addition of 4D-PET/CT is most likely to have an impact on those nodules initially classified as indeterminate on standard WB-PET/CT. In lesions classified as benign or malignant on standard WB-PET/CT the addition of a 4D-PET/CT is less likely to impact lesion classification. While 4D-PET/CT does improve the measurement of the metabolic signal, it does not overcome inherent limitations of FDG in differentiating a malignant lesion from inflammatory processes, correct for partial volume effects or compensate for the low intrinsic FDG-avidity of some malignancies.