Acute and subacute dual energy CT findings of pulmonary embolism in rabbits: correlation with histopathology

Objective

The purpose of this study was to describe quantitative dual energy CT (DECT) findings and their accuracy in the detection of acute and subacute pulmonary embolism (PE) in rabbits.

Methods

Pulmonary emboli were created in 24 rabbits by gelatin sponge femoral vein injection. Conventional CT pulmonary angiography (CTPA) and DECT were obtained at either 2 h, 1 day, 3 days or 7 days after embolisation (n=6 rabbits for each time point). The location and number of PEs in the different stages were recorded at CTPA and iodine maps from DECT on a per-lobe basis. With histopathology as the reference standard, sensitivity and specificity of CTPA and DECT were calculated. CT and iodine map overlay values of the embolic and non-embolic areas were measured for each scan.

Results

With histopathology as the reference standard, the overall sensitivity and specificity of CTPA were 98% and 100% and those of iodine maps were 100% and 95%, respectively. Conventional CT and iodine map values of the embolised and non-embolised areas were significantly different between 2 h and 1 day (p<0.001), but not between 3 days and 7 days (p>0.05). A statistical difference was found for overlay values measured in the embolic and non-embolic regions for four groups.

Conclusion

Iodine maps derived from DECT show alterations in lung perfusion for acute and subacute PE in an experimental rabbit model and show comparable sensitivity for PE detection and conventional CTPAIn the USA, more than 650 000 cases of pulmonary embolism (PE) occur each year, resulting in as many as 300 000 annual fatalities [1,2]. Despite the high morbidity, the diagnosis of PE may be delayed in the absence of typical clinical symptoms or when emboli are subsegmental and such scenarios may delay the treatment and increase the mortality of PE. Imaging plays an important role in the diagnosis and follow-up of PE. With improvements in multidetector row CT, CT pulmonary angiography (CTPA) has largely replaced digital subtraction angiography (DSA) for the diagnosis and follow-up of PE and has been recommended as the reference of standard for diagnosis of acute PE [3]. However, CTPA has shortcomings, such as a limited sensitivity to detect peripheral or subsubsegmental emboli of the pulmonary artery and an inability to show lung perfusion impairment resulting from acute or chronic PE.With the development of dual source CT (DSCT), in which two orthogonally mounted detectors and tubes arrays operate simultaneously and can be set to different tube potentials to allow for dual energy CT (DECT) acquisitions with minimal patient motion registration artefact, DECT imaging has been used to investigate iodine distribution maps in clinical and pre-clinical studies [4-13]. Such iodine maps, which have been termed blood flow imaging (BFI), have been shown to be valuable supplements to conventional anatomic CTPA for the evaluation of distal pulmonary artery emboli [4-13]. Many studies have focused on the feasibility or diagnostic accuracy of DECT iodine maps to improve the detection of PE, with CTPA, scintigraphy or histopathology as a reference standard in the clinical and experimental studies [5-13], or the evaluation of image quality of dual energy CTPA [14,15]. However, to the best of our knowledge, there are no reports that describe the evolution of CT and DECT imaging findings of PE over time after an embolic event with histopathological correlation. Histopathology correlation is most ethically obtained using an animal model. Therefore, we evaluated DECT findings with histopathology correlation in a rabbit model of PE with different time delays after embolisation and assessed the diagnostic accuracy of DECT in the detection of PE at these different time points.