key: cord-0821396-1n55u47p authors: Arru, C. D.; Digumarthy, S.; Hansen, J. V.; Lyhne, M. D.; Singh, R.; Rosovsky, R.; Nielsen-Kudsk, J. E.; Kabrhel, C.; Saba, L.; Kalra, M. K. title: Qualitative and quantitative DECT pulmonary angiography in COVID-19 pneumonia and pulmonary embolism date: 2021-02-25 journal: Clin Radiol DOI: 10.1016/j.crad.2021.02.009 sha: f662cd4f517af2ad2f7c7f84e0689d3abe66230b doc_id: 821396 cord_uid: 1n55u47p Aim To assess differences in qualitative and quantitative parameters of pulmonary perfusion from dual-energy computed tomography (CT) pulmonary angiography (DECT-PA) in patients with COVID-19 pneumonia with and without pulmonary embolism (PE). Materials and methods This retrospective institutional review board-approved study included 74 patients (mean age 61 ± 18 years, male:female 34:40) with COVID-19 pneumonia in two countries (one with 68 patients, and the other with six patients) who underwent DECT-PA on either dual-source (DS) or single-source (SS) multidetector CT machines. Images from DS-DECT-PA were processed to obtain virtual mono-energetic 40 keV (Mono40), material decomposition iodine (MDI) images and quantitative perfusion statistics (QPS). Two thoracic radiologists determined CT severity scores based on type and extent of pulmonary opacities, assessed presence of PE, and pulmonary parenchymal perfusion on MDI images. The QPS were calculated from the CT Lung Isolation prototype (Siemens). The correlated clinical outcomes included duration of hospital stay, intubation, SpO2 and death. The significance of association was determined by receiver operating characteristics and analysis of variance. Results One-fifth (20.2%, 15/74 patients) had pulmonary arterial filling defects; most filling defects were occlusive (28/44) located in the segmental and sub-segmental arteries. The parenchymal opacities were more extensive and denser (CT severity score 24 ± 4) in patients with arterial filling defects than without filling defects (20 ± 8; p=0.028). Ground-glass opacities demonstrated increased iodine distribution; mixed and consolidative opacities had reduced iodine on DS-DECT-PA but increased or heterogeneous iodine content on SS-DECT-PA. QPS were significantly lower in patients with low SpO2 (p=0.003), intubation (p=0.006), and pulmonary arterial filling defects (p=0.007). Conclusion DECT-PA QPS correlated with clinical outcomes in COVID-19 patients. infection [3] [4] [5] [6] [7] . Occlusions in the pulmonary arterial circulation are thought to be related to severe disease and higher mortality in COVID-19 infection [8] , although the exact causes for disease severity and host response remain unclear. It is also unclear if patients with COVID-19 pneumonia develop PE or in situ thrombi, and if imaging can differentiate between these two entities. Peripheral venous thrombosis was absent in most COVID-19 patients but these patients were diagnosed with PE [3] , raising the possibility of in situ thrombi in the pulmonary arterial circulation. Although prophylaxis and treatment of PE in patients with COVID-19 pneumonia is of increasing clinical interest, it is unclear if pulmonary arterial in situ thrombosis should be treated in a similar fashion to PE [3, 9] . To be detectable on computed tomography (CT), pulmonary arterial filling defects must extend beyond the pulmonary microcirculation to at least segmental or proximal subsegmental pulmonary arteries or lead to assessable changes in pulmonary perfusion [10] . Quantitative lung parenchymal perfusion (QPS) has been assessed in non-COVID-19 patients with PE using DECT pulmonary angiography (DECT-PA) perfusion maps and material decomposition iodine (MDI) images [11] . Recent publications in COVID-19 patients have described decreased perfusion in J o u r n a l P r e -p r o o f consolidative opacities surrounded by a "hyperaemic halo" of increased perfusion and dilated adjacent pulmonary arteries on DECT [12, 13] without a clear explanation for these findings. There is increasing evidence that DECT-PA can depict changes in pulmonary perfusion in the absence of visible PE and in situ thrombi [14, 15] . The present study assessed differences in qualitative and quantitative pulmonary perfusion from DECT-PA in patients with COVID-19 pneumonia with and without visible filling defects in the pulmonary arteries. The institutional review boards approved this retrospective study with a waiver of informed consent at both *** (site A) and ***(site B Two thoracic radiologists (*** and *** with 16 and 13 years of experience) reviewed Mono 40 keV and MDI images in consensus to assess COVID-19 pneumonia-related lung findings, filling defects in pulmonary arteries, and qualitative perfusion abnormalities. As the DS-DECT-PA MDI images segment the inflated lungs and J o u r n a l P r e -p r o o f exclude the opacified lungs, the 40 keV images were reviewed to assess contrast enhancement within regions of opacities to differentiate pulmonary opacities related to pneumonia and pulmonary infarction. Imaging findings and severity were assessed on 40 keV images to score severity and type of opacities. Based on prior publications [16, 17] , the COVID-19 pneumonia-related findings were graded separately in each of the five lung lobes for extent (0, no pulmonary opacity; 1, opacities involving <5% lobar volume; 2, 5-25% lobar involvement; 3, 26-50% lobar involvement; 4, 51-75% lobar involvement; 5, >76% lobar involvement) and type of opacities (1, ground-glass opacities 2, consolidation or mixed opacities such as ground-glass opacities with consolidation, interlobular septal thickening or nodules). For each lobe, the extent and type of pulmonary opacities were added to obtain lobar involvement scores (maximum score of 5). The entire lung severity score was obtained by adding lobar scores for all the five lobes (maximum score of 35). Also, contrast enhancement (from Mono 40 keV) and iodine uptake (from MDI) in regions of pulmonary opacities was recorded (as decreased, increased, or variable relative to the adjacent normal lung). Radiologists could adjust the window levels and widths at their discretion. Both radiologists assessed pulmonary arterial filling defects for location (from main pulmonary trunk to subsegmental arteries) and degree of occlusion (occlusive, nonocclusive). The number (one score for each positive pulmonary arterial filling defect) of pulmonary arterial filling defects was recorded. The presence of focal or diffuse dilatation, narrowing, wall thickening, and irregularity of pulmonary arteries and veins was also recorded. The presence and type of opacities (normal lung parenchyma, A p-value of <0.05 was considered a statistically significant difference. There were 74 adult patients with COVID-19 pneumonia (age range 21-96 years; mean age 61±18 years; 40 females and 34 males). At the time of DECT-PA, 54% (40/74) were on anticoagulants (heparin, warfarin, rivaroxaban, or enoxaparin) as part of their standard of care treatment, 45% were admitted for ≥10 days (33/74), 59% had SpO 2 of <90% (44/74), and 22% were intubated (16/74). The mortality rate in this group was 14% (10/74; Table 1 ). Lung parenchymal assessment and severity scores The deceased patients and patients with low SpO2 had significant differences in J o u r n a l P r e -p r o o f these QPS features compared to survivors and those with high SpO 2 (p<0.05; Table 3 ) but was also associated with AUC (<0.68) suggestive of significant overlap in perfusion statistics within the groups. [2] . These findings support observations that decreased QPS was noticed in patients without pulmonary arterial filling defects and was associated with severe diseases such as consolidation and mixed opacities. Lower kurtosis was noted in patients with adverse outcomes (disease survival, shorter hospital admission duration, and normal SpO 2 ) as opposed to those with favourable outcomes. Lower kurtosis implies lower probability of extreme values and a wider spread of values around the mean of distribution. With more severe disease, such as with cor pulmonale or increased pulmonary vascular resistance, there is greater lung involvement with denser opacities (consolidation) and fewer regions with normal lung parenchyma. These findings in turn decrease the probability of extreme attenuation and iodine values, which was likely responsible for a smaller kurtosis value in patients with adverse outcomes. A recent study reported that pulmonary perfusion defects on DECT-PA were not related to increased pulmonary vascular resistance or cor pulmonale [15] . Like DS-DECT-PA MDI images, the QPS software segments the inflated, nonopacified portion of the lungs and quantifies iodine distribution in those portions only. Thus, any portion of the lungs with dense pulmonary opacities, such as from consolidation, atelectasis, and pulmonary infarctions, are excluded from estimation of QPS features. The QPS software will therefore show decreased iodine distribution in the presence of ischaemic loss of perfusion (from pulmonary emboli, perfusion defects with and without pulmonary infarction) and from exclusion of opacified pulmonary parenchyma from any non-ischaemic process (Fig. 5) . In both instances, the overall estimated lung perfusion from QPS will decrease, and therefore, QPS can were found that could have favoured thrombosis in situ rather than an embolic cause. Although the lack of specific findings does not exclude in situ pulmonary thrombosis, DECT-PA differentiation of in situ thrombosis from PE is limited. The presence of mixed or consolidative opacities adjacent to most pulmonary arterial filling defects (12/25 patients, 80%) could suggest diffuse or advanced pneumonia in these patients or an increased thrombogenic potential of these opacities compared to pure ground-glass opacities. The qualitative interpretation of MDI for iodine is subject to errors due to variability in scanner type and image reconstruction techniques. The pure ground-glass opacities tend to have a higher qualitative perfusion irrespective of location in both SS-DECT and DS-DECT scanners. The qualitative hyperperfusion in ground-glass opacities on MDI images was likely a perception issue as there was no significant difference in QPS between ground-glass opacities and normal lung parenchyma (p=0.73). This perception issue may be related to the fact that the ground-glass opacities have low negative attenuation values (often well below -300 HU). Such low CT number implies that ground-glass opacities will not be excluded from MDI images, and thus, give a visual appearance of increased perfusion without a measurable increase in iodine content. To the authors' best knowledge, the exclusion of ground-glass opacities from processed MDI images has not been reported and underscores the importance of quantitative measurement of values on MDI images, which are typically acquired by subtracting water from iodine and will not visualise lesions with attenuation less than that of water (ground-glass opacities). In contrast, whereas consolidative opacities tend to have increased or heterogeneous iodine distribution in SS-DECT-PA and decreased iodine distribution in DS-DECT-PA. These differences were likely related to differences in how the vendors approach dual-energy image or data processing for generating MDI images or based perception of MDI images by the radiologists. The MDI images from DS-DECT-PA datasets identify the air attenuation portions of the lungs and exclude regions with higher attenuation, such as consolidation, which makes the latter appear hypoperfused. Although lung regions with higher attenuation, such as consolidation, can be included in the MDI images by changing the maximum threshold in the image processing software, we did not change the default threshold as it alters the image appearance and makes them less J o u r n a l P r e -p r o o f sensitive for detection of true ischaemia-related perfusion defects. Conversely, the MDI images from SS-DECT-PA does not isolate air-attenuation lungs and includes regions of consolidation; the latter could be therefore assessed qualitatively with increased or heterogeneous perfusion on MDI images. Previous studies have also reported differences in appearance of DECT-PA images between different vendors [19] . Therefore, the increased iodine distribution noted in ground glass halo around consolidation in DS-DECT-PA does not necessarily imply "hyperaemic halo" [12, 13] . 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