AI Lung Segmentation and Perfusion Analysis of Dual-Energy CT Can Help to Distinguish COVID-19 Infiltrates from Visually Similar Immunotherapy-Related Pneumonitis Findings and Can Optimize Radiological Workflows

(1) To explore the potential impact of an AI dual-energy CT (DECT) prototype on decision making and workflows by investigating its capabilities to differentiate COVID-19 from immunotherapy-related pneumonitis. (2) Methods: From 3 April 2020 to 12 February 2021, DECT from biometrically matching patients with COVID-19, pneumonitis, and inconspicuous findings were selected from our clinical routine. Three blinded readers independently scored each pulmonary lobe analogous to CO-RADS. Inter-rater agreement was determined with an intraclass correlation coefficient (ICC). Averaged perfusion metrics per lobe (iodine uptake in mg, volume without vessels in ml, iodine concentration in mg/mL) were extracted using manual segmentation and an AI DECT prototype. A generalized linear mixed model was used to investigate metric validity and potential distinctions at equal CO-RADS scores. Multinomial regression measured the contribution “Reader”, “CO-RADS score”, and “perfusion metrics” to diagnosis. The time to diagnosis was measured for manual vs. AI segmentation. (3) Results: We included 105 patients (62 ± 13 years, mean BMI 27 ± 2). There were no significant differences between manually and AI-extracted perfusion metrics (p = 0.999). Regardless of the CO-RADS score, iodine uptake and concentration per lobe were significantly higher in COVID-19 than in pneumonitis (p < 0.001). In regression, iodine uptake had a greater contribution to diagnosis than CO-RADS scoring (Odds Ratio (OR) = 1.82 [95%CI 1.10–2.99] vs. OR = 0.20 [95%CI 0.14–0.29]). The AI prototype extracted the relevant perfusion metrics significantly faster than radiologists (10 ± 1 vs. 15 ± 2 min, p < 0.001). (4) Conclusions: The investigated AI prototype positively impacts decision making and workflows by extracting perfusion metrics that differentiate COVID-19 from visually similar pneumonitis significantly faster than radiologists.

Severe COVID-19 pneumonia: Perfusion analysis in correlation with pulmonary embolism and vessel enlargement using dual-energy CT data

Background Gas exchange in COVID-19 pneumonia is impaired and vessel obstruction has been suspected to cause ventilation-perfusion mismatch. Dual-energy CT (DECT) can depict pulmonary perfusion by regional assessment of iodine uptake. Objective The purpose of this study was the analysis of pulmonary perfusion using dual-energy CT in a cohort of 27 consecutive patients with severe COVID-19 pneumonia. Method We retrospectively analyzed pulmonary perfusion with DECT in 27 consecutive patients (mean age 57 years, range 21–73; 19 men and 8 women) with severe COVID-19 pneumonia. Iodine uptake (IU) in regions-of-interest placed into normally aerated lung, ground-glass opacifications (GGO) and consolidations was measured using a dedicated postprocessing software. Vessel enlargement (VE) within opacifications and presence of pulmonary embolism (PE) was assessed by subjective analysis. Linear mixed models were used for statistical analyses. Results Compared to normally aerated lung 106/151 (70.2%) opacifications without upstream PE demonstrated an increased IU, 9/151 (6.0%) an equal IU and 36/151 (23.8%) a decreased IU. The estimated mean iodine uptake (EMIU) in opacifications without upstream PE (GGO 1.77 mg/mL; 95%-CI: 1.52–2.02; p = 0.011, consolidations 1.82 mg/mL; 95%-CI: 1.56–2.08, p = 0.006) was significantly higher compared to normal lung (1.22 mg/mL; 95%-CI: 0.95–1.49). In case of upstream PE, EMIU of opacifications (combined GGO and consolidations) was significantly decreased compared to normal lung (0.52 mg/mL; 95%-CI: -0.07–1.12; p = 0.043). The presence of VE in opacifications correlated significantly with iodine uptake (p<0.001). Conclusions DECT revealed the opacifications in a subset of patients with severe COVID-19 pneumonia to be perfused non-uniformly with some being hypo- and others being hyperperfused. Mean iodine uptake in opacifications (both ground-glass and consolidation) was higher compared to normally aerated lung except for areas with upstream pulmonary embolism. Vessel enlargement correlated with iodine uptake: In summary, in a cohort of 27 consecutive patients with severe COVID-19 pneumonia, dual-energy CT demonstrated a wide range of iodine uptake in pulmonary ground-glass opacifications and consolidations as a surrogate marker for hypo- and hyperperfusion compared to normally aerated lung. Applying DECT to determine which pathophysiology is predominant might help to tailor therapy to the individual patient´s needs.

Validation of Immunohistochemistry for Canine Proteins Involved in Thyroid Iodine Uptake and Their Expression in Canine Follicular Cell Thyroid Carcinomas (FTCs) and FTC-Derived Organoids

Thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, and thyroid peroxidase (TPO) are essential for the uptake of iodine by follicular thyroid cells. The aim of this study was to establish immunohistochemistry (IHC) protocols for TSHR, NIS, pendrin, and TPO in canine tissues and characterize their expression in organoids derived from canine follicular cell thyroid carcinoma (FTC) and in the respective primary tumors. This constitutes a fundamental step to establish organoids as a model to study the uptake of iodine in canine FTC. Commercially available antibodies directed against human proteins were selected. Antibody specificity was confirmed by western blot using lysates of the HTori-3 human thyroid cell line and healthy canine thyroid gland. IHC was validated using HTori-3 cells and a set of canine normal tissues including healthy thyroid gland. The expression of TSHR, NIS, pendrin, and TPO was evaluated in 3 organoid lines derived from FTC and respective primary tumors. All 4 antibodies produced specific bands by western blot and cytoplasmic labeling in follicular cells by IHC in both human HTori-3 cells and canine thyroid gland. NIS also showed basolateral membrane immunolabeling in follicular cells. All 4 proteins were highly expressed in organoids derived from FTC. The expression was similar or higher compared to the primary tumors. The results of this study characterize organoids derived from canine FTC as a suitable in vitro model to investigate iodine uptake, opening new research possibilities in the field of canine thyroid cancer therapy.