Simultaneous Imaging of Lung Perfusion and Glucose Metabolism in COVID-19 Pneumonia

Abstract

Severe hypoxemia in some patients with coronavirus disease (COVID-19) has been related to loss of hypoxic pulmonary vasoconstriction (1, 2). A 77-year-old male with 6 days of mild respiratory symptoms and no comorbidities was admitted with signs of respiratory failure (Pa O 2 /FI O 2 : 61 mm Hg/0.36 mm Hg = 169.4 mm Hg; reference values [RVs] of 400-500 mm Hg). Chest computed tomography (CT) showed extensive ground-glass opacities (50-75% right-lung involvement and 25-50% left-lung involvement). Laboratory findings showed a D-dimer concentration of 652 ng/ml (RV , 500 ng/ml) and a C-reactive-protein concentration of 93.5 mg/dl (RV , 0.1 mg/dl). Nasopharyngeal swab test (RT-PCR) results confirmed COVID-19. The standard institutional protocol was initiated with a nasal oxygen catheter (4.0 L/min), antibiotics, dexamethasone, and enoxaparin. The patient required invasive ventilation on the 10th day and died on the 35th day of hospitalization. Lung-perfusion single-photon-emission CT/CT using 99m Tc-labeled macroaggregated albumin (3) and positron emission tomography/CT using 18 F-fluorodeoxyglucose (4) were sequentially performed on the third day of hospitalization during the same visit to the Nuclear Medicine Service to simultaneously assess pulmonary perfusion and inflammation. Normal or increased lung perfusion was detected in most of the hypermetabolic areas evidenced by positron emission tomography/CT images (Figure 1). Image quantification was conducted using free, opensource image-processing software (5, 6). Quantification results showed 59% of the total pulmonary perfusion occurring in inflamed lung tissue, which corresponded to 39% of the total anatomic lung volume (Figure 1D). This suggested a high right-to-left shunt fraction in the inflamed areas, which was probably related to loss of hypoxic vasoconstriction, as has been proposed before to occur in COVID-19 pneumopathy (1, 2). The vasoconstriction reflex seemed preserved in a few areas of 18 F-fluorodeoxyglucose uptake. Inflammation and loss of hypoxic pulmonary vasoconstriction can be assessed and quantified using the described methodology.Further studies are needed to evaluate its possible clinical uses. nAuthor disclosures are available with the text of this article at www.atsjournals.org.

Role of total lung stress on the progression of early COVID-19 pneumonia

“…We had hypothesized this mechanism by exclusion at the very onset of the pandemic [2,27]. Since then, altered perfusion as a cause of hypoxemia has been increasingly recognized and documented [28][29][30]. The atypical features of CARDS have been challenged by several authors who maintain-based on the average value of lung mechanics of the population-that CARDS is little different from other, more familiar forms of ARDS [23,25,31].…”

Therapeutic Effects of Inhaled Nitric Oxide Therapy in COVID-19 Patients

“…Hypoxemia in the early stages of COVID-19 is caused by a dysregulated pulmonary perfusion [ 130 , 131 ]. Changes in pulmonary biomechanics demonstrate that at an early, well-defined stage of COVID-19 disease (between the admission to the high-dependency unit to the time of healing or admission to the ICU), the lung weight in C-ARDS was approximately half of what has been described in a typical ARDS.…”

Pathophysiology of coronavirus-19 disease acute lung injury

“…These alterations in pulmonary perfusion have been described early in the course of the pandemic and of the natural history of the disease. Some of these changes are ’functional’ leading to hyper-perfusion of poorly ventilated lung tissue (increase in venous admixture) and is consequent to a loss in hypoxic vasoconstriction [ 23 , 24 ], vasoplegia and inflammatory hyperaemia [ 25 , 26 ]; or to more 'structural’ anatomical changes caused by vascular enlargement [ 27 ] or new-vessel formation (intussusceptive neovascularisation) [ 28 ▪ ] in the poorly ventilated and hypoxic lung tissue. The combination of functional and anatomical changes leading to hyperperfusion of poorly and nonaerated tissue ultimately explains some of the findings of severe hypoxaemia despite the relatively normal lung gas volumes [ 13 ▪ , 29 ▪ ].…”

“…Thrombosis appears predominantly associated with pulmonary hypoperfusion observed with different imaging approaches (computed tomography (CT), positron emission tomography and single-photon emission computerized tomography, subtraction CT angiography) [ 30 ▪ , 36 , 37 ]. However, thrombi were not always detected in association with pulmonary hypoperfusion: it is plausible that the reduced levels of angiotensin-converting enzyme 2 (ACE2) lead to accumulation of angiotensin II and greater inflammation, causing vasoconstriction in the well-ventilated lung regions, and/or that vascular tone abnormalities such as the loss of the physiological hypoxic pulmonary vasoconstriction may determine a relative hyper-perfusion of nonaerated regions [ 12 , 22 , 24 , 38 ].…”