A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an acute respiratory distress syndrome in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days after virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of profibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early antifibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.

Current commercial micro-CT scanners have the capability of imaging objects ex vivo with high spatial resolution, but performing in vivo micro-CT on free-breathing small animals is still challenging because their physiological motions are non-periodic and much faster than those of humans. In this paper, we present a prototype physiologically gated micro-computed tomography (micro-CT) scanner based on a carbon nanotube field emission micro-focus x-ray source. The novel x-ray source allows x-ray pulses and imaging sequences to be readily synchronized and gated to non-periodic physiological signals from small animals. The system performance is evaluated using phantoms and sacrificed and anesthetized mice. Prospective respiratory-gated micro-CT images of anesthetized free-breathing mice were collected using this scanner at 50 ms temporal resolution and 6.2 lp mm(-1) at 10% system MTF. The high spatial and temporal resolutions of the micro-CT scanner make it well suited for high-resolution imaging of free-breathing small animals.

Although it has been demonstrated that quantitative measures of cerebral blood flow (CBF) can be obtained with the singular value decomposition (SVD) algorithm, the extent to which quantitative CBF measurements can be utilized under pathophysiological conditions has not been systematically studied. A total of five healthy volunteers and five patients with unilateral carotid artery occlusion were studied. Only magnetic resonance (MR) images were acquired for the volunteer group while both MR and positron emission tomography (PET) images were acquired for the patient group. Assessments of CBF from normal volunteers compared favorably with values reported in the literature. However, while a linear relationship was observed for each patient when MR measured CBF was compared to that obtained from PET, this linear relationship diminished when all patients were analyzed as a group (r = 0.41). A correction factor (CF) was proposed that was equal to the ratio of the area of the venous output function (VOF) in each patient to the mean VOF obtained from the volunteer group. After globally scaling the CBF of each patient based on the experimentally derived CF, a substantial improvement was observed (a slope of 1.02 and r = 0.8 for the linear regression line) in the relationship between MR estimated CBF and those obtained from PET. J. Magn. Reson. Imaging 2001;14:659–667.