Improved retrospectively gated in-vivo microCT for simultaneous assessment of lung function and anatomy in mice

Abstract

Retrospective gating (RG) is a well established technique in preclinical computed tomography (CT) to assess 3D morphology of the lung. In RG additional angular projections are recorded typically by performing multiple rotations. Consequently, the projections are sorted according to the expansion state of the chest and those sets are then reconstructed separately. Thus, the breathing motion artefacts are suppressed at a cost of strongly elevated x-ray dose levels. Here we propose to use the entire raw data to assess lung function in addition to retrospectively gated 3D reconstruction that visualize anatomical structures of the lung. Using this novel RG based x-ray lung function approach (RG based XLF) on the example of the mdx mouse model of Duchenne muscle dystrophy (mdx) we accurately obtained both the 3D anatomical morphology of the lung and the thoracic bones as well as the functional temporal parameters of the lung. Thus, RG-based XLF will remove the necessity for separate acquisition procedures by being able to reproduce comparable lung function results in a single low dose CT scan.

Imaging and Functional Imaging of the Lung

“…The results showed a strong correlation between the acquired lung volume by rXTF function in XLF technique and those extracted from the µCT data; however, the XLF data were obtained by only 7% of the x-ray dose and 13% of the acquisition time used in µCT, which shows the capability of XLF as a reliable technique for in vivo, noninvasive lung volume measurements in longitudinal studies on lung diseases. (Dullin et al, 2022). For assessment of the newly developed technique, they applied the rgXLF protocol on mdx mice, the most commonly used mouse model for studying Duchenne muscular dystrophy (DMD).…”

“…Search for finding a simpler way than WBP and XLF to monitor respiratory dynamics, resulted in introduction of an optical technique by Svetlove et al called optical respiratory dynamics tracking (ORDT) (Svetlove et al, 2022). This technique is especially useful for tracking diaphragm function of mice with neuromuscular diseases such as Duchenne muscular dystrophy (DMD).…”

Lung function measurements in preclinical research: What has been done and where is it headed?

“…Since 2D radiographs of the chest movements are used by XLF protocol, the acquired imaging data could only be used for monitoring the animal’s breathing during the measurements and no anatomical information could be obtained. To address this issue, Dullin et al proposed a new technique based on XLF to quantify lung function in the raw data of retrospectively gated lung µCT scans, which is called retrospective gating-based x-ray lung function measurement (rgXLF) ( Dullin et al, 2022 ). For assessment of the newly developed technique, they applied the rgXLF protocol on mdx mice, the most commonly used mouse model for studying Duchenne muscular dystrophy (DMD).…”

“… Retrospective gating-based x-ray lung function measurement (rgXLF) (A, C) µCT images of a healthy control mouse and a mdx mouse respectively, showing the difference in the shape of the diaphragms; (B, D) 3D renderings of the healthy and mdx mice; (E) Comparison of the breathing patterns of the healthy and mdx mice (healthy = blue and mdx = blue), showing a more rapid decay in the expiration phase of the mdx mouse [reprinted from Dullin et al (2022) ]. …”

“…In the past few decades, as pulmonary functional imaging, many non-invasive, novel µCT- and MR-based techniques have been introduced for ventilation and perfusion imaging as well as biomechanics evaluation. On one hand, CT-based methods such as XLF techniques ( Section 2.2.2.4 ), non-invasively offer pulmonary functional readouts related to lung volumes and elasticity in longitudinal in vivo animal studies [see ( Dullin et al, 2016 ; Markus et al, 2017 ; Khan et al, 2021 ; Dullin et al, 2022 )]. In addition, Xe-enhanced ventilation µCT can provide ventilation maps for regional ventilation assessments during the progression of pulmonary diseases with higher spatial resolution than any other imaging modality ( Ohno et al, 2021 ).…”