Cross-modal Imaging in Lung Research: From µCT dosimetry to synchrotron phase contrast microtomography biomechanical insights in preclinical lung injury models

• Lung diseases continue to present a large burden to public health, especially in industrialized countries. For abetter understanding of the underlying patho-mechanisms in lung related diseases as well as for testing theefficacy of novel therapies, preclinical studies in animal models are indispensable. The significance of preclinical X-ray based micro-computed tomography (µCT) research lies in its ability to provide high-resolution, non-invasive lung imaging of small animals as the air inside the lung acts as a natural contrast and to image the lung parenchyma longitudinally to assess functional and morphological alterations and test efficacy of therapeutic interventions. This often requires requires imaging protocols that balance between sufficient image quality and clinically relevant radiation absorbed doses. A reproducible method for evaluation of absorbed radiation absorbed doses is desirable. Absorbed radiation absorbed doses were measured in a polymethyl methacrylate (PMMA) phantom using standard TLD and a novel type of OSLD made form household salt. Four imaging protocols from MILabs “xUHR-µCT” scanner were tested. A large discrepancy was observed from results compared to vendor-provided values. The results indicate a need for thorough empirical dose measurements prior to performing longitudinal studies. Four-dimensional imaging, allows for investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. It is of significant interest to have direct visualization and quantification of interstitial lung diseases at spatial resolutions beyond the capabilities of clinical and conventional absorption-based only CT. Thus far, the high intensity of synchrotron X-ray light sources offer a tool to investigate dynamic morphological and mechanistic features, enabling dynamic in-vivo microscopy. This investigation elucidates the direct effects of interventions targeting the pathophysiology of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) on the terminal airways and alveolar microstructure within intact lungs. In such conditions, the relationship between microscopic strain within the mechanics of the alveolar structure and the broader mechanical characteristics and viscoelastic properties of the lungs remains poorly understood. A time-resolved synchrotron phase-contrast micro-computed tomography imaging acquisition protocol based on the synchronization between the mechanical ventilation and the cardiac activity was used to resolve the lung parenchyma motion with an effective isotropic voxel size of 6 µm. Quantitative maps of microscopic local lung tissue strain within aerated lung alveolar tissue under protective mechanical ventilation in anesthetized rats were obtained. This approach was used to assess the effect of alterations in lung tissue biomechanics induced by lung injury at 7 days after single-dose, intratracheal bleomycin instillation in combination with short-term high-tidal volume (VT) mechanical ventilation. Overall, this work address the aspects of radiation exposure to in experimental imaging of small animals and lays a foundation for a more nuanced understanding of lung injury and mechanical ventilation. In the future, it may result in a more effective and less injurious respiratory support for patients with acute lung injury or chronic lung diseases.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Annan medicin och hälsovetenskap -- Övrig annan medicin och hälsovetenskap (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Other Medical and Health Sciences -- Other Medical and Health Sciences not elsewhere specified (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Nyckelord

Thermoluminescent Dosimetry

Optically stimulated luminescence (OSL)

Computed tomography (CT)

4DCT

Phantoms, Imaging

X-rays

pre-clinical models

Pre-clinical

dosimetry: physical basis

biomedical strain

lung injury

mechanical ventilation

inflammation

lung function

synchrotron

histology

acute respiratory distress syndrome (ARDS)

Ventilator Inudced Lung Injury (VILI)

Histology

Forced Oscillation Technique (FOT)

Divergence Theorem

Registration techniques

Publikations- och innehållstyp

lic (ämneskategori)

vet (ämneskategori)