Birefringence microscopy platform for assessing airway smooth muscle structure and function in vivo

Abstract

The inability to visualize airway smooth muscle (ASM) cells in vivo is a major obstacle in understanding their role in normal physiology and diseases. At present, there is no imaging modality available to assess ASM in vivo. Confocal endomicroscopy lacks the penetration depth and field of view, and conventional optical coherence tomography (OCT) does not have sufficient contrast to differentiate ASM from surrounding tissues. We have developed a birefringence microscopy platform which leverages the micro-organization of tissue to add further dimension to traditional OCT. We have utilized this technology to validate ASM measurements in ex vivo swine and canine studies, visualize and characterize volumetric representations of ASM in vivo, and to quantify and predict ASM contractile force as a function of optical retardation. We provide in vivo images and volumetric assessments of ASM in living humans and document structural disease variations in subjects with mild asthma. The opportunity to link inflammatory responses to ASM responses, and to link ASM responses to clinical responses and outcomes could lead to an increased understanding of diseases of the airway and ultimately to improved patient outcomes.

Polarization sensitive optical coherence tomography – a review [Invited]

“…Figure 10 shows a PS-OCT example of ex-vivo human coronary artery. In pulmonology, endoscopic OCT is still at its infancy [137], an ex-vivo study has shown the potential for biopsy guidance in lung carcinoma [143], and recently PS-OCT results demonstrated the potential to visualize airway smooth muscle (ASM) cells ex vivo and imaging and volumetric assessments of ASM in humans in vivo [144].…”

Optical coherence elastography – OCT at work in tissue biomechanics [Invited]

“…Birefringence can be altered by stress in various ways, and stress-induced birefringence in rigid non-biological materials has been explored with OCT [196]. In soft tissues, it has recently been shown that stress induces changes in the birefringence of airway smooth muscle [197]. There has also been one preliminary study comparing OCE and PS-OCT [198].…”

Endoscopic optical coherence tomography: technologies and clinical applications [Invited]

“…OCT was also used to investigate tissue remodeling prior to and 2 years after bronchial thermoplasty in 2 asthma patients, where reduction in airway thickness was compared for treated and untreated patients [166]. Microvasculature, autofluorescence and birefringence: To further increase clinical utility of OCT in pulmonary medicine, multi-modal endobronchial OCT imaging techniques to enhance contrast and improve visualization of microstructure/function were introduced [167,168]. For example, visualization of the 3D vascular network in the lung has the potential to improve detection and monitoring of diseases like asthma, chronic obstructive pulmonary disease and cancer.…”

“…The multi-modal system provided rapid identification of pulmonary nodules while also highlighting major vessels for biopsy guidance [167], and visualizing vessels as small as 12 μm [170]. Another example of a contrast-enhancing technique is orientation resolved OCT (OR-OCT) that is based on polarization sensitive OCT [168]. This technology, utilizes the optical axis of tissue birefringence to highlight ordered structures within the tissue such as airway smooth muscle.…”

“…Such contrast can be an important biomarker in the assessment of asthma (Fig. 23) [168] and in other obstructive lung diseases such as COPD [168]. …”