Minimally invasive optical biopsy for oximetry

Abstract

The study of localised oxygen saturation in blood vessels can shed light on the etiology and progression of many diseases with which hypoxia is associated. For example, hypoxia in the tendon has been linked to early stages of rheumatoid arthritis, an auto-immune inflammatory disease. Vascular oximetry of deep tissue presents significant challenges as vessels are not optically accessible. In this paper, we present a novel multispectral imaging technique for vascular oximetry, and recent developments made towards its adaptation for minimally invasive imaging. We present proof-of-concept of the system and illumination scheme as well as the analysis technique. We present results of a validation study performed in vivo on mice with acutely inflamed tendons. Adaptation of the technique for minimally invasive microendoscopy is also presented, along with preliminary results of minimally invasive ex vivo vascular oximetry.

Oximetry using multispectral imaging: theory and application

“…MSI oximetry has been applied to diverse applications in vivo, including measurement of blood OS in the spinal cord [7], the brain [8], muscle tendons [9,10], the bowel [11], the oral microvasculature [12], and the skin [13]. In the eye, MSI oximetry has established the oxygen dynamics and physiological norms of the retina [6], the choroid [14], the bulbar conjunctiva [15], and the episcleral blood vessels [15].…”

“…Their study concluded that if the tissue surrounding a vessel is illuminated, then the vessel will be effectively back-illuminated [58]. This finding has subsequently been used to simplify multispectral oximetry models by enabling the use of annular illumination to eliminate double-pass contributions in MSI oximetry models [9,70].…”

“…Sarkar et al exploited oxygen diffusion to remove OS as a source of uncertainty in their experiments to non-invasively measure bulbar conjunctival haemoglobin concentration for anemia diagnosis [116]. van der Putten et al [9] utilized reoxygenation by diffusion as an intervention to alter OS and confirm oximetry capability [9]. It has been suggested that oxygen diffusion rates could be investigated as a parameter for the measurement of microvascular function, e.g.…”

“…the antecubital vein) was the first technique used to validate in vivo retinal oximetry [32]. However, direct blood sampling is now rarely done due to several reasons: (1) invasive procedures that cause a risk of harm to a subject should be avoided wherever possible [129]; 9 (2) suitably qualified staff are required to draw blood from a human subject; (3) pulse oximetry has provided a quick, convenient, and non-invasive alternative in humans (as well as other animals); and (4) a standardized set of reference OS values has been adopted for two-wavelength retinal oximetry [40]. However, ex vivo blood gas measurement may be used in Figure 14.…”

“…OS, to a degree not possible in in vivo experiments. 9 Medical research involving human subjects must be carried out in accordance with the tenants of The Declaration of Helsinki, as set out by the World Medical Association [129]. animal studies, where animal handling is done by suitably trained and suitably licensed individuals [130].…”