CAPoxy
Research type
Research Study
Full title
Towards development of a combined structure and oxygenation capillaroscopy system to measure microvascular changes in systemic sclerosis; a feasibility study (CAPoxy)
IRAS ID
314969
Contact name
Andrea Murray
Contact email
Sponsor organisation
The University of Manchester
Duration of Study in the UK
1 years, 2 months, 2 days
Research summary
Research Summary:
Systemic sclerosis (SSc; also referred to as scleroderma) is a rare connective tissue disease (affecting soft tissue) characterised by vasculopathy (damage to blood vessels) and fibrosis (thickening/scarring) of the skin and internal organs; and is associated with significant mortality (death) and morbidity (loss of quality of life). The imaging of the capillaries (small blood vessels) with high magnification microscopy, is well established as a research technique to observe the characteristic microvascular structural changes occurring in SSc where the capillaries lie in the plane of the skin allowing full observation of capillary loops. The structural aspects of microvascular change in SSc are well studied. Functional changes (for example measuring blood flow and oxygenation in the vessels) have been less studied, since technically more complex.
Whilst structural changes are characteristic of SSc, it is likely that function may play a larger role in assessing sensitivity to change (e.g. disease progression and response to treatment). Thus imaging e.g. oxygenation in the individual capillaries is of interest in order to more fully understand the relationship between capillary structure and oxygenation. Here, we aim to take a first step and assess the feasibility of measuring oxygenation in the capillaries. In this study, images will be taken of the capillaries using our existing bespoke microscope with the addition of a new camera on loan from Cambridge, allowing combined measurement of function and structure in up to 50 patients with SSc, 20 primary Raynaud's participants and 30 healthy controls. An initial small study of 10 patients and 10 healthy controls will be used to check the initial set-up of the equipment and to ensure that the images taken can be analysed (PART A). In the main study (PART B), imaging will take place over up to three visits; visit one, visit two (within one week of visit one, subset of 50 participants), and visit three (at six months, subset of 50 participants). We will repeat the imaging over time and between different technicians to see how robust the technique is.
Summary of Results:
Nailfold capillaroscopy is a well-established microscope (Imaging at high magnification) technique, to help diagnosis of a rare disease that causes problems with small blood vessels and thickened skin, called systemic sclerosis (SSc). Capillary (small blood vessels that carry blood to organs) shape and size changes observed as part of a characteristic ‘SSc pattern’ occur over long periods of time (months/years). The amount of oxygenation in the blood of the capillaries is less studied but may allow shorter-term changes (minutes/hours) to be observed. This could be useful as an outcome measures of change including treatment response. A lack of oxygen in vessels, is believed to play a role in the SSc process. Thus, understanding capillary oxygenation may also increase understanding of the disease progression.
Aims: The aim of this study was to assess the feasibility of measuring oxygenation in the nailfold capillaries. Oxygen can be measured with coloured light. The specific objectives were to obtain simultaneous images of the capillaries with different colours of light, before during and after occlusion (temporarily stopping blood and oxygen flow to the finger) in patients with SSc and healthy controls.
Methods: The study was carried out in two parts, first to test feasibility and second to look at sensitivity of the technique to measure change by occlusion. In both parts of the study the non-dominant ring finger was illuminated with a white light and imaged with a camera that has different colour filters between 550-830 nm.
For the first part of the study 10 controls and 10 patients with SSc were recruited and fingers imaged. Once it was established that we could obtain good images of the capillaries the second part of the study was carried out. As well as imaging the fingers, a finger occlusion was carried out at 200 mmHg for 2 mins with images taken at baseline and 60 sec intervals from 1-5 mins after occlusion. Images were also taken by the same person twice and a different observer to assess reliability. For both parts of the study images were processed to account for the illumination spectrum and noise. Oxygenation was calculated. Oxygenation data for baseline, occlusion, release and post release (to 5 mins) were compared between patients with SSc and healthy controls.
Results: The first part of the study confirmed that capillaries could be observed and oxygenation calculated. In the second part of the study changes in oxygenation could clearly be seen during and after occlusion. Significant differences in oxygenation were observed between patients with SSc and controls. Reliability of the first observer and between observers were excellent (Interclass correlation coefficient >0.8).
Conclusion: The technique offers promise in the observation and measurement of nailfold capillaries but further studies are needed to refine the technique.REC name
London - Harrow Research Ethics Committee
REC reference
22/LO/0537
Date of REC Opinion
29 Sep 2022
REC opinion
Further Information Favourable Opinion