FF-OCT: Advanced Diagnosis of Giant Cell Arteritis

Abstract

Histopathological examination of temporal artery biopsy (TAB) remains the gold standard for the diagnosis of giant cell arteritis (GCA) but is associated with essential limitations that emphasize the need for an upgraded pathological process. This study pioneered the use of full-field optical coherence tomography (FF-OCT) for rapid and automated on-site pathological diagnosis of GCA. Sixteen TABs (12 negative and 4 positive for GCA) were selected according to major histopathological criteria of GCA following hematoxylin-eosin-saffron-staining for subsequent acquisition with FF-OCT to compare structural modifications of the artery cell wall and thickness of each tunica. Gabor filtering of FF-OCT images was then used to compute TAB orientation maps and validate a potential automated analysis of TAB sections. FF-OCT allowed both qualitative and quantitative visualization of the main structures of the temporal artery wall, from the internal elastic lamina to the vasa vasorum and red blood cells, unveiling a significant correlation with conventional histology. FF-OCT imaging of GCA TABs revealed destruction of the media with distinct remodeling of the whole arterial wall into a denser reticular fibrous neo-intima, which is distinctive of GCA pathogenesis and accessible through automated Gabor filtering. Rapid on-site FF-OCT TAB acquisition makes it possible to identify some characteristic pathological lesions of GCA within a few minutes, paving the way for potential machine intelligence-based or even non-invasive diagnosis of GCA.

Introduction

Giant cell arteritis (GCA) is a large vessel vasculitis that mainly affects the aorta and the branches of the external carotid, with a predilection for the temporal arteries [1]. Even though we now have an accurate understanding of its complex pathogenesis, the causative agent of GCA is still unknown [2]. Mostly occurring in northern European females between 50 and 80 years old, the predominant cranial phenotype is usually revealed by new-onset headache, temporal artery tenderness, jaw claudication, and partial or complete visual loss associated with possible systemic symptoms, notably fever, weight loss and weakness [3]. The critical complications of GCA include anterior ischemic optic neuropathy, stroke, aortic aneurysm or dissection; these serious complications being responsible for the prognosis of the disease and the need for prolonged high-dose glucocorticoid treatment [4].

The diagnosis of GCA usually relies on the association of concurrent clinical, biological and pathological features of vasculitis that are revealed by temporal artery biopsy (TAB) [5]. Significant advances in the field of medical imaging have improved the assessment of the extent of vasculitis and refined non-invasive diagnosis and follow-up [6,7]. For instance, the validity of hypoechoic thickening surrounding the temporal artery wall with color duplex sonography (CDS), also referred to as the halo sign, was confirmed at least three times in a meta-analysis for the diagnosis and follow-up of GCA [8]. However, the combination of intense infiltration of mononuclear cells in the three layers of the artery, fragmentation of the internal elastic lamina (IEL), intimal hyperplasia and neoangiogenesis on TAB histological examination undoubtedly remains the gold standard for GCA diagnosis in all study group guidelines [9,10].

Apart from rare local complications [11], TAB is a safe procedure [12]. Nevertheless, the segmental and focal nature of transmural inflammation in GCA generates skip lesions [13] and is responsible for a significant false-negative rate of up to 30% [14] that makes it necessary to either increase biopsy length [15] or to perform a contralateral TAB [16]. These limitations emphasize the potential interest and need for an upgraded pathological procedure dedicated to the diagnosis of GCA.

Based upon an optimization of the technology described by Fujimoto and colleagues in the early 1990s [17,18], full-field optical coherence tomography (FF-OCT) exploits en face white-light interference microscopy to provide not only ultra-high resolution images of biological structures [19] but also subcellular metabolic contrast in the tissue depth [20]. When compared to other modalities such as conventional OCT or even confocal microscopy, FF-OCT was demonstrated to significantly improve spatial resolution by a factor varying from five to ten depending on the acquisition axis [21]. Until now, most groups have focused on the potential role of FF-OCT during oncologic interventions as new routine approach to surgical pathology [22], and, except for one preliminary study in which the superficial temporal arteries were imaged with dermal OCT [23], there has been no reported attempt to employ high definition interference microscopy for the pathological diagnosis of GCA. The present work pursues the hypothesis that FF-OCT could help both the clinician and pathologist to improve TAB performance, and compares, for the first time, FF-OCT and conventional histological examination for the pathological diagnosis of GCA.