Titel: Non-invasive diagnostic approaches for giant cell arteritis

Opponent: Gauti Jóhannesson (docent, överläkare), Associate professor, Umeå University, Umeå, Sweden

Abstract
Giant cell arteritis (GCA) is a treatable, but potentially sight-threatening form of primary systemic vasculitis. Prompt and correct diagnosis is important, as early intervention can prevent blindness and other serious vascular events. Diagnosing GCA presents a clinical challenge as there are no diagnostic criteria for the disease, and the symptoms are often initially diffuse. Temporal artery biopsy (TAB) has long been regarded as the gold standard for diagnosing GCA, but has low diagnostic sensitivity and is associated with surgical risks. A non-invasive diagnostic method would therefore be of great benefit. Previous attempts, employing methods like ultrasound, have shown variable accuracy in diagnostic performance.

The aim of the work presented in this thesis was to assess three novel non-invasive techniques for future GCA diagnosis: photoacoustic imaging (PAI), ultrasound center frequency shift (CFS), and tomographic three-dimensional (3D) ultrasound.

PAI is a biomedical technique that uses the combination of laser light and ultrasound and provides high-resolution images of biological tissues. The technique was evaluated with regard to its safety and patient tolerability, and the spectral signature of the temporal artery in healthy subjects was obtained. PAI was well tolerated by the participants and did not affect their visual function. The spectral signature of the temporal artery was unique, and the artery could be clearly differentiated from the surrounding tissue. PAI was also evaluated with respect to spectral and spatial characterization of the temporal artery ex vivo from subjects suspected of having GCA. PAI provided detailed spectral information allowing the architecture of the temporal artery to be mapped. Spectral analysis indicated a difference in the spectra obtained from GCA-positive and GCA-negative biopsies.

Ultrasound CFS, a novel ultrasound technique that provides objective information on tissue microstructure, was assessed on TAB specimens from subjects suspected of having GCA. The mean CFS, expressed as CFS (%), decreased significantly less in vessels with GCA than in vessels without GCA, indicating that ultrasound CFS has the potential to discriminate between GCA-positive and GCA-negative biopsies.

Tomographic 3D ultrasound was used to visualize the temporal artery in healthy subjects and in patients with suspected GCA. The inner and outer vessel diameters were measured, and the vessel wall fraction was calculated. This technique enabled 3D visualization of the temporal artery, and the high vessel wall fraction revealed vessel wall thickening and lumen narrowing, which may be indicative of GCA.

Histopathological examinations of TAB specimens were used as references for diagnosing GCA in the studies presented in this thesis, and since the diagnostic sensitivity of TAB may vary with biopsy length, it was investigated whether the length of the TAB specimen decreased after excision and formalin fixation, as indicated in previous studies. The length of the biopsy was measured before excision, after excision, and after formalin fixation. The median length decreased following excision, but no further reduction was seen as a result of formalin fixation. The surgeon can therefore be confident that the length of the biopsy after excision is the length examined histopathologically.

In conclusion, PAI, ultrasound CFS, and tomographic 3D ultrasound are promising non-invasive diagnostic tools for GCA. Further technical development and studies are needed before their clinical applicability can be assessed.