Mieke Bus

4 53 Introduction Optical Coherence Tomography (OCT) is a high resolution imaging technology originally applied in ophthalmology. (1) OCT is analogous to ultrasonography, using back-scattered light instead of back-reflected sound waves to produce micrometer-scale resolution, cross-sec- tional images in which layered tissue anatomy can be distinguished, e.g. the basement membrane, which status is indicative of stage in case of visible lesion. (2) Light scattering decreases the OCT signal magnitude with depth, and limits the imaging range to approxi- mately 2mm. This signal decrease is quantified by the attenuation coefficient µ oct that allows in-vivo differentiation between different tissue types. (3, 4) During carcinogenesis, changes occur in cellular architecture resulting in an increased nuclear-cytoplasm ratio and increased amount of mitochondria. Physically, this sub-cellular organization of tissue determines light scattering properties. (5) Therefore, we hypothesized that lesion stage is obtained from image- based assessment of presence of a visible basement membrane; and that lesion grade cor- relates with µ oct . Most research of OCT on urothelium is in the field of bladder cancer. After initial animal studies, several authors demonstrated the feasibility of OCT imaging in humans: Tearney et al first described the ability of OCT to distinguish anatomical layers (urothelium, lamina propria and muscularis propria) of non-diseased bladder wall tissue in an ex-vivo setting. (6) The potential of OCT for staging-diagnosis of UTUC has not yet been investigated in-vivo, although ex-vivo studies of the porcine ureter demonstrated that OCT could clearly distin- guish the ureteral wall layers, particularly the urothelium and lamina propria. (7, 8) Compared to endoluminal ultrasonography, OCT distinguishes significantly better the wall layers of ex-vivo porcine ureter. (9) An animal study by Xie et al showed differences in scattering properties between normal and cancerous urothelium. (5) Similar studies on lesions in the kidney, vulva, oral tissue and lymph node metastasis confirmed ability of OCT to distinguish tissue types based on µ oct . (3, 4, 10-12) However, our initial study on ex-vivo human bladder urothelial biopsies showed that factors typical for ex-vivo settings (e.g. cauterization of bladder tissue specimens) on µ oct - based grading of human bladder cancer were inconclusive but indicative of the need for in-vivo evaluation. (13) Radical nephroureterectomy is the standard of care for UTUC. (14) Conservative treatment preserves the renal unit, and is preferred because of the increased chance of recurrence in the contralateral renal unit, and is clearly advantageous in imperative situations. However, conservative treatment is only offered to a select group of UTUC patients with low-grade and low-stage disease. Nowadays, diagnosis of UTUC is based on imaging, ureterorenoscopy (URS) and cytology/ histology. Although considered to be the reference standards, these techniques have limita- tions: 1) No real-time intra-operative histological information is obtained on stage and grade