Multimodal 3D cancer-mimicking optical phantom

Abstract

Three-dimensional (3D) organ-mimicking phantoms provide realistic imaging environments for testing various aspects of optical systems, including for evaluating new probe designs, characterizing the diagnostic potential of new technologies, and assessing novel image processing algorithms prior to validation in real tissue. We introduce and characterize the use of a new material, Dragon Skin (Smooth-On Inc.), and fabrication technique, air-brushing, for fabrication of a 3D phantom that mimics the appearance of a real organ under multiple imaging modalities. We demonstrate the utility of the material and technique by fabricating the first 3D, hollow bladder phantom with realistic normal and multi-stage pathology features suitable for endoscopic detection using the gold standard imaging technique, white light cystoscopy (WLC), as well as the complementary imaging modalities of optical coherence tomography and blue light cystoscopy, which are aimed at improving the sensitivity and specificity of WLC to bladder cancer detection. The flexibility of the material and technique used for phantom construction allowed for the representation of a wide range of diseased tissue states, ranging from inflammation (benign) to high-grade cancerous lesions. Such phantoms can serve as important tools for trainee education and evaluation of new endoscopic instrumentation.

Keywords: (110.4500) Optical coherence tomography; (160.4760) Optical properties; (170.3880) Medical and biological imaging; (170.7230) Urology.

Fig. 1

Characterization of Dragon Skin. (a) Silicone solvent added (% by weight) to Dragon Skin vs. Young’s modulus for pure (no TiO₂) and adulterated (with 0.2% w/w TiO₂) Dragon Skin. Solid lines indicate regions in which air-brushing can be successfully applied, in contrast with dashed lines where it cannot. (b) Range of achievable attenuation coefficients (scattering-based) in Dragon Skin (blue circles) and in PDMS (green squares). Orange arrows indicate the attenuation coefficients associated with the various layers of the bladder (U:urothelium, LP: lamina propria, MP: muscularis propria).

Fig. 2

Characterization of air-brushing. (a) Total spray time vs. average achievable layer thicknesses with air-brushing. Error bars represent a standard deviation for n = 5 samples. (b) Intrasample variation in thickness for air-brushed layers is given as the standard deviation over a 2.5-mm-long sample (average thicknesses of samples are presented in (a). Representative B-scans for different spray times are also shown. Scale bars are 200 × 200 μm².

Fig. 3

Process diagram for the fabrication of a 3D bladder phantom. Circles labelled “D” represent sections of the phantom that are removed and then filled in to create various diseased regions (details provided in Supporting Information). An image of the full 3D bladder phantom is shown last.

Fig. 4

Comparison OCT images of human bladder tissue [24] with 3D phantom appearance under OCT, including healthy tissue and several stages of cancerous lesions. Scale bars in bladder tissue images represent 200 μm; white boxes in the phantom images represent 200 × 200 μm². U: urothelium, LP: lamina propria, MP: muscularis propria.

Fig. 5

Comparison WLC and BLC images of human bladder tissue with 3D phantom appearance, including healthy tissue, inflammation and cancer. Inflammation and cancer appear similarly under WLC and BLC (circled regions indicate fluorescent contrast in BLC and their corresponding locations in WLC images). Fluorescence contrast in inflammation may be slightly less than that seen in cancer, which is adequately mimicked in the phantom. Images are roughly 3 cm × 3 cm (notably, distance between probe and tissue varies between images).

Fig. 6

WLC images of papillary tumors in bladder tissue and the phantom, as marked by arrows. Papillary tumors protrude from the surface with a bubbly texture and are clearly discernible with WLC.