T staging esophageal tumors with x rays

Abstract

With histopathology results typically taking several days, the ability to stage tumors during interventions could provide a step change in various cancer interventions. X-ray technology has advanced significantly in recent years with the introduction of phase-based imaging methods. These have been adapted for use in standard labs rather than specialized facilities such as synchrotrons, and approaches that enable fast 3D scans with conventional x-ray sources have been developed. This opens the possibility to produce 3D images with enhanced soft tissue contrast at a level of detail comparable to histopathology, in times sufficiently short to be compatible with use during surgical interventions. In this paper we discuss the application of one such approach to human esophagi obtained from esophagectomy interventions. We demonstrate that the image quality is sufficiently high to enable tumor $T$ staging based on the x-ray datasets alone. Alongside detection of involved margins with potentially life-saving implications, staging tumors intra-operatively has the potential to change patient pathways, facilitating optimization of therapeutic interventions during the procedure itself. Besides a prospective intra-operative use, the availability of high-quality 3D images of entire esophageal tumors can support histopathological characterization, from enabling "right slice first time" approaches to understanding the histopathology in the full 3D context of the surrounding tumor environment.

Fig. 1.

(a) Top-view conceptual schematic of edge-illumination x-ray phase contrast imaging and (b) photograph of the actual system.

Fig. 2.

Example of cancer-free human esophagus with acquisition times of (a) 2 and (b) 10 h. Sections of the esophagus have been labeled in (b), with (1) the lumen, the space inside the esophagus; (2) mucosa, the membrane lining the interior of the esophagus; (3) muscularis mucosa, a thin layer of muscle separating the mucosa from the submucosa; (4) submucosa, a thin layer of connective tissue that supports the mucosa; (5) inner muscularis, the first of the two muscle layers with a circular arrangement; (6) outer muscularis, the second muscle layer with longitudinal alignment; and (7) adventitia, the outer layer of fibrous connective tissue. The color scale represents the attenuation coefficient ${\mu }_{\mathrm{e}\mathrm{f}\mathrm{f}}$ in ${\mathrm{m}\mathrm{m}}^{-1}$ [see Eq. (6) in Supplement 1], and the window width has been optimized to enhance the contrast of soft tissues. This has been applied in the same way to all presented images (which indeed all have a similar windowing); hence this is not repeated in the following captions.

Fig. 3.

T1 cancer example, with (a) XPCI CT slide presented side-by-side with (b) its histopathology counterpart. In this and in the following images, tumor segmentation by the radiologists is shown in the CT image as a dashed yellow line, and an example of tissue invasion into the outer muscular layers (or lack thereof) identified by the pathologist is indicated with a red arrow in the histopathology slice. The color scale represents the attenuation coefficient ${\mu }_{\mathrm{e}\mathrm{f}\mathrm{f}}$ in ${\mathrm{m}\mathrm{m}}^{-1}$ (see caption of Fig. 2 for details).

Fig. 4.

T2 cancer example, with (a) XPCI CT slide with lesion segmented by the radiologists presented side-by-side with (b) its histopathology counterpart, where two points where the tumor is just invading into the muscle layers have been highlighted with red arrows by the pathologist. The color scale represents the attenuation coefficient ${\mu }_{\mathrm{e}\mathrm{f}\mathrm{f}}$ in ${\mathrm{m}\mathrm{m}}^{-1}$ (see caption of Fig. 2 for details).

Fig. 5.

T3 cancer example, with (a) XPIC CT slide and segmented tumor presented side-by-side with (b) its histopathology counterpart. This is a much larger lesion than presented in previous cases, and the tumor invades into the adventitia at multiple points, three of which have been highlighted by the pathologist through red arrows. The color scale represents the attenuation coefficient ${\mu }_{\mathrm{e}\mathrm{f}\mathrm{f}}$ in ${\mathrm{m}\mathrm{m}}^{-1}$ (see caption of Fig. 2 for details).

Fig. 6.

3D rendering of an esophagus section showing (a) slice where the cancer is contained to the submucosa and the muscle layer intact as shown by the red arrow, i.e., a T1 stage tumor; (b) slice further up where the muscle layer has been penetrated as shown by the red arrow, indicative of a stage T2 tumor; and (c) full volume. In (c), segmentation has been performed outlining the inner muscularis, with the pink and blue lines showing the inside and outside, respectively. The green line is an interpolation of the position of the inside of the muscularis from slices above and below where no tumor was present, meaning the area between green and pink highlighted by the red arrow in (c) is the T2 stage of the tumor.