Field carcinogenesis has manifestations at the number of levels of tissue physiology and morphology including alterations in mucosal microvasculature (detectable with a fiber-optic polarization-gated spectroscopy probe) and ultrastructure (detectable with low-coherence enhanced backscattering (LEBS) and partial wave spectroscopic (PWS) microscopy). The ultrastructural changes include alterations in the structure of collagen matrix and cryptal architecture as well as the nanoarchitecture of colonocytes (e.g. increase in the nuclear nanoscale disorder associated with alterations in the fractal organization of chromatin and chromatin compaction).

(a): A photograph of a fiber-optic probe for quantitative measurement of mucosal microvasculature (e.g. early increase in microvascular blood supply, EIBS). The probe is about 2 mm in diameter and can be used either as an endoscopically compatible device or a stand-alone device for detection of EIBS in rectal mucosa.
(b): Fractal dimension of rectal mucosal microarchitecture is altered in patients harboring significant neoplasia (advanced adenomas) elsewhere in the colon. The measurements were obtained using low-coherence enhanced backscattering (LEBS) from the rectal histologically and endoscopically normal appearing mucosa.
(c): Microscale organization of collagen matrix in the lamina propria and the upper submucosa is a marker of field carcinogenesis. The images were obtained by use of second harmonic generation microscopy (SHG) performed on histologically normal appearing colonic mucosa in the AOM-treated rat model of colon carcinogenesis. The top two panels (i and ii) show representative SHG images of collagen matrix structure from saline-treated control rats while the lower panels (iii and iv) show the matrix structure in the AOM-treated rats. The two left panels (i and iii) show three-dimensional reconstructions while the panels on the right (ii and iv) show the images integrated over all depths.
(d): Effect of past history of adenomas on rectal mucosal ultrastructural marker of field carcinogenesis. The ultrastructural marker was created as a linear combination of ultrastructural alterations measured with LEBS from histologically normal rectal mucosa. Patients with adenomas removed on a prior colonoscopy but with no concurrent adenomas (n=14) had statistically insignificantly elevated LEBS marker (p=0.12) compared to patients with no prior history and no concurrent adenomas (n=121), whereas patients with both prior history and concurrent adenomas (n=14) had significantly elevated LEBS marker (p=0.001).
(e,f): Nanocytology enables detection of field carcinogenesis and colon cancer screening. Nanocytological analysis of histologically normal colonocytes demonstrated that the disorder of their nanoscale architecture was a marker of field carcinogenesis. Nanocytology was performed by use of partial wave spectroscopic (PWS) microscopy (e). In the nucleus, the increased disorder is associated with altered higher-order chromatin structure. (f) Increased nanoscale disorder of rectal histologically normal colonocytes is a marker of adenomas located elsewhere in the colon.