Biomedical Engineering Reference
In-Depth Information
17
SHG in Tumors: Scattering
and Polarization
17.1 Scattering Properties of SHG in Tumors ......................................392
Factors Affecting the
F
/
B
Signal •
F
/
B
Measurements in Tumor
Tissue • Technical Advances for Measuring
F
/
B
17.2 Polarization of SHG in Tumors ..................................................... 400
Polarization Properties of Collagen SHG • SHG Polarization
Measurements in Tumor Tissue
17.3 Summary and Conclusions .............................................................402
Acknowledgments ........................................................................................402
Appendix: Theory of Polarization Analysis ..............................................402
References......................................................................................................405
Seth W. Perry
University of Rochester
Xiaoxing Han
University of Rochester
Edward B. Brown
University of Rochester
Tumor physiology, biochemistry, structural organization, and cellular composition are believed to make
integrated contributions to cancer pathology. The tumor stroma for one includes the basement mem-
brane, the extracellular matrix (ECM), and nonmalignant cells in the tumor, and plays significant roles
in tumor growth and metastasis [1,2]. The biochemical and phenotypic changes in stromal cells sur-
rounding malignant tumor cells, including immune cells and connective tissue cells such as fibroblasts
(a principal collagen-producing cell type), modify the synthesis and breakdown of key ECM compo-
nents, resulting in a “reactive stroma” characteristic of neoplastic transformation and thus contribut-
ing to tumor progression and metastasis [1-4]. This key role that the “reactive stroma” plays in cancer
pathogenesis has led to significant interest in understanding the particular characteristics of reactive
stroma that may provide prognostic value for predicting cancer pathogenesis or its outcome [5-8]. Since
collagen is a key component of the ECM and is also believed to play important roles in cancer, recent
years have seen a burgeoning interest in monitoring the second-harmonic generation (SHG) signal from
fibrillar collagen in tumor stroma, with the idea that it may provide diagnostic or predictive value in
comparison of normal versus malignant tissue [9-16, and other references herein].
Indeed, SHG signal is proportional to the total collagen content and changes dynamically with tumor
growth and biochemical modification of the ECM [9], and several studies have demonstrated relative
changes in the overall SHG levels or intensity in comparison of control versus cancerous tissue from
both experimental animal models and humans [17-23, and reviewed in Ref. [24] and elsewhere in the
topic]. However, beyond gross changes in SHG intensity, SHG's coherent properties allow us to extract
other information about collagen's molecular structure from the SHG signal that is also relevant to
tumor pathology. Specifically, the ratio of forward-scattered (
F
) to backward-scattered (
B
) SHG signal
(
F
/
B
ratio) is sensitive to the axial length scale over which collagen scatterers are ordered for SHG [1,25-
32]. Monitoring these fibril characteristics can provide important insights into cancer pathophysiol-
ogy, since the reactive tumor stroma is characterized by altered collagen production and degradation
[2-4], and the changes in collagen fiber diameter or shape have been linked to human cancer [33-35].
(Collagen fibers are larger diameter bundles of collagen fibrils.)
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