Quantifying collagen fiber orientation in breast cancer using quantitative phase imaging

Abstract

Tumor progression in breast cancer is significantly influenced by its interaction with the surrounding stromal tissue. Specifically, the composition, orientation, and alignment of collagen fibers in tumor-adjacent stroma affect tumor growth and metastasis. Most of the work done on measuring this prognostic marker has involved imaging of collagen fibers using second-harmonic generation microscopy (SHGM), which provides label-free specificity. Here, we show that spatial light interference microscopy (SLIM), a label-free quantitative phase imaging technique, is able to provide information on collagen-fiber orientation that is comparable to that provided by SHGM. Due to its wide-field geometry, the throughput of the SLIM system is much higher than that of SHGM and, because of the linear imaging, the equipment is simpler and significantly less expensive. Our results indicate that SLIM images can be used to extract important prognostic information from collagen fibers in breast tissue, potentially providing a convenient high throughput clinical tool for assessing patient prognosis.

Quantitative Phase Imaging for Label-Free Analysis of Cancer Cells—Focus on Digital Holographic Microscopy

“…Important to note is that the different setups come with slightly different benefits and limitations, making them inherently well suited to a variety of purposes: High speed acquisition for high temporal resolution of flow imaging [70], in situ imaging of growing adherent cells [21,37,56], live cell tomography [71,72], or incubator monitoring [30,73].…”

Real-time halo correction in phase contrast imaging

“…However, we choose to use quantitative phase imaging[22] (QPI), which enables objective measurements of the phase shift in a reproducible, system-independent manner. Recently, such systems have found fertile ground in studies of cellular morphology[23-31], plate reader style screening of whole cell populations[24, 32-35], and histopathology sections[36, 37].…”

Tissue spatial correlation as cancer marker

“…10,11 Tissue refractive index-based markers have been used in the past for medical diagnosis and prognosis of several types of cancers and diseases. [12][13][14][15][16][17][18][19][20][21][22][23][24] By generating contrast, label-free QPI lends itself much more readily to automated image analysis than bright-field microscopy, since stain variation is no longer an issue. 13 In addition to the advantages of label-free imaging, the contrast mechanism in QPI provides access to additional markers of disease, which are of value to histopathology.…”