Abstract
The standard practice in histopathology of breast cancers is to examine a hematoxylin and eosin (H&E) stained tissue biopsy under a microscope to diagnose whether a lesion is benign or malignant. This determination is made based on a manual, qualitative inspection, making it subject to investigator bias and resulting in low throughput. Hence, a quantitative, label-free, and high-throughput diagnosis method is highly desirable. We present here preliminary results showing the potential of quantitative phase imaging for breast cancer screening and help with differential diagnosis. We generated phase maps of unstained breast tissue biopsies using spatial light interference microscopy (SLIM). As a first step toward quantitative diagnosis based on SLIM, we carried out a qualitative evaluation of our label-free images. These images were shown to two pathologists who classified each case as either benign or malignant. This diagnosis was then compared against the diagnosis of the two pathologists on corresponding H&E stained tissue images and the number of agreements were counted. The agreement between SLIM and H&E based diagnosis was 88% for the first pathologist and 87% for the second. Our results demonstrate the potential and promise of SLIM for quantitative, label-free, and high-throughput diagnosis.
Highlights
Breast cancer is the second most common form of cancer diagnosed worldwide, accounting for 11.9% of all cancers diagnosed in 2012.1 In spite of the high incidence and burden of the disease, the current histopathological analysis used for the diagnosis of breast cancers suffers from certain shortcomings
When an abnormality in the breast is discovered during a screening procedure such as mammography, a tissue biopsy is obtained by the pathologist and the section of tissue is stained using hematoxylin and eosin (H&E)
Our preliminary results show the capability of our label-free imaging modality in resolving morphological features relevant for diagnosis of breast cancer
Summary
Breast cancer is the second most common form of cancer diagnosed worldwide, accounting for 11.9% of all cancers diagnosed in 2012.1 In spite of the high incidence and burden of the disease, the current histopathological analysis used for the diagnosis of breast cancers suffers from certain shortcomings. When an abnormality in the breast is discovered during a screening procedure such as mammography, a tissue biopsy is obtained by the pathologist and the section of tissue is stained using hematoxylin and eosin (H&E) This staining provides the necessary contrast needed for investigation of key morphological features by a trained, board certified pathologist using a conventional bright-field microscope. As was shown by Wang et al, the four interferograms can be solved to obtain φ.17 It has been shown in previous publications from our group that SLIM provides diffraction-limited resolution as well as low spatial and temporal noise leading to optical path length sensitivity of less than a nanometer.[17,18,19,20] The utility of refractive index of tissue (accessible through the phase images obtained by SLIM) as a marker for prostate tissue malignancy has been shown in previous publications, which motivates the current application of SLIM as a histopathological analysis technique for breast tissue biopsies.[21,22]. As outlined in detail using the standard H&E staining
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