Fractal dimension analysis as an easy computational approach to improve breast cancer histopathological diagnosis

Abstract

Histopathology is a well-established standard diagnosis employed for the majority of malignancies, including breast cancer. Nevertheless, despite training and standardization, it is considered operator-dependent and errors are still a concern. Fractal dimension analysis is a computational image processing technique that allows assessing the degree of complexity in patterns. We aimed here at providing a robust and easily attainable method for introducing computer-assisted techniques to histopathology laboratories. Slides from two databases were used: A) Breast Cancer Histopathological; and B) Grand Challenge on Breast Cancer Histology. Set A contained 2480 images from 24 patients with benign alterations, and 5429 images from 58 patients with breast cancer. Set B comprised 100 images of each type: normal tissue, benign alterations, in situ carcinoma, and invasive carcinoma. All images were analyzed with the FracLac algorithm in the ImageJ computational environment to yield the box count fractal dimension (Db) results. Images on set A on 40x magnification were statistically different (p = 0.0003), whereas images on 400x did not present differences in their means. On set B, the mean Db values presented promissing statistical differences when comparing. Normal and/or benign images to in situ and/or invasive carcinoma (all p < 0.0001). Interestingly, there was no difference when comparing normal tissue to benign alterations. These data corroborate with previous work in which fractal analysis allowed differentiating malignancies. Computer-aided diagnosis algorithms may beneficiate from using Db data; specific Db cut-off values may yield ~ 99% specificity in diagnosing breast cancer. Furthermore, the fact that it allows assessing tissue complexity, this tool may be used to understand the progression of the histological alterations in cancer.

Classifying breast cancer and fibroadenoma tissue biopsies from paraffined stain-free slides by fractal biomarkers in Fourier Ptychographic Microscopy

“…Their investigation revealed that fractal dimension-based features extracted from stained WSI demonstrated remarkable capabilities in distinguishing breast carcinomas from normal tissue and benign breast alterations. These findings underscore the significance of fractal dimension analysis as a powerful tool in advancing our understanding and diagnostic capabilities in histopathological studies [75] .…”

Classifying breast cancer and fibroadenoma tissue biopsies from paraffined stain-free slides by fractal biomarkers in Fourier Ptychographic Microscopy

“…These findings underscore the significance of fractal dimension analysis as a powerful tool in advancing our understanding and diagnostic capabilities in histopathological studies. 64…”

“…These findings underscore the significance of fractal dimension analysis as a powerful tool in advancing our understanding and diagnostic capabilities in histopathological studies. 64 It is important to note that the histopathological analysis of breast cancer that we used as test case of our Digital Pathology approach can be critical due to its intrinsic complexity. Indeed, cell density and morphology alone cannot be sufficient for the differential diagnosis between a malignant and a benign lesion, as special cases such as florid adenosis or sclerosing adenosis could create outputs that may be associated with false-positive subjects.…”

Universal Markers Unveil Metastatic Cancerous Cross-Sections at Nanoscale

“…Fractal analysis is already used to study cancer [ 15 , 16 ], and it can lead to the improvement of the diagnostic validity of both cyto-histopathological and medical imaging findings [ 17 ]. For instance, fractal analysis has been used to elucidate various types of tumors: colorectal cancer (CRC) [ 18 ]; rectal cancer [ 19 ]; and breast cancer [ 20 , 21 , 22 ], to name a few. The fractal or Hausdorff dimension (FD) [ 23 ] is the index that has been used the most in cancer analysis.…”