Breast cancer is one of the most prevalent cancers among women worldwide, with over 2 million new cases diagnosed in 2018 alone 1. Early detection of breast cancer is critical, as it leads to higher survival rates and better treatment outcomes. The current standard screening method for breast cancer is mammography, which uses low-energy X-rays to create images of the breast tissue. However, mammography has limitations in detecting some breast tumors, leading to false negative results in 10-30% of screenings 2.
Raman spectroscopy can detect subtle molecular changes that occur in breast tissue before anatomical abnormalities are visible on a mammogram. Hence, Raman spectroscopy, when combined with mammography, substantially improves the sensitivity and specificity of breast cancer diagnosis.
Surface Enhanced Raman Spectroscopy Provides Molecular Fingerprints to Augment Mammography
The process leverages the strengths of both screening modalities – mammography’s ability to locate suspicious lesions, and Raman spectroscopy’s capacity to analyze those lesions’ biochemical makeup.
Cancerous tissues have been shown to have increased protein content and more metabolically active DNA compared to healthy tissues. These biochemical changes can be detected by Raman spectroscopy based on changes in the signals related to amino acids, proteins, and DNA/RNA that serve as fingerprints for malignancy.
During a breast cancer screening exam, a patient first undergoes a standard mammogram imaging procedure. X-ray images are examined by radiologists to identify areas of concern, like calcifications, architectural distortions, or masses that may indicate malignancy.
If any suspicious lesions are spotted on the mammogram, Raman spectroscopy is used on those specific sites to further evaluate the nature of those lesions. Fiber optic Raman probes are introduced through needle biopsies or placed directly on the lesion surface (in the case of noninvasive techniques) to acquire Raman spectra.
Computer-aided diagnostic algorithms compare the spectral signatures acquired from the lesions to reference Raman spectra from normal, benign, and malignant breast tissues. This spectral classification allows a definitive diagnosis of whether the abnormality spotted on mammography is likely malignant or benign.
By first locating the anatomical area of concern via mammogram, and then analyzing it with Raman spectroscopy, radiologists can make more confident diagnoses. Raman spectroscopy grades the severity of abnormalities that mammography flags, reducing false positives and negatives.
Multimodal Approach with Raman Spectroscopy and Mammography Is Shown to Improve Diagnostic Accuracy
Using Raman spectroscopy in coalition with mammography offers a multimodal approach that leverages the benefits of both techniques for improved breast cancer diagnosis. While mammography provides anatomical images to locate suspicious lesions, Raman spectroscopy analyzes the lesions at a molecular level to give chemical and biological information related to malignancy.
A 2017 meta-analysis of 12 studies found that Raman spectroscopy coupled with mammography increased the pooled sensitivity from 0.80 to 0.92 and specificity from 0.81 to 0.96 for differentiating malignant and normal breast tissues. 3
The synergistic combination of the two techniques addresses the limitations of each – mammography’s low sensitivity and Raman spectroscopy’s inability to localize lesions. This results in more accurate breast cancer diagnosis.
Raman Spectroscopy Shows Promise for Noninvasive, In Vivo Breast Cancer Detection
Conventional tissue Raman spectroscopy requires excisional biopsies before analysis. However, researchers are now focused on developing noninvasive Raman techniques that can be used in vivo on intact breast tissues.
- Fiber-optic Raman probes can collect Raman signals during clinical procedures like core needle biopsies and lumpectomies for real-time evaluation of resection margins and lymph nodes. 4
- Probe-based Raman spectroscopy has been applied in vivo on breast tissue surfaces to discriminate normal and malignant tissues with high accuracy (sensitivity of 93%, specificity of 91%).
- Advances in instrument designs now allow noninvasive in vivo transcutaneous Raman spectroscopy of breast lesions up to 40 mm below the skin surface, yielding spectra comparable to invasive Raman techniques. 5
These advances demonstrate the potential of Raman spectroscopy as a completely noninvasive breast cancer detection tool that could be used for screening high-risk patients.
Recent Strides in Machine Learning Will only Improve the Diagnostic Accuracy of Raman Spectra
Advances in machine learning have significantly improved the diagnostic accuracy of Raman spectroscopy for breast cancer. By training algorithms on large datasets of reference Raman spectra from normal and diseased breast tissues, automated classifiers can now reliably categorize unknown tissue samples based on their Raman fingerprints. Machine learning accounts for natural variances in Raman spectra and emphasizes key spectral differences between benign, premalignant, and malignant lesions. This reduces false classifications and makes the technique more practical for clinical implementation.
Frequently Asked Questions
What are the advantages of using Raman spectroscopy with mammography for breast cancer detection?
The main advantages are improved sensitivity and specificity compared to using mammography alone. Raman spectroscopy complements mammography by providing biochemical information to better differentiate malignant and normal/benign breast tissues.
How is Raman spectroscopy performed on breast tissues?
Conventional Raman spectroscopy requires excisional biopsies for analysis. But fiber-optic Raman probes now allow real-time in vivo measurements during biopsies and lumpectomies. Noninvasive transcutaneous Raman techniques are also being developed to obtain breast Raman spectra without any incisions.
Does Raman spectroscopy completely replace mammography for breast cancer screening?
No, Raman spectroscopy is not meant to replace mammography, but rather augment it. Mammography is still required to provide anatomical images and locate suspicious lesions. Raman spectroscopy then analyzes the lesions to improve diagnostic accuracy. The two modalities together provide both structural and biochemical data for better diagnosis.
What are some limitations of using Raman spectroscopy for breast cancer detection?
Limitations include the cost of Raman systems, the need for trained personnel, and data analysis challenges. Skin pigmentation and thickness can also interfere with transcutaneous Raman techniques. Ongoing research aims to address these limitations and translate Raman spectroscopy into a feasible clinical breast cancer screening tool.
How does Raman spectroscopy compare to other breast imaging modalities like MRI?
MRI is more sensitive but less specific than mammography. Raman spectroscopy improves upon the sensitivity and specificity of mammography for breast cancer diagnosis. While MRI provides complementary structural information, Raman spectroscopy specifically detects molecular changes associated with malignancy.
- Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018. 68, 394–424 ↩︎
- https://pubmed.ncbi.nlm.nih.gov/28972651/ ↩︎
- https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/jrs.6437 ↩︎
- https://onlinelibrary.wiley.com/doi/10.1002/tbio.202000018 ↩︎
- https://www.nature.com/articles/s41416-021-01659-5 ↩︎