Breast cancer differential diagnosis using diffuse optical spectroscopic imaging and regression with z-score normalized data

Significance: Current imaging paradigms for differential diagnosis of suspicious breast lesions suffer from high false positive rates that force patients to undergo unnecessary biopsies. Diffuse optical spectroscopic imaging (DOSI) noninvasively probes functional hemodynamic and compositional parameters in deep tissue and has been shown to be sensitive to contrast between normal and malignant tissues. Aim: DOSI methods are under investigation as an adjunct to mammography and ultrasound that could reduce false positive rates and unnecessary biopsies, particularly in radiographically dense breasts. Methods: We performed a retrospective analysis of 212 subjects with suspicious breast lesions who underwent DOSI imaging. Physiological tissue parameters were [Formula: see text]-score normalized to the patient’s contralateral breast tissue and input to univariate logistic regression models to discriminate between malignant tumors and the surrounding normal tissue. The models were then used to differentiate malignant lesions from benign lesions. Results: Models incorporating several individual hemodynamic parameters were able to accurately distinguish malignant tumors from both the surrounding background tissue and benign lesions with area under the curve (AUC) [Formula: see text]. [Formula: see text]-score normalization improved the discriminatory ability and calibration of these predictive models relative to unnormalized or ratio-normalized data. Conclusions: Findings from a large subject population study show how DOSI data normalization that accounts for normal tissue heterogeneity and quantitative statistical regression approaches can be combined to improve the ability of DOSI to diagnose malignant lesions. This improved diagnostic accuracy, combined with the modality’s inherent logistical advantages of portability, low cost, and nonionizing radiation, could position DOSI as an effective adjunct modality that could be used to reduce the number of unnecessary invasive biopsies.