In vivo molecular subtyping of malignant human breast cancer using multispectral optoacoustic tomography

Abstract Objectives This exploratory study aimed to characterize high-resolution in vivo optoacoustic signal characteristics of the different breast cancer molecular subtypes using second-generation handheld multispectral optoacoustic tomography (MSOT). Materials and methods Patients with suspected breast cancer were prospectively recruited between July 2021 and August 2022 ( n = 33, 54 ± 14 years) and underwent gray-scale ultrasound, as well as core needle biopsy of the suspicious lesion as part of the routine diagnostic workflow. The biopsies were used for diagnosis and molecular subtyping into one of four groups (luminal A n = 11, luminal B n = 5, human epidermal growth factor receptor 2 (HER2, n = 6), and triple-negative (TN, n = 11)) based on hormone receptor (HR) expression. Bidirectional MSOT scans of the tumors were taken prior to biopsy to visualize relative optoacoustic signal components corresponding to oxygenated hemoglobin (HbO 2 ), deoxygenated hemoglobin (Hb), and total blood volume (TBV). Mean wavelength-specific and spectrally unmixed relative signal intensities were compared between molecular subtypes using one-way ANOVA and Welch’s t -tests. Results HR-negative tumors showed significantly higher wavelength-specific signal intensities at 750 nm, 800 nm, and 850 nm, as well as higher relative Hb- and TBV-related signal intensities ( p < 0.05). When molecular subtypes were compared, luminal A tumors showed lower signal intensities at 750 nm compared with TN tumors, and luminal B tumors showed lower relative TBV-related signal intensities than TN tumors. Conclusion In vivo MSOT demonstrated differences in wavelength-specific and spectrally unmixed relative optoacoustic signal intensities between breast cancer molecular subtypes, particularly between HR-positive and HR-negative tumors. These preliminary findings suggest that MSOT may provide complementary non-invasive information regarding tumor biology. Key Points Question Molecular subtyping of breast cancer currently relies on histopathological, immunohistochemical, and molecular analysis of biopsy specimens. MSOT may provide complementary non-invasive information regarding tumor biology, but its role remains exploratory . Findings TN tumors demonstrated higher relative optoacoustic signal intensities related to Hb and TBV, whereas HR-positive tumors showed lower wavelength-specific signal intensities compared with HR-negative tumors . Relevance statement In vivo MSOT revealed group-level differences in relative optoacoustic signal characteristics between HR-positive and HR-negative breast cancers, suggesting that MSOT may provide complementary non-invasive information regarding tumor biology .