Clinical breast cancer imaging.

Breast cancer is the leading type of cancer in women with an incidence of about 1.6 mn cases p.a. It accounts for 25% of all cancers and causes more than 500,000 deaths per year.

To reduce these numbers, breast screening programs have been implemented in many countries. However, there are concerns of inaccurate diagnosis, especially in dense breasts, as well as of overuse of follow-up biopsies, x-ray CT or MRI imaging after initial suspicious mammographic findings. Recall rates for additional diagnostics from national screening programs vary between 4-10% of screened women.

The recalled cases as well as suspicious lesions detected by patients or physicians during other exams, require additional diagnostics. An ideal diagnostic modality to identify the 5-20% malignant cases out of the 3.5-5 mn suspicious lesions should be accurate, non-invasive, not expose the patient to harmful radiation and should not cause excessive cost to the health care system.

MSOT shows promise to fill this gap in examination of suspicious breast lesions. Several clinical research trials to examine breast lesions by MSOT have been conducted [1,2]. They rely on the unique MSOT capabilities to monitor hallmarks of cancerous lesions, including changes in vascular anatomy, hemoglobin content, tissue oxygenation, as well as lipid and water content.

Multispectral imaging, as used with the MSOT Acuity, can differentiate the signal from chromophores with distinct absorption spectra, and thus distinguish blood from water, fat and/or melanin. It also becomes possible to examine oxygenation changes [1,2,5] and potentially variations in lipid-water ratios in breast tissue.

MSOT images of healthy breast tissue and cancerous breast tissue are shown (Figure 1). Vasculature in the cancerous region gives rise to more heterogeneous hemoglobin-derived MSOT signals compared to the healthy tissue.

Figure 1: MSOT breast cancer imaging

Left (A-E): MSOT images of healthy volunteer
Right (F-J): non-specific malignant breast cancer lesion
(A,F) Hb and HbO2 (B, G) total Hb (C, H) lipid (D, I) water (E, J) merged composite image

Total hemoglobin was quantified in non-specific breast cancer patients (Figure 2) [1] or patients with ductal carcinoma in situ (Figure 3) [2], and compared to healthy controls, showing an elevation of MSOT-derived hemoglobin signals in malignant lesions of the breast.

Figure 2: Quantitative analysis of total hemoglobin (HbT) values in patients with non-specific malignant breast cancer

Total blood volume (TBV) measurements in healthy vs. malignant cases, either in the entire region of interest (a), or expressed as a gradient from the outside to the inside of the lesion (b).

Figure 3: Quantitative analysis of hemoglobin and oxygenation values in ductal carcinoma in situ

Deoxygenated (a), oxygenated (b), or total hemoglobin (c), in addition to oxygen saturation (d) measurements in healthy vs. malignant cases.

In conclusion, label-free MSOT can assess total hemoglobin, oxygenation and vascular structures. It shows promise to complement current diagnostic methods as a non-invasive, real-time tool to assess suspicious breast lesions. As MSOT poses no radiation burden to the patient, it might one day also play a role in breast cancer screening. Potentially, combining MSOT with labeled near-infrared markers could increase the specificity further.

[1] Diot G et al., Multi-Spectral Optoacoustic Tomography (MSOT) of human breast cancer, Clin Cancer Res. 2017 Sep 12.
[2] Becker A et al., Multispectral optoacoustic tomography of the human breast: characterisation of healthy tissue and malignant lesions using a hybrid ultrasound-optoacoustic approach, Eur Radiol. 2017 Aug 7.
[3] Heijblom M et al., Photoacoustic image patterns of breast carcinoma and comparisons with Magnetic Resonance Imaging and vascular stained histopathology, Sci Rep. 2015 Jul 10;5:11778.
[4] Kitai T et al., Photoacoustic mammography: initial clinical results. Breast Cancer, 2014 Mar;21(2):146-53.
[5] Li X et al., High resolution functional photoacoustic tomography of breast cancer, Med Phys. 2015 Sep;42(9):5321-8.

  • Diot G et al.,
    Multi-Spectral Optoacoustic Tomography (MSOT) of human breast cancer,
    Clin Cancer Res. 2017 Sep 12. DOI: 10.1158/1078-0432.CCR-16-3200.
    Link
  • Becker A et al.,
    Multispectral optoacoustic tomography of the human breast: characterisation of healthy tissue and malignant lesions using a hybrid ultrasound-optoacoustic approach,
    Eur Radiol. 2017 Aug 7. DOI: 10.1007/s00330-017-5002-x.
    Link
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