Page 53 - Fluorescence-guided cancer surgery

Detection of breast cancer using methylene blue 51
(arteriovenous shunting), which leads to less perfusion of the capillary bed. Complicating the understanding of mechanism even further is the fact that MB can be converted to a non- uorescent leuco form under certain intracellular redox and pH conditions11. Because the exact mechanism of 99mTc-MIBI and MB uptake in breast tumors is still unclear, future studies have to be done regarding this e ect. In the present study, though, no di erence was seen between di erent administration groups in TBR and background signal, suggesting that the more convenient early imaging protocol could be used in future studies.
As NIR uorescence imaging is a surface technology (≈ 5 mm penetration depth), it is important to understand its capabilities and limitations. To date, research and development of new imaging modalities for oncology mainly focus on the detection of small tumor deposits in the human body. In breast cancer, these small tumor deposits can change surgical decision making, but do not provide such prognostic relevance in breast conserving surgery, as postoperative radiation eliminates microscopic tumor deposits in most cases26. For example, the rate of small tumor deposits is 2–3 times higher than the incidence of local recurrence using preoperative MR imaging, resulting in mastectomies that may not be bene cial to patient survival27. On the other hand, adequate visualization of tumor margins intraoperatively would be bene cial to lower the number of R1 resections and to avoid the need for re-resections and radiotherapeutic boost therapy28. Using intraoperative NIR uorescence imaging, it is not possible to image the whole breast for small tumor deposits due to the limited penetration depth. However, the optical properties of NIR uorescence are very well suited for the visualization of possible residual tumor cells at the resection margin. Additionally, NIR uorescence has an exceptionally high spatial resolution compared to conventional imaging techniques.
To bene t from the full potential for NIR uorescence imaging several factors are of paramount importance and need to be optimized: 1) the concentration of the NIR uorophore in the target tissue, 2) minimizing photon absorption and scattering in the tissue, 3) maximizing excitation power of NIR excitation without inducing photobleaching or photo damage to tissue, and 4) the sensitivity of the CCD chip on the detector. Methylene Blue becomes a moderate-strength uorophore when used at low concentrations, with an excitation maximum of 670 nm. Contrast agents with an emission peak of ≈700 nm have several limitations compared to 800 nm uorophores with respect to quantum yield, penetration depth, and auto uorescence. It is hoped that new