Moreover, on testing these compounds for dark toxicity on oral squamous carcinoma cell line (OSCC) for varying concentrations (1 to 100 μM), they exhibited more than 50% cell viability for concentrations up to 100 μM of PpIX and MB, 50 μM of Ce6 and 10 μM of Sq and ZnPc ( supplementary information, Fig S1). This vast range of concentrations tested was inclusive of the in vivo dose range for PDT for most of them (see SI Table S1) thus making a point that they can be used as PA imaging contrast agents at concentrations that do not induce much toxicity in vivo. Panel A shows the transabdominal imaging approach, which uses the same detector for laser light emission and ultrasonic detection of signal levels by means of multispectral optoacoustic tomography (MSOT). Erythrocytes are the target for laser-light absorption and ultrasonic emission. Six different wavelengths (700, 730, 760, 800, 850, and 900 nm) were used for MSOT data acquisition; MSOT measurements, such as total hemoglobin (Hb), oxygenated Hb, deoxygenated Hb, and oxygen saturation, are calculated from these measurements. These hemoglobin-based measurements permit the evaluation of tissue perfusion and oxygenation as surrogates of inflammation with MSOT. Panel B shows MSOT-derived total Hb signal levels in the intestinal wall (in both the large bowel and the small intestine) in 44 patients with Crohn’s disease with different degrees of endoscopic inflammation. Such evaluation was performed by means of the Simplified Endoscopic Score for Crohn’s Disease (SES-CD), which ranges from 0 to 56, with higher scores indicating a greater severity of intestinal inflammation; remission is defined as a score of less than 3, low disease activity as a score of 3 to 6, moderate disease activity as a score of 7 to 15, and high disease activity as a score of 16 or more. The signal levels are expressed as normalized z scores and transformed into a linear scale of arbitrary units (au). The red dots represent single measurements for each patient; the horizontal lines indicate medians, and I bars the interquartile range. A single asterisk denotes P<0.05 and a double asterisk P<0.001 for the comparison with remission. Panel C shows representative images of MSOT measurements of total Hb in the large bowel and small intestine in patients with different grades of endoscopic disease activity (as evaluated by means of SES-CD). The top row shows representative MSOT measurements of total Hb as color-coded maps with an overlay of B-mode ultrasonographic images. The middle row shows schematic representations of the images shown in the top row. The bottom row shows the corresponding endoscopic evaluation. Buehler, A., Kacprowicz, M., Taruttis, A. & Ntziachristos, V. Real-time handheld multispectral optoacoustic imaging. Opt. Lett. 38, 1404–1406 (2013).

Rosenthal, A., Razansky, D. & Ntziachristos, V. Fast semi-analytical model-based acoustic inversion for quantitative optoacoustic tomography. IEEE Trans. Med. Imag. 29, 1275–1285 (2010). Luke, G. P., Yeager, D. & Emelianov, S. Y. Biomedical applications of photoacoustic imaging with exogenous contrast agents. Ann. Biomed. Eng. 40, 422–437 (2012). The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. Yano, S. et al. Current states and future views in photodynamic therapy. J. Photochem. Photobiol. C: Photochem. Rev. 12, 46–67 (2011).iTHERAU Large Infrared Light Therapy Belt is an innovative product that uses advanced technology to distribute 360 LED beads on a 31.49*11.81 inch extra-large treatment pad, each bead inside has three chips, emitting 660nm red light and 850nm infrared light respectively.

de la Zerda, A. et al. Family of enhanced photoacoustic imaging agents for high-sensitivity and multiplexing studies in mice. ACS Nano. 6, 4694–4701 (2012). All animal experimental procedures were performed in accordance with the protocol #120774 approved by the Institutional Animal Care and Use Committee (IACUC). Xenograft mice models were established by injecting subcutaneously into the right flank of mouse, 0.2 mL of cell suspension containing 5–6 × 10 6 MCF-7, a human metastatic breast cancer cell line or OSCC, a human oral squamous carcinoma cell line and matrigel (BD biosciences) in 1:1 volume ratio. When the tumor volume reached a palpable size, the mouse was used for in vivo PA imaging. In vivo longitudinal monitoring of probe biodistribution in mouse xenograft model de la Zerda, A. et al. Carbon nanotubes as photoacoustic molecular imaging agents in living mice. Nat. Nanotech. 3, 557–562 (2008).ZnPc at a dosage of 0.21 mg/kg was injected via a catheter into the tail vein of tumor-bearing mice anaesthetized under isoflurane and the probe biodistribution was monitored over time in various organs using PA imaging. Before image acquisition, a volume ROI consisting of transverse slices with a step size of 0.3 mm spanning from the liver to the lower abdomen was selected by manual inspection of live MSOT images and the 6 laser excitation wavelengths of 680, 700, 750, 800, 850 and 900 nm were selected for correspondence with the major turning points in the absorption spectra of ZnPc, oxy- and deoxy-haemoglobin. Multispectral imaging was then performed with 10 signal averages per wavelength per transverse slice, before injection, during injection and 1, 3, 5 and 24 hr postinjection. Image reconstruction and multispectral processing Taruttis, A., Morscher, S., Burton, N. C., Razansky, D. & Ntziachristos, V. Fast multispectral optoacoustic tomography (MSOT) for dynamic imaging of pharmacokinetics and biodistribution in multiple organs. PLoS ONE 7, e30491 (2012).