Optical coherence angiography for pre-treatment assessment and treatment monitoring following photodynamic therapy: a basal cell carcinoma patient study.

Microvascular networks of human basal cell carcinomas (BCC) and surrounding skin were assessed with optical coherence angiography (OCA) in conjunction with photodynamic therapy (PDT). OCA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3-12 months post-treatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success.

Accurate early prediction of tumour response to PDT using optical coherence angiography.

Prediction of tumour treatment response may play a crucial role in therapy selection and optimization of its delivery parameters. Here we use optical coherence angiography (OCA) as a minimally-invasive, label-free, real-time bioimaging method to visualize normal and pathological perfused vessels and monitor treatment response following vascular-targeted photodynamic therapy (PDT). Preclinical results are reported in a convenient experimental model (CT-26 colon tumour inoculated in murine ear), enabling controlled PDT and post-treatment OCA monitoring. To accurately predict long-term treatment outcome, a robust and simple microvascular metric is proposed. It is based on perfused vessels density (PVD) at t = 24 hours post PDT, calculated for both tumour and peri-tumour regions. Histological validation in the examined experimental cohort (n = 31 animals) enabled further insight into the excellent predictive power of the derived early-response OCA microvascular metric. The results underscore the key role of peri-tumour microvasculature in determining the long-term PDT response.

In-vivo longitudinal imaging of microvascular changes in irradiated oral mucosa of radiotherapy cancer patients using optical coherence tomography.

Mucositis is the limiting toxicity of radio(chemo)therapy of head and neck cancer. Diagnostics, prophylaxis and correction of this condition demand new accurate and objective approaches. Here we report on an in vivo longitudinal monitoring of the oral mucosa dynamics in 25 patients during the course of radiotherapy of oropharyngeal and nasopharyngeal cancer using multifunctional optical coherence tomography (OCT). A spectral domain OCT system with a specially-designed oral imaging probe was used. Microvasculature visualization was based on temporal speckle variations of the full complex signal evaluated by high-pass filtering of 3D data along the slow scan axis. Angiographic image quantification demonstrated an increase of the vascular density and total length of capillary-like-vessels before visual signs or clinical symptoms of mucositis occur. Especially significant microvascular changes compared to their initial levels occurred when grade two and three mucositis developed. Further, microvascular reaction was seen to be dose-level dependent. OCT monitoring in radiotherapy offers a non-invasive, convenient, label-free quantifiable structural and functional volumetric imaging method suitable for longitudinal human patient studies, furnishing fundamental radiobiological insights and potentially providing useful feedback data to enable adaptive radiotherapy (ART).

Photodynamic therapy monitoring with optical coherence angiography.

Photodynamic therapy (PDT) is a promising modern approach for cancer therapy with low normal tissue toxicity. This study was focused on a vascular-targeting Chlorine E6 mediated PDT. A new angiographic imaging approach known as M-mode-like optical coherence angiography (MML-OCA) was able to sensitively detect PDT-induced microvascular alterations in the mouse ear tumour model CT26. Histological analysis showed that the main mechanisms of vascular PDT was thrombosis of blood vessels and hemorrhage, which agrees with angiographic imaging by MML-OCA. Relationship between MML-OCA-detected early microvascular damage post PDT (within 24 hours) and tumour regression/regrowth was confirmed by histology. The advantages of MML-OCA such as direct image acquisition, fast processing, robust and affordable system opto-electronics, and label-free high contrast 3D visualization of the microvasculature suggest attractive possibilities of this method in practical clinical monitoring of cancer therapies with microvascular involvement.

Giant strain-sensitivity of acoustic energy dissipation in solids containing dry and saturated cracks with wavy interfaces.

Mechanisms of acoustic energy dissipation in heterogeneous solids attract much attention in view of their importance for material characterization, nondestructive testing, and geophysics. Due to the progress in measurement techniques in recent years, it has been revealed that rocks can demonstrate extremely high strain sensitivity of seismoacoustic loss. In particular, it has been found that strains of order 10(-8) produced by lunar and solar tides are capable of causing variations in the seismoacoustic decrement on the order of several percent. Some laboratory data (although obtained for higher frequencies) also indicate the presence of very high dissipative nonlinearity. Conventionally discussed dissipation mechanisms (thermoelastic loss in dry solids, Biot and squirt-type loss in fluid-saturated ones) do not suffice to interpret such data. Here the dissipation at individual cracks is revised taking into account the influence of wavy asperities of their surfaces quite typical of real cracks, which can drastically change the values of the relaxation frequencies and can result in giant strain sensitivity of the dissipation without the necessity of assuming the presence of unrealistically thin (and, therefore, unrealistically soft) cracks. In particular, these mechanisms suggest interpretation for observations of pronounced amplitude modulation of seismo-acoustic waves by tidal strains.