Photoacoustic visualization of the fluence rate dependence of photodynamic therapy

Abstract

This study investigates the fluence rate effect, an essential modulating mechanism of photodynamic therapy (PDT), by using photoacoustic imaging method. To the best of our knowledge, this is the first time that the fluence rate dependence is investigated at a microscopic scale, as opposed to previous studies that are based on tumor growth/necrosis or animal surviving rate. This micro-scale examination enables subtle biological responses, including the vascular damage and the self-healing response, to be studied. Our results reveal the correlations between fluence rate and PDT efficacy/self-healing magnitude, indicating that vascular injuries induced by high fluence rates are more likely to recover and by low fluence rates (≤126 mW/cm2) are more likely to be permanent. There exists a turning point of fluence rate (314 mW/cm2), above which PDT practically produces no permanent therapeutic effect and damaged vessels can fully recover. These findings have practical significance in clinical setting. For cancer-related diseases, the ‘effective fluence rate’ is useful to provoke permanent destruction of tumor vasculature. Likewise, the ‘non effective range’ can be applied when PDT is used in applications such as opening the blood brain barrier to avoid permanent brain damage.

Catalase Nanocrystals Loaded with Methylene Blue as Oxygen Self‐Supplied, Imaging‐Guided Platform for Photodynamic Therapy of Hypoxic Tumors

“…Thus, the relative 1 O 2 generation efficiency for different MB and Cat formulations was compared using photochemical method, by assessing rate of a singlet oxygen-specific reaction of analyte (ABDA); it can be assessed spectrophotometrically by measuring the decrease in optical absorbance at 380 nm (the absorption peak of anthracene chromophore). [52] As shown in Figure 2e, a significant decrease of ABDA absorbance was observed in CatCry-MB suspension, while notably less change was registered in free MB solution with and without catalase; no decrease in ABDA absorbance was found in CatCry suspension. It is worth noting that ABDA absorbance reduction after irradiation for 30 min was about two times stronger for CatCry-MB suspension than for other MB formulations (free MB and free MB with catalase) of the same MB concentration, pointing toward a high 1 O 2 generation ability of CatCry-MB.…”

“…The changes in oxy-hemoglobin intratumoral concentration after different treatments were monitored by photoacoustic (PA) imaging. [52] As shown in Figure 5c, the PA signal from oxygenated -hemoglobin in the CatCry-MB injected tumor surged at first imaging point (1 h post-injection) and was at the noticeable level for 4 h of PA imaging. In contrast, the PA signal from oxy-hemoglobin in Cat-MB injected tumor was significantly weaker and almost completely disappeared 4 h post-injection.…”

Achieving depth-independent lateral resolution in AR-PAM using the synthetic-aperture focusing technique

“…Meanwhile, PA imaging preserves the rich optical absorption contrast, which is derived from photon absorption, as opposed to conventional ultrasound imaging techniques, where the imaging contrast is a result of mechanical properties. These features, i.e., a large penetration depth and rich optical contrast [13] , [14] , [15] , [16] , [17] , [18] , make PA imaging a revolutionary modality suitable for wide applications in biomedical research [19] , [20] , [21] , [22] , [23] , [24] , [25] .…”

Breaking Acoustic Limit of Optical Focusing Using Photoacoustic‐Guided Wavefront Shaping

“…[ 7–9 ] Furthermore, the scattering of light imposes limitations on other applications, such as optogenetic control over neurons and targeted optical‐based treatment in modern medicine. [ 10–13 ] Photothermal therapy (PDT) [ 14–17 ] and photodynamic therapy (PTT), [ 18–22 ] for example, require light to be precisely delivered to the specified region of interest inside biological tissues. This is because, in PDT, photosensitizers are introduced into the tissue and respond to a targeted beam of light by generating singlet oxygen that destroys nearby cells.…”