No abstract

Many types of cancer therapies target the tumor microenvironment, causing biochemical and morphological changes in tissues. In therapies using ultrasound activated microbubbles, vascular collapse is typically reported. Red blood cells (RBCs) that leak out of the vasculature become exposed to the ceramide that is released from damaged endothelial cells. Ceramide can induce programmed cell death in RBCs (eryptosis), and is characterized by cell shrinkage, membrane blebbing and scrambling. Since the effect of eryptotic cells on generated photoacoustics (PA) signals has not been reported, we investigated the potential PA may have for cancer treatment monitoring by using PA spectral analysis to sense eryptosis. To induce eryptosis, C2-ceramide was added to RBC suspensions and that were incubated for 24 hours at 37 o C. A control and ceramide-induced sample was imaged in a vessel phantom using a high frequency PA system (VevoLAZR, 10 -45 MHz bandwidth) irradiated with multiple wavelengths ranging from 680 to 900 nm. PA spectral parameters were measured and linked to changes in RBCs as it underwent eryptosis. These samples were examined using optical microscopy, a blood gas analyzer and an integrating sphere setup to measure optical properties (wavelengths 600 -900 nm). The results of the experiment demonstrate how PA spectral analysis can be used to identify eryptosis at a depth of more than 1 cm into the phantom using ultrasound derived the y-intercept and mid bandfit (MBF) parameters at optical wavelengths of 800 -900 nm. These parameters were correlated to the morphological and biochemical changes that eryptotic RBCs display. The results establish the potential of PA in cancer treatment monitoring through sensing treatment induced eryptosis.

No abstract

Red blood cell (RBC) aggregation was correctly reported in early 1768 as the increased deposition for blood to form spots of red in pathological conditions. However only recently have there been advances in technology to allow possible detection of RBC aggregation in vivo. Photoacoustic imaging (PA) shows a promising future in the detection of simultaneous in vivo RBC aggregation and oxygen saturation. This work presents, for the first time, the results of investigating aggregated RBCs using high frequency (> 20 MHz) photoacoustic (PA) imaging. Aggregation was induced by using 3% w/v concentration of 70 kDa Dextran and PA measurements were taken by a 25 MHz center frequency transducer. It was found that the spectral slope (SS) of the photoacoustic signals decreased by ~0.25 dB/MHz with RBC aggregation. The results are consistent with the findings of low frequency PA RBC aggregation study which also reported decrease in SS with increased aggregation.

Red blood cell (RBC) aggregation was correctly reported in early 1768 as the increased deposition for blood to form spots of red in pathological conditions. However only recently have there been advances in technology to allow possible detection of RBC aggregation in vivo. Photoacoustic imaging (PA) shows a promising future in the detection of simultaneous in vivo RBC aggregation and oxygen saturation. This work presents, for the first time, the results of investigating aggregated RBCs using high frequency (> 20 MHz) photoacoustic (PA) imaging. Aggregation was induced by using 3% w/v concentration of 70 kDa Dextran and PA measurements were taken by a 25 MHz center frequency transducer. It was found that the spectral slope (SS) of the photoacoustic signals decreased by ~0.25 dB/MHz with RBC aggregation. The results are consistent with the findings of low frequency PA RBC aggregation study which also reported decrease in SS with increased aggregation.