Photoacoustic ultrasound spectroscopy for assessing red blood cell aggregation and oxygenation

Abstract

Abstract. Red blood cell (RBC) aggregation and oxygenation are important markers for a variety of blood disorders. No current technique is capable of simultaneously measuring aggregation/oxygenation levels noninvasively. We propose using photoacoustic ultrasound spectroscopy (PAUS) for assessing both phenomena. This technique relies on frequency-domain analysis of the PA signals by extracting parameters such as the ultrasound spectral slope and the midband fit. To investigate the effect of hematocrit, aggregation, and oxygenation levels on PAUS parameters, a Monte Carlo-based theoretical model and an experimental protocol using porcine RBCs were developed. The samples were illuminated at 750 and 1064 nm and changes in the PAUS parameters were compared to the oxygendependent optical absorption coefficients to assess the oxygenation level. Good agreement between the theoretical and experimental spectral parameters was obtained for the spectral slope of the nonaggregated spectra (∼0.3 dB∕MHz). The experimental midband fit increased by ∼5 dB for the largest aggregate size. Based on the analysis of the PA signals, the oxygen saturation level of the most aggregated sample was >20% greater than the nonaggregated sample. The results provide a framework for using PA signals' spectroscopic parameters for monitoring the aggregation and oxygenation levels of RBCs.

Computational modeling of photoacoustic signals from mixtures of melanoma and red blood cells

“…15 The validity of the prediction was confirmed by conducting in vitro experiments with human and porcine RBCs. 16,17 The framework was also used to investigate the PAs of mixtures of oxygenated and deoxygenated RBCs and provided results consistent with that of experiments. 18 The possibility of using the PA technique to differentiate intraerythrocytic stages of malarial parasite was examined using this theoretical tool.…”

“…Recent experimental studies also reported that these parameters can influence PA spectral characteristics. 17,[22][23][24] These theoretical and experimental findings essentially opened up a possibility that tissue characterization might be feasible with PAs. Wang et al accurately assessed the dimensions of microparticles hidden in turbid phantoms using a spatial auto-correlation function to perform PA spectral analysis.…”

Photoacoustic spectral analysis to sense programmed erythrocyte cell death (eryptosis) for monitoring cancer response to treatment

“…The resultant power spectra from different elements are presented in Figure 1d. The power spectra were normalized to a reference (Figure 1e) to reduce the effect of the transducer bandwidth on calculated spectral parameters [18], [21]. The reference sample was prepared using a 200 nm layer of gold mounted on top a microscopy slide with a 10 nm of chromium to strengthen the adhesion of the gold to the glass slide.…”

“…A reference is used to reduce the effect of the transducer to attain system independent parameters [16], [17]. These approaches have provided information about the size and shape of the ultrasound source at scales smaller than the working wavelength of the system [18]- [20]. The information can be related to the dimension, distribution and concertation of the ultrasound sources which, in the case of PA imaging, are RBCs [17].…”

Simultaneous measurement of erythrocyte aggregarion and oxygen saturation under in vitro pulsatile blood flow by high-frequency photoacoustics

“…In the previous studies by our group [12,13], the PA measurement of SO 2 and EA was preliminarily conducted under the static conditions. In order to further advance the clinical applicability of PA imaging, the SO 2 and EA should be investigated simultaneously under flowing conditions.…”