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In photoacoustic (PA) imaging, time domain reconstruction techniques are the current gold standard for image formation. While these techniques provide high-resolution spatial maps of optical absorption, they neglect the structural information encoded in the frequency domain of the broadband PA signals. In this work, we introduce a frequency domain technique for PA image formation, termed F-Mode. By leveraging information contained in the frequency content of PA signals, F-Mode can be used to generate images with scale-specific contrast. To demonstrate the robustness of our technique, we apply F-Mode to datasets acquired using both PA tomography and PA microscopy systems, utilizing linear array and singleelement transducers with central frequencies ranging from 40–400MHz. Here we show that the technique can be used to: differentiate between vessels and microspheres of different size in phantoms, enhance visualization of organelles in cultured cells, and selectively display single blood vessels in vivo in zebrafish larvae.

Frequency analysis of the photoacoustic radiofrequency signals and oxygen saturation estimates were used to monitor the in-vivo response of a novel, thermosensitive liposome treatment. The liposome encapsulated doxorubicin (HaT-DOX) releasing it rapidly (Photoacoustic imaging (VevoLAZR, 750/850 nm, 40 MHz) of EMT-6 breast cancer tumors was performed 30 min pre- and post-treatment and up to 7 days post-treatment (at 2/5/24 h timepoints). HaT-DOX-treatment responders exhibited on average a 22% drop in oxygen saturation 2 h post-treatment and a decrease (45% at 750 nm and 73% at 850 nm) in the slope of the normalized PA frequency spectra. The spectral slope parameter correlated with treatment-induced hemorrhaging which increased the optical absorber effective size via interstitial red blood cell leakage. Combining frequency analysis and oxygen saturation estimates differentiated treatment responders from non-responders/control animals by probing the treatment-induced structural changes of blood vessel.

We investigate the feasibility of photoacoustic (PA) imaging for assessing the correlation between red blood cell (RBC) aggregation and the oxygen saturation (sO2) in a simulated pulsatile blood flow system. For the 750 and 850 nm illuminations, the PA amplitude (PAA) increased and decreased as the mean blood flow velocity decreased and increased, respectively, at all beat rates (60, 120 and 180 bpm). The sO2 also cyclically varied, in phase with the PAA for all beat rates. However, the linear correlation between the sO2 and the PAA at 850 nm was stronger than that at 750 nm. These results suggest that the sO2 can be correlated with RBC aggregation induced by decreased mean shear rate in pulsatile flow, and that the correlation is dependent on the optical wavelength. The hemodynamic properties of blood flow assessed by PA imaging may be used to provide a new biomarker for simultaneous monitoring blood viscosity related to RBC aggregation, oxygen delivery related to the sO2 and their clinical correlation.

Roughly 10% of the world’s population has chronic kidney disease (CKD). In its advanced stages, CKD greatly increases the risk of hospitalization and death. Although kidney transplantation has revolutionized the care of advanced CKD, clinicians have limited ways of assessing donor kidney quality. Thus, optimal donor kidney–recipient matching cannot be performed, meaning that some patients receive damaged kidneys that function poorly. Fibrosis is a form of chronic damage often present in donor kidneys, and it is an important predictor of future renal function. Currently, no safe, easy-to-perform technique exists that accurately quantifies renal fibrosis. We describe a potentially novel photoacoustic (PA) imaging technique that directly images collagen, the principal component of fibrotic tissue. PA imaging noninvasively quantifies whole kidney fibrotic burden in mice, and cortical fibrosis in pig and human kidneys, with outstanding accuracy and speed. Remarkably, 3-dimensional PA imaging exhibited sufficiently high resolution to capture intrarenal variations in collagen content. We further show that PA imaging can be performed in a setting that mimics human kidney transplantation, suggesting the potential for rapid clinical translation. Taken together, our data suggest that PA collagen imaging is a major advance in fibrosis quantification that could have widespread preclinical and clinical impact.

In ultrasound imaging, fully-developed speckle arises from the spatiotemporal superposition of pressure waves backscattered by randomly distributed scatterers. Speckle appearance is affected by the imaging system characteristics (lateral and axial resolution) and the random-like nature of the underlying tissue structure. In this work, we examine speckle formation in acoustic-resolution photoacoustic (PA) imaging using simulations and experiments. Numerical and physical phantoms were constructed to demonstrate that PA speckle carries information related to unresolved absorber structure in a manner similar to ultrasound speckle and unresolved scattering structures. A fractal-based model of the tumor vasculature was used to study PA speckle from unresolved cylindrical vessels. We show that speckle characteristics and the frequency content of PA signals can be used to monitor changes in average vessel size, linked to tumor growth. Experimental validation on murine tumors demonstrates that PA speckle can be utilized to characterize the unresolved vasculature in acoustic-resolution photoacoustic imaging. Keywords: Photoacoustic speckle, Ultrasound speckle, Spatial resolution, Autocovarience function, Tumor vasculature, In-vivo imaging, Vascular trees

This dissertation describes the development of functional and structural photoacoustic (PA) imaging biomarkers that can be used to monitor cancer treatment response and potentially predict treatment outcome. An imaging method that can indicate individualized treatment success could improve therapeutic outcome. Assessing the effectiveness of therapies as early as possible may spare the patient from unnecessary treatments and save precious clinical resources. In order for PA imaging to enter mainstream radiology and become a treatment monitoring tool, rigorous development of biomarkers that are easy-to-use and representative of the treatment-induced changes in the tumor microenvironment are needed. In this work, I have developed imaging biomarkers that rely on the analysis of the radiofrequency signals in acoustic resolution PA imaging. Specifically, I show through simulations and experiments that biomarkers sensitive to the size, number density and spacing of tumor blood vessels can be extracted through time and frequency domain analysis of PA signals. This information is encoded in the speckle that forms during diffuse optical illumination, which was previously thought to be noise. Moreover, I demonstrate that PA imaging can detect the response of a thermosensitive liposome by measuring a >10% drop in the oxygenation of the tumor as early as 30 minutes post-treatment. This change in oxygenation is due to vascular disruption, a phenomenon that can be detected through frequency analysis of the PA signals. The spectral slope parameter decreases by as much as 73% in 2 hours post-treatment and can be used to differentiate alongside the oxygenation biomarker between responders and non-responders. Lastly, I demonstrate that these PA imaging biomarkers correlate well with the histologically measured biophysical changes of two novel, bubble-based cancer treatments. In this dissertation, PA imaging biomarkers for cancer treatment monitoring are developed, advancing the modality towards clinical translation.

The potential of photoacoustic imaging for detecting red blood cell (RBC) aggregation is explored. Enhanced aggregation is observed in disorders such as diabetes impairing oxygen release into tissue. Simultaneous measurements of aggregation and oxygenation levels cannot be made using current tools. Photoacoustic detection of aggregation and assessment of oxygen saturation was investigated. A theoretical and experimental model of aggregation was developed using human and porcine RBCs. Frequency-domain analysis of the PA signals was used to derive the spectral slope and midband fit of the normalized power spectra for various hematorit and aggregation conditions. Oxygen saturation was assessed using multiple wavelengths of illumination. The experimental spectral slope (~0.3 dB/MHz) for non-aggregated samples agreed with the theory decreasing with increasing aggregate size. The midband fit increased by ~5 dB when the aggregate size reached the largest level while the oxygen saturation increased by > 20%. These results suggest that photoacoustic-radio-frequency-spectroscopic-parameters have the potential to monitor RBC aggregation and oxygenation level.

Delayed graft function (DGF) is a significant complication that contributes to poorer graft function and shortened graft survival. In this review, we sought to evaluate the current and emerging role of medical imaging modalities in the assessment of DGF and how it may guide clinical management.PubMed, Google Scholar, and ClinicalTrial.gov up until February 2021.This narrative review first examined the pathophysiology of DGF and current clinical management. We then summarized relevant studies that utilized medical imaging to assess posttransplant renal complications, namely, DGF. We focused our attention on noninvasive, evolving imaging modalities with the greatest potential for clinical translation, including contrast-enhanced ultrasound (CEUS) and multiparametric magnetic resonance imaging (MRI).A kidney biopsy in the setting of DGF can be used to assess the degree of ischemic renal injury and to rule out acute rejection. Biopsies are accompanied by complications and may be limited by sampling bias. Early studies on CEUS and MRI have shown their potential to distinguish between the 2 most common causes of DGF (acute tubular necrosis and acute rejection), but they have generally included only small numbers of patients and have not kept pace with more recent technical advances of these imaging modalities. There remains unharnessed potential with CEUS and MRI, and more robust clinical studies are needed to better evaluate their role in the current era.The adaptation of emerging approaches for imaging DGF will depend on additional clinical trials to study the feasibility and diagnostic test characteristics of a given modality. This is limited by access to devices, technical competence, and the need for interdisciplinary collaborations to ensure that such studies are well designed to appropriately inform clinical decision-making.La reprise retardée de la fonction du greffon (RRFG) est une complication importante susceptible d’affecter négativement la fonction du greffon et de réduire sa survie. Dans cette revue, nous cherchions à évaluer le rôle actuel et grandissant des modalités d’imagerie médicale dans l’évaluation de la RRFG et la façon dont cela pourrait orienter la prise en charge clinique.PubMed, Google Scholar et ClinicalTrial.gov jusqu’à février 2021.Notre revue narrative portait d’abord sur la physiopathologie de la RRFG et la prise en charge clinique actuelle. Nous avons par la suite résumé les études pertinentes ayant utilisé l’imagerie médicale pour évaluer les complications rénales post- transplantation, notamment la RRFG. Nous avons concentré notre attention sur les modalités d’imagerie non effractives et évolutives présentant le plus grand potentiel d’application clinique, notamment l’échographie de contraste (CEUS) et l’imagerie par résonance magnétique (IRM) multiparamétrique.Dans les cas de RRFG, une biopsie du rein peut être utilisée pour évaluer l’ampleur des lésions rénales ischémiques et pour exclure le rejet aigu. Les biopsies s’accompagnent de complications et pourraient être limitées par des biais d’échantillonnage. Des études préliminaires examinant les CEUS et l’IRM ont montré que ces modalités permettaient une distinction entre les deux causes les plus fréquentes de la RRFG (nécrose tubulaire aiguë et rejet aigu), mais ces études portaient généralement sur de petits nombres de patients et n’avaient pas suivi les plus récents progrès techniques de ces modalités d’imagerie. Il subsiste un potentiel non exploité avec les CEUS et l’IRM. Des études cliniques plus robustes sont nécessaires pour mieux évaluer leur rôle à l’heure actuelle.L’adaptation des approches émergentes pour l’imagerie en contexte de RRFG dépendra d’essais cliniques supplémentaires qui examineront la faisabilité et les caractéristiques des tests diagnostiques d’une modalité donnée. Cela est limité par l’accès aux appareils, la compétence technique et la nécessité de collaborations interdisciplinaires afin de s’assurer que ces études sont bien conçues et qu’elles puissent éclairer adéquatement la prise de décisions cliniques.

Significance: We demonstrate the potential of probing the sO2 change under blood flow in vivo using photoacoustic (PA) imaging and sheds light on the complex relationship between RBC aggregation and oxygen delivery. Aim: To conduct in vivo assessments of the sO2 in the radial artery of healthy volunteers and simultaneously probe the relation between the sO2 and hemodynamic behavior such as red blood cell (RBC) aggregation. Approach: The effects of PA-based measurements of blood hemodynamics were studied as a function of the subjects’ age (20s, 30s, and 40s). The pulsatile blood flow in the human radial artery of 12 healthy subjects was imaged in the 700 to 900 nm optical wavelength range using a linear array-based PA system. Results: The PA power when blood velocity is minimum (Pamax) was larger than the one attained at maximum blood velocity (Pamin), consistent with predictions based on the cyclical variation of RBC aggregation during pulsatile flow. The difference between Pamin and Pamax at 800 nm (ΔPa800) increased with age (1.7, 2.2, and 2.6 dB for age group of 20s, 30s, and 40s, respectively). The sO2 computed from Pamax was larger than the one from Pamin. Conclusions: The ΔPa800 increased with participant age. The ΔPa800 metric could be a surrogate of noninvasively monitoring the age-induced changes in RBC aggregation. The sO2 change during a cycle of pulsatile blood flow also increased with age, demonstrating that RBC aggregation can affect the sO2 change.

Graphical abstract, The development of novel anticancer therapies warrants the parallel development of biomarkers that can quantify their effectiveness. Photoacoustic imaging has the potential to measure changes in tumor vasculature during treatment. Establishing the accuracy of imaging biomarkers requires direct comparisons with gold histological standards. In this work, we explore whether a new class of submicron, vascular disrupting, ultrasonically stimulated nanobubbles enhance radiation therapy. In vivo experiments were conducted on mice bearing prostate cancer tumors. Combined nanobubble plus radiation treatments were compared against conventional microbubbles and radiation alone (single 8 Gy fraction). Acoustic resolution photoacoustic imaging was used to monitor the effects of the treatments 2- and 24-hs post-administration. Histological examination provided metrics of tumor vascularity and tumoral cell death, both of which were compared to photoacoustic-derived biomarkers. Photoacoustic metrics of oxygen saturation reveal a 20 % decrease in oxygenation within 24 h post-treatment. The spectral slope metric could separate the response of the nanobubble treatments from the microbubble counterparts. This study shows that histopathological assessment correlated well with photoacoustic biomarkers of treatment response.

The goal of this study was to develop an ultrasound (US) scatterer spacing estimation method using an enhanced cepstral analysis based on continuous wavelet transforms (CWTs). Simulations of backscattering media containing periodic and quasi-periodic scatterers were carried out to test the developed algorithm. Experimental data from HT-29 pellets and in vivo PC3 tumors were then used to estimate the mean scatterer spacing. For simulated media containing quasi-periodic scatterers at 1-mm and 100- $\mu \text{m}$ spacing with 5% positional variation, the developed algorithm yielded a spacing estimation error of ~1% for 25- and 55-MHz US pulses. The mean scatterer spacing of HT-29 cell pellets (31.97 $\mu \text{m}$ ) was within 3% of the spacing obtained from histology and agreed with the predicted spacing from simulations based on the same pellets for both frequencies. The agreement extended to in vivo PC3 tumors estimation of the spacing with a variance of 1.68% between the spacing derived from the tumor histology and the application of the CWT to the experimental results. The developed technique outperformed the traditional cepstral methods as it can detect nonprominent peaks from quasi-random scatterer configurations. This work can be potentially used to detect morphological tissue changes during normal development or disease treatment.

In photoacoustic (PA) imaging, time domain reconstruction techniques are the current gold standard for image formation. While these techniques provide high-resolution spatial maps of optical absorption, they neglect the structural information encoded in the frequency domain of the broadband PA signals. In this work, we introduce a frequency domain technique for PA image formation, termed F-Mode. By leveraging information contained in the frequency content of PA signals, F-Mode can be used to generate images with scale-specific contrast. To demonstrate the robustness of our technique, we apply F-Mode to datasets acquired using both PA tomography and PA microscopy systems, utilizing linear array and single-element transducers with central frequencies ranging from 40–400 MHz. Here we show that the technique can be used to: differentiate between vessels and microspheres of different size in phantoms, enhance visualization of organelles in cultured cells, and selectively display single blood vessels in vivo in zebrafish larvae. Standard time domain photoacoustic imaging techniques neglect the abundant information encoded in the frequency domain of photoacoustic signals. The authors present an imaging technique that utilizes features in photoacoustic signal power spectra to visualize structures of different scale in image datasets acquired using classical methods.

Over the last two and a half decades, photoacoustic (PA) imaging has become an important area of research in biomedical optics. Combining the high contrast of optical imaging with the high spatial resolution of ultrasound (US) imaging, PA imaging can simultaneously visualize anatomical structures while interrogating their functionality through multiwavelength optical spectroscopy. Alongside technological developments and imaging applications in optical and acoustic resolution PA imaging, a family of PA signal analysis techniques can extract additional information about the sample being imaged. This Tutorial focuses on techniques that rely on the analysis of PA signals in a manner similar to that in the complimentary field of quantitative ultrasound (QUS) imaging of soft tissues. In QUS, signal analysis techniques have been developed to analyze the US signals resulting from the scattering of many unresolved scatterers within the resolution volume of the imaging device. The implementation of these US techniques in PA can enable new applications in biomedicine beyond traditional anatomical PA imaging, further increasing the utilization and impact of this promising modality.

Photoacoustic (PA) signals encode information about the optical absorption and spatial distribution of absorbing chromophores as well as the light distribution in the medium. The wavelength dependence of the latter affects the accuracy in chromophore quantification, including estimations of oxygen saturation (sO2) with depth. We propose the use of the ratio of the PA radiofrequency (RF) spectral slopes (SS) at different optical wavelengths to generate frequency filters which can be used to match the fluence profiles across separate images generated with different optical wavelengths. Proof-of-principle experiments were carried on a plastic tube with blood of a known oxygenation inserted into a porcine tissue. The algorithm was tested in-vivo in the hind leg of six CD1 mice, each under three different breathing conditions (100 % O2, room air and 100 % CO2). Imaging was done using the VevoLAZR system at the wavelengths 720 and 870 nm. The SS was calculated from the linear fit of the ratio of the photoacoustic RF power spectra at the two wavelengths. An ultrasound frequency filter was designed and applied to each segmented PA signal in the frequency domain and inversely transformed into the time domain to correct for the differences in the fluence profiles at both wavelengths. Linear spectral unmixing was used to estimate sO2 before and after applying the ultrasound frequency filter. The estimated blood sO2 in the plastic tube for the porcine tissue experiment improved by 10.3% after applying the frequency filter when compared to the sO2 measured by a blood gas analyzer. For the in-vivo mouse experiments, the applied sO2 correction was 2.67, 1.33 and -3.33% for every mm of muscle tissue for mice breathing 100% O2, room air and 100% CO2, respectively. The approach presented here provides a new approach for fluence matching that can potentially improve the accuracy of sO2 estimates by removing the fluence depth dependence at different optical wavelengths.

Solid tumors are typically supplied nutrients by a network of irregular blood vessels. By targeting these vascular networks, it might be possible to hinder cancer growth and metastasis. Vascular disrupting agents induce intertumoral hemorrhaging, making photoacoustic (PA) imaging well positioned to detect bleeding due to its sensitivity to hemoglobin and its various states. We introduce a fractal-based numerical model of intertumoral hemorrhaging to simulate the PA signals from disrupted tumor blood vessels. The fractal model uses bifurcated cylinders to represent vascular trees. To mimic bleeding from blood vessels, hemoglobin diffusion from microvessels was simulated. In the simulations, the PA signals were detected by a linear array transducer (30 MHz center frequency) of four different vascular trees. The power spectrum of each beamformed PA signal was computed and fitted to a straight line within the −6-dB bandwidth of the receiving transducer. The spectral slope and midband fit (MBF) based on the fit decreased by 0.11 dB / MHz and 2.12 dB, respectively, 1 h post bleeding, while the y-intercept increased by 1.21 dB. The results suggest that spectral PA analysis can be used to measure changes in the concentration and spatial distribution of hemoglobin in tissue without the need to resolve individual vessels. The simulations support the feasibility of using PA imaging and spectral analysis in cancer treatment monitoring by detecting microvessel disruption.

Imaging methods capable of indicating the potential for success of an individualized treatment course, during or immediately following the treatment, could improve therapeutic outcomes. Temperature Sensitive Liposomes (TSLs) provide an effective way to deliver chemotherapeutics to a localized tumoral area heated to mild-hyperthermia (HT). The high drug levels reached in the tumor vasculature lead to increased tumor regression via the cascade of events during and immediately following treatment. For a TSL carrying doxorubicin (DOX) these include the rapid and intense exposure of endothelial cells to high drug concentrations, hemorrhage, blood coagulation and vascular shutdown. In this study, ultrasound-guided photoacoustic imaging was used to probe the changes to tumors following treatment with the TSL, HaT-DOX (Heat activated cytoToxic). Levels of oxygen saturation (sO2) were studied in a longitudinal manner, from 30 min pre-treatment to 7 days post-treatment. The efficacious treatments of HT-HaT-DOX were shown to induce a significant drop in sO2 (>10%) as early as 30 min post-treatment that led to tumor regression (in 90% of cases); HT-Saline and non-efficacious HT-HaT-DOX (10% of cases) treatments did not show any significant change in sO2 at these timepoints. The changes in sO2 were further corroborated with histological data, using the vascular and perfusion markers CD31 and FITC-lectin. These results allowed us to further surmise a plausible mechanism of the cellular events taking place in the TSL treated tumor regions over the first 24 hours post-treatment. The potential for using photoacoustic imaging to measure tumor sO2 as a surrogate prognostic marker for predicting therapeutic outcome with a TSL treatment is demonstrated.

The feasibility of detecting red blood cell (RBC) aggregation with photoacoustics (PAs) was investigated theoretically and experimentally using human and porcine RBCs. The theoretical PA signals and spectra generated from such samples were examined for several hematocrit levels and aggregates sizes. The effect of a finite transducer bandwidth on the received PA signal was also examined. The simulation results suggest that the dominant frequency of the PA signals from non-aggregated RBCs decreases towards clinical frequency ranges as the aggregate size increases. The experimentally measured mean spectral power increased by ~6 dB for the largest aggregate compared to the non-aggregated samples. Such results confirm the theoretical predictions and illustrate the potential of using PA imaging for detecting RBC aggregation.

The ability to assess treatment response on a case-by-case basis in a non-invasive and longitudinal manner has the potential to maximize treatment success. In this work temperature sensitive liposomes (TSLs) have been combined with non-invasive high frequency ultrasound (US) and photoacoustic (PA) imaging to assess structural (cell death) and functional (oxygenation) aspects of tumor response, indicative of therapeutic effect, within a few hours post-treatment in a preclinical model. A TSL is a drug delivery vehicle designed to release its payload at mild-hyperthermic temperatures (39-42°C). The TSL passes through the systemic circulation (37°C), until it reaches a tumor undergoing localized heating (42°C), where it releases its contents rapidly, creating a high local concentration of drug within the tumor vasculature. This leads to high tumoral drug uptake and a number of functional changes within the tumor, resulting in a therapeutic response. Conventional assessment of treatment success is measured by the change in tumor volume over time, but this may not be noticeable until several days post-treatment and no further insight into the biology of the tumor response kinetics is provided. By using US and PA imaging in a non-invasive co-registered manner, structural and functional imaging surrogates of tumor response can be visualized in 3D. These images allow the observation of changes in the first few hours post-treatment and provide both an early indication of overall therapeutic effect and insight into the kinetics of the drug-tumor interaction. Here we have used a simple 2 component TSL called HaT (Heat activated cytoToxic, DPPC/Brij78, 96:4 mol%), designed to deliver doxorubicin (DOX), which has been shown to rapidly release drug at mild-hyperthermic temperatures (100% in 30% decrease in sO2 within the first 5 h post-treatment and showed >50% tumor regression after 14 days. Furthermore, the extent of tumor regression was observed to be proportional the magnitude of this early decrease in sO2. The observed longitudinal variations in sO2 represent the unique ability of US/PA imaging to monitor structural and functional changes within tumor vasculature and can be used as a rapid, non-invasive early indicator of HaT-DOX treatment efficacy. Citation Format: Jonathan P. May, Eno Hysi, Lauren Wirtzfeld, Elijus Undzys, Michael C. Kolios, Shyh-Dar Li. Early detection of the therapeutic effect in tumors treated with a thermosensitive liposome (TSL) using noninvasive ultrasound and photoacoustic imaging. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-165. doi:10.1158/1538-7445.AM2014-LB-165

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 oxygen-dependent 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.

A theoretical model investigating the dependence of optoacoustic (OA) signal on blood oxygen saturation (SO2) is discussed. The derivations for the nonbandlimited and bandlimited OA signals from many red blood cells (RBCs) are presented. The OA field generated by many RBCs was obtained by summing the OA field emitted by each RBC approximated as a fluid sphere. A Monte Carlo technique was employed generating the spatial organizations of RBCs in two-dimensional. The RBCs were assumed to have the same SO2 level in a simulated configuration. The fractional number of oxyhemoglobin molecules, confined in a cell, determined the cellular SO2 and also defined the blood SO2. For the nonbandlimited case, the OA signal amplitude decreased and increased linearly with blood SO2 when illuminated by 700 and 1000 nm radiations, respectively. The power spectra exhibited similar trends over the entire frequency range (MHz to GHz). For the bandlimited case, three acoustic receivers with 2, 10, and 50 MHz as the center frequencies were considered. The linear variations of the OA amplitude with blood SO2 were also observed for each receiver at those laser sources. The good agreement between simulated and published experimental results validates the model qualitatively. © 2012 Society of Photo-Optical