Optical and photoacoustic radiofrequency spectroscopic analysis for detecting red blood cell death

Fadhel, Muhannad N.; Hysi, Eno; Strohm, Eric M.; Kolios, Michael C.

doi:10.1002/jbio.201800431

Cited by 13 publications

(9 citation statements)

References 83 publications

(115 reference statements)

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“…Furthermore, new products derived from hemoglobin such as methemoglobin and bilirubin are formed [31,32]. PA imaging and spectral unmixing were used to detect an increase in methemoglobin concentration resulting from the biochemical changes of RBCs that were exposed to external stressors in vitro [33]. Spectral unmixing was possible due to the unique optical absorption of methemoglobin compared with oxy and deoxyhemoglobin.…”

Section: Introductionmentioning

confidence: 99%

Use of photoacoustic imaging for monitoring vascular disrupting cancer treatments

Fadhel

Baskoy

Wang

et al. 2020

Journal of Biophotonics

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Vascular disrupting agents disrupt tumor vessels, blocking the nutritional and oxygen supply tumors need to thrive. This is achieved by damaging the endothelium lining of blood vessels, resulting in red blood cells (RBCs) entering the tumor parenchyma. RBCs present in the extracellular matrix are exposed to external stressors resulting in biochemical and physiological changes. The detection of these changes can be used to monitor the efficacy of cancer treatments. Spectroscopic photoacoustic (PA) imaging is an ideal candidate for probing RBCs due to their high optical absorption relative to surrounding tissue. The goal of this work is to use PA imaging to monitor the efficacy of the vascular disrupting agent 5,6‐Dimethylxanthenone‐4‐acetic acid (DMXAA) through quantitative analysis. Then, 4T1 breast cancer cells were injected subcutaneously into the left hind leg of eight BALB/c mice. After 10 days, half of the mice were treated with 15 mg/kg of DMXAA and the other half were injected with saline. All mice were imaged using the VevoLAZR X PA system before treatment, 24 and 72 hours after treatment. The imaging was done at six wavelengths and linear spectral unmixing was applied to the PA images to quantify three forms of hemoglobin (oxy, deoxy and met‐hemoglobin). After imaging, tumors were histologically processed and H&E and TUNEL staining were used to detect the tissue damage induced by the DMXAA treatment. The total hemoglobin concentration remained unchanged after treatment for the saline treated mice. For DMXAA treated mice, a 10% increase of deoxyhemoglobin concentration was detected 24 hours after treatment and a 22.6% decrease in total hemoglobin concentration was observed by 72 hours. A decrease in the PA spectral slope parameters was measured 24 hours after treatment. This suggests that DMXAA induces vascular damage, causing red blood cells to extravasate. Furthermore, H&E staining of the tumor showed areas of bleeding with erythrocyte deposition. These observations are further supported by the increase in TUNEL staining in DMXAA treated tumors, revealing increased cell death due to vascular disruption. This study demonstrates the capability of PA imaging to monitor tumor vessel disruption by the vascular disrupting agent DMXAA.

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Section: Introductionmentioning

confidence: 99%

Use of photoacoustic imaging for monitoring vascular disrupting cancer treatments

Fadhel

Baskoy

Wang

et al. 2020

Journal of Biophotonics

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“…RBC death was probed by computing the quantity of the by-product (methemoglobin) produced during RBCs depth with multispectral PA frequency spectra. By using a spectral unmixing approach, the authors detected a 7% enhancement in methemoglobin concentration [134].…”

Section: Single Cell Characterizationmentioning

confidence: 99%

Biomedical Application of Photoacoustics: A Plethora of Opportunities

2022

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The photoacoustic (PA) technique is a non-invasive, non-ionizing hybrid technique that exploits laser irradiation for sample excitation and acquires an ultrasound signal generated due to thermoelastic expansion of the sample. Being a hybrid technique, PA possesses the inherent advantages of conventional optical (high resolution) and ultrasonic (high depth of penetration in biological tissue) techniques and eliminates some of the major limitations of these conventional techniques. Hence, PA has been employed for different biomedical applications. In this review, we first discuss the basic physics of PA. Then, we discuss different aspects of PA techniques, which includes PA imaging and also PA frequency spectral analysis. The theory of PA signal generation, detection and analysis is also detailed in this work. Later, we also discuss the major biomedical application area of PA technique.

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“…24 (11) of deoxyhemoglobin and methemoglobin rises due to changes in the surrounding environment. 29,43,44 These changes can lead to alteration in PA signals that depend on the optical wavelength. We confined these simulations to early time points, so we would not have to consider the new chromophores that are expected to be created due to the oxidation of hemoglobin (such as methemoglobin and hemichrome).…”

Section: Modeling Photoacoustic Signals Of Vasculature Before and Aft...mentioning

confidence: 99%

Photoacoustic simulations of microvascular bleeding: spectral analysis and its application for monitoring vascular-targeted treatments

Fadhel¹,

Hysi²,

Zalev³

et al. 2022

Preprint

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<p>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 <em>y</em>-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.</p>

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Optical and photoacoustic radiofrequency spectroscopic analysis for detecting red blood cell death

Cited by 13 publications

References 83 publications

Use of photoacoustic imaging for monitoring vascular disrupting cancer treatments

Use of photoacoustic imaging for monitoring vascular disrupting cancer treatments

Biomedical Application of Photoacoustics: A Plethora of Opportunities

Photoacoustic simulations of microvascular bleeding: spectral analysis and its application for monitoring vascular-targeted treatments

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