Mü Mustafa Arabul

Visualization of vasculature using a hand-held photoacoustic probe: phantom and in vivo validation

Abstract. Assessment of microvasculature and tissue perfusion can provide diagnostic information on local or systemic diseases. Photoacoustic (PA) imaging has strong clinical potential because of its sensitivity to hemoglobin. We used a hand-held PA probe with integrated diode lasers and examined its feasibility and validity in the detection of increasing blood volume and (sub) dermal vascularization. Blood volume detection was tested in custom-made perfusion phantoms. Results showed that an increase of blood volume in a physiological range of 1.3% to 5.4% could be detected. The results were validated with power Doppler sonography. Using a motorized scanning setup, areas of the skin were imaged at relatively short scanning times (<10  s/cm2) with PA. Three-dimensional visualization of these structures was achieved by combining the consecutively acquired cross-sectional images. Images revealed the epidermis and submillimeter vasculature up to depth of 5 mm. The geometries of imaged vasculature were validated with segmentation of the vasculature in high-frequency ultrasound imaging. This study proves the feasibility of PA imaging in its current implementation for the detection of perfusion-related parameters in skin and subdermal tissue and underlines its potential as a diagnostic tool in vascular or dermal pathologies.

Ex vivo photoacoustic imaging of atherosclerotic carotid plaques

Vulnerability assessment of carotid plaques is vital to prevent atherosclerosis-related mortality and disability. Photoacoustic imaging (PAI) in combination with plane-wave ultrasound (PUS) may have the ability to reveal the composition and the anatomical structure of the plaque, which infers its mechanical properties and vulnerability. In this study, we used PAI and PUS imaging to scan endarterectomy samples ex vivo, targeting intraplaque hemorrhage, and compared the results with those obtained in healthy (porcine) carotids and histology. A fully integrated hand-held photoacoustic probe was used, consisting of a pulsed diode laser (tp = 130 ns, Ep = 1 mJ, λ = 808 nm) and a linear array transducer (fc = 7.5 MHz). Three porcine carotid arteries and six carotid plaque samples were obtained from a local slaughterhouse and hospital respectively, and were mounted to the imaging setup. Data of endarterectomy samples revealed that PAI of carotid plaques at 808 nm wavelength is capable of detecting blood clots, which can be extensions of vasculature in the plaque, intra-plaque hemorrhage, or the result of trauma inflicted on the medial vascularization. Due to calcification and the limited optical penetration, imaging depth was mostly limited to the proximal wall of the samples. The porcine carotids revealed no hemorrhaging, which was corroborated by the lack of PAI contrast.

Toward the detection of intraplaque hemorrhage in carotid artery lesions using photoacoustic imaging

Abstract. Photoacoustic imaging (PAI) may have the ability to reveal the composition and the anatomical structure of carotid plaques, which determines its mechanical properties and vulnerability. We used PAI and plane wave ultrasound (PUS) imaging to obtain three-dimensional (3-D) images of endarterectomy samples ex vivo and compared the results with histology to investigate the potential of PAI-based identification of intraplaque hemorrhage. Seven carotid plaque samples were obtained from patients undergoing carotid endarterectomy and imaged with a fully integrated hand-held photoacoustic (PA) probe, consisting of a pulsed diode laser (tpulse=130  ns, Epulse=1  mJ, λ=808  nm) and a linear array transducer (fc=7.5  MHz). The samples were rotated 360 deg with 10 deg steps, and data were spatially compounded to obtain complete 3-D images of the plaques. Areas of high absorption in the 3-D datasets were identified and compared to histological data of the plaques. Data in six out of seven endarterectomy samples revealed the presence of intraplaque hemorrhages that were not visible in the PUS images. Due to the noninvasive nature of PAI, this ex vivo study may elucidate preclinical studies toward the in vivo, noninvasive, vulnerability assessment of the atherosclerotic carotid plaque.

Optical absorbance measurements and photoacoustic evaluation of freeze-thawed polyvinyl-alcohol vessel phantoms

Multispectral photoacoustic (MPA) imaging is a promising tool for the diagnosis of atherosclerotic carotids. Excitation of different constituents of a plaque with different wavelengths of the light may provide morphological information to evaluate plaque vulnerability. Preclinical validation of in vivo photoacoustic (PA) imaging requires a comprehensive phantom study. In this study, the design of optically realistic vessel phantoms for photoacoustics was examined by characterizing their optical properties for different dye concentrations, and comparing those to PA measurements. Four different concentrations of Indian ink and molecular dye were added to a 15 wt% PVA and 1 wt% orgasol mixture. Next, the homogeneously mixed gels were subjected to five freeze - thaw cycles to increase the stiffness of vessel phantoms (rinner = 2:5mm, router = 4mm). For each cycle, the optical absorbance was measured between 400 nm 990 nm using a plate reader. Additionally, photoacoustic responses of each vessel phantom at 808 nm were tested with a novel, hand-held, integrated PA probe. Measurements show that the PA signal intensity increases with the optical absorber concentration (0.3 to 0.9) in close agreement with the absorbance measurements. The freeze - thaw process has no significant effect on PA intensity. However, the total attenuation of optical energy increases after each freeze-thaw cycle, which is primarily due to the increase in the scattering coefficient. In future work, the complexity of these phantoms will be increased to examine the feasibility of distinguishing different constituents with MPA imaging.

Optical and acoustic characterization of freeze-thawed polyvinyl alcohol gels

Preclinical validation of non-invasive photoacoustic imaging of carotid artery atherosclerosis requires vessel phantoms that imitate optical, acoustic and mechanical properties of vascular tissue. Polyvinyl alcohol (PVA) phantoms that are widely used as ultrasound phantoms due to their elastic properties are also promising for photoacoustics. This study contributes to the field by quantifying the optical and acoustic properties of PVA gel, and aims at the characterization of realistic phantoms for future studies. In this study, we investigated the relation between acoustic scatterers and optical absorbers to quantify optical and acoustic properties of the PVA phantoms. Four different concentrations of orgasol acoustic scatterers, and varying concentration of Indian ink and molecular dye absorbers were added to a 15 wt% PVA solution. Samples were subjected to 1 to 5 freeze-thaw cycles and were examined after each cycle to quantify the effect on the optical and the acoustic properties. Optical attenuation was measured between 400 nm and 990 nm using a plate reader. Additionally, pulse-echo plane wave ultrasound was used for acoustic characterization. Changing the concentration of orgasol between 0.5 wt% and 4 wt% increased the mean optical attenuation of PVA by 35% after the first freeze thaw cycle. Likewise, each freeze-thaw cycle increased the optical attenuation due to scattering of light by the microstructure of PVA. The absorbance of pure PVA increased 40% between the first and second cycle and 3% between the fourth and fifth cycle. While the orgasol concentration and the freeze-thaw cycles altered the acoustic speed and attenuation, the ink and the dye inclusions did not significantly affect the acoustic properties of PVA.

Characterization of human carotid plaques using multi-wavelength photoacoustic imaging

Recently, multi-spectral photoacoustic (PA) imaging has been explored to aid in the diagnosis of atherosclerosis in carotid arteries. Using multiple wavelengths, PA has the potential to reveal vital morphological information in plaques, such as intraplaque hemorrhages, lipid pools, and the fibrous cap. In this study, we used multispectral PA and plane wave ultrasound (US) hybrid-imaging to reveal the composition of human plaques ex-vivo.

Investigation of the effects of multi-angle compounding in photoacoustic imaging

The signal-to-noise ratio (SNR) of photoacoustic (PA) images of carotid arteries is considerably low for in vivo measurements. Compounding of the acquisitions from multiple locations might improve SNR of PA images. In this study, we investigated the effects of spatial compounding based on SNR comparison of PA images of a polyvinyl alcohol (PVA) phantom and an ex vivo carotid plaque, both imaged in an experimental setting. PA and plane wave ultrasound (PUS) data were acquired in a cross-section of each sample. The sample was rotated by 10° and measurements were repeated for 36 angles. Results showed that PA compounding elevated the SNR by 28.7±5.1 dB for the PVA sample and 5.5±2.4 dB for the plaque sample. Additionally, the compounding results for the limited range of rotation as would be feasible in vivo ( -30 to +30) showed an enhancement in SNR of 7.02 ± 2.73 dB. For the future, extra characterization parameters such as resolution, contrast, and sensitivity will be investigated under in vivo conditions.

Photoacoustic perfusion measurements:a comparison with Power Doppler in phantoms

Ultrasound-based measurements using Doppler, contrast, and more recently photoacoustics (PA), have emerged as techniques for tissue perfusion measurements. In this study, the feasibility of in vitro perfusion measurements with a fully integrated, hand-held, photoacoustic probe was investigated and compared to Power Doppler (PD). Three cylindrical polyvinyl alcohol (PVA) phantoms were made (diameter = 15 mm) containing 100, 200 and 400 parallel polysulfone tubes (diameter = 0.2 mm), resulting in a perfused cross-sectional area of 1.8, 3.6 and 7.1% respectively. Each phantom was perfused with porcine blood (15 mL/min). Cross-sectional PA images (λ = 805nm, frame rate = 10Hz) and PD images (PRF = 750Hz) were acquired with a MyLab One and MyLab 70 scanner (Esaote, NL), respectively. Data were averaged over 70 frames. The average PA signal intensity was calculated in a region-of-interest of 4 mm by 6 mm. The percentage of colored PD pixels was measured in the entire phantom region. The average signal intensity of the PA images increased linearly with perfusion density, being 0.54 (± 0.01), 0.56 (± 0.01), 0.58 (± 0.01) with an average background signal of 0.53 in the three phantoms, respectively. For PD, the percentage of colored pixels in the phantom area (1.5% (± 0.2%), 4.4% (± 0.2%), 13.7% (± 0.8%)) also increased linearly. The preliminary results suggest that PA, like PD, is capable of detecting an increase of blood volume in tissue. In the future, in vivo measurements will be explored, although validation will be more complex.