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.
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.
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.
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.
Photoacoustic microscopy, as an imaging modality, has shown promising results in imaging angiogenesis and
cutaneous malignancies like melanoma, revealing systemic diseases including diabetes, hypertension, tracing drug
efficiency and assessment of therapy, monitoring healing processes such as wound cicatrization, brain imaging and
mapping. Clinically, photoacoustic microscopy is emerging as a capable diagnostic tool. Parameters of lasers used
in photoacoustic microscopy, particularly, pulse duration, energy, pulse repetition frequency, and pulse-to-pulse
stability affect signal amplitude and quality, data acquisition speed and indirectly, spatial resolution. Lasers used
in photoacoustic microscopy are typically Q-switched lasers, low-power laser diodes, and recently, fiber lasers.
Significantly, the key parameters cannot be adjusted independently of each other, whereas microvasculature and
cellular imaging, e.g., have different requirements. Here, we report an integrated fiber laser system producing
nanosecond pulses, covering the spectrum from 600 nm to 1100 nm, developed specifically for photoacoustic
excitation. The system comprises of Yb-doped fiber oscillator and amplifier, an acousto-optic modulator and a
photonic-crystal fiber to generate supercontinuum. Complete control over the pulse train, including generation
of non-uniform pulse trains, is achieved via the AOM through custom-developed field-programmable gate-array
electronics. The system is unique in that all the important parameters are adjustable: pulse duration in the range
of 1-3 ns, pulse energy up to 10 μJ, repetition rate from 50 kHz to 3 MHz. Different photocoustic imaging probes
can be excited with the ultrabroad spectrum. The entire system is fiber-integrated; guided-beam-propagation
rendersit misalignment free and largely immune to mechanical perturbations. The laser is robust, low-cost and
built using readily available components.
In this work, Fourier transform based analytical solution to photoacoustic wave equation is obtained for an optically absorbing spherical object warmed up by a pulsed laser for rectangular and Gaussian radial profiles by treating the temporal profile of the laser as Gaussian. The photoacoustic signal is investigated as a function of time for different locations outside the spherical object. An expression including the dependency of the laser parameters on the photoacoustic signal is presented.