H.M. Heres

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.

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.

Perfusion dynamics assessment with Power Doppler ultrasound in skeletal muscle during maximal and submaximal cycling exercise

PurposeAssessment of limitations in the perfusion dynamics of skeletal muscle may provide insight in the pathophysiology of exercise intolerance in, e.g., heart failure patients. Power doppler ultrasound (PDUS) has been recognized as a sensitive tool for the detection of muscle blood flow. In this volunteer study (N = 30), a method is demonstrated for perfusion measurements in the vastus lateralis muscle, with PDUS, during standardized cycling exercise protocols, and the test–retest reliability has been investigated.MethodsFixation of the ultrasound probe on the upper leg allowed for continuous PDUS measurements. Cycling exercise protocols included a submaximal and an incremental exercise to maximal power. The relative perfused area (RPA) was determined as a measure of perfusion. Absolute and relative reliability of RPA amplitude and kinetic parameters during exercise (onset, slope, maximum value) and recovery (overshoot, decay time constants) were investigated.ResultsA RPA increase during exercise followed by a signal recovery was measured in all volunteers. Amplitudes and kinetic parameters during exercise and recovery showed poor to good relative reliability (ICC ranging from 0.2–0.8), and poor to moderate absolute reliability (coefficient of variation (CV) range 18–60%).ConclusionsA method has been demonstrated which allows for continuous (Power Doppler) ultrasonography and assessment of perfusion dynamics in skeletal muscle during exercise. The reliability of the RPA amplitudes and kinetics ranges from poor to good, while the reliability of the RPA increase in submaximal cycling (ICC = 0.8, CV = 18%) is promising for non-invasive clinical assessment of the muscle perfusion response to daily exercise.

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.

Muscle blood volume assessment during exercise with Power Doppler Ultrasound

Assessment of perfusion adaptation in muscle during exercise can provide diagnostic information on cardiac and endothelial diseases. Power Doppler Ultrasound (PDUS) is known for its feasibility in the non-invasive measurement of moving blood volume (MBV), a perfusion related parameter. In this study, we show how PDUS can be used to assess the MBV kinetics in muscle, before, during, and after exercise. In a volunteer study, PDUS signal was obtained continuously on the gastrocnemius muscle and rectus femoris muscle, during calf raise (N=11) and leg extension exercises (N=11), respectively. To test reproducibility, the measurements were repeated on two different days. A clear increase of PDUS signal was obtained in both exercises. MBV kinetics during leg extension and after calf raise are assessed by linear and mono-exponential fitting of the data. The reproducibility of the obtained slope and time constants of the signal increase and decay were moderate to good between measurement days, with intra-class correlations (ICC) values of 0.6 - 0.8. Future studies will focus on protocol standardization and the monitoring of muscle perfusion during whole body exercise.

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.