Bahman Lashkari

Frequency-domain photothermoacoustics: Alternative imaging modality of biological tissues

Frequency-domain photothermoacoustic (FD-PTA) imaging of biological tissues is presented and compared with the conventional time-domain methodology. We demonstrate that tissue imaging can be performed with high axial resolution without the necessity to employ short-pulse and high peak-power laser systems to generate acoustic transients. The presented analysis shows that depth information in the FD-PTA method can be recovered by using linear frequency-modulated (chirped) optical excitation and frequency-domain signal processing algorithms. The signal-to-noise ratio can be increased significantly using correlation processing, which can compensate for the small amplitude of acoustic waves typical to the periodic excitation mode. Additionally, narrow-band signal demodulation enables depth-specific and confocal tissue imaging using the optically induced photothermoacoustic effect. Application of the FD-PTA is demonstrated in experiments with turbid phantoms and ex vivo tissue specimens.

Comparison between pulsed laser and frequency-domain photoacoustic modalities: Signal-to-noise ratio, contrast, resolution, and maximum depth detectivity

In this work, a detailed theoretical and experimental comparison between various key parameters of the pulsed and frequency-domain (FD) photoacoustic (PA) imaging modalities is developed. The signal-to-noise ratios (SNRs) of these methods are theoretically calculated in terms of transducer bandwidth, PA signal generation physics, and laser pulse or chirp parameters. Large differences between maximum (peak) SNRs were predicted. However, it is shown that in practice the SNR differences are much smaller. Typical experimental SNRs were 23.2 dB and 26.1 dB for FD-PA and time-domain (TD)-PA peak responses, respectively, from a subsurface black absorber. The SNR of the pulsed PA can be significantly improved with proper high-pass filtering of the signal, which minimizes but does not eliminate baseline oscillations. On the other hand, the SNR of the FD method can be enhanced substantially by increasing laser power and decreasing chirp duration (exposure) correspondingly, so as to remain within the maximum permissible exposure guidelines. The SNR crossover chirp duration is calculated as a function of transducer bandwidth and the conditions yielding higher SNR for the FD mode are established. Furthermore, it was demonstrated that the FD axial resolution is affected by both signal amplitude and limited chirp bandwidth. The axial resolution of the pulse is, in principle, superior due to its larger bandwidth; however, the bipolar shape of the signal is a drawback in this regard. Along with the absence of baseline oscillation in cross-correlation FD-PA, the FD phase signal can be combined with the amplitude signal to yield better axial resolution than pulsed PA, and without artifacts. The contrast of both methods is compared both in depth-wise (delay-time) and fixed delay time images. It was shown that the FD method possesses higher contrast, even after contrast enhancement of the pulsed response through filtering.

Linear frequency modulation photoacoustic radar: Optimal bandwidth and signal-to-noise ratio for frequency-domain imaging of turbid media

The development of the pulse compression photoacoustic (PA) radar using linear frequency modulation (LFM) demonstrated experimentally that spectral matching of the signal to the ultrasonic transducer bandwidth does not necessarily produce the best PA signal-to-noise ratio, and it was shown that the optical and acoustic properties of the absorber will modify the optimal bandwidth. The effects of these factors are investigated in frequency-domain (FD) PA imaging by employing one-dimensional and axisymmetric models of the PA effect, and a Krimholtz-Leedom-Matthaei model for the employed transducers. LFM chirps with various bandwidths were utilized and transducer sensitivity was measured to ensure the accuracy of the model. The theory was compared with experimental results and it was shown that the PA effect can act as a low-pass filter in the signal generation. Furthermore, with the PA radar, the low-frequency behavior of two-dimensional wave generation can appear as a false peak in the cross correlation signal trace. These effects are important in optimizing controllable features of the FD-PA method to improve image quality.

Photoacoustic radar imaging signal-to-noise ratio, contrast, and resolution enhancement using nonlinear chirp modulation.

Cross-correlation (radar) frequency-domain photoacoustic (PA) imaging parameters [signal-to-noise ratio (SNR), contrast, and spatial resolution] are explored. The application of nonlinear frequency modulation instead of the standard linear frequency chirps is investigated. In addition to the image produced by the amplitude of the cross correlation between input and detected signals, the phase of the correlation signal is used as a filter of the PA amplitude combined with linear or nonlinear frequency chirps to improve SNR, contrast, and spatial resolution. The experimental results with a high-frequency transducer exhibit more than 10 and 8 times contrast enhancement using nonlinear and linear chirps, respectively. Concomitant improvements in SNR and image resolution were also observed.

Slow and fast ultrasonic wave detection improvement in human trabecular bones using Golay code modulation

The identification of fast and slow waves propagating through trabecular bone is a challenging task due to temporal wave overlap combined with the high attenuation of the fast wave in the presence of noise. However, it can provide valuable information about bone integrity and become a means for monitoring osteoporosis. The objective of this work is to apply different coded excitation methods for this purpose. The results for single-sine cycle pulse, Golay code, and chirp excitations are compared. It is shown that Golay code is superior to the other techniques due to its signal enhancement while exhibiting excellent resolution without the ambiguity of sidelobes.

Coregistered photoacoustic and ultrasonic signatures of early bone density variations

Abstract. This study examines the application of backscattered ultrasound (US) and photoacoustic (PA) signals for assessment of bone structure and density variations. Both methods were applied in the frequency-domain, employing linear frequency modulation chirps. A near-IR laser (800 nm) was used for inducing the PA signal. The backscattered pressure waves were detected with a 2.2-MHz US transducer. Experiments were focused on detection and evaluation of PA and US signals from in-vitro animal and human bones with cortical and trabecular sublayers. It was shown that PA signals can be detected as deep as a few millimeters below trabecular and cortical layers. The occurrence of multiple scattering was demonstrated in PA detected signals from cancellous bone. Osteoporotic changes in the bone were simulated by using a very mild demineralization ethylenediaminetetraacetic acid solution. Changes in the time-domain signals as well as integrated backscattering spectra were compared for the samples before and after demineralization. The results demonstrated the sensitivity of PA to variations in bone minerals. In comparison to PA, US was capable of generating detectable signals from deeper bone sublayers (few centimeters). However, while US signal variations with changes in the cortical layer were insignificant, PA proved to be sensitive even to minor variations of the cortical bone density.

Simultaneous dual-wavelength photoacoustic radar imaging using waveform engineering with mismatched frequency modulated excitation

The spectroscopic imaging capability of photoacoustics (PA) without the depth limitations of optical methods offers a major advantage in preclinical and clinical applications. Consecutive PA measurements with properly chosen wavelengths allow composition related information about blood or tissue. In this work, we propose and experimentally introduce modulation waveform engineering through the use of mismatched (uncorrelated or weakly correlated) linear frequency modulated signals for PA characterization and imaging. The feasibility of the method was tested on oxygen saturated hemoglobin and deoxygenated hemoglobin in vitro in a blood circulating rig. The method was also employed for in vivo imaging of a neck carcinoma tumor grown in a mouse thigh. The proposed method can increase the accuracy and speed of functional imaging by simultaneous PA probing with two wavelengths using portable laser-diode based PA imaging systems.

Photoacoustic radar phase-filtered spatial resolution and co-registered ultrasound image enhancement for tumor detection.

Co-registered ultrasound (US) and frequency-domain photoacoustic radar (FD-PAR) imaging is reported for the first time in this paper. The merits of ultrasound and cross-correlation (radar) frequency-domain photoacoustic imaging are leveraged for accurate tumor detection. Commercial US imagers possess sophisticated, optimized software for rapid image acquisition that could dramatically speed-up PA imaging. The PAR image generated from the amplitude of the cross-correlation between detected and input signals was filtered by the standard deviation (SD) of the phase of the correlation signal, resulting in strong improvement of image spatial resolution, signal-to-noise ratio (SNR) and contrast. Application of phase-mediated image improvement is illustrated by imaging a cancer cell-injected mouse. A 14-15 dB SNR gain was recorded for the phase-filtered image compared to the amplitude and phase independently, while ~340 μm spatial resolution was seen for the phase PAR image compared to ~840 μm for the amplitude image.

Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS) for noninvasive early cancer detection and tissue hypoxia monitoring.

This study introduces a novel noninvasive differential photoacoustic method, Wavelength Modulated Differential Photoacoustic Spectroscopy (WM-DPAS), for noninvasive early cancer detection and continuous hypoxia monitoring through ultrasensitive measurements of hemoglobin oxygenation levels (StO2 ). Unlike conventional photoacoustic spectroscopy, WM-DPAS measures simultaneously two signals induced from square-wave modulated laser beams at two different wavelengths where the absorption difference between maximum deoxy- and oxy-hemoglobin is 680 nm, and minimum (zero) 808 nm (the isosbestic point). The two-wavelength measurement efficiently suppresses background, greatly enhances the signal to noise ratio and thus enables WM-DPAS to detect very small changes in total hemoglobin concentration (CHb ) and oxygenation levels, thereby identifying pre-malignant tumors before they are anatomically apparent. The non-invasive nature also makes WM-DPAS the best candidate for ICU bedside hypoxia monitoring in stroke patients. Sensitivity tunability is another special feature of the technology: WM-DPAS can be tuned for different applications such as quick cancer screening and accurate StO2 quantification by selecting a pair of parameters, signal amplitude ratio and phase shift. The WM-DPAS theory has been validated with sheep blood phantom measurements. Sensitivity comparison between conventional single-ended signal and differential signal.

Frequency-Domain Photoacoustic Phase Spectroscopy: A Fluence-Independent Approach for Quantitative Probing of Hemoglobin Oxygen Saturation

In this paper, it is shown that the phase of the frequency-domain photoacoustic (PA) signal can be used to measure the absorption coefficient (μα) of the chromophore. This method can be referred to as a calibration-free approach in the sense that it is not affected by the attenuation of fluence in the tissue. This helps to enhance the accuracy of quantitative PA functional imaging. However, the premise for employing the aforementioned method is that chromophore geometry should be known a priori. As a proof of applicability of the theory, the method was applied to a simplified geometry and the extension of the method to more complicated geometries is discussed. One of the key subjects of functional imaging in medicine is blood. Parameters such as total hemoglobin concentration and hemoglobin oxygen saturation are valuable for diagnostics as well as for treatment of many diseases. The developed method was employed for in vitro monitoring of blood oxygenation on heparinized sheep blood and is applicable to characterization problems in biological tissues and other turbid media.