Edem Dovlo

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.

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.

Wavelength-modulated differential photoacoustic radar imager (WM-DPARI): accurate monitoring of absolute hemoglobin oxygen saturation

Accurate monitoring of blood oxy-saturation level (SO2 ) in human breast tissues is clinically important for predicting and evaluating possible tumor growth at the site. In this work, four different non-invasive frequency-domain photoacoustic (PA) imaging modalities were compared for their absolute SO2 characterization capability using an in-vitro sheep blood circulation system. Among different PA modes, a new WM-DPAR imaging modality could estimate the SO2 with great accuracy when compared to a commercial blood gas analyzer. The developed WM-DPARI theory was further validated by constructing SO2 tomographic images of a blood-containing plastisol phantom.

Coded excitation waveform engineering for high frame rate synthetic aperture ultrasound imaging

&NA; Coded excitation was initially introduced to ultrasound imaging as a method for enhancing the signal‐to‐noise ratio (SNR). However, this method was also shown to be helpful in conjunction with synthetic aperture transmission for high frame rate imaging. Recently, we introduced two families of mismatched coded excitations based on frequency modulation chirp and combined frequency modulation and Golay code. Here “mismatched” indicates that the coded excitations generate very small cross‐correlations among themselves while each has a very strong autocorrelation. Employing weakly correlated coded excitations enables performing simultaneous insonifications from several elements of the ultrasonic transducer and receiving distinguishable responses to each code. In this work, we propose and experimentally demonstrate another set of mismatched correlated coded excitations based on Golay codes. The generated phase codes share identical duration and center frequency which results in similar SNR and image resolution. HighlightsMismatched coded excitations enable simultaneous insonifications from multiple elements.Mismatched coded excitation is used to enhance the frame rate of ultrasound imaging.A new family of mismatched coded excitations introduced based on Golay codes.The new coded excitations share identical duration and center frequency.

Quantitative phase-filtered wavelength-modulated differential photoacoustic radar tumor hypoxia imaging toward early cancer detection

Overcoming the limitations of conventional linear spectroscopy used in multispectral photoacoustic imaging, wherein a linear relationship is assumed between the absorbed optical energy and the absorption spectra of the chromophore at a specific location, is crucial for obtaining accurate spatially-resolved quantitative functional information by exploiting known chromophore-specific spectral characteristics. This study introduces a non-invasive phase-filtered differential photoacoustic technique, wavelength-modulated differential photoacoustic radar (WM-DPAR) imaging that addresses this issue by eliminating the effect of the unknown wavelength-dependent fluence. It employs two laser wavelengths modulated out-of-phase to significantly suppress background absorption while amplifying the difference between the two photoacoustic signals. This facilitates pre-malignant tumor identification and hypoxia monitoring, as minute changes in total hemoglobin concentration and hemoglobin oxygenation are detectable. The system can be tuned for specific applications such as cancer screening and SO2 quantification by regulating the amplitude ratio and phase shift of the signal. The WM-DPAR imaging of a head and neck carcinoma tumor grown in the thigh of a nude rat demonstrates the functional PA imaging of small animals in vivo. The PA appearance of the tumor in relation to tumor vascularity is investigated by immunohistochemistry. Phase-filtered WM-DPAR imaging is also illustrated, maximizing quantitative SO2 imaging fidelity of tissues. Oxygenation levels within a tumor grown in the thigh of a nude rat using the two-wavelength phase-filtered differential PAR method.

Wavelength-Modulated Differential Photoacoustic (WM-DPA) imaging: a high dynamic range modality towards noninvasive diagnosis of cancer

This study explores wavelength-modulated differential photo-acoustic (WM-DPA) imaging for non-invasive early cancer detection via sensitive characterization of functional information such as hemoglobin oxygenation (sO2) levels. Well-known benchmarks of tumor formation such as angiogenesis and hypoxia can be addressed this way. While most conventional photo-acoustic imaging has almost entirely employed high-power pulsed lasers, frequency-domain photo-acoustic radar (FD-PAR) has seen significant development as an alternative technique. It employs a continuous wave laser source intensity-modulated and driven by frequency-swept waveforms. WM-DPA imaging utilizes chirp modulated laser beams at two distinct wavelengths for which absorption differences between oxy- and deoxygenated hemoglobin are minimum (isosbestic point, 805 nm) and maximum (680 nm) to simultaneously generate two signals detected using a standard commercial array transducer as well as a single-element transducer that scans the sample. Signal processing is performed using Lab View and Matlab software developed in-house. Minute changes in total hemoglobin concentration (tHb) and oxygenation levels are detectable using this method since background absorption is suppressed due to the out-of-phase modulation of the laser sources while the difference between the two signals is amplified, thus allowing pre-malignant tumors to become identifiable. By regulating the signal amplitude ratio and phase shift the system can be tuned to applications like cancer screening, sO2 quantification and hypoxia monitoring in stroke patients. Experimental results presented demonstrate WM-DPA imaging of sheep blood phantoms in comparison to single-wavelength FD-PAR imaging. Future work includes the functional PA imaging of small animals in vivo.

Photoacoustic cross-correlation high-frame-rate and phase spectroscopy: two new biomedical imaging modalities

In this study, we present some examples of waveform engineering applications in frequency-domain photoacoustics (PA). An example of using linear frequency modulation (LFM) for PA spectroscopy is the capability of simultaneous probing/imaging with multiple wavelengths. Use of mismatched coded waveforms enables encoding the signal sources and, therefore, facilitates simultaneous probing and imaging. This method enables high frame rate functional imaging with reduced motion artifacts. Furthermore, it is shown than that phase of the PA cross-correlation induced with a LFM can yield the absolute absorption coefficient of the chromophores. This method is not affected by fluence attenuation or variation due to the absorption and scattering of the overlayer material.

Co-registration of ultrasound and frequency-domain photoacoustic radar images and image improvement for tumor detection

This paper demonstrates the co-registration of ultrasound (US) and frequency domain photoacoustic radar (FD-PAR) images with significant image improvement from applying image normalization, filtering and amplification techniques. Achieving PA imaging functionality on a commercial Ultrasound instrument could accelerate clinical acceptance and use. Experimental results presented demonstrate live animal testing and show enhancements in signal-to-noise ratio (SNR), contrast and spatial resolution. The co-registered image produced from the US and phase PA images, provides more information than both images independently.

Building a symbolic computer algebra toolbox to compute 2D Fourier transforms in polar coordinates

Graphical abstract