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Reconstruction of 3D light distribution produced by cylindrical diffuser in deep tissues based on photacoustic imaging
Abstract
Measurement of light distribution in biological tissue contributes to selecting strategy and optimizing dose for biomedical application. In this letter, a photoacoustic method combined with Monte Carlo simulation was used to estimate the three-dimensional light distribution in biological tissue. The light distribution was produced by a cylindrical diffuser which interposed into tissues. The light profiles obtained by the method were compared to those detected by photo diodes. The experimental results demonstrate the feasibility of this method. The approach can play a significant role for photo-dosimetry in biomedical phototherapy.
... In conclusion, a robust and computationally efficient imaging system using multiple modes of vortex beams and the "LGDiffNet" architecture is developed. The results suggest that the imaging system that uses beams carrying topological charges, combined with a CNN to reconstruct the images, has numerous medical imaging and microscopy applications, among others 34,50,[64][65][66] . ...
Optical imaging through diffuse media is a challenging issue and has attracted applications in many fields such as biomedical imaging, non-destructive testing, and computer-assisted surgery. However, light interaction with diffuse media leads to multiple scattering of the photons in the angular and spatial domain, severely degrading the image reconstruction process. In this article, a novel method to image through diffuse media using multiple modes of vortex beams and a new deep learning network named “LGDiffNet” is derived. A proof-of-concept numerical simulation is conducted using this method, and the results are experimentally verified. In this technique, the multiple modes of Gaussian and Laguerre-Gaussian beams illuminate the displayed digits dataset number, and the beams are then propagated through the diffuser before being captured on the beam profiler. Furthermore, we investigated whether imaging through diffuse media using multiple modes of vortex beams instead of Gaussian beams improves the imaging system's imaging capability and enhances the network's reconstruction ability. Our results show that illuminating the diffuser using vortex beams and employing the “LGDiffNet” network provides enhanced image reconstruction compared to existing modalities. An enhancement of ~ 1 dB, in terms of PSNR, is achieved using this method when a highly scattering diffuser of grit 220 and width 2 mm (7.11 times the mean free path) is used. No additional optimizations or reference beams were used in the imaging system, revealing the robustness of the “LGDiffNet” network and the adaptability of the imaging system for practical applications in medical imaging.
... The scatterers are modeled such that the amplitude and phase term governing the impulse phase response of the scatterer with respect to the input beam, is randomized, i.e., the images acquired at the camera for each iteration of the simulation, for the same beam parameters, is unique with a very slight variation to the remaining images. This is used to simulate the randomness of the structure and properties of particles in real-life objects which, while having the same properties in general, are still unique from one another [15,[28][29][30]. Employing the randomness of scatterers used also makes it harder for the machine learning algorithm to reconstruct the object. ...
Reconstructing objects behind scattering media is a challenging issue with applications in biomedical imaging, non-distractive testing, computer-assisted surgery, and autonomous vehicular systems. Such systems’ main challenge is the multiple scattering of the photons in the angular and spatial domain, which results in a blurred image. Previous works try to improve the reconstructing ability using deep learning algorithms, with some success. We enhance these methods by illuminating the set-up using several modes of vortex beams obtaining a series of time-gated images corresponding to each mode. The images are accurately reconstructed using a deep learning algorithm by analyzing the pattern captured in the camera. This study shows that using vortex beams instead of Gaussian beams enhances the deep learning algorithm’s image reconstruction ability in terms of the peak signal-to-noise ratio (PSNR) by ~ 2.5 dB and ~1 dB when low and high scattering scatterers are used respectively.
... 22 In previous work by our team, we proposed a PA method for the estimation and reconstruction of 3D light distribution produced by a CD in biological tissue. 23 This paper describes a co-registered PA and US imaging system for EEC detection based on a CD. ...
In illuminating tissues, a cylindrical diffuser (CD) has an advantage over regular laser sources due to its ability to illuminate a larger volume of the target tissue. This paper presents a co-registered large volume photoacoustic (PA) and ultrasonic (US) imaging for early endometrial cancer (EEC) detection using CD. It has the advantage that the US imaging system is outside the body and only the PA excitation device is inside the body, which makes the system more efficient and less invasive for EEC detection. The paper reports on two sets of experiments. The first set produced real-time PA images of blood vessel phantom. The second set demonstrated the imaging of pig uterus ex vivo. The results show that the system has the potential for imaging and characterizing of EEC.
... In our study, the continuous-wave laser light emitted from an interstitial di®usion tip was approximated as fourth degree polynomial function distributed along the tip. 30 Photon propagation from the source was described by di®usion approximation 9 : ...
Interstitial laser immunotherapy (ILIT) is designed to use photothermal and immunological interactions for treatment of metastatic cancers. The photothermal effect is crucial in inducing anti-tumor immune responses in the host. Tissue temperature and tissue optical properties are important factors in this process. In this study, a device combining interstitial photoacoustic (PA) technique and interstitial laser photothermal interaction is proposed. Together with computational simulation, this device was designed to determine temperature distributions and tissue optical properties during laser treatment. Experiments were performed using ex-vivo porcine liver tissue. Our results demonstrated that interstitial PA signal amplitude was linearly dependent on tissue temperature in the temperature ranges of 20–60∘C, as well as 65–80∘C, with a different slope, due to the change of tissue optical properties. Using the directly measured temperature in the tissue around the interstitial optical fiber diffusion tip for calibration, the theoretical temperature distribution predicted by the bioheat equation was used to extract optical properties of tissue. Finally, the three-dimensional temperature distribution was simulated to guide tumor destruction and immunological stimulation. Thus, this novel device and method could be used for monitoring and controlling ILIT for cancer treatment.
Determining the light absorption distribution (LAD) of uterine tissue helps the detection of endometrial carcinoma. In this work, a 3-dimensional optical model of the human uterus is proposed and examined. The model is filled with strong scattering medium (undiluted raw and homogenized milk, URHM) or air at 630 nm and 800 nm wavelengths. Monte Carlo simulations are used to find the absorption profiles of photons by transcervical laser illumination, with a cylindrically diffused light source (CDLS) or spherically diffused light source (SDLS). The results show that 800 nm is a good laser wavelength value for the detection of endometrial carcinoma by photoacoustic imaging (PAI). At the same time, the shape of the light source becomes less important in a relatively large cavity. The impacts of different scattering coefficients of CDLS on the irradiated area are demonstrated. Strong scattering medium is helpful to the illumination of the uterus cavity.
Photoacoustic (PA) and ultrasonic (US) imaging are promising techniques for imaging biological tissue and diagnosing internal organs. This paper presents a real-time PA and US dual-modality imaging system for early gastric cancer (EGC) based on a clinical US transducer. It has the advantage that only the PA excitation is inside the body but the US imaging system is outside the body, which makes the system less invasive for EGC detection and will be a potential tool for clinical use. The first experiments produced real-time PA images of blood vessel phantoms. Cross-sectional 2D PA images and reconstructed 3D PA images of the blood vessel phantoms demonstrate the system can clearly identity tissue structure. The experiments show that the system has a high axial spatial resolution but a relatively low lateral spatial resolution. The second experiments combining US and PA imaging, an artificial slightly elevated tumor and three artificial superficial flat tumors embedded inside the pig stomach mucosa ex vivo, demonstrate that the system is able to detect EGC accurately.
Determination of light absorption distribution in biological tissue contributes to selecting strategy and optimizing dose for biomedical applications. As an efficient illumination scheme for cylinder-like hollow organs such as prostate, interstitial light delivery is commonly employed in the treatment method of photodynamic therapy. In this paper, a simplified optical model of internal light irradiated columnar tissue using cylindrical diffusing source at 633 nm is developed. The light distribution in the tissue is predicted noninvasively by combining the optical model with Monte Carlo method. The related simulation results are almost consistent with the experimental results. The related simulation method and model have an important value for the study of light transport in the complex tissue and would be helpful to the choice of dose and treatment plan when using an interstitial cylindrical diffusing source in clinical medical applications.
In this work two different fluorochromes (Alexa 594 and Alexa 680) are conjugated to the same monoclonal antibody (Cetuximab) for obtaining a characteristic M-shaped dual-peak spectrum. Dual-labeling of Cetuximab by mixing both fluorochromes before the conjugation step gives spectral results similar to those of mixing of fluorochrome-labeled Cetuximab after the conjugation step (P>0.05). In conclusion, both methods may be used equivalently for producing a dual-labeled single-antibody probe. Future studies may test whether the M-shaped spectrum may increase the diagnostic confidence in tumor-targeted multispectral optical imaging.
Interstitial diffuse optical tomography (DOT) has been used to characterize spatial distribution of optical properties for prostate photodynamic therapy (PDT) dosimetry. We have developed an interstitial DOT method using cylindrical diffuse fibers (CDFs) as light sources, so that the same light sources can be used for both DOT measurement and PDT treatment. In this novel interstitial CDF-DOT method, absolute light fluence per source strength (in unit of 1 cm(-2)) is used to separate absorption and scattering coefficients. A mathematical phantom and a solid prostate phantom including anomalies with known optical properties were used, respectively, to test the feasibility of reconstructing optical properties using interstitial CDF-DOT. Three dimension spatial distributions of the optical properties were reconstructed for both scenarios. Our studies show that absorption coefficient can be reliably extrapolated while there are some cross talks between absorption and scattering properties. Even with the suboptimal reduced scattering coefficients, the reconstructed light fluence rate agreed with the measured values to within ±10%, thus the proposed CDF-DOT allows greatly improved light dosimetry calculation for interstitial PDT.
For interstitial photodynamic therapy (PDT), cylindrical diffusing fibers (CDFs) are often used to deliver light. This study examines the feasibility and accuracy of using CDFs to characterize the absorption (μ(a)) and reduced scattering (μ'(s)) coefficients of heterogeneous turbid media. Measurements were performed in tissue-simulating phantoms with μ(a) between 0.1 and 1 cm(-1) and μ'(s) between 3 and 10 cm(-1) with CDFs 2 to 4 cm in length. Optical properties were determined by fitting the measured light fluence rate profiles at a fixed distance from the CDF axis using a heterogeneous kernel model in which the cylindrical diffusing fiber is treated as a series of point sources. The resulting optical properties were compared with independent measurement using a point source method. In a homogenous medium, we are able to determine the absorption coefficient μ(a) using a value of μ'(s) determined a priori (uniform fit) or μ'(s) obtained by fitting (variable fit) with standard (maximum) deviations of 6% (18%) and 18% (44%), respectively. However, the CDF method is found to be insensitive to variations in μ'(s), thus requiring a complementary method such as using a point source for determination of μ'(s). The error for determining μ(a) decreases in very heterogeneous turbid media because of the local absorption extremes. The data acquisition time for obtaining the one-dimensional optical properties distribution is less than 8 s. This method can result in dramatically improved accuracy of light fluence rate calculation for CDFs for prostate PDT in vivo when the same model and geometry is used for forward calculations using the extrapolated tissue optical properties.
Absorption coefficient of biological tissue is an important factor for photothermal therapy and photoacoustic imaging. However, its determination remains a challenge. In this paper, we propose a method using focusing photoacoustic imaging technique to quantify the target optical absorption coefficient. It utilizes the ratio of the amplitude of the peak signal from the top boundary of the target to that from the bottom boundary based on wavelet transform. This method is self-calibrating. Factors, such as absolute optical fluence, ultrasound parameters, and Grüneisen parameter, can be canceled by dividing the amplitudes of the two peaks. To demonstrate this method, we quantified the optical absorption coefficient of a target with various concentrations of an absorbing dye. This method is particularly useful to provide accurate absorption coefficient for predicting the outcomes of photothermal interaction for cancer treatment with absorption enhancement.
We present a new Monte Carlo model of cylindrical diffusing fibers that is implemented with a graphics processing unit. Unlike previously published models that approximate the diffuser as a linear array of point sources, this model is based on the construction of these fibers. This allows for accurate determination of fluence distributions and modeling of fluorescence generation and collection. We demonstrate that our model generates fluence profiles similar to a linear array of point sources, but reveals axially heterogeneous fluorescence detection. With axially homogeneous excitation fluence, approximately 90% of detected fluorescence is collected by the proximal third of the diffuser for μ(s)'∕μ(a) = 8 in the tissue and 70 to 88% is collected in this region for μ(s)'∕μ(a) = 80. Increased fluorescence detection by the distal end of the diffuser relative to the center section is also demonstrated. Validation of these results was performed by creating phantoms consisting of layered fluorescent regions. Diffusers were inserted into these layered phantoms and fluorescence spectra were collected. Fits to these spectra show quantitative agreement between simulated fluorescence collection sensitivities and experimental results. These results will be applicable to the use of diffusers as detectors for dosimetry in interstitial photodynamic therapy.
A rapid and sensitive technique for quantitatively examining the three-dimensional light distribution from optical-fiber diffusers for photodynamic therapy applications was developed. We have used this system to evaluate the longitudinal and azimuthal uniformity of the light output from cylindrical diffusing tips and have determined a standard detector configuration for assessing the optical quality of these diffusers. As an example of the sensitivity and the accuracy of this method, the effect of microbending of the fiber on the output intensity distribution, as well as the effect of the choice of laser used, was investigated and was seen to have a significant impact on the uniformity of these diffusers.
Interstitial photodynamic therapy (PDT) has seen a rebirth, partially prompted by the development of photosensitizers with longer absorption wavelengths that enable the treatment of larger tissue volumes. Here, we study whether using diffusers with customizable longitudinal emission profiles, rather than conventional ones with flat emission profiles, improves our ability to conform the light dose to the prostate. We present a modified Cimmino linear feasibility algorithm to solve the treatment planning problem, which improves upon previous algorithms by (1) correctly minimizing the cost function that penalizes deviations from the prescribed light dose, and (2) regularizing the inverse problem. Based on this algorithm, treatment plans were obtained under a variety of light delivery scenarios using 5-15 standard or tailored diffusers. The sensitivity of the resulting light dose distributions to uncertainties in the optical properties, and the placement of diffusers was also studied. We find that tailored diffusers only marginally outperform conventional ones in terms of prostate coverage and rectal sparing. Furthermore, it is shown that small perturbations in optical properties can lead to large changes in the light dose distribution, but that those changes can be largely corrected with a simple light dose re-normalization. Finally, we find that prostate coverage is only minimally affected by small changes in diffuser placement. Our results suggest that prostate PDT is not likely to benefit from the use of tailored diffusers. Other locations with more complex geometries might see a better improvement.
We developed a technique for constructing light diffusing devices comprised of a flexible shape memory polymer (SMP) cylindrical diffuser attached to the tip of an optical fiber. The devices are fabricated by casting an SMP rod over the cleaved tip of an optical fiber and media blasting the SMP rod to create a light diffusing surface. The axial and polar emission profiles and circumferential (azimuthal) uniformity are characterized for various blasting pressures, nozzle-to-sample distances, and nozzle translation speeds. The diffusers are generally strongly forward-directed and consistently withstand over 8 W of incident IR laser light without suffering damage when immersed in water. These devices are suitable for various endoluminal and interstitial biomedical applications.
The uniformity of the emission profile produced by a cylindrical light diffuser is an important parameter for determining the light dose received by the target tissue during laser therapies such as photodynamic therapy (PDT) and interstitial laser photocoagulation (ILP). A technique originally used for determining the profile of a laser beam with a commercial video camera is adapted in order to measure the distribution of light from a cylindrical diffuser. The method can produce quantitative one-dimensional beam profiles in both the circumferential and axial direction of the light diffuser. The system allows the use of tissue phantoms that provide a convenient and effective method for comparing manufacturer's measurements often made in air with those to be expected in vivo. The technique is a quick and easy method for assessing light diffusers before treatment, and utilises readily available equipment that does not require specialist knowledge. Also, the response of the video camera facilitates the assessment of diffusers over a relatively broad optical spectrum, which encompasses the range of wavelengths currently used for both PDT (515-675 nm) and ILP (800-1064 nm).
In photodynamic therapy (PDT) the uniform distribution of intratumor or externally applied light is desirable but often difficult to achieve. An optical fiber tip producing cylindrical or lateral light emission can facilitate the application of laser energy by direct implantation of the tip into solid tumors or within tubular cavities of the body such as the bronchus or esophagus. A procedure is described for fabricating such a fiber tip, the main component of which is a hollow glass cylinder containing a light-scattering material. Light distributions emitted from the tip in air are documented. Useful properties of the tip include good light distribution, durability, heat resistance, and simplicity of construction.
The distribution of the light emitted by linear light diffusers commonly employed in photodynamic therapy (PDT) has been investigated. A device is presented which measures the angular distribution of the exiting light at each point of the diffuser. With these data the fluence rate in air or in a cavity at some distance from the diffuser can be predicted. The results show that the light is scattered from the diffuser predominantly in the forward direction. Experiments and calculations show that the fluence rate in air and in a cavity of scattering tissue at some distance from the diffuser has a maximum near the tip of the diffuser, instead of near the middle. However, the fluence rate resulting from an interstitial diffuser in a purely scattering tissue phantom shows a maximum in the bisecting plane of the diffuser as would be predicted when the diffuser emitted light isotropically. The scattering nature of the tissue is expected to cancel the anisotropy of the diffuser.