In photothermal therapy, heat generated from absorbed light energy is used to treat cancerous tissue. Thus, determining laser parameters that control temperature elevation prior to therapy is crucial for an effective outcome. These parameters can be defined by modeling the expected temperature increase via numerical simulations. The quality of these simulations highly depends on the accurate knowledge of optical properties of the treated tissue. Multi-wavelength Photo Magnetic Imaging (PMI) utilizes four laser wavelengths from the near infrared (NIR) window to induce a relatively low temperature increase, while measuring the laser-induced temperature increase using Magnetic Resonance Thermometry. These measured temperature maps are then used by the PMI image reconstruction algorithm to provide high spatial resolution absorption maps at these wavelengths. These absorption maps are then processed to recover the concentration of the main chromophores of the tissue, and consequently obtain its total optical absorption spectrum at any wavelength in the NIR region based on the Beer-Lambert law. In this paper, PMI was used to recover the absorption coefficient of a gelatin tissuesimulating phantom at four wavelengths. These spatially-resolved absorption values were used to successfully recover the concentration of the chromophores of the phantom and calculate its total absorption spectrum in the NIR spectral window with an error as low as ∼ 2.3%. Therefore, applications of photothermal therapy applied in NIR window can benefit from the absorption spectrum recovered by PMI to achieve accurate simulations and determine important laser parameters, which are key for accurate therapy planning.
KEYWORDS: Absorption, Chromophores, Temperature metrology, Spatial resolution, Inverse problems, Finite element methods, Magnetic resonance imaging, Image restoration, Near infrared
Although diffuse optical tomography (DOT) is able to obtain valuable functional information, its routine use in clinic is hampered by its poor spatial resolution and quantitative accuracy. Previously, our team introduced Photo-Magnetic Imaging (PMI) to overcome the limitation of DOT. PMI is a hybrid modality that synergistically utilizes optics and Magnetic Resonance Imaging (MRI). While illuminating the imaged medium by near-infrared laser, the induced internal temperature increase is measured using Magnetic Resonance Thermometry (MRT). Using these MRT maps, optical absorption maps at the laser's wavelength can be recovered using the dedicated PMI image reconstruction algorithm. In this paper, we present the result of the first validation simulation study of multi-wavelength PMI that utilizes five different laser wavelengths ranging between 760 and 980 nm. Using the high resolution wavelength specific absorption maps, PMI successfully recovered the concentration of three dyes, used as chromophore in the composition of our phantom, with high spatial resolution and quantitative accuracy. By providing functional information at high resolution, multi-wavelength PMI will be a valuable tool for monitoring tissue physiology, cancer detection and monitoring.
In this study, we present a fast analytical approach for laser induced temperature increase in biological tissue. The whole problem consists of two main steps. These steps are the light propagation and heat transfer in tissue. We first obtain a detailed analytical solution for the diffusion equation based on an integral approach for specific boundary conditions. Secondly, we also solve the Pennes' bio-heat transfer equation analytically using the separation of variables technique and obtain the temperature induced by optical absorption of tissue. Here, heat source term consists of the local absorption and photon density, which will be determined from the diffusion equation. We find a very comprehensive solution for the diffusion equation by using an integral method for the Robin boundary condition. In other words, we obtain a particular Green's function in a different way. Next, we use this solution as a source term in the Pennes’ bio-heat equation by utilizing the heat convection boundary condition. It is important to note that these boundary conditions are good approximations for imaging of biological tissue. As a result, we obtain spatio-temporal temperature distribution inside the medium. First, our approach is validated by a numerical approach using a Finite Element Method (FEM). Next, we also validate our method by performing phantom and tissue experiments. Experimental data corresponding to spatio-temporal temperature distribution are recorded using magnetic resonance thermometry. The analytical results obtained by our method are in a very good agreement with ones obtained by the FEM and experiment.
One major advantage of using gold nanoparticles is the possibility of tuning their absorption peak by modifying their surface plasma resonance. They are proven to be a promising multi-functional platform that can be used for many imaging and therapeutic applications. As a true multi-modality imaging technique, Photo-Magnetic Imaging (PMI) has a great potential to monitor the distribution of gold nanoparticles non-invasively with MR resolution. With a simple addon of a continuous wave laser to an MRI system, PMI uses the laser induced temperature increase, measured by MR Thermometry (MRT), to provide tissue optical absorption maps at MR resolution. PMI utilizes a Finite Element Method (FEM) based algorithm to solve the combined diffusion and bio-heat equations. This system of combined equations models the photon distribution in the tissue and heat generation due to the absorption of the light and consequent heat diffusion. The key characteristic of PMI is that its spatial resolution is preserved at any depth as long as the temperature change within the imaged medium is detectable by MRT. Agar phantoms containing gold nanoparticles are used to validate the ability of PMI in monitoring their distribution. To make PMI suitable for diagnostic purposes, the laser powers has been kept under the American National Standard Institute maximum skin exposure limits in this study.
We present experimental results that validate our imaging technique termed photomagnetic imaging (PMI). PMI illuminates the medium under investigation with a near-infrared light and measures the induced temperature increase using magnetic resonance imaging. A multiphysics solver combining light and heat propagation is used to model spatiotemporal distribution of temperature increase. Furthermore, a dedicated PMI reconstruction algorithm has been developed to reveal high-resolution optical absorption maps from temperature measurements. Being able to perform measurements at any point within the medium, PMI overcomes the limitations of conventional diffuse optical imaging. We present experimental results obtained on agarose phantoms mimicking biological tissue with inclusions having either different sizes or absorption contrasts, located at various depths. The reconstructed images show that PMI can successfully resolve these inclusions with high resolution and recover their absorption coefficient with high-quantitative accuracy. Even a 1-mm inclusion located 6-mm deep is recovered successfully and its absorption coefficient is underestimated by only 32%. The improved PMI system presented here successfully operates under the maximum skin exposure limits defined by the American National Standards Institute, which opens up the exciting possibility of its future clinical use for diagnostic purposes.
Multi-modality imaging leverages the competitive advantage of different imaging systems to improve the overall resolution
and quantitative accuracy. Our new technique, Photo-Magnetic Imaging (PMI) is one of these true multi-modality imaging
approaches, which can provide quantitative optical absorption map at MRI spatial resolution. PMI uses laser light to
illuminate tissue and elevate its temperature while utilizing MR thermometry to measure the laser-induced temperature
variation with high spatial resolution. The high-resolution temperature maps are later converted to tissue absorption maps by
a finite element based inverse solver that is based on modeling of photon migration and heat diffusion in tissue. Previously,
we have demonstrated the feasibility of PMI with phantom studies. Recently, we have managed to reduce the laser power
under ANSI limit for maximum skin exposure therefore, we have well positioned PMI for in vivo imaging. Currently we are
expanding our system by adding multi-wavelength imaging capability. This will allow us not only to resolve spatial
distribution of tissue chromophores but also exogenous contrast agents. Although we test PMIs feasibility with animal
studies, our future goal is to use PMI for breast cancer imaging due to its high translational potential.
We introduce an entirely new technique, termed Photo-Magnetic Imaging (PMI), which overcomes the limitation of pure optical imaging and provides optical absorption at MRI spatial resolution. PMI uses laser light to heat the medium under investigation and employs MR thermometry for the determination of spatially resolved optical absorption in the probed medium. A FEM-based PMI forward solver has been developed by modeling photon migration and heat diffusion in tissue to compare simulation results with measured MRI maps. We have successfully performed PMI using 2.5 cm diameter agar phantom with two low optical absorption contrast (x 4) inclusions under the ANSI limit. Currently, we are developing the PMI inverse solver and undertaking further phantom and in vivo experiments.
Since diffuse optical tomography (DOT) is a low spatial resolution modality, it is desirable to validate its quantitative accuracy with another well-established imaging modality, such as magnetic resonance imaging (MRI). In this work, we have used a polymer based bi-functional MRI-optical contrast agent (Gd-DTPA-polylysine-IR800) in collaboration with GE Global Research. This multi-modality contrast agent provided not only co-localization but also the same kinetics, to cross-validate two imaging modalities. Bi-functional agents are injected to the rats and pharmacokinetics at the bladder are recovered using both optical and MR imaging. DOT results are validated using MRI results as "gold standard"
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