Spatial Frequency Domain Optical Tomography For In Vivo Assessment Of Skin Cancer Photodynamic Therapy (PDT)

Photodynamic therapy(PDT)has became a powerful tool for the treatment of skin cancer in recent years.Nevertheless,there are still obstacles preventing the widespread use of PDT in clinical.The bottleneck affecting the effect of PDT is how to achieve accuracy and personalization of light and photosensitizer doses according to the individual difference of patients.The effective solution to this issue is to develop in vivo assessment methodologies for real-time dose adjustment and process optimization.Among the numerous researches on the in vivo assessment methodologies of PDT,spatial frequency domain(SFD)imaging has attracted more and more interests since it features rapid,non-contact and wide-field imaging.This technique could provide the multi-wavelength optical properties and the photosensitizer concentration of skin tissues for the in vivo assessment of PDT,which can be adopted for obtaining the oxygen saturation[SO₂],the concentration of cytotoxic agent singlet oxygen[¹O₂]and the minimum singlet oxygen threshold[¹O₂]_th during PDT process.To achieve the accurate determination of PDT dose,the[SO₂]in diseased and normal tissues are measured and compared in real time during PDT process.As the[SO₂]in diseased tissues is higher than that of normal tissues,the power of treatment light and the coating amount of photosensitizer are adjusted in real time,to keep the[¹O₂]in diseased tissues higher than[¹O₂]_th.When the[SO₂]in diseased tissues is decreased to be equal to that of the normal tissues,the PDT is ceased immediately to avoid damage.This paper focuses on the SFD imaging measurement method,the optical properties and the photosensitizer concentration reconstruction algorithms for study.The study is the further development of SFD imaging,which will not only provide an efficient method for the precision of PDT dose,but also provide an important evaluation tool for the development of new photosensitizers.In terms of the SFD imaging measurement method,the conventional camera-based SFD imaging system requires switching between wavelengths for the in vivo assessment of PDT,results in long time to complete data collection.Moreover,the high-sensitivity cameras are more costly,using general scientific grade cameras for SFD imaging applications required to significantly increasing source power,while the high-power source is clinically unacceptable.In this paper,with the aim at SFD imaging of multi-wavelength parallel and fluorescence measurement under weak light,a multi-wavelength and high-sensitivity single-pixel SFD imaging system that incorporated the single-pixel imaging technology and the lock-in photon counting detection was developed.The source power in SFD imaging system was significantly reduced,and thereby the safety of optical measurement and the cost-effective of the conventional camera-based SFD imaging system were improved.According to the wavelength requirements of the in vivo assessment of PDT,the single-pixel SFD imaging system included three wavelengths(450,520 and 650 nm),where 450 nm was used to achieve the quantitative concentration of photosensitizer,and calculate the[SO₂]distribution together with the optical properties at the wavelength of 520 nm.650 nm is the emission wavelength of photosensitizer and the treatment wavelength of PDT,the tissue optical properties at this wavelength were used to model the photon transport of emission light,and calculate[¹O₂]and[¹O₂]_th.With the prior knowledge that the spatial frequencies of wide-field sinusoidal illumination patterns were known in advance and the spatially modulated reflectance images were sparse in two-dimensional discrete cosine domain,this paper proposes a two-dimensional discrete cosine transform-based single-pixel imaging(DCT-SPI)scheme for rapidly recovering spatially modulated reflectance images for SFD imaging measurement.Numerical simulations and phantom experiments demonstrated that the sampling patterns were effectively reduced by the use of DCT-SPI scheme,and thereby the single-pixel SFD imaging system achieves a fast acquisition speed that is desired for the dynamic in vivo assessment and real-time monitoring of PDT.For further shortening the measurement time of the single-pixel SFD imaging system,a composited illumination of multi-frequency sinusoidal patterns was adopted,and the spatially modulated reflectance images with multi-frequency components were demodulated by the use of single snapshot multiple frequency demodulation method.The result shows that the single-pixel SFD imaging system could simultaneously obtained multiple frequency components of the tissue with only once illumination,thereby the measurement efficiency and real-time of SFD imaging were enhanced.In terms of the reconstruction of the optical properties and the photosensitizer concentration,the conventional SFD imaging fails to obtain the depth-resolved optical properties and quantitative photosensitizer concentration.This paper herein proposes a spatial frequency domain diffuse optical tomography(SFD-DOT)based on the linear inversion of the first-order Rytov approximation and a spatial frequency domain fluorescence molecular tomography(SFD-FMT)based on the linear inversion of the normalized Born-ratio formulation.For SFD-DOT,tomographic images of the tissue optical properties were acquired by establishing the relationships of the optical properties sensitivity matrixes of detected light intensity relative to different spatial positions in tissues.For SFD-FMT,according to the optical properties obtained from SFD-DOT,the quantitative photosensitizer concentration were acquired by simultaneously modeling the photon transport of excitation and emission light.Numerical simulations were performed to investigate the performances of the proposed SFD-DOT/FMT algorithms,the investigation has concluded that using different components for SFD-DOT/FMT reconstruction leads to obvious difference among the tomographic images,the adoption of the multi-frequency strategy to the SFD-DOT/FMT can substantially improve the reconstruction quality,as well as the shift phenomena in current reflection tomography imaging methods.Finally,we performed experiments using several phantoms and in vitro tissues,respectively,to verify the proposed single-pixel SFD imaging system could effectively obtained the three wavelength optical properties and fluorescence tomographic images with the SFD-DOT/FMT algorithms,which can be used for obtaining the[SO₂],[¹O₂]and[¹O₂]_thdistribution in PDT process,so as to achieve the accuracy of PDT dose.