Quantitative Photoacoustic Tomography Of Small Animals Supported By Diffuse Optics Theory

Photoacoustic tomography(PAT)is a non-invasive and non-ionizing biomedical optical imaging method,which combines the advantages of optical imaging and ultrasonic imaging.PAT has shown great potential in preclinical and clinical researches for its ability to image deep tissue with high resolution.However,only the distribution of the light absorbed energy density(initial acoustic pressure)is directly obtained by the conventional PAT,which is in principle the product of the absorption coefficients and the photon fluence within the irradiated regions of the tissue.When imaging the deep tissue,due to the attenuation of photon density along the depth direction and the difference of optical parameters of organs,the distribution of photon density in deep tissue will be seriously uneven.At this time,the image of the light absorbed energy density cannot objectively and accurately reflect the distribution of intrinsic optical properties of tissue.Therefore,in order to enhance the application of PAT in functional imaging of biological tissue,this paper aims to establish a set of approaches for quantitatively reconstructing the distribution of optical absorption coefficients by the light absorbed energy density of the tissue,also known as quantitative PAT(q-PAT)technology.In performing PAT measurements on complex biological tissue,in order to ensure high signal-to-noise ratio(SNR)of the received photoacoustic signals,a wide-field multi-directional illumination mode is generally used.In this way,the difficulty of modeling the light source term is greatly increased when building the photon transport model in q-PAT reconstruction,which leads to the inability to accurately estimate the regional photon density distribution.In this paper,first,a computed-tomography analogous(CT-analogous)PAT/DOT dual-modality system has been built,focusing on future whole-body applications.Meanwhile,a PAT-guided DOT approach is introduced with both soft-and hard-prior regularizations.Since the DOT measurements usually adopt multi-angle point sources collimated incidence mode,and the DOT results can directly provide the distribution of optical parameters inside the tissue,the proposed strategy can avoid the problem of modeling complex light sources in q-PAT.Compared with other simple anatomical image modalities,PAT can provide more appropriate optical absorption structure prior information reflecting the functional status of biological tissue with high spatial resolution for DOT reconstruction,so as to reduce the high ill-posedness exhibited by the DOT inversion.At the same time,the distribution of optical parameters obtained from the PAT-guided DOT approach can provide more accurate initial estimation of optical absorption and scattering coefficients for q-PAT direct reconstruction method.The results show that the proposed schemes are capable of effectively improving the quantitative accuracy and spatial resolution of the optical absorption coefficients map.In the implementation of q-PAT theory,in order to reduce the complexity of light source modeling in optical inversion process,several attempts have been investigated using point sources or a single-angle wide-field illumination.However,these schemes normally suffer from low SNR or poor quantification in imaging applications on large-size domains,due to the limitation of ANSI-safety incidence and incom-pleteness in the data acquisition.Therefore,this paper presents a q-PAT implementation that uses multi-angle light-sheet illuminations and calibrated recovering-and-averaging iterations.The scheme can obtain more complete information on the intrinsic absorption from the multi-angle illumination mode,and collect SNR-boosted photoacoustic signals in the selected planes from the wide-field light-sheet excitation.Therefore,the sliced absorption maps over whole body of small-animals can be recovered in a measurement-flexible,noise-robust and computation-economic way.The proposed approach is validated by phantom,ex vivo and in vivo experiments,exhibiting promising performances in image fidelity and quantitative accuracy for practical applications.When q-PAT is realized by the time-division multi-angle excitation mode,the PAT measurements need to be performed under each illumination angle.Therefore the overall implementation cost of the q-PAT is greatly increased.To fully realize the potential of q-PAT in preclinical and clinical applications,sparse-view measurements can be adopted to effectively reduce the number of data acquisition positions,so as to achieve rapid measurements.However,since the reconstruction from the sparse-view sampling data is challenging,both the effective measurement and the appropriate reconstruction should be taken into account.In this paper,we present an iterative sparse-view PAT reconstruction scheme,where a concept of "virtual parallel-projection" matching the measurement condition is introduced to aid the "compressive sensing" in the reconstruction procedure,and meanwhile the non-local spatially adaptive filtering exploring the a priori information of the mutual similarities in natural images is adopted to recover the unknowns in the transformed sparse domain.Consequently,the reconstructed images with the proposed sparse-view scheme can be evidently improved in comparison to those with the universal back-projection method,for the cases of same sparse views.The proposed approach has been validated by the simulations and ex vivo experiments,which exhibits desirable performances in image fidelity even from a small number of measuring positions.