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面向小動(dòng)物成像的擴(kuò)散熒光層析先進(jìn)方法研究

發(fā)布時(shí)間:2018-05-23 07:57

  本文選題:擴(kuò)散熒光層析成像 + 擴(kuò)散方程; 參考:《天津大學(xué)》2013年博士論文


【摘要】:擴(kuò)散熒光層析成像(DFT)技術(shù)作為一種能夠定量提供特異性分子探針空間分布信息的高靈敏度光學(xué)分子成像手段,被逐漸地應(yīng)用于疾病小動(dòng)物模型體內(nèi)生化過程的在體跟蹤和檢測。生物醫(yī)學(xué)研究的深入發(fā)展對DFT技術(shù)的應(yīng)用范圍、功能和指標(biāo)都提出了更高的要求。本文致力于研究面向小動(dòng)物成像的DFT先進(jìn)方法,,其主要內(nèi)容包括基于穩(wěn)態(tài)擴(kuò)散方程的差分DFT成像方法研究和實(shí)驗(yàn)驗(yàn)證,基于時(shí)域擴(kuò)散方程的特征數(shù)據(jù)和全時(shí)間分辨DFT先進(jìn)成像方法研究和實(shí)驗(yàn)驗(yàn)證,以及基于先進(jìn)光子輸運(yùn)模型的DFT成像方法研究和模擬驗(yàn)證。 本文發(fā)展了一種用于pH值敏感性檢測的穩(wěn)態(tài)差分DFT成像方法。該方法基于一種特殊設(shè)計(jì)的仿CT掃描模式的光子計(jì)數(shù)檢測系統(tǒng)和Born歸一化的差分圖像重建算法,來實(shí)現(xiàn)對pH異常引起的熒光參數(shù)變化圖像的快速測量和重建。在仿體實(shí)驗(yàn)中,通過定量性實(shí)驗(yàn)驗(yàn)證了該成像方法具有高精確度的定量能力,并在三種不同的目標(biāo)體與背景熒光對比度下進(jìn)行了pH敏感性檢測實(shí)驗(yàn)驗(yàn)證。 基于時(shí)域擴(kuò)散方程,本文分別發(fā)展了基于多級離散小波變換的特征數(shù)據(jù)時(shí)域DFT成像方法和基于重疊時(shí)間門技術(shù)的全時(shí)間分辨DFT成像方法。前者利用多級離散小波變換來減少逆向模型中的重建參數(shù),從而改善計(jì)算模型的病態(tài)性,提高熒光參數(shù)重建圖像質(zhì)量。后者使用了全時(shí)間分辨數(shù)據(jù),采用重疊時(shí)間門技術(shù)最大限度地挖掘測量數(shù)據(jù)中所包含的信息,從而提高熒光產(chǎn)率重建圖像的分辨率及量化度。此外,采用了基于時(shí)間相關(guān)單光子計(jì)數(shù)技術(shù)的時(shí)域測量系統(tǒng)對發(fā)展的時(shí)域DFT成像方法進(jìn)行了實(shí)驗(yàn)驗(yàn)證。實(shí)驗(yàn)結(jié)果表明兩種DFT成像方法均能夠有效地提高熒光參數(shù)重建圖像的量化度和空間分辨率。 為了克服擴(kuò)散近似光子輸運(yùn)模型本身的限制條件,本文分別發(fā)展了基于穩(wěn)態(tài)輻射傳輸方程的DFT成像方法和基于早期到達(dá)光熒光輸運(yùn)模型的DFT成像方法。前者聯(lián)合了離散立體角元法和有限差分法數(shù)值求解二維穩(wěn)態(tài)輻射熒光傳輸方程,并采用了自然邊界條件及準(zhǔn)直光源模型。利用熒光蒙特卡羅模擬方法產(chǎn)生的正向數(shù)據(jù)對該成像方法進(jìn)行了數(shù)值模擬驗(yàn)證,并且與基于擴(kuò)散方程的穩(wěn)態(tài)DFT算法的重建結(jié)果進(jìn)行了比較。后者將早期到達(dá)光近似為直線傳輸?shù)膹椀拦獍l(fā)展了熒光早期到達(dá)光輸運(yùn)模型。并利用全時(shí)間分辨時(shí)域DFT成像方法的正向數(shù)據(jù)進(jìn)行了數(shù)值模擬驗(yàn)證,模擬結(jié)果證明了該方法的有效性以及對于熒光產(chǎn)率重建圖像在空間分辨率上的提高。
[Abstract]:Diffusion fluorescence Tomography (DFT), as a highly sensitive optical molecular imaging method which can provide quantitative information on the spatial distribution of specific molecular probes, has been gradually applied to the in vivo tracking and detection of biochemical processes in small animal models of disease. The further development of biomedical research has put forward higher requirements for the application scope, function and index of DFT technology. This paper is devoted to the study of advanced DFT methods for small animal imaging, including the research and experimental verification of differential DFT imaging method based on steady-state diffusion equation. The characteristic data based on time-domain diffusion equation and the full-time resolved DFT advanced imaging method are studied and verified by experiments, and the DFT imaging method based on advanced photon transport model is studied and simulated. In this paper, a steady-state differential DFT imaging method for pH sensitivity detection is developed. This method is based on a specially designed photon counting detection system imitating CT scanning mode and Born normalized differential image reconstruction algorithm to realize the fast measurement and reconstruction of the fluorescence parameter change image caused by pH anomaly. The quantitative experiments show that the imaging method has high accuracy, and the pH sensitivity is tested under three different object and background fluorescence contrast. Based on the diffusion equation of time domain, this paper develops the time domain DFT imaging method based on multistage discrete wavelet transform and the full time resolved DFT imaging method based on overlapping time gate technique. In the former, multilevel discrete wavelet transform is used to reduce the reconstruction parameters in the reverse model, thus improving the ill-condition of the computational model and improving the quality of the reconstructed image with the fluorescence parameters. The latter uses full time resolved data and uses overlapping time gate technique to mine the information contained in the measurement data to improve the resolution and quantization of the reconstructed image. In addition, a time-domain measurement system based on time-dependent single-photon counting technique is used to verify the developed time-domain DFT imaging method. Experimental results show that both DFT imaging methods can effectively improve the quantization and spatial resolution of reconstructed images with fluorescence parameters. In order to overcome the limitation of the diffusion approximation photon transport model, the DFT imaging method based on the steady state radiation transfer equation and the DFT imaging method based on the early arrival photoluminescence transport model are developed in this paper. The former combines the discrete solid element method and the finite difference method to numerically solve the two-dimensional steady-state radiative fluorescence transfer equation and adopts the natural boundary conditions and the collimation light source model. The forward data generated by the fluorescence Monte Carlo simulation method are used to validate the proposed method, and the results are compared with the reconstruction results of the steady-state DFT algorithm based on diffusion equation. The latter developed an early arrival light transport model by approximating the early arrival light as a linear ballistic light. The forward data of full time resolved time domain DFT imaging method is simulated and validated. The simulation results show that the method is effective and the spatial resolution of the reconstructed image is improved.
【學(xué)位授予單位】:天津大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2013
【分類號】:R310

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