分子影像是新興的生醫研究領域。它是一種以非入侵式影像方式，顯示活體內分子或基因層次的空間與時間功能訊息。分子影像的研究進展，能夠增加人類對疾病的認識與了解，進而提升對疾病早期診斷的能力，並加速藥物的開發。分子影像的成功發展，需跨領域地結合化學、生物、物理、醫藥等知識。在這個論文研究中, 我們嘗試發揮生醫物理的專業，開發研製非侵入式造影系統、研究分子影像的性能精進及影像融合等相關軟硬體的影像技術，希望能有益於分子影像的應用。
在核能研究所，我們研製了一部專為小動物實驗和植物造影用的positron emission Imager (PEImager)。這部有四個偵檢頭的PEImager具有平面和斷層掃描功能。PEImager的平面投影掃描模式，不旋轉偵檢頭可以獲得二維平面影像。此平面影像在中心或離心處的空間解析度並無顯著不同，其平均空間解析度為3.11 mm FWHM (full width of half maximum)。此模式可以應用於觀察小動物或植物內影像顯示劑(imaging agent)的動態分佈。PEImager的斷層掃描，需旋轉偵檢系統擷取足夠的數據做影像重建，以獲得三維斷層影像。此系統斷層影像的空間解析度在中心點為2.73 mm FWHM，在20 mm離心處，空間解析度降為3.48 mm FWHM。斷層影像模式可以應用於有較高空間解析需求的造影研究。除了傳統的平面和斷層影像重建外，我們也開發了一種稱為planar tomography的影像重建方法，此方法可以重建平面投影數據，即使不旋轉偵檢頭，亦能獲得三維斷層影像。planar tomography的空間解析度在X, Y方向上，與傳統斷層影像無顯著差異。但在Z方向上，planar tomography的空間解析度是傳統斷層影像的2.63倍。在考慮偵檢效率、衰減及幾何等因素下，利用planar tomography可以量測並估計乳房假體內熱點的位置與大小。與傳統聚焦平面重建方法比較，planar tomography有較佳的影像對比品質與腫瘤檢出能力。
在臨床前動物造影研究上，為融合microPET、microCT 和 microSPECT的造影訊息，我們開發了軟體方式的自動對位方法。這個三維自動對位方法簡單、數據無需前置與後續處理、無需使用者主觀介入、也與造影物體無關。此對位方法已成功應用於microPET/CT、microPET/CT/SPECT的假體和動物造影的影像融合。該方法最大對位誤差約為1個體素大小。除了以軟體方式融合microPET/CT的影像對位方法研究外，以硬體方式結合microPET/CT造影與影像融合的計畫正在核能研究所進行。為達成此計畫，我們研製了一部microCT系統，可以與Concode’s microPET R4合併為microPET/CT系統。這台microPET/CT具有內建的對位矩陣，可以提供解剖性CT影像作為microPET影像的參考。這部microPET/CT預期將有助於分子影像的定性與定量研究，並將在藥物開發的臨床前動物實驗上扮演重要的角色。

Molecular imaging is a rapidly emerging biomedical research field, in which the images produced the noninvasive visualization in space and time of normal as well as abnormal cellular processes at a molecular or genetic level of function. Advancements arising from this research can enhance our knowledge of disease, lead to earlier disease detection and accelerate drug discovery. At the imaging system level, many challenges, such as to improve imaging performance and to integrate molecular imaging studies, remain in molecular imaging. In this dissertation, we have investigated both software and hardware techniques to develop non-invasive imaging systems for molecular imaging applications.
We have successfully constructed a positron emission imager－PEImager in the Institute of Nuclear Energy Research (INER) for imaging small animals and plants. The PEImager can be used to monitor living objects with planar and tomographic imaging modes. For planar projection imaging acquisition mode, the average spatial resolution is 3.11 mm FWHM (full width of half maximum). There are no significant resolution differences through center to peripheral region of the image. The planar imaging can be applied to dynamic studies of small animals or plants. For collecting data using the tomographic imaging mode, the scanner can be rotated to acquire sufficient views to reconstruct a full volume images. The spatial resolution is 2.73 mm FWHM at the axis of rotation and 3.48 mm FWHM at 20 mm away from the center in tomographic imaging mode. The tomographic imaging can be used in studies, which require more spatial information in images. A planar tomography method was developed also to reconstruct projection data to obtain tomographic images without rotating detectors. The resolutions in the X or Y directions do not differ significantly between planar tomography and conventional tomography. However, The mean FWHM of planar tomography in the Z direction was 2.63 times that of conventional tomography. Locations and sizes of hot spots in a breast phantom can be estimated by using this planar tomography with consideration of efficiency of detector elements, attenuation and geometric factors. Compared with conventional focal-plane reconstruction, the images using planar tomography have better quality of contrast, and have greater tumor-detection capability.
In order to integrate multi-modality molecular imaging studies, a software approach to register animal images among microPET, microCT and microSPECT modalities was developed. The 3D registration method is automatic, simple, and object independent. It does not depend on any preparation and post-processing of data sets and requires no user intervention. The 3D registration method is successfully applied to microPET/CT, microPET/CT/SPECT fusion for phantom and animal studies. The maximum registration errors of this method were one voxel for microPET/CT fusion and microPET/SPECT fusion. Besides the software approach for image fusion, a hardware approach is processing by building integrated microPET/CT scanner in the INER. An in-house microCT was constructed to combine with a microPET R4 for this purpose. The availability of microPET/CT scanner, which provide inherent, co-registered CT images as anatomic reference for PET images, is expected to benefit both qualitative and quantitative molecular imaging studies, and to play a key role in drug discovery, development, and delivery at the pre-clinical level.

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