VX2腫瘤擴散加權及顯影增強動態磁振造影之探討

Investigation of Diffusion-Weighted and Contrast-Enhanced Dynamic MRI on VX2 tumor

呂心瀅(Hsin-Ying Lu)

指導教授 ： 饒若琪

高雄醫學大學/健康科學院/醫學影像暨放射科學系碩士班/碩士(2010年)

摘要

中文摘要
目的
根據國人十大死因調查結果發現，從1982年開始，惡性腫瘤一直位居於第一位。有鑑於此，藉由影像科學來了解關於腫瘤發展的過程，對於醫學診斷上相信可以提供一定程度的幫助。VX2 腫瘤為目前國內外許多文獻中所使用的動物模型，而本篇研究是以兔子腿部之 VX2 腫瘤為模型，第一部份為探討腫瘤與正常組織表現擴散係數 ( apparent diffusion coefficient，ADC ) 的差異；第二部分為比較注射 Gd-DTPA 顯影劑前後表現擴散係數的差異；第三部份為探討注射 Gd-DTPA 和 Gd-BOPTA 顯影劑在腫瘤的顯影情形，並比較兩者差異。期待可以藉由本研究了解腫瘤的發展情形，提供給他人參考。
材料與方法
本研究所用的磁振造影掃描儀為臨床用1.5T全身掃描儀，所用的線圈為膝線圈，並使用GE公司的 Advantage Window 影像處理工作站進行影像的分析。
主要分成三個部份來探討，第一個實驗的部分，將7隻接種 VX2 腫瘤的兔子，於三方向定位掃描後，藉由擴散加權影像 ( Diffusion Weighted Imaging，DWI ) 波序掃描後，將取得的 VX2 腫瘤影像進行分析及統計，觀測腫瘤與肌肉表現擴散係數的差異。
第二個實驗的部分，將7隻接種 VX2 腫瘤的兔子，於三方向定位掃描後，藉由擴散加權影像波序掃描後，再使用梯度回訊 ( gradient echo，GRE ) 波序進行掃描。先取得注射 Gd-DTPA 顯影劑前的 T1 加權磁振影像，再經由耳靜脈注射 Gd-DTPA，注射後連續掃描3分鐘，接者每分鐘掃描一次，直到注射 Gd-DTPA 後30分鐘為止。最後，再做一次擴散加權影像掃描。然後將取得注射 Gd-DTPA 顯影劑前後的 VX2 腫瘤擴散加權影像進行分析及統計，觀測注射顯影劑前後是否有差異。
第三個實驗的部分，將8隻接種 VX2 腫瘤的兔子分成兩組，每組 4 隻。 Group 1 注射 Gd-BOPTA，Group 2 則注射 Gd-DTPA 。於三方向定位掃描後，使用 GRE 波序進行掃描。先取得注射顯影劑前的 T1 加權磁振影像後，再經由耳靜脈注射 Gd-BOPTA 或 Gd-DTPA 顯影劑，注射後連續掃描3分鐘，接著每分鐘掃描一次直到注射顯影劑後30分鐘為止。最後，將取得的 VX2 腫瘤動態影像進行分析及統計，觀測腫瘤與肌肉顯影增強情形，並比較注射兩種顯影劑的差異。
結果
第一部份的實驗結果顯示，在擴散加權影像中，VX2 腫瘤細胞擴散現象較明顯，所以在影像上有較亮的表現。再利用 Microsoft Excel 軟體計算出腫瘤和正常組織的 ADC 值，且使用成對 t-test 作統計分析，得到的p值小於0.05，顯示正常組織與 VX2 腫瘤在訊號上有顯著差異。
第二部分的實驗結果顯示，在擴散加權影像中，注射 Gd-DTPA 顯影劑前後 VX2 腫瘤的 ADC 值並沒有差異。使用成對 t-test 作統計分析，結果顯示p值大於0.05，故並無顯著差異。
第三部分的實驗結果顯示，在動態磁振造影中，注射 Gd-BOPTA 後的腫瘤影像訊號上升比注射 Gd-DTPA 後的腫瘤影像訊號上升明顯較多且持續較亮的顯影。兩相比較之下，使用成對 t-test 作統計分析，p值小於0.05，顯示相同劑量的兩種顯影劑是有顯著的差異。同時，個別比較注射 Gd-DTPA 或 Gd-BOPTA 顯影劑後在腫瘤、壞死以及正常組織三者之間是否有顯著差異的結果顯示，注射 Gd-DTPA 或 Gd-BOPTA 後，腫瘤快速顯影增強，正常組織有些許增強，而壞死區域幾乎是沒有改變。使用 ANOVA 進行分析，結果顯示 VX2 腫瘤、壞死區塊以及正常組織三者之間是有顯著差異。
結論
理論上，擴散加權影像可以顯示水分子的運動以及細胞的完整性，因此能夠深入觀察腫瘤的顯微結構，對於評估腫瘤反應有相當大的參考價值。在此 VX2 腫瘤兔子實驗中，也得到正常組織與 VX2 腫瘤在訊號上有顯著差異，且腫瘤的 ADC 值高於正常組織的 ADC 值，有助於腫瘤的評估。而且注射 Gd-DTPA 顯影劑後也不會影響擴散加權影像的判讀。
利用靜脈注射顯影劑來取得動態顯影影像分佈的方式已普遍使用在臨床醫學上。在利用磁振造影掃描的同時，藉由 Gd-DTPA 或 Gd-BOPTA 顯影劑的注射，我們可以預期腫瘤部位會因為血管的增生而導致訊號增強。在實驗結果發現 Gd-BOPTA 的顯影增強效果在同濃度下顯著優於 Gd-DTPA。因此，Gd-BOPTA 的注射濃度可以減少，使用低濃度顯影劑之效益除可節省成本，亦可降低顯影劑之毒性。

關鍵字

VX2腫瘤 ； 擴散加權磁振造影 ； 動態磁振造影

並列摘要

Abstract
PURPOSE
Since 1982, cancer is the most mortal disease in Taiwan. Therefore, understanding more about the process of tumor development is believed to be helpful for clinical diagnosis. VX2 tumor model is a widely used animal model and was used in this study. This research contains three parts: first, investigation of MR ADC ( apparent diffusion coefficient ) between VX2 tumor and normal tissue; second, comparison between pre-contrast and post-contrast ADC values of VX2 tumor; third, investigation of signal enhancement for VX2 tumor by using Gd-DTPA and Gd-BOPTA contrast agents.
MATERIALS AND METHODS
The MR scanner used in this study was clinical 1.5T whole body scanner equipped with a knee coil. Advantage window workstation was used for image analysis.
This research included three parts. First, seven rabbits with VX2 tumor were scanned using diffusion-weighted pulse sequence. To compare the VX2 tumor and normal muscle, both VX2 tumor and normal muscle images were obtained for ADC calculation.
Second, seven rabbits with VX2 tumor were scanned to obtain diffusion-weighted images. Then, a pre-contrast T1-weighted image was obtained with a gradient echo ( GRE ) pulse sequence before contrast agent, Gd-DTPA, injection. After injecting Gd-DTPA via the rabbit’s ear vein, scan was performed continuously for 3 minutes and then once a minute until 30 minutes. Afterwards, scan was performed with diffusion-weighted pulse sequence again. Pre-contrast and post-contrast diffusion-weighted images were obtained for image analysis to evaluate whether there was significant difference between pre-contrast and post-contrast ADC values.
Third, eight rabbits with VX2 tumor were divided into two groups. Each group had four rabbits. Group 1 was injected with Gd-BOPTA and group 2 was injected with Gd-DTPA. After 3-plane localizer scan was performed, a pre-contrast T1-weighted image using GRE pulse sequence was obtained before contrast agent injection. After injecting Gd-BOPTA or Gd-DTPA via the rabbit’s ear vein, scan was performed continuously for 3 minutes and then once a minute until 30 minutes. The dynamic images of VX2 tumor were analyzed to evaluate the signal enhancement of tumor and muscle for both contrast agents.
RESULTS
The first part of this study showed that ADC value of VX2 tumor was higher than that of normal tissue. There was significant difference between VX2 tumor and normal tissue ( p < 0.05 ).
The second part of this study showed that there was no significant difference between pre-contrast and post-contrast ADC value of VX2 tumor ( p > 0.05 ).
The third part of this study showed that the tumor signal intensity after injecting 0.1 mmol/kg Gd-BOPTA was increased more than that of injecting 0.1 mmol/kg Gd-DTPA in the dynamic MRI. There was significant difference between signal enhancement after injecting both contrast agents ( p < 0.05 ). It was also found that the MR signal of tumor was increased rapidly after injecting both contrast agents. On the contrary, normal tissue was enhanced a little, and the enhancement ratio of necrotic area was almost equal to 1. The result of statistical analysis by using ANOVA showed that the enhancement ratios had significant differences between these three kinds of tissues.
CONCLUSION
Theoretically, the diffusion-weighted imaging is capable of showing the movement of water molecular and the integrity of cells. Therefore, it can be used to investigate the microstructure of tumor. In this study, we found that there was significant difference between ADC values of normal tissue and VX2 tumor. The ADC value of tumor is higher than that of normal tissue, which is helpful for tumor evaluation.
Dynamic contrast-enhanced imaging has been widely used in clinical diagnosis. After injection of Gd-DTPA or Gd-BOPTA, it is expected that tumor has positive signal enhancement because of vascular proliferation. It was also found that the signal enhancement after Gd-BOPTA injection was obviously superior to that of Gd-DTPA injection with the same injection dosage ( 0.1 mmol/kg ). Therefore, the dosage of Gd-BOPTA can be reduced. The benefits of using lower dosage contrast agents will be reduction of both cost and toxicity.

並列關鍵字

VX2 tumor ； Diffusion-Weighted MRI ； Dynamic MRI

參考文獻

參考文獻

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