以擴散磁振造影評估加馬刀治療後腦膜瘤及轉移性腦瘤的反應

Diffusion Magnetic Resonance Imaging in the Evaluation of the Response of Meningioma and Metastatic Brain Tumor Treated by Gamma Knife Radiosurgery

黃全福(Chuan-Fu Huang)

指導教授 ： 林隆堯

中山醫學大學/醫學院/醫學研究所/博士(2009年)

https://doi.org/10.6834/CSMU.2009.00005

摘要

背景：
立體定位放射手術治療後的效果，通常經由一系列磁振造影(MRI)檢查測量治療前後體積大小的改變來評估。但其成功的治療可能造成腫瘤壞死卻未必會造成體積的變小，但這種細胞數量的減少卻造成細胞間空間的變大，導致表現擴散係數（ADC）上升，使水分子運動速度增加。本研究假設表現擴散係數的變化可用來評估腦瘤（腦膜瘤及轉移性腦瘤）於加馬刀手術治療後的變化且ADC變化先於腫瘤體積變化。
材料與方法：
2004年1月至2005年12月，6位顱內腦膜瘤及21位轉移性腦瘤病人共32個轉移性腦瘤接受加馬刀立體定位手術。病人於術前、術後接受一系列擴散核磁共振影像檢查，同時每隔3個月接受完整的磁振造影檢查檢測腫瘤體積變化，二群病人在治療前後不同的時間點以統計等方法比較ADC變化的差異。
結果：
腦膜瘤平均的表現擴散係數為0.6±0.07×10-3 mm2/s，ADC值在治療後4小時至4天呈現有顯著的下降，後再上升與治療前平均值沒有差異，但一個月後開始呈現有意義上升至於2年的追蹤期。其中6個治療病人有3例於一般磁振造影檢查呈現腫瘤變小。
轉移性腦瘤ADC術前1.05±0.12×10-3 mm2/s，術後第7天起ADC與術前比較開始呈顯著上升（P值0.009）的趨勢，顯影劑造影檢查以腫瘤體積變小或不變為成功治療者有91%。ADC於治療後呈囊狀或明顯壞死組為2.13±0.18×10-3 mm2/s，顯著高於無中央壞死腫瘤組（1.61±0.14×10-3 mm2/s）。
討論：
放射手術不像開顱手術，沒有將腫瘤取出，而是將放射線集中於腫瘤本身，一定給予較大的劑量。效果已獲肯定，文獻上腦膜瘤治療成功率為90%以上，但仍有相當比率（31至62%）的腫瘤於最後追蹤結果體積沒有變化，這群病人雖然大小沒有改變，但腫瘤細胞的數量可能會有變化，因此病理學觀點細胞可能是不同的。
腦膜瘤的ADC比一般腦實質稍低可能是源自於腫瘤本身較高的細胞核、細胞質比（nuclear-to cytoplasmic ratio）使細胞外空間相對受到壓縮。當加馬刀治療後，ADC早期較低可能是急性放射線效應使細胞更為腫脹，細胞外空間更小所致，這種效應於腦梗塞早期所測ADC下降是一致的。一個月後ADC上升則是由於細胞外的空間因腫瘤細胞凋零(apoptosis)或壞死而變大。造成這種變化的機轉仍不明，但是有一種解釋為急性放射手術造成細胞急性傷害使鈉－鉀離子幫浦（Na+-K+ pump）受損致能源缺乏，無法維持細胞內外滲透壓平衡，水分子大量進入細胞內,致使細胞腫脹細胞外空間變小ADC降低，後來ADC上升則是由於腫瘤細胞壞死細胞膜崩解或血管性水腫發炎使細胞外水分增加，事實上在一些壞死性或囊狀病灶所測的ADC也較高（1.5-2.5×10-3 mm2/s）。轉移性腦瘤ADC也於治療一個月後上升且明顯中央壞死病灶尤其明顯著。
擴散磁振造影曾被用於測量腫瘤生長，分辨腫瘤類別或良惡性度。DWI的信號強度及ADC可用於分辨不同腫瘤及偵測治療後的變化。化療放射治療、放射手術或基因療法皆會改變腫瘤構造。有些報告顯示治療後造成細胞毒殺反應使ADC上升，而ADC上升先於腫瘤體積變化也出現於一些文獻上，我們的研究顯示類似的結果。
ADC於治療後由於細胞數減少而上升，動物實驗甚至快至一週即可見到變化，反之當腫瘤再復發生長則可見到ADC恢復到治療前的數值，在我們的研究中腦膜瘤有一例治療失敗的病例，及新生腫瘤ADC都停留在治療前的平均值，轉移性腫瘤也有一例再復發的病例。但對於放射性壞死腫瘤MRI也可見顯影病灶（類似再復發病灶），但ADC卻明顯上升，可見ADC可用於鑑別兩者，也可用於預測腫瘤再復發。
此研究總結，ADC可用於預測治療反應及結果，對於分辨再復發或放射性壞死也有幫助。

關鍵字

轉移性腦瘤 ； 擴散加權影像 ； 放射手術 ； 腦膜瘤 ； 磁振造影

並列摘要

Background: Patients usually receive serial magnetic resonance imaging (MRI) examinations to assess stereotactic radiosurgery (SRS) effects by volume change. But loss of tumor cell after radiosurgical treatment results in a relative increase in extracellular space and may lead to alteration of apparent diffusion constant (ADC). Our hypothesis is to investigate if the ADC can be used, rather than with methods depending on changes in tumor size, to predict treatment success after treatment of meningioma and brain metastases with SRS.
Methods: We conducted a prospective trial involving 6 patients with intracranial meningiomas and 21 patients with 32 solid or solid-dominated lesions treated by SRS with 201-source cobalt in our Gamma Knife center. Patients received complete diffusion MRI before treatment and at multiple intervals following SRS. We followed up MRI findings and clinical outcomes at 3 months, and thereafter in 3-month intervals. We detected the long-term results of diffusion MRI in 7 patients treated for at least 5 years. We calculated apparent diffusion coefficients (ADC) from echoplanar diffusion weighted imaging, and compared mean ADC values.
Mean ADC values at the various time intervals were compared with each other to see whether or not the ADC might be used as an early indicator of treatment success or failure.
Results: The ADC for meningioma was 0.55-0.64 x 10-3 mm2/s (mean ± SD). We observed 2 ADC phase changes after SRS: a significant (p < 0.05) reduction phase beginning at 4 hours and lasting 4 days after SRS followed by an elevation phase to pseudonormalized values. ADC significantly increased 30 days after SRS, reaching a plateau in 3 months. MRI follow-up at 3-month intervals showed stable tumor size in all patients, with 3 patients revealing evidence of tumor necrosis. The ADC value for the long-term group was 1.26 x 10-3 mm2/s. (p < 0.05); however, MRI follow-up showed tumor shrinkage in 3 patients.
The mean pre-treatment value of the ADC in the metastatic tumors was 1.05 ± 0.12 x10-3 mm2/s. This value for the tumors rose significantly (P=0.009) seven days after SRS and continued to rise with time. Magnetic resonance imaging (MRI) showed that 91% of these tumors had been controlled by the SRS. ADC values in cystic/necrotic tumor tissue (2.13 ± 0.18 x 10-3 mm2/s) were significantly (P<0.001) higher than in non-central necrotic tumor tissue (1.61 ± 0.14 x 10-3 mm2/s).
Conclusion: Gamma knife treatment is efficacious for meningioma and metastatic brain tumors. Serial changes in ADC values might eventually be useful to evaluate treatment success and in some patients even detected at early time points, and to distinguish radiation-induced central necrosis from tumor re-growth in cases where other imagery is not definitive.

並列關鍵字

brain metastasis ； diffusion-weighted imaging ； magnetic resonance imaging ； radiosurgery ； meningioma

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