發(fā)布時(shí)間：2018-08-16 13:18

【摘要】：重離子束由于其倒轉(zhuǎn)的深度劑量分布(Bragg峰)特性和高的相對(duì)生物學(xué)效應(yīng),使其在殺死腫瘤細(xì)胞的同時(shí)正常組織得到有效保護(hù),被譽(yù)為二十一世紀(jì)最優(yōu)越的放療手段。在治療如頭頸部等相對(duì)位置比較固定的腫瘤靶區(qū),只要照射前對(duì)患者進(jìn)行有效的固定就能達(dá)到精確放療的目的。然而,臨床上一些腫瘤處于運(yùn)動(dòng)器官上,靶區(qū)運(yùn)動(dòng)給治療計(jì)劃的實(shí)施制造了很多困難。由于靶區(qū)處于運(yùn)動(dòng)狀態(tài),實(shí)際照射點(diǎn)和計(jì)劃照射點(diǎn)位置可能發(fā)生偏移,這樣導(dǎo)致靶區(qū)內(nèi)照射點(diǎn)相對(duì)位置發(fā)生改變,致使局部產(chǎn)生劑量熱點(diǎn)和冷點(diǎn),使劑量分布發(fā)生嚴(yán)重畸變,甚至對(duì)周圍的正常組織產(chǎn)生輻射損害,使離子束治療療效大幅下降。為了使腫瘤靶區(qū)接受高劑量照射,同時(shí)使靶區(qū)周圍的正常組織得到有效保護(hù),進(jìn)一步發(fā)揮離子束放療的優(yōu)勢(shì),本論文基于HIRFL-CSR深層治療終端和HIMM治療裝置的被動(dòng)式和主動(dòng)式束流配送系統(tǒng)開展了一系列針對(duì)運(yùn)動(dòng)腫瘤靶區(qū)的離子束適形調(diào)強(qiáng)放射治療技術(shù)研究,主要研究成果與內(nèi)容如下:(1)建立了運(yùn)動(dòng)靶體的4D-CT掃描方法、開發(fā)了一套運(yùn)動(dòng)腫瘤靶區(qū)的定位裝置并建立了CT-WEPL調(diào)正曲線�；谖鏖T子Sensation Open CT以及AZ-733V呼吸門控系統(tǒng)實(shí)現(xiàn)了運(yùn)動(dòng)腫瘤靶區(qū)的4D-CT掃描。發(fā)明設(shè)計(jì)了一種放射治療中胸腹部隨患者呼吸運(yùn)動(dòng)腫瘤靶區(qū)的定位裝置及方法。由于該裝置使患者在CT掃描,制定治療計(jì)劃以及計(jì)劃實(shí)施均在相同的坐標(biāo)系內(nèi)進(jìn)行,因此能夠確保靶區(qū)定位和放療計(jì)劃的精確實(shí)施。為了獲得腫瘤靶區(qū)的ITV(內(nèi)靶),本工作通過實(shí)驗(yàn)依托HIRFL-CSR建立了近物所自己的CT-WEPL調(diào)正曲線。(2)提出了可調(diào)控慢引出時(shí)間點(diǎn)掃描應(yīng)用于運(yùn)動(dòng)腫瘤靶區(qū)的適形照射治療方法,并通過計(jì)算機(jī)模擬驗(yàn)證了該方法的有效性。結(jié)果顯示,隨著束流慢引出時(shí)間的增加靶區(qū)內(nèi)劑量分布均勻性逐漸變好。對(duì)于可調(diào)控慢引出時(shí)間結(jié)合體多次掃描的情況,需要合理的選擇慢引出時(shí)間才能得到理想的均勻劑量分布。對(duì)于可調(diào)控慢引出時(shí)間結(jié)合層多次掃描的情況,盡管施加了10次的層多次掃描,但劑量均勻性沒有得到有效改善。對(duì)于可調(diào)控慢引出時(shí)間結(jié)合增大相鄰掃描點(diǎn)束斑重疊度的情況,采用增大束斑半高寬的方法可以有效提高靶區(qū)內(nèi)的劑量分布均勻性,而采用減小相鄰掃描點(diǎn)間距的方法并沒有起到提高靶區(qū)劑量分布均勻性的效果。(3)設(shè)計(jì)加工了一套人體呼吸模擬系統(tǒng)并基于該系統(tǒng)開展了一系列靶區(qū)運(yùn)動(dòng)補(bǔ)償實(shí)驗(yàn)。人體呼吸模擬系統(tǒng)由四部分組成:二維運(yùn)動(dòng)平臺(tái),雙楔系統(tǒng),多楔系統(tǒng)和系統(tǒng)臺(tái)架。除系統(tǒng)臺(tái)架外其它子系統(tǒng)的運(yùn)動(dòng)模式包括:函數(shù)模式、數(shù)列模式、傳感器模式、加速器外控模式以及補(bǔ)償模式�；谠撓到y(tǒng)我們開展了運(yùn)動(dòng)靶區(qū)的多次掃描實(shí)驗(yàn),增大束斑半高寬對(duì)靶區(qū)運(yùn)動(dòng)的補(bǔ)償實(shí)驗(yàn),手動(dòng)多葉光柵主動(dòng)跟蹤實(shí)驗(yàn)以及縱向運(yùn)動(dòng)補(bǔ)償實(shí)驗(yàn)。多次掃描和增大束斑半高寬有效的提高了運(yùn)動(dòng)靶區(qū)的劑量分布均勻性,但這兩種方法都會(huì)導(dǎo)致劑量半影的增大,若應(yīng)用于臨床上對(duì)周圍正常組織的輻射損害相應(yīng)也會(huì)變大。(4)在HIRFL-CSR深層治療終端建立了呼吸門控系統(tǒng)。該系統(tǒng)通過opto NCDT1700-750激光位移傳感器間接獲取靶區(qū)運(yùn)動(dòng)信息。由于從探測(cè)到靶區(qū)位置到束流照射有一個(gè)時(shí)間延遲,我們發(fā)展了一種交互式多模型的機(jī)動(dòng)目標(biāo)跟蹤算法,并將其應(yīng)用于呼吸運(yùn)動(dòng)預(yù)測(cè)。結(jié)果顯示,呼吸預(yù)測(cè)算法的引入使劑量分布均勻性得到大幅提高。對(duì)HIRFL-CSR深層治療終端建立的呼吸門控系統(tǒng)進(jìn)行實(shí)驗(yàn)測(cè)試表明,在被動(dòng)式束流配送系統(tǒng)下采用呼吸門控照射方法,劑量半影明顯減小,基本恢復(fù)到與靜態(tài)情況下相類似的劑量分布。然而,采用呼吸門控照射方式使照射時(shí)間大幅提高,有效劑量率明顯下降。(5)提出了生物視聽反饋呼吸引導(dǎo)技術(shù)并通過實(shí)驗(yàn)測(cè)試驗(yàn)證了該方法的有效性。鑒于現(xiàn)有技術(shù)在基于同步加速器脈沖式束流配送治療運(yùn)動(dòng)靶區(qū)時(shí)過程繁瑣,效率低和系統(tǒng)誤差較大的問題,我們提出了一種呼吸引導(dǎo)方法,該方法有效地將個(gè)體化視聽反饋系統(tǒng)、呼吸屏氣技術(shù)和基于同步加速器的呼吸門控技術(shù)結(jié)合起來,幫助患者將自己的呼吸周期與加速器磁激勵(lì)周期同步。通過志愿者測(cè)試發(fā)現(xiàn),在被動(dòng)式束流配送系統(tǒng)下,采用呼吸引導(dǎo)技術(shù)使照射效率提高了1.73~4.65倍,照射精度提高了10倍左右,并且該方法在分次治療間具有重復(fù)性。在主動(dòng)式束流配送系統(tǒng)下,我們對(duì)呼吸引導(dǎo)技術(shù)進(jìn)行了劑量模擬驗(yàn)證。結(jié)果顯示,采用呼吸引導(dǎo)的照射模式使劑量分布基本恢復(fù)到了與靜態(tài)情況下相類似的均勻分布。與常規(guī)自由呼吸模式下呼吸門控治療效果相比,呼吸引導(dǎo)不但提高了治療效率而且降低了門控窗內(nèi)靶區(qū)的殘余運(yùn)動(dòng),因此大幅提高了治療的療效。
[Abstract]:Heavy ion beams, due to their inverted depth dose distribution (Bragg peak) characteristics and high relative biological effects, can effectively protect normal tissues while killing tumor cells. They are considered as the best radiotherapy in the 21st century. However, in clinic, some tumors are located in moving organs. Target movement makes it difficult to implement the treatment plan. As the target is in motion, the actual and planned positions of the irradiation points may be offset, resulting in the relative position of the irradiation points in the target area. In order to protect the normal tissues around the target area and protect the normal tissues effectively, ion beam radiation therapy can be further developed. Based on the passive and active beam delivery systems of HIRFL-CSR and HIMM, a series of ion beam conformal intensity modulated radiation therapy (IMRT) techniques for moving tumor targets have been developed in this paper. The main research results and contents are as follows: (1) A 4D-CT scanning method for moving target has been developed. Based on Siemens Sensation Open CT and AZ-733V respiratory gating system, the 4D-CT scanning of the moving tumor target area was realized. A device and method for locating the moving tumor target area in the chest and abdomen with patients breathing in radiotherapy were invented and designed. In order to obtain the ITV (internal target) of tumor target area, we established the CT-WEPL correction curve of the near object through the HIRFL-CSR experiment. The results show that the uniformity of dose distribution in the target area gradually improves with the increase of the slow extraction time of the beam. For the case of multiple scans of the adjustable slow extraction time combination, a reasonable selection of slow extraction time is needed. The uniformity of dose distribution can be obtained only when the extraction time is controlled. For the case of multiple scan of the slow extraction time binding layer, the uniformity of dose is not improved effectively although 10 times of multiple scan are applied. The method of height and width can effectively improve the uniformity of dose distribution in the target area, but the method of reducing the distance between adjacent scanning points can not improve the uniformity of dose distribution in the target area. (3) A human respiratory simulation system was designed and manufactured and a series of motion compensation experiments were carried out based on the system. The system consists of four parts: two-dimensional motion platform, double-wedge system, multi-wedge system and system bench. The motion modes of other subsystems besides the system bench include: function mode, sequence mode, sensor mode, accelerator external control mode and compensation mode. Experiments of half-width compensation for target motion, manual multi-leaf grating active tracking and longitudinal motion compensation. Multiple scanning and increasing the half-width of the beam spot effectively improve the uniformity of dose distribution in the moving target area, but both methods will lead to the increase of dose penumbra. (4) A respiratory gating system was established at the HIRFL-CSR terminal. The system obtains target motion information indirectly by opto NCDT1700-750 laser displacement sensor. Since there is a time delay from the detection of target location to the beam irradiation, an interactive multi-model maneuvering target tracking system was developed. The results show that the uniformity of dose distribution is greatly improved by introducing the respiratory prediction algorithm. The experimental results of the respiratory gating control system of HIRFL-CSR deep-seated treatment terminal show that the dose penumbra is significantly reduced by using the respiratory gating irradiation method in passive beam delivery system. However, breath-gated irradiation greatly increases the irradiation time and significantly reduces the effective dose rate. (5) A bio-audiovisual feedback breath guidance technique is proposed and its effectiveness is verified by experimental tests. Pulsed beam delivery is a complex, inefficient and error-prone method for the treatment of moving targets. We propose a breathing guidance method which effectively combines the individualized audio-visual feedback system, breath holding technology and breathing gating technology based on synchrotron to help patients to adjust their breathing cycles with their own. The results of volunteer test show that the irradiation efficiency and the irradiation accuracy are increased by 1.73-4.65 times and 10 times respectively in passive beam delivery system, and the method is repeatable in the course of fractional treatment. Respiratory-guided irradiation was used to restore the dose distribution to a uniform distribution similar to that of static irradiation. Compared with conventional free-breathing ventilation, respiratory-guided irradiation not only improved the treatment efficiency, but also reduced the residual movement of target area in the door-controlled window. Therefore, the therapeutic effect has been greatly improved.
【學(xué)位授予單位】：中國(guó)科學(xué)院研究生院（近代物理研究所）
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R73-36

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