放射治療以CT影像或MR影像轉為偽CT影像進行治療計劃製作，依據影像衰減資訊進行劑量計算。然而，BNCT治療計劃針對感興趣區域的組織材料多使用均質材料組成，此方式有失於模擬組織非均勻性。中子捕獲治療劑量主要貢獻源自於硼載體空間分佈與中子空間分佈的乘積，而硼載體的自屏蔽效應影響中子空間分佈。多數治療計劃系統假設硼濃度於腫瘤內分佈均勻，即為均質硼分佈。然而，使用假設TBR或透過標記放射核素硼載體之PET影像獲得平均TBR，皆有失於描述硼分佈的不均勻性。組織元素材料與硼載體分佈描述的失真，即使在高可信度的蒙地卡羅計算下，劑量結果與評估仍有失真的疑慮。因此，有依據的透過醫學影像模擬組織和硼載體的不均勻性，可提升劑量結果與治療反應關聯性，使劑量結果具有高可信度的評估價值。並且，當BNCT與其他放射治療方式合併使用時，可準確地順形和均勻腫瘤處方劑量以提升腫瘤控制率。
本研究透過文獻之CT影像HU值對應組織密度關係建立96組HU值範圍相對應組織元素組成與密度的通用材料庫，並進行腦瘤與頭頸癌案例劑量計算與分析。組織元素材料組成會影響中子遷移的過程，導致均質材料與異質材料的劑量計算結果與分佈有差異。由於正常組織最大劑量之背景劑量占總生物有效劑量約40%~60%，因此，元素組成對劑量的影響於正常組織更顯著於腫瘤組織。然而，組織考量其非均勻性的平均密度應與ICRU-46報告的參考數據相近，且通用材料庫無法有效區別HU範圍重疊的組織。因此，建立針對特定組織建立材料庫並進行劑量探討。針對受限於影像空間解析度而無法清楚辨識完整輪廓的組織給予均質材料模擬以保守評估OAR劑量，即ROI之HU值呈現與該組織不吻合，如皮膚、口腔黏膜、中樞神經等等。針對HU值體現密度不均勻的ROI，依特定組織元素組成建立材料庫，如腦組織材料庫可對應於白質、灰質、腦脊液等元素比例與密度變化，而腦瘤材料庫考量有鈣化的可能性而擴展HU值對應元素組成與密度範圍。針對指定ROI給予單一均質材料或多種異質材料，可兼顧保守劑量評估和組織結構變化，使中子治療的劑量計算評估有更高的可信度。
本研究利用目前診斷技術獲得相對硼載體分佈信息的PET影像，依其原理進行非均勻硼分佈模擬。透過影像融合技術，將對位融合後的功能影像之硼分佈信息於治療計畫製作的解剖影像上讀取並進行量化，以建立異質硼分佈蒙地卡羅運算模型。考量使用ROI異質材料組成搭配異質硼分佈後的計算材料數量過多，且過於細緻的硼濃度分佈變化於劑量變化不顯著。因此，利用群化硼濃度分佈以模擬其非均勻性。在確保群化前後之ROI內總硼原子數一致的情況下，採用均質或異質硼分佈劑量計算之中子總通量於理論上為相等，因此，ROI平均劑量於二者模型亦是相近。然而，解剖影像和功能影像體素尺寸差異產生的部分體積效應，使平均劑量計算結果與理論值有所差異，且當ROI越小，則部分體積效應越顯著。異質硼分佈劑量計算方式可應用於危及器官與腫瘤以正確評估劑量熱區與冷區，有利於治療計畫優化與評估可信度。該技術的應用使中子通量運算符合個案狀況的正確變化，針對高攝取硼載體之危及器官有安全評估接受劑量以降低輻射損傷；針對低攝取腫瘤劑量冷區，則需透過其他放射治療補足處方劑量以加強腫瘤控制率。儘管可使用功能影像獲得硼載體分佈進行異質硼分佈劑量計算以有效提升劑量冷點的評估準確性。然而，獲取該影像數據的設備和時間點可能會影響劑量結果的評估性，且沒有標準影像對位配準規範而存在不可避免的人為誤差。
在有限的中子有效治療深度下使用多照野技術可分散正常組織最大劑量，並有效提升深部腫瘤最小劑量和劑量均勻度以提升BNCT治療效益。然而，多照野技術應用於腦瘤治療容易受正常腦組織耐受平均劑量的限制。中子治療搭配重水置換技術，相比於氫元素，氘元素有較強的氫鍵作用力且中子作用截面小，可增加中子於體內穿透深度、有效降低表淺組織劑量與二次光子的生成。針對中線腦瘤，在正常腦組織耐受平均劑量的條件下，重水置換技術允許較長的照射時間而提升腫瘤接受劑量。然而，若腫瘤位於表淺或具有鈣化表現，則重水置換技術可能對腫瘤劑量的提升適得其反或效果不彰。低濃度重水取代生物分子的氫元素並不產生毒素，卻無法針對局部或特定組織器官進行氘化。

In conventional radiotherapy, the treatment plan uses CT images or pseudo-CT images, which are converted from MR images, and dose calculation is performed based on attenuation information. However, BNCT treatment plans mostly use homogeneous materials intraROI, which fails to simulate tissue heterogeneity. The main dose contribution of BNCT comes from the product of the spatial distribution of boron carrier and the spatial distribution of neutrons, which is affected by the self-shielding effect of the boron carrier. Most TPSs assume that boron concentration is uniformly distributed within the tumor, i.e., homogeneous boron distribution. However, using hypothetical TBR or average TBR obtained through PET images of labeled radionuclide boron carriers fails to describe the inhomogeneity of boron distribution. Even under high-confidence Monte Carlo calculations, there are still doubts about the evaluation of dose calculation results due to distortion in the distribution simulation of tissue elemental compositions and boron carriers. Therefore, a well-founded simulation of the heterogeneity of tissues and boron carriers through medical imaging can improve the correlation between dose results and treatment response, making the dose results have a high-reliability assessment. When BNCT combined with other radiotherapies, it can accurately conform and uniformly dose the tumor to improve tumor control probability.
This research conducts dose analysis on brain tumor and head-and-neck cancer cases with general material library which 96-group of tissue elemental compositions and densities corresponding to HU value ranges were established based on the relationship between HU values of CT images and tissue densities in the literature. The elemental compositions affect the neutron transport process, resulting in differences in dose distribution between homogeneous and heterogeneous materials of intraROI. Since the background dose of the maximum normal tissue dose accounts for approximately 40%~60% of the total biologically equivalent dose, the impact of elemental composition on dose is more significant in normal tissue than in tumor. However, the average density of tissue considering its non-uniformity should be close to the reference data of ICRU-46, and the general material library cannot effectively distinguish tissues with overlapping HU ranges. Therefore, this study established tissue-specific material library for ROI and conducted dose analysis. For ROIs cannot clearly identify the complete contour due to the limitation of spatial resolution, that is, the HU values of the ROI do not match the tissue feature, homogeneous material is used to conservatively evaluate the OAR dose such as skin, mucosa, cranial nerves, etc. For ROIs where HU values reflect uneven density, a material library is established based on the elemental composition of specific tissue. For example, the brain material library can correspond to the proportion and density changes of elements such as white matter, gray matter, and cerebrospinal fluid. Expanding the brain tumor database to consider the possibility of calcification. Homogeneous or heterogeneous materials are given to the designated ROI to take into account conservative dose assessment and tissue characteristics, making the dose calculation and evaluation of neutron therapy more reliable.
This study utilizes existing diagnostic techniques to obtain relative boron carrier distribution information and simulate the non-uniform boron distribution. Image fusion technique is used to align different imaging modalities, the boron distribution of functional images is read and quantified on the anatomical images used in the treatment plan, and a Monte Carlo calculation model of heterogeneous boron distribution is established. Considering that the large amounts of material numbers for MC calculation using intraROI heterogeneous material composition and boron concentration, and the subtle boron concentration does not change significantly in dose. Therefore, groupwise boron concentration distribution is used to simulate its inhomogeneity. Under the condition of ensuring that the total number of boron atoms intraROI before and after grouping is consistent, since the theoretically calculated total neutron fluence is equal, the ROI mean dose will be the same regardless of homogeneous or heterogeneous boron distribution model. However, the partial volume effect caused by the difference in voxel size between anatomical and functional images makes the calculated mean dose results somewhat different, and as the ROI is smaller, the partial volume effect becomes more significant. The heterogeneous boron distribution dose calculation method can be applied to OARs and tumors to correctly evaluate dose hot spot and cold spot, which is beneficial to treatment plan optimization and assessment reliability. The application of this technique allows the neutron fluence calculation to have correct changes in line with individual conditions. For OARs with high boron uptake, the dose can be safely assessed to reduce radiation damage. For cold spot of tumor with low uptake, it is necessary to supplement the prescribed dose through other radiotherapies to enhance the tumor control prabability. Although functional imaging can be used to obtain the boron distribution for heterogeneous boron dose calculation and effectively improve the assessment accuracy of dose cold spots, the equipment and time at which the image data is acquired may affect the evaluability of dose results, and there are inevitable human errors without standard image fusion technique.
Using multi-field technique under the limited advantage depth of neutron therapy can disperse the maximum normal tissue dose and effectively improve the minimum dose and dose uniformity of deep-seated tumors. However, the application in brain tumor treatment is easily limited by the tolerance of the mean brain dose. Compared with hydrogen, deuterium has stronger hydrogen bond and smaller neutron cross-section, which can increase the neutron penetration depth in the body and effectively reduce the superficial tissue dose and induced photon. For midline brain tumors, under the condition that normal brain tissue can tolerate the mean dose, D2O replacement allows longer irradiation time and increases the dose received by the tumor. However, if the tumor is superficial or has calcification, the D2O replacement may be counterproductive or ineffective in increasing tumor dose. Low-concentration heavy water replaces the hydrogen of biomolecules without producing toxins, but it cannot deuterate local or specific tissues and organs.

摘要 i
Abstract iii
Tables of Contents vi
List of Tables viii
List of Figures xii
Chapter 1 Introduction and Research Motivation 1
Chapter 2 Literature Review 4
2-1 BNCT principle 4
2-2 BNCT dosimetry 5
2-4 BNCT treatment technology 11
2-4-1 Deuterium oxide replacement research 11
2-4-2 BNCT clinical trials 13
Chapter 3 Deconstruction of Tissue Materials for Improved Dose Assessment 17
3-1 Deconstruction of proportions of tissue elements in anatomical images 17
3-2 Effects of material deconstruction on dose distribution 20
3-2-1 Establishment of MC model for GM case 20
3-2-2 Effect of GM case materials on biologically equivalent dose 22
3-2-3 Effect of GM case materials on physically absorbed dose 26
3-2-4 Establishment of MC model for HNC case 29
3-2-5 Effect of HNC case materials on biologically equivalent dose 31
3-2-6 Effect of HNC case materials on physically absorbed dose 34
3-2-7 Summary 36
3-3 Refined deconstruction for ROI 38
3-3-1 Homogeneous material in ROI 39
3-3-2 Heterogeneous material in ROI 41
3-4 Effects of refined deconstruction on dose distribution 44
3-4-1 Dose effect of refined MC model for GM case 44
3-4-2 Dose effect of refined MC model for HNC case 47
3-4-3 Summary 51
Chapter 4: Quantification of Boron Distribution in ROI for Refinement of Dose Assessment 52
4-1 Quantification of boron carrier information in functional imaging 52
4-1-1 Groupwise heterogeneous boron distribution 54
4-2 Heterogeneous boron distribution dose distribution performance 57
4-2-1 Dose effect of boron distribution of Case 1 58
4-2-2 Dose effect of boron distribution of Case 2 62
4-2-3 Dose effect of boron distribution of Case 3 67
4-2-4 Summary 71
4-3 Segmentation of heterogeneous boron distribution 72
4-3-1 Dose effects on segmentation of boron distribution in OAR 72
4-3-2 Dose effects on segmentation of boron distribution in GTV 77
4-3-3 Boron distribution quantification to define BNCT target 79
4-3-4 Summary 82
Chapter 5 Improvement of Treatment Benefit by Deuterium Oxide Replacement 83
5-1 Clinical practical cases 83
5-2 Monte Carlo simulation conditions 86
5-3 Therapeutic benefits of D2O replacement 87
5-3-1 Case 1: Brainstem tumor in the mid-brain 87
5-3-2 Case 2: Hemilateral deep-seated GBM 95
5-3-3 Case 3: Calcified deep-seated GBM 104
5-4 Summary 108
Chapter 6 Conclusions and Future Work 110
6-1 Conclusions 110
6-2 Future work and suggestions 113
References 115
Appendix A 121
Appendix B 125

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