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研究生:陳永介
研究生(外文):Yung-Chieh Chen
論文名稱:丘腦前核之擴散張量磁振影像分析:巴貝茲迴路之臨床記憶功能理論在常壓性水腦疾病模式之印證
論文名稱(外文):Diffusion tensor imaging analysis of the anterior thalamic nucleus: validating the role of Papez circuit in clinical memory performance within idiopathic normal pressure hydrocephalus disease model
指導教授:吳育德
指導教授(外文):Yu-Te Wu
學位類別:博士
校院名稱:國立陽明大學
系所名稱:生物醫學影像暨放射科學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:94
中文關鍵詞:丘腦丘腦核區切割法丘腦前核磁振擴散張量影像擴散張量影像神經追蹤術約束球形反褶積巴貝茲路徑原發性常壓水腦症腦室腹膜引流管置放術神經心理評估測驗
外文關鍵詞:ThalamusThalamic nuclei segmentationAnterior thalamic nucleusDiffusion tensor imagingDiffusion tensor tractographyConstrained spherical deconvolutionPapez circuitIdiopathic normal pressure hydrocephalusVentriculoperitoneal shuntNeuropsychological assessment battery
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丘腦(Thalamus)是人類大腦位於間腦中最大的深部灰質核團結構,在神經 解剖學上是由許多具有具專一性腦區及結構連結的丘腦核區(Thalamic nuclei) 所組成的複合式結構。丘腦在大腦功能上扮演著負責調控各大腦結構間神經連結 與訊號傳遞的重要角色,而近年來許多臨床研究也發現,丘腦在多種神經與精神 性疾病的致病機轉中皆佔有一席之地。然而,現今大部分針對丘腦所進行的非侵 入式磁振擴散張量影像(Diffusion Tensor Imaging, DTI)研究皆容易受到丘腦因 各核區在解剖空間分佈以及功能上的特性而受到影響,導致研究結果失真或缺乏 可信度的狀況發生。另外,針對特定丘腦核區的功能性研究,在實際執行上也時 常缺乏一簡易、精準、實用的丘腦核區切割法來輔佐研究的進行。特此,本篇研 究設計出以擴散影像神經追蹤術(diffusion tractography)為基礎的丘腦核定位術 來簡易而準確的定位丘腦核區的丘腦前核(anterior thalamic nucleus)。丘腦前核 在巴貝茲路徑(Papez circuit)上居有樞紐的地位,這個路徑為掌管人類記憶的重 要傳遞通道,基本上由顳葉海馬迴(hippocampus)將與記憶相關之神經訊息經由 乳突核(Mammillary body)傳遞至丘腦前核,待神經訊息經丘腦前核整合調控後 再投射至帶狀迴(Cingulum),最終再轉遞回海馬迴,形成掌管記憶的神經迴圈。 本研究先嘗試使用約束球形反褶積神經追蹤術(Constrained spherical deconvolution tractography)來在健康人腦中完整重建巴貝茲路徑,並利用乳突核 丘腦帶狀迴路徑(Mammillo-thalamo-cingulate tract)來精準定位丘腦前核的位置。 接著,利用一般擴散張量影像神經追蹤術(Diffusion tensor tractography)使用相 同技巧來量測原發性常壓性水腦症(idiopathic normal pressure hydrocephalus, iNPH)患者之丘腦前核的擴散張量影像參數,如不等項擴散指標(fractional anisotropy, FA)與單純不等向擴散係數(pure anisotropy diffusivity)等,並觀察 這類患者與正常控制組間的丘腦前核擴散張量影像參數的差異,且同時比較兩組 對象的記憶表現分數以及其與擴散張量影像參數的相關性。我們的統計分析結果 顯示,有記憶方面缺損的原發性常壓水腦症病人組在接受治療前,其丘腦前核的 擴散張量參數有顯著的代償性增加。另外,有接受手術治療的病人組在術後追蹤 的數值顯示,其丘腦前核的 FA 值有恢復到正常值範圍的趨勢,而這現象與記憶 分數相關。我們認為大腦與丘腦在代償調整腦功能受損的現象可使用磁振擴散張 量影像技術來評估,而此技術也可應用於瞭解腦與丘腦間的相互調控機制以及丘 腦與其他不同疾病的病程相關性。
The human thalamus plays a pivotal role in modulating and subserving complex functions of the brain. Diffusion tensor imaging (DTI) studies of the thalamus and its role in processing functional tasks are generally limited by the topographic orientation of its various function-specific thalamic nuclei, as well as the availability of simple yet reliable methods for localizing particular thalamic nuclei-of-interest in subjects under both normal and diseased state. This dissertation aims at establishing a simple yet practical, and topographically accurate tract-deterministic nuclei identification method under DTI that is capable of effectively localizing the anterior thalamic nucleus (AN), a pivotal component within the Papez circuit for memory, and quantitatively assess its reactive changes in terms of diffusion metrics, such as fractional anisotropy (FA) and q value, among patients with early idiopathic normal pressure hydrocephalus (iNPH) presented with memory impairment both before and after surgical management, in comparison with normal control subjects. Correlation analyses between changes in diffusion metrics of AN and neuropsychologic performance in memory among patients before treatment were also performed. On the other hand, the Papez circuit within the human brain was reconstructed by constrained spherical deconvolution tractography method for the first time. The findings of this dissertation highlight the potential compensatory role of the AN within the Papez circuit in response to functional compromise during the pathogenesis of iNPH, and further support the concept that effective thalamic evaluations in various disease models can offer a more disease- specific perspective to understand the structure and function of the thalamus and its nuclei.
Table of contents
誌謝... i
中文摘要...iii
Abstract...v
Table of contents...vii
List of figures...xi
List of tables...xiii
Chapter I: Introduction ...1
1.1 General background...1
1.2 The human thalamus and thalamic nuclei segmentation...3
1.2.1 The structure and function of the thalamus...3
1.2.2 Modern trends and concerns in studies of the thalamus with diffusion tensor imaging...5
1.2.3 Methods for thalamic nuclei segmentation, the past and present...7
1.3 Motivation and purpose of study...10
1.3.1 Limitations of connectivity-based thalamic nuclei segmentation...10
1.3.2 Trends and limitations of prior research in idiopathic normal pressure hydrocephalus with diffusion tensor imaging...11
1.3.3 Recommendations from prior research...13
1.3.4 Study hypothesis and strategies for solving problems...14
1.4 Outline...15
Chapter II: Methods of diffusion imaging and constrained spherical deconvolution tractography of the Papez circuit...17
2.1 Overview...17
2.2 Diffusion imaging and constrained spherical deconvolution tractography...17
2.3 Visualization of the Papez circuit with constrained spherical deconvolution tractography...19
2.3.1 Introduction...19
2.3.2 Materials and methods...21
2.3.2.1 Study participant and image acquisition...21
2.3.2.2 Image processing and data analysis...22
2.3.2.3 Procedures of regions-of-interest placement and tractography...23
2.3.3 Results...24
Chapter III: Assessment of the anterior thalamic nuclei by tract-deterministic nuclei identification method in early idiopathic normal pressure hydrocephalus patients with neuropsychologic impairments in memory via diffusion tensor imaging...26
3.1 Overview...26
3.2 Introduction to idiopathic normal pressure hydrocephalus and the involvement of the Papez circuit...26
3.3 Functional and clinical significance of the anterior thalamic nucleus...29
3.4 Purpose of study...31
3.5 Materials and methods...31
3.5.1 Study participants...31
3.5.2 Image acquisition...33
3.5.3 Neuropsychologic assessment battery...34
3.5.4 Image Processing and Data Analysis...35
3.5.5 Procedures of the tract-deterministic nuclei identification method for the localization of anterior thalamic nucleus...35
3.5.6 Statistical Analysis...36
3.6 Results...38
3.6.1 Cross-group comparisons of diffusion metrics within AN between normal control and iNPH patient groups across all time points...38
3.6.2 Cross-group comparisons of neuropsychologic test scores between normal control and iNPH patient groups across all time points...39
3.6.3 Correlation analyses between diffusion metrics of AN and neuropsychologic test scores within iNPH patient group at baseline only...39
3.6.4 Correlation analyses between diffusion metrics of AN and neuropsychologic test scores within iNPH patients from every group...40
Chapter IV: Discussion and conclusion...41
4.1 Reconstruction of the Papez circuit via streamline constrained spherical deconvolution tractography...41
4.2 Localization of the anterior thalamic nucleus via tract-deterministic nuclei identification method...42
4.3 Changes in diffusion metrics of AN in patients with early idiopathic normal pressure hydrocephalus both before and throughout the treatment process...43
4.4 Differences in neuropsychologic test scores on memory between normal control and patients with early idiopathic normal pressure hydrocephalus both before and
throughout the treatment process...45
4.5 Correlation analyses between diffusion metrics of AN and neuropsychologic test scores among patients with idiopathic normal pressure hydrocephalus...46
4.6 Implications for the role of AN in the disease process of iNPH...48
4.7 Limitations...50
4.8 Conclusion...51
4.9 Future work...52
References...54
Figures...77
Tables...90
個人履歷...92

List of Figures
Figure 1. The reconstructed cingulum...77
Figure 2. ROI of superior cingulum...78
Figure 3. ROIs of the anterior and descending cingulum...78
Figure 4. The reconstructed fornix...79
Figure 5. ROI of the commissure of the fornix...80
Figure 6. ROI of the fimbria of hippocampus...80
Figure 7. The reconstructed mammillo-thalamo-cingulate pathway...81
Figure 8. ROIs of the mammillary bodies...82
Figure 9. ROIs of the anterior thalamic radiation...82
Figure 10. The reconstructed Papez circuit...83
Figure 11. The locations of the anterior thalamic nuclei...84
Figure 12. Track-based delineation of the AN in normal control subjects and iNPH patients via DTI, demonstrated on the axial and sagittal planes. In normal control subjects, the two deterministic seeds were placed in the mammillary body (A) and the anterior thalamic radiation (B). With this approach, the regions of AN (C) were identified via tracking the mammillo-thalamo-cingulate connections within the Papez circuit (D). The same process was repeated in iNPH patients, yielding highly consistent results on tractography (E)...85
Figure 13. Evolution of diffusion tensor metrics of AN in iNPH patient, as compared to normal control, at different time points, including (A) FA, (B) q value, (C) axial diffusivity, and (D) radial diffusivity. P denotes statistical significances between control group and patient groups at each time points. Error bars indicate standard deviation...86
Figure 14. Ranked correlation scatterplot of FA and neuropsychological test scores including data from both patient and control groups. Note the discrete visual separations between the two groups of data. White and black dots represent data from control and early iNPH patients, respectively...87
Figure 15. Ranked correlation scatterplot of q value and neuropsychological test scores including data from both patient and control groups. Note the discrete visual separations between the two groups of data. White and black dots represent data from control and early iNPH patients, respectively...87
Figure 16. Result of Spearman partial rank-order correlation analyses between FA of iNPH patients and scores of verbal and non-verbal memory tests, including verbal immediate recall (A), p=0.03; verbal delayed recall, (B), p=0.003; verbal recognition memory (C), P=0.012; non-verbal immediate recall (D), p=0.012; non-verbal delayed recall (E), p=0.031; and non-verbal recognition memory (F), p=0.16....88
Figure 17. Result of Spearman partial rank-order correlation analyses between q value of iNPH patients and scores of verbal and non-verbal memory tests, including verbal immediate recall (A), p=0.03; verbal delayed recall, (B), p=0.003; verbal recognition memory (C), P=0.012; non-verbal immediate recall (D), p=0.012; non-verbal delayed recall (E), p=0.031; and non-verbal recognition memory (F), p=0.16....89

List of Tables
Table 1: Demographic Features and Clinical Information of Idiopathic Normal Pressure Hydrocephalus Patients and Control...90
Table 2: Neuropsychologic test performances among control subjects and iNPH patients from Baseline to post-operative follow-up...90
Table 3: Comparison of tractography and AN delineation results between CSD and conventional DTI techniques...91
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