Diffusion tensor imaging of cerebral white matters in children younger than 16 years of age

研究計畫之背景 兒童的腦部白質在不同年齡層不同的區域髓鞘化的程度各有不同，尤其在一歲半以 前，腦部各區域的髓鞘化相當活躍。由晚近的幼鼠腦組織研究則顯示出擴散張度影像應用 在白質髓鞘化相關疾病的潛力。然而，不同年齡層兒童尤其是三歲以下兒童的第一、第二、 第三eigen 值以及部份非等向係數(fractional anisotropy)正常值在文獻上不易查到；各種張 量係數在不同年齡層的變化在文獻上亦少有參考資料。 研究計畫之目的與重要性 本研究目的在於以擴散張度影像評估不同年齡層的大腦白質通路的第一、第二、第三eigen 值以及部份非等向係數(fractional anisotropy)的變化，作為應用磁振張度影像於腦部白質疾 病診斷的基礎。 研究方法與原因 預計包括一百位十六歲以下兒童，因為非因局部神經症狀、全身性代謝、腫瘤或感染 症而接受頭部磁振掃描且在傳統FLAIR, T1, T2影像無可見訊號變化者；在取得家屬同意之 下，接受磁振擴散張度影像掃描檢查，無法合作的兒童施以口服適當量之鎮靜劑(chloral hydrate, 0.5-1cc/kg body weight)。 磁振掃描儀為1.5T, Sonata (Siemens, Germany), echoplanar scanner 以下各脈序進行成 像包括: 1)axial fast spin-echo (FSE) T2WI, 2) axial fast inversion recovery (IR) T1-weighted image, 3) Spin-echo echo-planar diffusion-weighted imaging sequence: effective b value of 1500 sec/mm2 依序施於六個方向: {±1,0,1},{0,1,±1},{±1,1,0}, were applied with a b value of 1500 s/mm2. The parameters for DTI sequence were TR/TE = 240/124 ms, slice thickness = 4 to 5 mm without gap, and five acquisitions. Maps of the first, second and third eigenvalues of the diffusion tensor, trace of apparent diffusion coefficient (Trace ADC), and fractional anisotropy were generated off-line.就在腦室最高或以上一張的parietal-occipital central white maters, frontal central white maters，anterior corpus callosum, posterior corpus callosum 以及corona radiata 五 個區域圈選出region-of-interest；在後側腦室角的水平面圈選出temporal central white matter 以及occipital central white matter 各圈選區域主要選取相似白質走向的區域，測量此三區域 的第一、第二、第三eigen 值、擬似擴散係數以及部份非等向係數。一歲半以前以每三個 月為一組共分為六組；一歲半以上則每兩歲為一組共有八組，比較這十四組之間各區域之 第一、第二、第三eigen 值以及部份非等向係數等的差異，比較都採用Mann-Whitney rank-sum test, p value 小於0.05 則認為是有顯著差異意義。以求出各年齡層間有明顯變化的 區域及張度係數。另外採用Spearman’s rank-order correlation test 求取各項張度係數在不同 選取區域與年齡、性別的相關性變化。p value 小於0.05 則認為是有顯著差異意義。 執行期限內預期完成之工作項目。 一、完成一百位十六歲以下兒童磁振掃描檢查包括axial fast spin-echo (FSE) T2WI, axial fast IR T1WI, 擴散張度影像以及第一、第二、第三eigen值、擬似擴散係數值圖以及部份非等 向係數(fractional anisotropy)的檢者查及計算。 二、axial FSE 影像, 擴散影像、擴散張度影像、擬似擴散係數值圖、eigen 值圖、擴散非 等向係數、部分非對稱性圖計算及比較，完成其統計分析。 三、完成十六歲以下兒童不同在不同年齡層十四組在擴散張度影像上的訊號表現。 對於學術研究、國家發展及其他應用方面預期之貢獻。 一、完成目前文獻上仍少探討的在不同年齡層十六歲以下兒童擬似擴散係數值圖、eigen 值 圖、部分非對稱性圖評估研究，以作為擴散張度影像在兒童腦部臨床應用的研究基礎。 二、進一步研究了解十六歲以下兒童在不同年齡層所具有的不同張度係數變化表現；可找出 各相鄰年齡層在張度各係數圖主要的變化區域所在，並與傳統T1, T2 影像所慣用的發展里 程埤做對照。Background: Before the age of 18 months, myelination process is active in various regions of the brain and the degree of myelination varies in different regions of the brain from decades to decades of ages. A recent cerebral histologic study of rats suggest the potential of applying diffusion tenosor (DT) imaging in evaluating the cerebral whit matter diseases arising from disordered myelination. However, the normal developmental data of first, second and third eigenvalues (EV 1-3) as well as fractional anisotropy (FA) of children before the age of three years were hardly found in literature. Purpose: The study is designed to obtain the developmental changes of Ev1, EV2, EV3, and FA of white matter tracts in children under 16 years of age. The result of the study will become the basis of applying DT indices to the diagnosis of white matter diseases. Method: About 100 children before the age of sixteen years who are free of focal neurologic deficits, metabolic disturbances, tumors or infectious signs will be recruited if their cerebral fluid-attenuated inversion recovery (FLAIR), T1-weighted, T2-weighted images show no significant signal changes. After obtaining informed consent from their family, these children will receive MR DT imaging in addition to the routine MR examinations and chloral hydrate (0.5-1cc/kg body weight) will be given to the uncooperative children. All patients in the study received MR examinations using a 1.5-T MR scanner (Sonata; Siemens, Erlangen, Germany). Fast spin-echo (FSE) T2-weighted images in the axial plane were first obtained with TR/TE = 4330/100 msec, echo train length = 11, matrix size = 256 x 256, field of view = 14 x 14 to 20 x 20 according to the patient’s head size, slice thickness = 4–5 mm with gap of 1–1.5 mm, and one acquisition. DT images were then acquired with diffusion encoding gradients in six directions (i.e., [1, ±1, 0], [0, ±1, 1], and [±1, 0, 1]) and diffusion sensitivity b = 1500 s/mm2. The parameters for DTI sequence were TR/TE = 240/124 ms, slice thickness = 4 to 5 mm without gap, and five acquisitions. Maps of the first, second and third eigenvalues of the diffusion tensor, trace of apparent diffusion coefficient (Trace ADC), and fractional anisotropy were generated off-line. ROIs were also deposited on the bilateral parietal-occipital central white maters, frontal central white maters, anterior and posterior corpus callosum and corona radiata at the level of above the lateral ventricular bodies. ROIs were also deposited on bilateral inferior longitudinal fasciculus and sagittal stratum near the level of the occipital horn. In all ROIs, EV1-3, trace ADC and FA will obtained. Patients before the ages of 18 months will be divided into 6 groups every three months of age. The other patients will be divided into 8 groups every two years. We will use Mann-Whitney rank-sum test to find out the areas and DT indices of significant difference. In addition, Spearman’s rank-order correlation test will be used to correlate the age and gender with DT indices at various ROIs. P values smaller than 0.05 will be considered significant. We will perform the axial FSE T2-weighted images, axial fast IR T1-weighted images and DT imaging examinations. DT indices including EV1, EV2, EV3, trace ADC and FA will be obtained and analyzed in various ROIs of all patients from all age groups. The results of the study will be the basis of applying DT indices to evaluate myelination milestones of children. It will become the important reference when diagnosing white matter diseases using DT images