本篇論文之研究是利用腦血流，血體積和血氧程度相關功能性磁振造影來探討給予視覺刺激後，相同腦功能區中被活化之體積像素之間血流動力反應(hemodynamic responses)之沉潛時間的變異性(latency variability)。此研究由兩部分實驗所組成。第一部分有六位受試者參與，包含腦血流[利用切片選擇反向回覆(slice-selective inversion recovery, SSIR)技術]和血氧程度相關(BOLD1)兩組實驗。而第二部份則有三位受試者參與，包含血體積[利用非切片選擇反向回覆(non-slice-selective inversion recovery, NSIR)技術]和血氧程度相關(BOLD2)兩組實驗。每一組實驗重複五十次(第一部分)或三十次(第二部份)單一試驗，其中每單一試驗由一秒視覺刺激緊接著十三秒(第一部分)或十九秒(第二部份)十字凝視所構成。從每一個被活化的體積像素中，隨機選擇不同試驗次數來平均，以獲得訊號時間程序(time courses)之不同的對比雜訊比(contrast-to-noise ratio, CNR)。於對比雜訊比之每一特定水平上，對每一體積像素之平均訊號時間程序定義其沉潛時間。隨後計算視覺區中沉潛時間之變異性(△τ)，亦即沉潛時間分布上之標準差。對所有功能性磁振造影技術，當越多試驗次數被平均，所測得的對比雜訊比會越高，而沉潛時間變異則越低。當平均相同試驗次數，由腦血流和血體積功能性磁振造影所測得的對比雜訊比則明顯地比由血氧程度相關技術所測得的對比雜訊比低。對於所有實驗，進一步決定出沉潛時間變異與對比雜訊比(或選擇平均的試驗次數)之間的經驗關係。對比雜訊比在相同的水平下，切片選擇反向回覆與非切片選擇反向回覆兩技術之沉潛時間變異結果均明顯地顯示出低於血氧程度相關之結果。而比較切片選擇反向回覆與非切片選擇反向回覆兩技術之結果，在偵測敏感性與沉潛時間變異性上均沒有顯著的差異。本篇論文研究說明了藉由單一試驗平均可以明顯地改善對比雜訊比，進一步幫助改善功能性磁振造影反應時間的變異。當對比雜訊比在相同的水平下做比較時，切片選擇反向回覆與非切片選擇反向回覆兩技術所測得的沉潛時間變異會低於血氧程度相關之結果，其原因可能是因為此二技術可以得到較好的腦實質區之空間定位的特性。

The latency variability of hemodynamic responses between activated voxels, within the same functional area, was studied by cerebral blood flow- (CBF-), cerebral blood volume- (CBV-) and blood oxygenation level dependent- (BOLD-) based functional MRI (fMRI) using visual stimulations. This study consisted of two parts. The first part included CBF- (using slice-selective inversion recovery, SSIR) and BOLD-based (BOLD1) experiments performed on six subjects, while the second part included CBV- (using non-slice-selective inversion recovery, NSIR) and BOLD-based (BOLD2) experiments performed on three subjects. Fifty (Part I) or thirty (Part II) repeated single trials, each with 1-s visual stimulus followed by 13-s (Part I) or 19-s (Part II) fixation, were conducted in each experimental run. From each activated voxels, different numbers of trials were randomly selected for averaging, in order to obtain signal time courses with different contrast-to-noise ratios (CNRs). At each specific CNR level, the latency of the averaged signal time course was determined on a voxel-by-voxel basis. And the latency variability was then calculated as the standard deviation of the latency distribution within the visual area (△τ). For all the fMRI techniques, the measured CNR increased and the △τ decreased as more trials were averaged. The CNRs obtained by CBF- and CBV-based fMRI were significantly lower than that by BOLD, when the same numbers of trials were averaged. The relationship between the △τ and the CNR (or number of trials selected for averaging) was empirically determined for all the experiments. Under the same CNR levels, both the SSIR and the NSIR results appeared significantly lower latency variations than those obtained from BOLD. No significant differences were observed between the SSIR and the NSIR results, in both sensitivity and latency variability. This study demonstrated that the CNR could be significantly improved by single-trial averaging, which led to improved temporal variability of fMRI responses. When comparing at the same CNR levels, lower △τ for the SSIR and the NSIR than the BOLD may be due to their improved spatial localization to the brain parenchyma.

Bandettini PA, Wong EC, Hinks RS, Tikofsky RS, Hyde JS (1992): Time course EPI of human brain function during task activation. Magn Reson Med 25:390-397.

Bandettini PA, Wong EC, Jesmanowicz A, Hinks RS, Hyde JS (1994): Spin-echo and gradient-echo EPI of human brain activation using BOLD contrast: a comparative study at 1.5 T. NMR in Biomed 7:12-20.

Boynton GM, Engel SA, Glover GH, Heeger DJ (1996): Linear systems analysis of functional magnetic resonance imaging in human V1. J Neurosci 16:4207-4221.

Buckner RL (1998): Event-related fMRI and the hemodynamic response. Hum Brain Mapp 6:373–377.

Calhoun V, Adali T, Kraut M, Pearlson G (2000): A weighted least-squares algorithm for estimation and visualization of relative latencies in event-related functional MRI. Magn Reson Med 44:947-954.

Cohen MS (1997): Parametric analysis of fMRI data using linear systems methods. Neuroimage. 6:93-103.

Culver JP, Siegel AM, Franceschini MA, Mandeville JB, Boas DA (2005): Evidence that cerebral blood volume can provide brain activation maps with better spatial resolution than deoxygenated hemoglobin. Neuroimage. 27:947-959.

DeYoe EA, Bandettini P, Neitz J, Miller D, Winans P (1994): Functional magnetic resonance imaging (FMRI) of the human brain. J Neurosci Meth 54:171–187.

Frahm J, Merboldt KD, Hanicke W, Kleinschmidt A, Boecker H (1994): Brain or vein--oxygenation or flow? On signal physiology in functional MRI of human brain activation. NMR in Biomed 7:45-53.

Friston KJ, Fletcher P, Josephs O, Holmes A, Rugg MD, Turner R (1998): Event-related fMRI: characterizing differential responses. Neuroimage 7:30-740.

Glover GH (1999): Deconvolution of impulse response in event-related BOLD fMRI. Neuroimage 9:416-429.

Handwerker DA, Ollinger JM, D'Esposito M (2004): Variation of BOLD hemodynamic responses across subjects and brain regions and their effects on statistical analyses. NeuroImage 21:1639-1651.

Hernandez L, Badre D, Noll D, Jonides J (2002): Temporal sensitivity of event-related fMRI. Neuroimage 17:1018-1026.

Huettel SA, McCarthy G (2001): The effects of single-trial averaging upon the spatial extent of fMRI activation. Neuroreport 12:2411-2416.

Jacco ADZ, Afonso CS, Peter van G, Peter K, Masaki F, Renxin C, Alan PK, Joseph AF, Jeff HD (2005): Temporal dynamics of the BOLD fMRI impulse response. NeuroImage 24:667– 677.

Kim SG (1995): Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping. Magn Reson Med 34:293-301.

Kim SG, Richter W, Ugurbil K (1997): Limitations of temporal resolution in functional MRI. Magn Reson Med 37:631-636.

Kim SG, Tsekos NV (1997): Perfusion imaging by a flow-sensitive alternating inversion recovery (FAIR) technique: application to functional brain imaging. Magn Reson Med 37:425-435.

Kruggel F, von Cramon DY (1999): Temporal properties of the hemodynamic response in functional MRI. Hum Brain Mapp 8:259 –271.

Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP (1992): Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci (USA) 89:5675-5679.

Liao CH, Worsley KJ, Poline JB, Aston JAD, Duncan GH, Evans AC (2002): Estimating the delay of the fMRI response. Neuroimage 16:593-606.

Liu HL, Feng CM, Li J, Su FC, Li N, Glahn D, Gao JH (2005a): Disparity of activation onset in sensory cortex from simultaneous auditory and visual stimulation: differences between perfusion and blood oxygenation level-dependent functional magnetic resonance imaging. J Magn Reson Imaging 21:111–117.

Liu HL, Gao JH (1999): Perfusion-based event-related functional MRI. Magn Reson Med 42:1011-1013.

Liu HL, Huang JC, Wai YY, Wan YL, Wang JJ (2005b): The effects of single-trial averaging on the temporal resolution of functional MRI. Magn Reson Imag 1334: in press.

Liu HL, Pu Y, Nickerson LD, Liu Y, Fox PT, Gao JH (2000): Comparison of the temporal response in perfusion and BOLD-based event-related functional MRI. Magn Reson Med 43:768-772.

Lu H, Golay X, Pekar JJ, Peter van Zijl CM (2003): Functional magnetic resonance imaging based on changes in vascular space occupancy. Magn Reson Med 50:263–274.

Menon RS, Kim SG (1999): Spatial and temporal limits in cognitive neuroimaging with fMRI. Trend in Cogn Sci 3:207-216.

Menon RS, Luknowsky DC, Gati JS (1998): Mental chronometry using latency-resolved functional MRI. Proc Natl Acad Sci (USA) 95:10902-10907.

Ogawa S, Tank DW, Menon RS, Ellermann JM, Kim SG, Merkle H, Ugurbil K (1992): Intrinsic signal changes accompanying sensory stimulation: functional brain mapping using MRI. Proc Natl Acad Sci (USA) 89:5951-5955.

Robson MD, Dorosz JL, Gore JC (1998): Measurements of the temporal fMRI response of the human auditory cortex to trains of tones. Neuroimage 7:185-198.

Rosen BR, Buckner RL, Dale AM (1998): Event-related functional MRI: past, present, and future. Proc Natl Acad Sci (USA) 95:773-780.

Saad ZS, DeYoe EA, Ropella KM (2003): Estimation of FMRI response delays. Neuroimage 18:494-504.

Saad ZS, Ropella KM, Cox RW, DeYoe EA (2001): Analysis and use of fMRI response delays. Hum Brain Mapp 13:74–93.

Su FC, Chu TC, Wai YY, Wan YL, Liu HL (2004): Temporal resolving power of perfusion- and BOLD-based event-related functional MRI. Med Phys 31:154-160.

Yang Y, Engelien W, Pan H, Xu S, Silbersweig DA, Stern E (2000): A CBF-based event-related brain activation paradigm: characterization of impulse-response function and comparison to BOLD. Neuroimage 12:287–297.