Abstract：
OBJECTIVE: To introduce a study design and statistical analysis framework to assess the repeatability, reproducibility, and minimal detectable changes (MDCs) of metabolite concentrations determined by in vivo MRS.
METHODS: An unbalanced nested study design was chosen to acquire in vivo MRS data within different repeatability and reproducibility scenarios. A spin-echo, full-intensity acquired localized (SPECIAL) sequence was employed at 7 T utlizing three different inversion pulses: a hyperbolic secant (HS), a gradient offset independent adiabaticity (GOIA), and a wideband, uniform rate, smooth truncation (WURST) pulse. Metabolite concentrations, Cramér-Rao lower bounds (CRLBs) and coefficients of variation (CVs) were calculated. Both Bland-Altman analysis and a restricted maximum-likelihood estimation (REML) analysis were performed to estimate the different variance contributions of the repeatability and reproducibility of the measured concentration. A Bland-Altmann analysis of the spectral shape was performed to assess the variance of the spectral shape, independent of quantification model influences.
RESULTS: For the used setup, minimal detectable changes of brain metabolite concentrations were found to be between 0.40 µmol/g and 2.23 µmol/g. CRLBs account for only 16 % to 74 % of the total variance of the metabolite concentrations. The application of gradient-modulated inversion pulses in SPECIAL led to slightly improved repeatability, but overall reproducibility appeared to be limited by differences in positioning, calibration, and other day-to-day variations throughout different sessions.
CONCLUSIONS: A framework is introduced to estimate the precision of metabolite concentrations obtained by MRS in vivo, and the minimal detectable changes for 13 metabolite concentrations measured at 7 T using SPECIAL are obtained.
METHODS: An unbalanced nested study design was chosen to acquire in vivo MRS data within different repeatability and reproducibility scenarios. A spin-echo, full-intensity acquired localized (SPECIAL) sequence was employed at 7 T utlizing three different inversion pulses: a hyperbolic secant (HS), a gradient offset independent adiabaticity (GOIA), and a wideband, uniform rate, smooth truncation (WURST) pulse. Metabolite concentrations, Cramér-Rao lower bounds (CRLBs) and coefficients of variation (CVs) were calculated. Both Bland-Altman analysis and a restricted maximum-likelihood estimation (REML) analysis were performed to estimate the different variance contributions of the repeatability and reproducibility of the measured concentration. A Bland-Altmann analysis of the spectral shape was performed to assess the variance of the spectral shape, independent of quantification model influences.
RESULTS: For the used setup, minimal detectable changes of brain metabolite concentrations were found to be between 0.40 µmol/g and 2.23 µmol/g. CRLBs account for only 16 % to 74 % of the total variance of the metabolite concentrations. The application of gradient-modulated inversion pulses in SPECIAL led to slightly improved repeatability, but overall reproducibility appeared to be limited by differences in positioning, calibration, and other day-to-day variations throughout different sessions.
CONCLUSIONS: A framework is introduced to estimate the precision of metabolite concentrations obtained by MRS in vivo, and the minimal detectable changes for 13 metabolite concentrations measured at 7 T using SPECIAL are obtained.
摘要：
目的：介绍研究设计和统计分析框架以评估可重复性，再现性，和通过体内MRS确定的代谢物浓度的最小可检测变化（MDC）。
方法：选择不平衡的嵌套研究设计，以在不同的可重复性和再现性情况下获取体内MRS数据。一个自旋回波,在7T下使用全强度采集的局部(特殊)序列，利用三个不同的反演脉冲：双曲割线(HS)，梯度偏移独立绝热性(GOIA)，和一个宽带，均匀率，平滑截断（WURST）脉冲。代谢物浓度，计算了Cramér-Rao下界（CRLB）和变异系数（CV）。进行了Bland-Altman分析和受限最大似然估计（REML）分析，以估计测量浓度的可重复性和再现性的不同方差贡献。进行光谱形状的Bland-Altmann分析以评估光谱形状的方差，独立于量化模型的影响。
结果：对于使用的设置，发现脑代谢物浓度的最小可检测变化在0.40µmol/g至2.23µmol/g之间。CRLB仅占代谢物浓度总方差的16%至74%。在SPECIAL中应用梯度调制的反转脉冲导致重复性略有改善，但总体可重复性似乎受到定位差异的限制，校准,和其他日常变化在不同的会议。
结论：引入了一个框架来估计体内MRS获得的代谢物浓度的精确度，并获得了使用SPECIAL在7T测量的13种代谢物浓度的最小可检测变化。
方法：选择不平衡的嵌套研究设计，以在不同的可重复性和再现性情况下获取体内MRS数据。一个自旋回波,在7T下使用全强度采集的局部(特殊)序列，利用三个不同的反演脉冲：双曲割线(HS)，梯度偏移独立绝热性(GOIA)，和一个宽带，均匀率，平滑截断（WURST）脉冲。代谢物浓度，计算了Cramér-Rao下界（CRLB）和变异系数（CV）。进行了Bland-Altman分析和受限最大似然估计（REML）分析，以估计测量浓度的可重复性和再现性的不同方差贡献。进行光谱形状的Bland-Altmann分析以评估光谱形状的方差，独立于量化模型的影响。
结果：对于使用的设置，发现脑代谢物浓度的最小可检测变化在0.40µmol/g至2.23µmol/g之间。CRLB仅占代谢物浓度总方差的16%至74%。在SPECIAL中应用梯度调制的反转脉冲导致重复性略有改善，但总体可重复性似乎受到定位差异的限制，校准,和其他日常变化在不同的会议。
结论：引入了一个框架来估计体内MRS获得的代谢物浓度的精确度，并获得了使用SPECIAL在7T测量的13种代谢物浓度的最小可检测变化。
