Background

Advances in the understanding of the pathophysiology of frontotemporal dementia (FTD) and related disorders, along with the development of novel candidate disease modifying treatments, have stimulated the need for tools to assess the efficacy of new therapies. While perfusion imaging by arterial spin labeling (ASL) is an attractive approach for longitudinal imaging biomarkers of neurodegeneration, sources of variability between sessions including arterial transit times (ATT) and fluctuations in resting perfusion can reduce its sensitivity. Establishing the magnitude of perfusion changes that can be reliably detected is necessary to delineate longitudinal perfusion changes related to disease processes from the effects of these sources of error.

Purpose

To assess the feasibility of ASL for longitudinal monitoring of patients with FTD by quantifying between-session variability of perfusion on a voxel-by-voxel basis.

Methods and materials

ASL data were collected in 13 healthy controls and 8 patients with FTD or progressive supra-nuclear palsy. Variability in cerebral blood flow (CBF) by single delay pseudo-continuous ASL (SD-pCASL) acquired one month apart were quantified by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Additionally, CBF by SD-pCASL and ATT by low-resolution multiple inversion time ASL (LowRes-pCASL) were compared to Hadamard encoded sequences which are able to simultaneously measure CBF and ATT with improved time-efficiency.

Results

Agreement of grey-matter perfusion between sessions was found for both patients and controls (CV = 10.8% and 8.3% respectively) with good reliability for both groups (ICC > 0.6). Intensity normalization to remove day-to-day fluctuations in resting perfusion reduced the CV by 28%. Less than 5% of voxels had ATTs above the chosen post labelling delay (2 s), indicating that the ATT was not a significant source of error. Hadamard-encoded perfusion imaging yielded systematically higher CBF compared to SD-pCASL, but produced similar transit-time measurements. Power analysis revealed that SD-pCASL has the sensitivity to detect longitudinal changes as low as 10% with as few as 10 patient participants.

Conclusion

With the appropriate labeling parameters, SD-pCASL is a promising approach for assessing longitudinal changes in CBF associated with FTD.

中文翻译：

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动脉自旋标记对额颞叶痴呆及相关疾病纵向灌注变化表征的敏感性

背景

对额颞叶痴呆 (FTD) 和相关疾病的病理生理学理解的进步，以及新的候选疾病修饰疗法的开发，激发了对评估新疗法疗效的工具的需求。虽然通过动脉自旋标记 (ASL) 进行的灌注成像对于神经退行性变的纵向成像生物标志物来说是一种有吸引力的方法，但包括动脉转运时间 (ATT) 和静息灌注波动在内的会话之间的变异性来源会降低其敏感性。确定可以可靠检测到的灌注变化幅度对于从这些误差源的影响中描绘与疾病过程相关的纵向灌注变化是必要的。

目的

通过在逐个体素的基础上量化灌注的会话间变异性来评估 ASL 对 FTD 患者进行纵向监测的可行性。

方法和材料

在 13 名健康对照者和 8 名患有 FTD 或进行性核上性麻痹的患者中收集 ASL 数据。通过变异系数 (CV) 和组内相关系数 (ICC) 对间隔一个月获得的单延迟伪连续 ASL (SD-pCASL) 的脑血流量 (CBF) 的变异性进行量化。此外，将 SD-pCASL 的 CBF 和低分辨率多重反转时间 ASL (LowRes-pCASL) 的 ATT 与 Hadamard 编码序列进行了比较，后者能够同时测量 CBF 和 ATT，提高了时间效率。

结果

患者和对照组的灰质灌注一致（CV 分别为 10.8% 和 8.3%），两组均具有良好的可靠性（ICC > 0.6）。强度标准化以消除静息灌注的日常波动，使 CV 降低了 28%。不到 5% 的体素的 ATT 高于所选的标记后延迟（2 秒），这表明 ATT 不是重要的错误来源。与 SD-pCASL 相比，Hadamard 编码灌注成像产生了系统性更高的 CBF，但产生了相似的传输时间测量值。功效分析显示，SD-pCASL 具有检测低至 10% 的纵向变化的灵敏度，只需 10 名患者参与者。

结论

使用适当的标记参数，SD-pCASL 是评估与 FTD 相关的 CBF 纵向变化的有前途的方法。