Del Favero Simone, Facchinetti Andrea, Sparacino Giovanni, Cobelli Claudio
IEEE Trans Biomed Eng. 2014 Apr;61(4):1044-53. doi: 10.1109/TBME.2013.2293531.
Frequent and accurate reference measurements of blood-glucose (BG) concentration are key for modeling and for computing outcome metrics in clinical trials but difficult, invasive, and costly to collect. Continuous glucose monitoring (CGM) is a minimally-invasive technology that has the requested temporal resolution to substitute BG references for such a scope, but still lacks of precision and accuracy. In this paper, we propose an algorithm that retrospectively reconstructs a reliable continuous-time BG profile for the aforementioned purposes, by simultaneously exploiting the high accuracy of (possibly sparse) BG references and the high temporal resolution of CGM data. The algorithm performs a constrained semiblind deconvolution in two steps: first, it estimates the unknown parameters of a model accounting for plasma-interstitum diffusion and sensor inaccurate calibration; then, it estimates BG performing a regularized deconvolution of CGM data, subject to the additional constraint that the reconstructed BG profile has to lay within the confidence interval of the available BG references. The algorithm was tested on 24 datasets collected in a 20 h clinical trial where CGM records and a median of 13 BG samples per day were available. Mean absolute relative deviation was reduced (from 15.71% to 8.84%) with respect to unprocessed CGM and so did the error in the evaluation of the outcomes metrics (e.g., halved the error in the time-in-hypo assessment). The reconstructed BG profile, in view of its improved accuracy and precision, is suitable for clinical trial assessment, modeling and other offline applications.
频繁且准确地测量血糖(BG)浓度是临床试验中进行建模和计算结果指标的关键,但采集过程困难、具有侵入性且成本高昂。连续血糖监测(CGM)是一种微创技术,具有所需的时间分辨率,可在此范围内替代BG参考值,但仍缺乏精度和准确性。在本文中,我们提出了一种算法,该算法通过同时利用(可能稀疏的)BG参考值的高精度和CGM数据的高时间分辨率,为上述目的回顾性重建可靠的连续时间BG曲线。该算法分两步进行约束半盲反卷积:首先,估计一个考虑血浆 - 间质扩散和传感器校准不准确的模型的未知参数;然后,在重建的BG曲线必须落在可用BG参考值的置信区间内这一附加约束下,对CGM数据进行正则化反卷积来估计BG。该算法在一项20小时临床试验收集的24个数据集上进行了测试,其中有CGM记录且每天中位数有13个BG样本。相对于未处理的CGM,平均绝对相对偏差降低了(从15.71%降至8.84%),结果指标评估中的误差也降低了(例如,低血糖评估时间的误差减半)。鉴于其提高的准确性和精度,重建的BG曲线适用于临床试验评估、建模和其他离线应用。