Varghese Babu, Rajan Vinayakrishnan, Van Leeuwen Ton G, Steenbergen Wiendelt
MIRA Institute for Biomedical Technology and Technical Medicine, Biomedical Photonic Imaging Group, University of Twente, P.O. Box 217, 7500 AE Enschede, the Netherlands.
Lasers Surg Med. 2010 Nov;42(9):692-700. doi: 10.1002/lsm.20969.
In laser Doppler measurements, perfusion values averaged over different and basically unknown path lengths are recorded. To facilitate quantitative path length resolved perfusion measurements, we developed a phase modulated Mach-Zehnder interferometer with spatially separated fibers for illumination and detection. The goal of this study is to measure in vivo optical path lengths and path length resolved Doppler shifts and to compare these with conventional laser Doppler perfusion measurements.
STUDY DESIGN/MATERIALS AND METHODS: With a phase modulated Mach-Zehnder interferometer, we performed path length resolved perfusion measurements on human skin and its variations to external stimuli and compared these with conventional laser Doppler perfusion measurements. The method was evaluated in three human subjects on the dorsal side of the forearm to establish inter-individual within-site variations. Measurements were performed at three different locations of one individual for observing intra-individual inter-site variations resulting from the heterogeneity of the tissue, both in the static matrix and in the microvascular architecture of the skin. In all measurements, perfusion was simultaneously measured with a conventional laser Doppler perfusion monitor.
In this study, we show the first results of path length resolved perfusion measurements in skin and its variations to occlusion and Capsicum cream provocation. From our data, we deduced the Doppler shifted fraction of photons, which is related to the blood volume, and the path length dependent average Doppler shift, which is related to the mean velocities of red blood cells. The Doppler shifted fraction of photons is decreased from 28% to 18% during occlusion and increases to 41% when capsicum cream was applied to the skin. Inter- and intra-individual inter-site measurements demonstrated variations in optical path length distributions and path length resolved Doppler shifts. The Doppler shifted fraction of photons measured on the fingertip is about 38% and that measured on the dorsal and palmar sides of the forearm are 32% and 17%, respectively. The path length distributions depend on the skin site that is being probed and the intra-individual inter-site variability is higher than the inter-individual within-site variability measured on comparable sites between different individuals.
In this study, we demonstrated, for the first time to our knowledge, that in vivo path length resolved perfusion measurements are feasible. Optical path length distributions of multiply scattered light, spanning a range of 0-6 mm, and their response to external stimuli such as occlusion and capsicum cream provocation have been measured. This method will enable better interpretation of inter- and intra-individual inter-site variations in the LDF readings that are introduced by the variance in tissue optical properties. The inter- and intra-individual inter-site variations measured with our setup results indicate that that these variations should be taken into account while comparing the perfusion readings from comparable sites between individuals and from different sites of the same individual. Furthermore, the observed inter- and intra-individual inter-site variations in path length resolved Doppler measurements indicate the inherent limitation of conventional LDPM that restrict its clinical usefulness, due to its dependence on the unknown photon path length. Consequently, this method will enable to correctly interpret or counter-act the inter- and intra-individual inter-site variations in the LDF readings introduced by the variance in tissue optical properties. This approach also enables to discriminate between the Doppler-shifted photons resulting from interaction with the moving red blood cells and the non-shifted light scattered only by the surrounding static tissue matrices.
在激光多普勒测量中，记录的是在不同且基本未知的光程长度上平均得到的灌注值。为便于进行光程长度分辨的定量灌注测量，我们开发了一种具有空间分离光纤用于照明和检测的相位调制马赫 - 曾德尔干涉仪。本研究的目的是测量体内光程长度和光程长度分辨的多普勒频移，并将其与传统激光多普勒灌注测量结果进行比较。
研究设计/材料与方法：我们使用相位调制马赫 - 曾德尔干涉仪对人体皮肤及其对外部刺激的变化进行光程长度分辨的灌注测量，并将这些结果与传统激光多普勒灌注测量结果进行比较。该方法在三名受试者的前臂背侧进行评估，以确定个体间的部位内差异。在一名个体的三个不同位置进行测量，以观察由于组织异质性（包括静态基质和皮肤微血管结构）导致的个体内部位间差异。在所有测量中，同时使用传统激光多普勒灌注监测仪测量灌注。
在本研究中，我们展示了皮肤中光程长度分辨的灌注测量及其对闭塞和辣椒素乳膏激发的变化的首批结果。从我们的数据中，我们推导了与血容量相关的光子多普勒频移分数，以及与红细胞平均速度相关的光程长度依赖性平均多普勒频移。光子的多普勒频移分数在闭塞期间从28%降至18%，而当在皮肤上涂抹辣椒素乳膏时增加到41%。个体间和个体内部位间测量显示了光程长度分布和光程长度分辨的多普勒频移的变化。在指尖测量的光子多普勒频移分数约为38%，在前臂背侧和掌侧测量的分别为32%和17%。光程长度分布取决于所探测的皮肤部位，并且个体内部位间变异性高于在不同个体的可比部位测量的个体间部位内变异性。
据我们所知，在本研究中我们首次证明了体内光程长度分辨的灌注测量是可行的。已测量了多重散射光的光程长度分布，范围为0 - 6毫米，以及它们对诸如闭塞和辣椒素乳膏激发等外部刺激的响应。该方法将有助于更好地解释由组织光学特性差异引入的激光多普勒血流仪（LDF）读数中的个体间和个体内部位间变化。用我们的装置测量的个体间和个体内部位间变化结果表明，在比较个体间可比部位和同一人不同部位的灌注读数时应考虑这些变化。此外，在光程长度分辨的多普勒测量中观察到的个体间和个体内部位间变化表明了传统激光多普勒灌注测量（LDPM）的固有局限性，由于其依赖于未知的光子光程长度，限制了其临床应用。因此，该方法将能够正确解释或抵消由组织光学特性差异引入LDF读数中的个体间和个体内部位间变化。这种方法还能够区分与移动红细胞相互作用产生的多普勒频移光子和仅由周围静态组织基质散射的未频移光。
