The microcirculation is a term used to describe the small vessels in the vasculature network which are responsible for the distribution of blood and nutrients through the body; as opposed to larger vessels in the macrocirculation which transport the blood to and from the organs. The microcirculation serves several key functions within the body including regulation of blood pressure, body temperature, blood flow within tissues and delivery of nutrients and removal of metabolic waste products.
Structural and functional changes within the microcirculation have previously been associated with various pathological conditions including diabetes [1
], Alzheimer’s [2
], cancer [3
], Raynaud’s disease [4
] and psoriasis [5
]. Weidlicy et al.
has recently demonstrated that monitoring changes within the microcirculation can provide an early indication of disease prior to clinical suspicion [6
]. Thus the clinical diagnostic value of techniques that enable imaging of the microcirculation is of key importance as detecting early changes within the microcirculation provides early indication of disease.
A key issue with microcirculation imaging however is the limited non-invasive techniques available. To date extensive study of the microcirculation has been achieved under various pathological conditions using capillaroscopy based techniques [4
]. These techniques use a microscope with a magnification > 100x to enable capillary imaging. These techniques are limited to imaging vessels close to the surface of the skin, thus have been limited to regions such as the nail fold where the vessels can be clearly visualized. Other techniques have been combined to enhance imaging capabilities. Techniques based on orthogonal polarization spectral imaging has been demonstrated to enhance visualization depth [9
] while optical Doppler imaging and speckle variance techniques have enabled quantification of blood flow within the microcirculation [10
]. One issue with all these methods is the limit of depth ambiguity. It is therefore difficult to assess which vessels are being examined. This has led to a recent drive towards the development of tools that enable 3D imaging of the microcirculation.
In recent years photoacoustic imaging has as a powerful tool in 3D microcirculation imaging. The principle behind the technique is that as light energy gets absorbed by a chromophore within the tissue, a resulting acoustic wave is generated. This can be detected to generate 3D maps of the desired chromophore. Through the selection of suitable wavelengths of light various chromophores such as blood, melanin [13
] or other contrast agents [14
] can be can be mapped. The technique however, is limited by the spatial resolution of ultrasound detection. The use of focused ultrasonic transducers in photoacoustic microscopy (PAM) enhances spatial resolution to ~45 µm [15
]. Further enhancements in the resolution are achievable through the use of highly focused light in optical resolution photoacoustic microscopy (OR-PAM) achieving a resolution of ~5 µm [16
]. This technique has demonstrated high resolution capillary level imaging of the microcirculation. However, the resulting depth of focus is greatly reduced and the structural imaging of the surrounding tissue layers is still limited by the acoustic resolution. High resolution structural imaging combined with microcirculation imaging can provide additional clinical information thus the low acoustic resolution can be an issue. Another limitation of photoacoustic techniques is that a coupling medium is required to provide direct contact with the tissue under investigation. This coupling can interact with the tissue function and affect the microcirculation.
Optical coherence tomography (OCT) addresses many of the limitations of photoacoustic imaging providing non-contact structural imaging of the tissue with micron resolution. OCT itself does not directly produce microcirculation imaging; however several technologies have been developed to extend the capabilities of OCT to visualize the microcirculation. The original technique demonstrated was Doppler OCT (DOCT) [17
]. The technique operates on the Doppler shift caused by moving scatters within the tissue. DOCT has enabled quantification of blood flow dynamics with high spatial resolution [18
] and has been demonstrated in various in vivo
]. The technique suffers from an angular dependence and is unable to detect flow perpendicular to the scanning beam. This is a key limitation for microcirculation imaging as blood vessels within the tissue are orientated at varying angles and can be tortuous in shape. Thus DOCT would produce incomplete maps of the microcirculation. Another technique that has been demonstrated is termed speckle variance OCT (svOCT) [21
]. This technique is based on the change in speckle pattern caused by moving scattering particles from the structural OCT signal. The svOCT signal is determined by calculation of the variance of the signal intensity using either a spatial window [21
] or temporal window [22
]. The key advantage of svOCT is that it does not suffer from angular dependence like DOCT. One issue with svOCT is in interpreting the variance results. The calculated variance is in the range of ± ∞ and depends on the chosen window size. Thus the variance values itself does not directly indicate flow and a prior knowledge of the structure is required to separate regions with and without flow. Another technique that has shown very promising results is optical microangiography (OMAG) that has emerged to enable microcirculation imaging [23
]. The original OMAG technique did not provide flow velocity information, but a hybrid method termed Doppler OMAG (DOMAG) has enabled velocity measurements [24
] which offers higher signal to noise ratio compared to standard DOCT. The technique was originally demonstrated in small animal cerebral blood flow imaging, but has since been demonstrated to image the microcirculation at various anatomical locations such as retinal and choroid [25
], sentinel lymph node [26
] and the cochlea [27
]. The flow sensitivity has recently been enhanced using a new processing technique termed ultra-high sensitive OMAG (UHS-OMAG) which has enabled vivo imaging of the microcirculation for human skin [28
]. However, the OMAG technique requires extensive post processing on data which is reported to require up to 35 min to process a single volume [23
] which can limit clinical suitability.
To overcome the limitations associated with existing technologies we has recently developed a new technique termed correlation mapping OCT (cmOCT) [29
]. In this paper we will demonstrate the suitability of cmOCT techniques as a tool that enables non-invasive, non-contact mapping of the microcirculation. We apply the cmOCT technique to in vivo
imaging of the human volar forearm and demonstrate the vascular maps that can be produced.