Sample records for investigating extremity lymphoedema. Velocity and turbulence characteristics were measured using a combination of Laser Doppler Velocimetry (LDV) and Particle Image Velocimetry (PIV). Manual lymphatic drainage showed no significant changes in any of the outcomes Conclusion: Although there are no significant differences. 830,, FEM FLEX LIGHT PIPE 204619, $ 1,323.00. 882,, DRAIN SUCTION 7MM 139126, $ 46.00. 1588,, FIBER HOLMIUM LASER SINGLE 200, $ 1,467.00. 5565,, SHEET XOM SILICON.020 #113015, $ 81.70. 13851,, AB ID LYMPH.
Biomedical optics is a rapidly emerging field for medical imaging and diagnostics. This paper reviews several biomedical optical technologies that have been developed and translated for either clinical or pre-clinical applications. Specifically, we focus on the following technologies: 1) near-infrared spectroscopy and tomography, 2) optical coherence tomography, 3) fluorescence spectroscopy and imaging, and 4) optical molecular imaging. There representative biomedical applications are also discussed here.
Biomedical optics is a rapidly emerging field for medical imaging and diagnostics. This paper reviews several biomedical optical technologies that have been developed and translated for either clinical or pre-clinical applications. Specifically, we focus on the following technologies: 1) near-infrared spectroscopy and tomography, 2) optical coherence tomography, 3) fluorescence spectroscopy and imaging, and 4) optical molecular imaging. There representative biomedical applications are also discussed here. 1. Introduction Optical technologies are currently emerging as promising tools for medical imaging and diagnostics.
Optics has several advantages, including non-ionizing radiation, low-cost, portable, and high molecular and biochemical specificity. These advantages enable functional imaging using light and open up new opportunities for light-based applications in clinical medicine. This paper reviews several optical technologies that have been developed and translated for either clinical or pre-clinical applications. Specifically, we focus on the following technologies: 1) near-infrared spectroscopy and tomography, 2) optical coherence tomography, 3) fluorescence spectroscopy and imaging, and 4) optical molecular imaging. There representative biomedical applications are also discussed here. Historical Perspective and Technology Development Biological molecules have unique absorption spectra against a range of light wavelengths, thus can be detected with accurate concentration by spectroscopy.
The spectroscopy system was pioneered in the Cambridge University ,. However, biological sample is usually opaque and therefore the light absorption spectra would be disrupted due to scattering. In 1950, Britton Chance invented “double beam spectrometer” using two wavelengths in the visible region with a small spectral interval to eliminate the effect of scattering. This double beam concept was adapted to the optical spectroscopy used for biological systems even up to date for medical use. Pulse oximeter may be the first use of optics for human in vivo, which utilizes near-infrared light to monitor arterial hemoglobin oxygen saturation.
It was first made by Takuo Aoyagi in a Japanese company, Nihon Kouden in 1972. Because arterial pulse induces changes in arterial blood volume between systolic and diastolic heart contraction, light intensity difference between these two conditions is only caused by arterial blood. Thus arterial blood oxygen saturation can be quantified with a simple linear equation , ignoring scattering effects of tissue. This concept is similar to the “double beam spectroscopy” dated back to 1940s, when Glenn Milliken tried to observe differences of light transmitting intensity through human tissues using green and red color filters to measure oxygenation in human tissue. The first demonstration of NIR light on human tissue in vivo was reported by Franz Jobsis in 1977.
Jobsis demonstrated that NIR light can carry information of not only hemoglobin but mitochondrial chromophore, cytochrome a,a3 in the neonatal brain measured non-invasively. Since then, many papers were published along the line of proving tissue oxygenation and mitochondrial redox states by means of those hemoglobin and cytochrome a,a3 signals in the NIR region in many animal models and human tissues. Many researchers use continuous-wave (CW) technology as the system is simple, low-cost, and robust.
Shows a representative CW near-infrared (NIR) imaging system with three-wavelength light emitting diode (LED) at 760 nm, 805 nm, and 850 nm, and 8 silicon photodiode detectors. Many companies such as Somanetics have commercialized this technology to measure tissue hemoglobin saturation. Since only intensity attenuation is measured with CW system, it is difficult to separate scattering coefficient from absorption coefficient in the tissue. A photograph of the whole apparatus (a) illustrates the handheld puck or probe, the coupling to the circuit box which contains the drivers for the LED, the amplifiers for the detectors, the digitally controlled gain adjustment amplifier, the electronic. Time-Resolved Spectroscopy (TRS) technology gave a solution for this problem of absolute quantification of chemical concentrations in the turbid media such as the in vivo human investigation in 1988–1989 by B. TRS machines are commercially available then in 1993 by Hamamatsu, and it has been made for many applications ,. Alternatively frequency-domain (FD) NIR spectroscopy (NIRS) can be also used for quantization –.
FD technology is available commercially by ISS, Inc. These two technologies have been used for obtaining more accurate information from the turbid tissue, namely absorption and reduced scattering coefficients.
NIRS can be extended to imaging mode by using multiple source-detector channels. One way to form an image is using back-projection and interpolation algorithms. This approach, sometimes referred to as diffuse optical topography, can provide a quick and good estimate of 2D spatial distribution of the optical properties of interested.
The drawback of this relatively simpler approach is that the tissue optical properties are not reconstructed with good accuracy, and the spatial resolution is lower. Another approach is to perform 3D tomographic reconstruction, therefore, is referred to as diffuse optical tomography (DOT). In principle, DOT is similar to other tomographic schemes such as X-ray computerized tomography, and involves image reconstruction by solving the inverse problem. DOT can accurately reconstructed the spatially-resolved changes in optical properties in tissue. Breast Imaging Breast cancer is the most commonly diagnosed cancer among women in the United States and worldwide.
Early detection through mammography and clinical breast exams is essential for effective breast cancer screening. For women between the ages of 50–69, regular mammograms can reduce the chance of death from breast cancer by approximately 30%. X-ray mammography may miss up to 25% of breast tumors in women in their 40s, and about 10% of women over age 50. Other imaging techniques, such as magnetic resonance imaging (MRI) and ultrasound (US), have been developed for breast cancer detection and staging without using X-rays ,.
In general, mammography, MRI and US provide mostly anatomic information, rather than quantitative tissue function and composition. Positron Emission Tomography (PET) could provide the metabolic information, but requires the injection of exogenous radionuclides. Compared with those modalities, NIR diffuse optical imaging has its own merits of non-ionizing, economic and biochemical specificity. The use of light in breast cancer detection dates back to the 1920s. In the past two decades, with the development of advanced light sources and detector, as well as modeling of light propagation in tissue, the application of diffuse optical imaging for breast imaging (often referred to as “optical mammography”) have been developing rapidly.
The development of tumor is generally associated with increased vascularization (also called “angiogenesis”) and lower oxygen partial pressure (pO 2) ,. NIR light is sensitive to intrinsic chromophores such as oxygenated and deoxygenated hemoglobin (HbO 2 and Hb), water (H 2O) and lipids ,. Therefore, NIR diffuse optical spectroscopy and imaging can provide sensitive and specific physiological information for breast cancer diagnosis ,.
Nioka et al introduced endogenous contrast NIR imaging of the human breast in 1994. Blood volume and oxygen saturation are two important parameters. Studies indicate that there are two to four folds of contrast between normal and tumor regions for blood volume, and oxygen saturation in the tumor is generally lower than normal ,. There exist variations in normal breast tissue optical properties.
For example, Durduran et al reported the averaged blood volume and oxygen saturation on healthy female breast tissues are 34 ± 9 μM and 68 ± 8%, respectively. These baseline values are important to assess the potential contrasts available for diffuse optical imaging to discriminate healthy and diseased tissues. The scattering properties of tissue also contain important information for lesion diagnosis. The scattering coefficients are related to the tissue structure properties and the concentration or size of organelles. The clinical niche for NIR diffuse optical spectroscopy and imaging in breast cancer are tumor detection in pre-menopausal women and monitoring neoadjuvant chemotherapy –. CW systems are relatively inexpensive and compact.
It can be interfaced with a handheld probe to image the breast. Using the handheld puck shown in, Chance et al reported a 6 year, two-site study on 116 patients of whom 44 patients had confirmed malignancy by biopsy and histopathology. The absorbance increments of the cancerous regions are referred to the mirror image location on the contra-lateral breast. This technique was able to distinguish cancer from non-cancer breasts with 96% sensitivity and 93% specificity.
In another pilot clinical trial of 48 patients, Xu et al used a portable handheld NIR imaging device, “P-Scan”, a pre-commercial prototype of ViOptix Inc. (Fremont, CA, USA), to image suspicious breast lesions identified on diagnostic clinical ultrasound (US). An external mechanical compression was applied to breast tissue to dynamically record the oxygen saturation and hemoglobin concentration. Indocyanine Green (ICG) is an organic dye that has been approved by US Food and Drug Administration (FDA) for clinical use. ICG can be used to enhance the tumor-to-normal contrast to aid in the detection of lesions in the breast, as first demonstrated by Nioka et al. Shows an example of CW DOT system for imaging the uptake of ICG by breast tumors. This instrument employs a circular configuration with 16 sources and 16 detectors to collect light in parallel on the surface of the tumor-bearing breast.
ICG was injected by bolus, and the absorption changes induced by ICG were recorded dynamically. DOT successfully localized the tumor regions, which was in good agreement with a priori information. A two-compartment model composed of plasma and extracellular-extravascular space was used to analyze the pharmacokinetics of ICG. Moreover, different dynamical features were observed for different pathologies. The malignant cases exhibited slower rate constants (uptake and outflow) compared to healthy tissue. Further studies enabled direct forming of the pharmacokinetics-rate image by DOT, and found statistically different rates from the tumor region compared to those outside the tumor region. These results demonstrated that in vivo pharmacokinetics of ICG in breast tumors could be a useful diagnostic tool for differentiation of benign and malignant pathologies.
Schmitz et al developed a more sophisticate CW system for bi-lateral breast imaging, DYnamic Near-Infrared Optical Tomography (DYNOT) system (NIRx Medical Technologies). This system enables simultaneous imaging of hemodynamics within both breasts. (A) CW imager configuration. The sources are sequentially shining upon the breast and so the configuration is equivalent to a fan-beam configuration. (B) The dashed curve represents the intensity drop associated to the ICG-uptake for source 6 and detector.
Frequency-domain measurement can quantify the concentration of chromophores. Culver et al developed a hybrid CW/frequency-domain breast imaging system which combines the benefits of high-speed and low-cost of CW techniques with more accurate quantitative nature of frequency-domain techniques. Using this system, Choe et al found that malignant cancers (n=41) showed significantly higher total hemoglobin, oxy-hemoglobin concentration, and scattering compared to normal tissue.
Benign tumors (n=10) did not exhibit statistical significance in the tumor-to-normal ratios of any parameter. These results demonstrate that benign and malignant lesions can be distinguished by quantitative three-dimensional DOT. Such a system also has been applied to monitor neoadjuvant chemotherapy. DOT revealed tumor shrinkage and decrease in relative total hemoglobin concentration during the course of chemotherapy, therefore demonstrated the potential for monitoring physiological parameters of breast lesions during chemotherapy. Tromberg’s group at UC Irvine also developed a handheld NIR diffuse optical spectroscopic imaging (DOSI) system for breast cancer detection and monitoring neoadjucant chemotherapy.
Time-domain DOT systems have been also developed for breast imaging. Ntziachristos et al developed a time-domain imaging system using time-correlated single photon counting (TCSPC) technique, and demonstrated concurrent MRI and DOT imaging of breast after contrast enhancement using ICG. Other prototype instruments have been developed by groups at Politecnico di Milano, Italy – and Physikalisch-Technische-Bundesanstalt of Berlin, Germany , –, as part of Optimamm, a consortium funded by the European Union, and have acquired data from more than 300 clinical cases. They reported successful identification of 80%–85% mammographically identified lesions. A prototype time-domain DOT breast imaging system has been developed by Advanced Research Technologies (ART, Canada).
Initial results suggested that optical imaging can discriminate benign and malignant tumors, therefore, held great clinical promise for breast cancer imaging. One of the recent trends in NIR DOT is to combine with other imaging modalities such as X-ray CT, MRI or US, which can provide high spatial resolution map of tissue structures. Those maps can be used as a priori information to improve the reconstruction of DOT images ,.
Representative multi-modality breast imaging systems include the combined DOT and X-ray mammography system developed at the Massachusetts General Hospital , , the combined DOT and MRI multi-modal imaging system developed at Dartmouth College , , and the combined ultrasound and frequency-domain diffuse optical imaging/tomography systems –. Brain Imaging Since Seiji Ogawa’s discovery that deoxyhemoglobin signal changes in NMR can detect brain cognition in early 1990s , researchers are interested in using NIR light to detection brain function –. NIRS can quantify the concentration of both Hb and HbO 2, thereby revealing the blood volume and oxygenation saturation changes associated with brain functions. NIR diffuse optical imaging (DOI) has found widespread applications in clinical settings ,. One major research area is to understand how the brain functions.
DOI offers unique capability to non-invasively monitor the functional activations in vivo without disturbing the organ. Various applications such as visual responses , , somatosensory responses , auditory responses , language stimuli , , and problem solving have been explored. Another important area for DOI brain imaging is to diagnose and monitor the diseases such as stroke , , epilepsy , brain injury , and post-traumatic stress disorder. Optical techniques are well-suited for early detection of hemorrhage , and discrimination between ischemic and hemorrhagic stroke leading to a better management of the patient treatment. Commercial CW brain imaging systems have been developed by Hitachi Medical Corporation (Tokyo, Japan) ,.
This optical topography system (ETG-100) uses 8 laser diodes at 780 nm and another 8 at 830 nm. 8 avalanche photodiodes (APDs) are used to detect the signals. Multiple channels are encoded by different frequencies from 1 to 6.5 kHz. The Hitachi system has been applied to investigate healthy brain functions such as language development , the emotional response to music , cognitive functions , , and brain development in newborn infants , , as well as pathological conditions such as epilepsy , post-traumatic stress disorder , and cognitive function study in patients with motor neuron disease. The clinical applications of the Hitachi system have been quite successful despite using a simple CW system and relatively simple image reconstruction method. Other companies such as Shimadzu Corporation (Japan) also developed optical topography system from brain imaging. Franceschini et al reported the development of the CW imaging system (CW4 and CW5) at the Massachusetts General Hospital ,.
The newer system (CW5) employs 32 sources and 32 detectors to cover most of the areas in the adult head, which enables simultaneous collection of optical signals from prefrontal, sensorimotor, and visual cortices in both hemispheres. Using this system, they investigated the spatiotemporal patterns of physiological signals during rest.
This information will help to understand the physiological signals and develop signal processing algorithms to distinguish them from the functional activation signals. White et al applied a high-performance, high-density CW DOT system to map resting-state networks in the human brain , which enables studies of the functional connectivity of different cortical regions. These studies demonstrated that high-density DOT has become a practical and powerful tool for mapping function in the human cortex. Has developed a commercial frequency-domain brain imaging system (Imagent™). Frequency-domain DOI has been shown to measure the hemodynamic (slow) signals and neuronal (fast) signals ,. Especially, the fast signals are thought to be associated with the neuronal scattering changes, which will induce phase delay in the modulated diffuse photons. Therefore frequency-domain imaging system is required to measure the phase delay which indicates the event-related optical signals (EROS).
Time-domain imaging systems have been actively developed for brain imaging, especially for tomographic imaging of whole brain. Hintz et al reported the early development of time-domain optical tomographic system for neonatal brain imaging by reconstructing measurements of mean photon flight time.
More recently, the group at University College London (UCL) has developed a 32-channel time-resolved optical imaging system for 3D neonatal brain imaging. This system has been successfully used to image the brain of a premature infant with a cerebral hemorrhage and monitor the blood volume and oxygenation changes in the newborn infant brain during ventilation. Muscle Imaging Non-invasive monitoring of muscle tissues using light can be dated back to the 1930s by Millikan.
Since then, optical imaging of muscles has received steadily increased interests. Optical methods can probe hemoglobin, myoglobin, blood flow, and metabolism, therefore provide an ideal means for monitoring muscle functions under different physiological or pathological conditions –. Using CW imaging system similar to that shown in, Lin et al demonstrated fast imaging of blood volume and oxygenation changes in peroneus and gastrocnemius muscles during exercise. This 8-channel imager can differentiate the regions corresponding to extensors and flexors since they show different responses during exercise.
Using a higher density (200-channel) CW imager which covers 45 cm × 15 cm 2 area, Hamaoka et al recently showed DOI of quadriceps muscles before, during, and after exercise (see ). These results demonstrated the spatial differences within muscles during exercise and recovery, which would be an important tool to study muscular physiology. NIR DOI images from the quadriceps muscles before, during, and after intermittent isometric knee-extension exercise. The top left image indicates the approximate location of specific muscles.
Contractions 1, 3, and 5 indicate images obtained during a. Maris et al used frequency-domain NIR optical topography system to map the differences in the hemoglobin concentration in finger extensor muscle during exercise. Yu et al later demonstrated a hybrid frequency-domain diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) system for simultaneous monitoring of muscle hemodynamics and blood flow. DRS can quantify the total hemoglobin concentration and oxygenation saturation, while DCS, an emerging extension of diffuse optical imaging techniques , , quantifies the relative blood flow in deep tissues.
Together, this hybrid technique provides a method for evaluation of muscle microcirculation and metabolism in vivo. Time-domain methods have also been extended into muscle imaging. Hillman et al have used the 32-channel time-domain DOT system to measure the absorption changes of human forearm in response to finger flexion exercise. Zhao et al also developed a time-resolved (TR) DOT system and demonstrated the capability of imaging the forearm during hand-gripping test.
The group at Milan has developed a compact and fast multi-channel TR DOI system to image the calf muscle oxygenation and hemoglobin content during dynamic plantar flexion exercise. These results strengthen the role of DOI as a powerful tool for investigating the spatial and temporal features of muscle physiology. These above results clearly demonstrated that NIR diffuse optical imaging has been widely used for imaging muscle functions and diseases. Although it is difficult to decouple the relative contributions from hemoglobin and myoglobin in the muscle , , DOI will continue to play an important role in imaging muscle functions for athletic training and disease diagnostics. Principle and Instrumentation of OCT OCT is an emerging medical imaging technology which enables cross-sectional imaging of tissue microstructure in situ and in real time.
OCT can achieve 1–10 μm resolutions and 1–2 mm penetration depths, approaching those of standard excisional biopsy and histopathology, but without the need to remove and process tissue specimens. OCT is analogous to ultrasound imaging, except that imaging is performed by measuring the echo time delay and intensity of back-reflected or backscattered light rather than sound. OCT imaging can be performed fiber-optically using delivery devices such as handheld probes, endoscopes, catheters, laparoscopes, and needles which enable non-invasive or minimally invasive internal body imaging.
OCT measurements are performed using a Michelson interferometer with a low coherence length light source. One arm of the interferometer illuminates the light on the tissue and collects the backscattered light (typically referred to as “sample arm”). Another arm of the interferometer has a reference path delay which is scanned as a function of time (typically referred to as “reference arm”). Optical interference between the light from the sample and reference arms occurs only when the optical delays match to within the coherence length of the light source. This technique is generally referred to as “time-domain OCT”. Alternatively, OCT interference signals can be detected in frequency or Fourier domain. In Fourier-domain OCT, the reference mirror position is fixed, and echoes of light are obtained by Fourier transforming the interference spectrum.
These techniques are somewhat analogous to Fourier transform spectroscopy and have a significant sensitivity and speed advantage compared to time-domain OCT because they measure the optical echo signals from different depths along the entire axial scan simultaneously rather than sequentially. Fourier-domain detection enables 10–100 folds improvement in detection sensitivity and speed over the time-domain configuration –.
These advances not only greatly improve the performance of OCT, but enables three-dimensional OCT (3D-OCT) imaging in vivo. Fourier-domain OCT can be performed using two complementary techniques, known as spectral / Fourier domain OCT and swept source / Fourier domain OCT (SS-OCT, also known as Optical Frequency Domain Imaging, OFDI). Three-dimensional imaging of biological tissue in vivo enabled by Fourier-domain OCT promises to have a powerful impact in disease diagnosis ,. To image internal organs, miniaturized catheter/endoscope imaging devices have been developed for intraluminal and intravascular imaging ,.
Other imaging devices such as laparoscopes and needle imaging device have been developed to enable solid organ imaging ,. Nowadays, various OCT imaging probes have been developed for different clinical applications.
Development of such devices facilitates the translation of OCT to clinical applications and allows clinicians to use the enhanced imaging capabilities of this technique to benefit the patients. Clinical Applications of OCT OCT was first demonstrated in 1991. Since then, OCT has rapidly developed as a non-invasive biomedical imaging modality that enables cross-sectional visualization of tissue microstructures in vivo –. The resolution of OCT is one to two orders of magnitude higher than conventional ultrasound, approaching that of histopathology, thereby allowing architectural morphology to be visualized in situ and in real time. OCT enables imaging of structures in which biopsy would be hazardous or impossible, and promise to reduce the sampling errors associated with excisional biopsy.
OCT has been increasingly translated from bench to various clinical applications including ophthalmology –, cardiology –, gastroenterology –, dermatology , dentistry , , urology –, gynecology –, among others. The most developed clinical OCT applications are those focusing on ophthalmic, cardiovascular, and oncologic imaging. Ophthalmic Imaging OCT was first applied for imaging in the eye ,.
To date, OCT has made the largest and most significant clinical impact in ophthalmology. OCT provides cross-sectional views of eye with high resolution, thereby allowing detailed structures to be discerned. The non-contact and non-invasive nature of OCT enables a new way to image the structures in the anterior eye and retina, and reveal the information not available through standard ophthalmoscopes ,. Ophthalmic OCT was first commercialized by Carl Zeiss Meditec, Inc., and is now considered superior to the current standard of care for the evaluation of many retinal diseases. Over 6000 units of Status OCT™ system has been sold to date, and it is estimated that more than 37,000 OCT scans are performed daily in the U.S. With the development of high-speed OCT using spectral/Fourier domain methods, several companies have introduced new OCT instruments into the ophthalmic market in the past few years. The increased availability of high performance OCT will enable a wide range of clinical studies.
The high axial resolution of OCT makes it an ideal imaging modality for the evaluation of fine features such as intra-retinal layers and the vitreal-retinal interface. OCT has been demonstrated for the detection and monitoring of a variety of macular diseases , including macular edema –, macular holes , , central serous chorioretinopathy , age-related macular degeneration and choroidal neovascularization. OCT can also image and quantify the retinal nerve fiber layer thickness, which is a predictor for early glaucoma.
Quantitative nerve fiber layer thickness has been measured with OCT, and correlated with the optic nerve structure and function –. The increasing impact in clinical medicine promotes the rapid development in OCT imaging technologies, which dramatically enhance the imaging performance and clinical utilities of OCT. A comprehensive review of the state-of-the-art ophthalmic OCT has been provided elsewhere. Here we provide a concise overview of these technology advances and their translation into ophthalmic applications. One of the key parameters in OCT imaging is axial resolution.
This is of particular interests in retinal imaging owing to the layered structures of the retina. Enhanced axial resolution enables better visualization of the intraretinal structural details and more accurate diagnosis of diseases. The axial resolution of OCT is inverse proportional to the bandwidth of the low-coherence light source.
Therefore, increasing the bandwidth of the light source enables the improvement in axial resolution ,. Ultrahigh resolution (UHR) OCT achieves superior axial image resolutions of 2–3 μm as compared to 10 μm in standard OCT systems using superluminescent diode (SLD), thereby enabling the visualization of intraretinal structures. UHR OCT is a key technology advance towards achieving non-invasive optical biopsy of the human retina. UHR OCT technology has been investigated in clinical settings to assess its clinical utility. Cross-sectional studies in 1,000 eyes with different pathologies demonstrated unprecedented visualization of all major intraretinal layers especially the photoreceptor layer , –. All intraretinal layers, especially the inner and outer photoreceptor segment, are significantly better visualized by UHR OCT (see ). These studies demonstrated visualization of photoreceptor layer impairment in macular pathologies such as macular holes, central serous chorioretinopathy, age related macular degeneration, foveomacular dystrophies, Stargardt’s dystrophy and retinitis pigmentosa.
Therefore, UHR OCT holds strong potential to enhance early diagnosis by detecting subtle morphological changes in a wide range of retinal diseases. ( A) Improved interpretation of intraretinal layers using ultrahigh-resolution OCT (UHR OCT).
(B) Standard resolution OCT (10 μm axial resolution performed with a commercial OCT system) versus (C) ultrahigh resolution OCT (UHR OCT) with 3 μm. Transverse resolution is also an important imaging parameter. The transverse resolution is determined by the numerical aperture (NA) of the focusing lens. For ophthalmic retinal imaging, the cornea and lens act as the “imaging objective”. In practice, ocular aberrations limit the minimum focused spot size on the retina. Adaptive optics (AO) is a promising approach to correct ocular aberrations in order to decrease the spot size on the retina to improve the OCT transverse resolution ,.
Combining AO with UHR OCT provides isotropic high resolution in the 3D dataset, thereby enabling cellular resolution retinal imaging –. Ultrahigh transverse resolution imaging can also be achieved by using high NA objectives (also called optical coherence microscopy - OCM).
Parallel detection using full-field OCM has been demonstrated on cellular-level imaging of cornea and retina tissues ,. This technology has shown strong promises in clinical translation for in vivo ophthalmic imaging. Imaging speed is another critical parameter in clinical OCT imaging. High speed imaging not only reduces the motion artifacts, but enables comprehensive visualization of the three-dimensional structures. Fourier-domain OCT is a key enabling technology which dramatically increase the OCT imaging speed for three-dimensional (3D) imaging in vivo.
Spectral OCT, commonly operates at 800 nm, has been rapidly developed and translated into retinal imaging. The first demonstration of retinal imaging using spectral OCT was performed in 2002 , and high-speed video-rate imaging was achieved 2003 ,. Three-dimensional ultrahigh-resolution ophthalmic imaging in vivo has been demonstrated on numerous clinical studies –. Three-dimensional OCT provides quantitative measurement of intraretinal layers for early diagnosis of diseases such as glaucoma or diabetic retinopathy, and enables assessment of disease progression or response to therapy.
Shows an example of topographic information of optical disk similar to that obtained by scanning laser tomography system. In addition, spectral OCT systems working at 1000 nm range promise to improve the penetration depth for better visualization of choroidal tissues ,. Topography using three-dimensional, ultrahigh-resolution OCT. Quantitative topography using ultrahigh-resolution 3D-OCT (A) of a normal human optic disk, as compared to those performed by Heidelberg retinal tomography (Heidelberg Engineering, Germany).
Other technological advancements have been applied to ophthalmic imaging as well. Doppler OCT – enables measuring of blood flow velocity in the tissue. Spectral/Fourier domain OCT with Doppler flow imaging has been demonstrate –.
Three-dimensional Doppler OCT enables visualization of 3D retinal vasculature (also called optical coherence angiography , ). Another functional OCT method, polarization-sensitive (PS) OCT , enables detection of depth-resolved tissue birefringence and scattering properties. PS-OCT has been used for imaging the retinal nerve fiber layer (RNFL) changes in glaucoma patients. This method has been applied to image both the anterior and posterior eye imaging –. Recently, significant advances has been made on detecting OCT scattering signals due to functional responses of the retina (also called optophysiology). Functional responses have been observed in vivo on human subjects.
This technique could detect functional impairment before morphological changes. Lastly, multi-modal technology combing OCT with other optical imaging modalities, such as scanning laser ophthalmoscopy (SLO) and fluorescence angiography promises to integrate the information from different methods and enhance the diagnostic capability. Cardiovascular Imaging Another major area for OCT clinical application is cardiology. The potential of OCT for cardiology imaging has been extensively investigated over the past decade –, –. Compared to intravascular ultrasound (IVUS), OCT has an order of magnitude higher resolution, therefore enables visualization of fine structures in the luminal wall (such as the differentiation of intimal, medial, and adventitial layers). Several technological advances, including catheter-based imaging probes and high-speed OCT imaging, have enabled the translation of OCT cardiovascular imaging from the bench to the bedside. Development of small-diameter fiber catheters facilitates the manual feeding of the imaging catheters through the vasculature.
In intravascular OCT imaging, blood will significantly attenuate the signal, which can be alleviated by saline flush or temporary vascular occlusion with balloon. To scan a long segment of an artery within a short interval of saline flush or blood occlusion, high-speed imaging is critical. Recent advancement in high-speed Fourier domain OCT provides exciting new avenue to diagnose vascular diseases and guide the intravascular interventions in real time.
OCT has unique ability to visualize atherosclerotic lesions in microscopic details, and in particular, to detect the vulnerable plaques which has high risks of rupture ,. OCT can distinguish the characteristic morphology of vulnerable plaques including a thin fibrous cap and a large lipid pool, and is able to quantity the increase of macrophage activity ,. The potential of OCT imaging of vulnerable plaques was.