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HindawiJournal of Medical EngineeringVolume 2017, Article ID 3409327, 20 pageshttps://doi.org/10.1155/2017/3409327Review ArticleOptical Coherence Tomography: Basic Concepts andApplications in Neuroscience ResearchMobin Ibne MokbulNotre Dame College, Motijheel Circular Road, Arambagh, Motijheel, Dhaka 1000, BangladeshCorrespondence should be addressed to Mobin Ibne Mokbul; mobin.glab@gmail.comReceived 26 April 2017; Revised 22 June 2017; Accepted 14 September 2017; Published 29 October 2017Academic Editor: Nicusor IftimiaCopyright 2017 Mobin Ibne Mokbul. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Optical coherence tomography is a micrometer-scale imaging modality that permits label-free, cross-sectional imaging of biologicaltissue microstructure using tissue backscattering properties. After its invention in the 1990s, OCT is now being widely used inseveral branches of neuroscience as well as other fields of biomedical science. This review study reports an overview of OCT’sapplications in several branches or subbranches of neuroscience such as neuroimaging, neurology, neurosurgery, neuropathology,and neuroembryology. This study has briefly summarized the recent applications of OCT in neuroscience research, including acomparison, and provides a discussion of the remaining challenges and opportunities in addition to future directions. The chiefaim of the review study is to draw the attention of a broad neuroscience community in order to maximize the applications of OCTin other branches of neuroscience too, and the study may also serve as a benchmark for future OCT-based neuroscience research.Despite some limitations, OCT proves to be a useful imaging tool in both basic and clinical neuroscience research.1. IntroductionAdvances in biomedical engineering have made severalimaging modalities to be an integral part of everyday neuroscience research. Robust efforts of scientists from all overthe world consequently resulted in the development of brainimaging modalities such as magnetic resonance imaging(MRI), functional MRI (fMRI), positron emission tomography (PET), electroencephalography (EEG), and near-infraredspectroscopy (NIRS) [1, 2]. Existing techniques are playinga critical role in visualizing, quantifying, and understandingbrain morphology and function in both clinical and experimental studies. Now both basic and clinical neuroscienceresearch are somehow dependent on the utility of neuroimaging methods. To make the best use of these methods’ potentials and to overcome their limitations by either improvingexisting methods or developing new methods have become afundamental phenomenon today.Rodent models are crucial to the understanding of howblood flow responds to different structures of the humanbrain, in either a healthy or a diseased state [3]. A goodnumber of neuroimaging methods have been developed inthis regard, but they have one or more limitations of thefollowing: they have a low spatiotemporal resolution, they areexpensive, they need the use of contrast agents, they have ashallow depth, they are impractical for rodent brain imaging,they are limited in superficial two-dimensional (2D) images,and so on [3]. Consequently, there has been a growing needof an in vivo noninvasive label-free imaging method with amicrometer-scale spatial resolution and with a good temporalresolution along with comparatively less expensive detectionsystem.Optical coherence tomography (OCT) was first developed by Fujimoto’s group at Massachusetts Institute of Technology (MIT) in 1991 that works based on tissue backscattering properties [4]. OCT takes the advantage of shortcoherence length of broadband light sources to performmicrometer-scale, cross-sectional imaging of biologic tissuesample. Within a short period of time after its invention inthe 1990s, it became an important clinical imaging modalityin several fields of biomedical science such as ophthalmologywhere imaging can be performed through transparent media

2of the anterior eye and the retina [5, 6]. As OCT usesoptical sources at longer wavelengths, OCT can image highlylight scattering soft tissue. OCT’s applications now includecardiology [7, 8], gastroenterology [9, 10], urology [11, 12],dermatology [13, 14], dentistry [15], and even both basic andclinical neuroscience [3, 16–18]. The reason behind its gainingpopularity within this short span of time is OCT’s numerousadvantages that are offered to researchers and clinicians. Theyare (i) quality images (OCT has demonstrated the abilityto render images within a range of 1–10 𝜇m axial resolutionusually and even submicrometer (0.5 𝜇m) resolution too[19]); (ii) imaging speed (OCT can give a temporal resolutionup to milliseconds [20]); (iii) label-free imaging (OCT cangive fine images of cerebral cortex without the need of anycontrast agents [3, 21]); (iv) low cost (compared to someother imaging techniques, OCT is less expensive in mostcases and even researchers from developing countries, wherelaboratories cannot afford to buy other expensive imagingsystems, can use it); (v) additional functionality (while abasic OCT imaging method is able to render depth-resolvedstructural images of the target, more sophisticated OCTimaging strategies can provide additional functional information, such as blood flow (through Doppler OCT), tissuestructural arrangement (through birefringence OCT), andthe spatial distribution of specific contrast agents (throughmolecular contrast OCT) [19]).It is readily apparent that OCT’s unique capability hasmade it an appropriate modality for rodent brain imaging. However, today’s applications of OCT in neuroscienceresearch are not limited to rodent brain imaging. OCTis now being used in neurosurgery [18, 22–24] and evenin several neurologic disorders [17, 25, 26] and in otherbranches/subbranches of neuroscience [27, 28]. The firstintraoperative use of OCT in neurosurgery was demonstratedby Giese et al. in 2006 [23]. OCT has now gained popularityfor intraoperative guidance during brain tumor resectionwhich will be discussed later [18, 22]. Moreover, OCT can beperformed as a noninvasive and no-contact technique overfocal distances of several centimeters and it can be integratedinto surgical microscopes which potentially allows a continuous analysis of the tissue in view by a tomographic image ofthe resection edge in microneurosurgery [6, 24, 29]. A potential application of OCT in experimental neuroendoscopy isalso demonstrated by Böhringer et al. (2006) [30]. Again,in neurology, neuroimaging is central to the exploration fora biological foundation of psychiatric diagnosis, but so farit has not yielded clinically relevant biomarkers for mentaldisorders [1]. However, there has been a recent trend toestablish retina as a reliable and clinically relevant biomarkerand outcome measure for several neurological disorders [17,26]. This important point enabled OCT to be a reproducible,reliable, and quick test for retina-derived biomarker development of some neurodegenerative disorders. Eye and braincome from the same embryological origin and the eye’s retinahas unmyelinated axons and a relatively lower concentrationof glial cells [17, 26]. Moreover, retina reflects brain atrophy inneurodegenerative diseases [25, 26]. Retinal data can be usedto get “meaningful difference” between images within a shortneurodegenerative period [17, 26]. As a result, retinal imagingJournal of Medical Engineeringhas started to shed some new light on clinically relevantbiomarker development of several neurological diseases. Ifwe take into account the fact that the retina is considereda peripheral extension of the brain and both share somecommon features, it becomes easy to understand why OCThas become today a widespread diagnostic tool in manyneurological diseases.Early reviews by Boppart (2003) summarized the utilityof OCT in neuroimaging [16] and Baran and Wang (2016)summarized the utility of OCT angiographic methods inneuroimaging and in some specific neurological diseasessuch as stroke and traumatic brain injury (TBI) [3]. However,this review study is intended for a wider neurosciencecommunity. It will provide an overview of OCT’s applications in several fields of neuroscience (e.g., neuroimaging,neurology, neurosurgery, neuropathology, and neuroembryology). Examples of each of them will be described. Thestudy focused more on OCT’s applications than on imageprocessing algorithms and other basic methodological issues.This study has briefly summarized the recent applications ofOCT in neuroscience, including a comparison, and providesa discussion of the remaining challenges and opportunitiesas well as future directions. It is the author’s hope that thecomparisons provided here can also be of service to the fieldsoutside of neuroscience. The aim of the study is to drawthe attention of a wider neuroscience community in orderto make the best use of OCT’s potentials and to serve as abenchmark for future OCT-based neuroscience research.2. Basic Principle of OCTFigure 1 shows a generic time domain OCT system. Anarchetypal OCT system contains a low-coherence broadbandlight source. The emitted light is coupled into an interferometer. Then the light is divided into two arms: referencearm and sample arm. The reference arm transmits the lighttoward a reference mirror. The sample arm sends the lighttoward the tissue of interest. The sample arm also contains anobjective lens which focuses the light onto the sample tissue(e.g., brain, retina, and carotid artery). The light which isbackscattered from the tissue structures is recombined withthe reference light reflected from a highly reflective ( 95%)moving reference mirror, producing an interference patternthat is detected by a light detector. To reconstruct the twodimensional (2D) or three-dimensional (3D) cross-sectionalobjects, the beam is scanned across the sample surface. Morecomplex systems may include a CCD camera and diffractiongrating.Since the initialization of OCT, two types of OCT implementations have been introduced: time domain OCT (TDOCT) and Fourier domain OCT (FD-OCT) [3]. Besides, FDOCT has two versions: swept source OCT (SS-OCT) andspectral domain OCT (SD-OCT). A typical SD-OCT schemeis very similar to that of a typical TD-OCT scheme (Figure 1).The difference is that the moving reference mirror in Figure 1is immobilized, and the detector in Figure 1 is replaced by alow-loss spectrometer in an SD-OCT scheme. In comparisonbetween these two versions, SD-OCT provides a significantly more detailed microstructure of brain tissues than

Journal of Medical puterReferenceFigure 1: Schematic of a generic time domain OCT system (reprinted with permission from [4]).Table 1: Basic principles of some of the OCT techniques used in neuroscience research.OCT techniquesTime domain OCT (TD-OCT)Fourier domain OCT (FD-OCT)Doppler OCT (D-OCT)Basic principlesA moving mirror in the reference arm, which centers the interference signal on a fixedDoppler frequency. Coherent demodulation, with a lock-in amplifier set to this frequency,enables detection of interference fringes produced by light scattered from the specimenData is acquired from the whole sample depth simultaneously with a fixed path length inthe reference armSpeed of a moving particle is measured by detecting frequency shifts of the light scatteredby the particlePolarization-sensitive OCT (PS-OCT)Sample is exposed to light from multiple polarizations to measure birefringenceSpectroscopic OCT (S-OCT)Wavelength-dependent absorption and light scattering are used to elucidate functionSee [31].conventional TD-OCT [32]. SD-OCT has a higher OCT scanacquisition rate, better sensitivity, enhanced signal-to-noiseratio (SNR), and superior depth penetration or improves thesensitivity of the various functional OCT methods [19]. Thereare some functional OCT extensions as well such as multicontrast OCT (MC-OCT) [25], polarization-sensitive OCT (PSOCT) [33], Doppler OCT (D-OCT) [34], dynamic contrastOCT (Dyc-OCT) [35], second harmonic OCT [36], and thenmost recently molecular imaging true-color spectroscopicOCT (METRiCS OCT) [37]. Optical coherence microscopy(OCM) [13], optical microangiography (OMAG), and so on[3] are some other complex versions based on OCT principle.Table 1 represents a short description of the basic principlesof some of the OCT techniques used in neuroscience researchso far.3. OCT in NeuroimagingCurrent neuroimaging methods like CT scan, MRI, and PETscan provide excellent images of the brain but those imagesoften lack the spatial resolution and imaging speed that isrequired to image in cellular/neuronal level in real time[39]. On the other hand, OCT can provide high-resolutioncross-sectional and volumetric images of nerve fiber bundlesat real-time imaging speed [40]. Table 2 shows a shortcomparison of spatiotemporal resolution of OCT with someother neuroimaging techniques.3.1. Neuroanatomical Imaging. OCT has bridged the gapbetween classical macroscopic methods (e.g., MRI, ultrasounds) and shallow depth microscopic methods (e.g.,confocal microscopy, two-photon microscopy) with itsmicrometer-scale resolution and 2-3 mm imaging depth. Forinstance, Watanabe et al. (2011) reported in vivo 3D visualization of the layered organization of a rat olfactory bulb (OB)by an SS-OCT system [41]. However, before this approach,with methods such as MRI, or confocal microscopy, OBdepth structure in vivo had not been clearly visualized asthese do not satisfy the criterion of simultaneously providingmicron-scale spatial resolution and imaging up to a fewmillimeters in depth. Chong et al. (2015) presented an invivo noninvasive OCT imaging platform in order to imagedeep subcortical brain regions in living mouse with a spatialresolution of 1.7 𝜇m (see Figure 2) [38]. Figure 2(a) showsmouse hippocampal image with 1.7 𝜇m resolution and Figure 2(b) shows white matter vasculature by OCT angiography performed in the same mouse brain. This imagingplatform is also supposed to have applications to monitordisease progression and pathophysiology in rodent modelsof Alzheimer’s disease and subcortical dementias, includingvascular dementia.Rat somatosensory cortex refractive index has been alsomeasured by full-field OCT (ff-OCT) [42]. OCT has beenused in label-free imaging of single myelin fibers in livingrodents that required a time-consuming and invasive histological method in the past [43].

4Journal of Medical EngineeringTable 2: Comparison of spatiotemporal resolution of OCT with other neuroimaging techniques.TechniquesSpatial resolutionTemporal resolutionMillimeter, in someCan be used to trackcases (ultrahigh field)longitudinal changessubmillimeterMagnetic resonance imaging (MRI)Functional MRI entimeter (SPECT)to millimeter (PET)Minutes[1]Minutes[1]Magnetoencephalography hy (EEG)/event-related potentials (ERP)CentimeterMilliseconds[1]Near-infrared spectroscopy (NIRS)CentimeterMilliseconds[2]Optical coherence tomography (OCT)MicrometerMilliseconds[20, 38]Magnetic resonance spectroscopy (MRS)Positron emission tomography (PET)/single positron emission andcomputed tomography (SPECT)1.7 G OCT(deep focus)White mattervasculatureB(a)(b)Figure 2: In vivo imaging of mouse brain subcortical regions noninvasively through the thinned skull by deep focusing using 1.7 𝜇m OCT.(a) A maximum intensity projection of a series of cross-sectional images shows subcortical structures, including the hippocampus proper. (b)Microvasculature in deep white matter regions is visualized using an OCT angiography method and a maximum intensity projection. Scalebars: 0.2 mm (reprinted with permission from [38]).A fundamentally unsolved question in neuroscience ishow the neurons are coordinated and communicated witharchitectural pathways and dynamic circuits to form perception, thought, emotion, and motion [44]. As a result,understanding the neural connectivity has become crucialand it is pressing a need for micrometer-scale advancedbrain imaging methods. Early studies by Nakaji et al. (2008)demonstrated the utility of polarization-sensitive OCT (PSOCT) to image micrometer-meter scale nerve fiber pathwaysin brain [40]. Recently multicontrast OCT (MC-OCT) andserial optical coherence scanner (SOCS) have come intospotlight for quantitative investigations of fiber orientationsand connectome studies of human and nonhuman primatebrains [33, 44, 45]. In addition, there is still no technologythat can be used to acquire microscopic images in undistorted3D space for mapping human brain connectivity. At present,PS-OCT has gained much attention from the investigatorsfor high-resolution ex vivo imaging of the human brainconnectome. Very recently, Boas et al. (2017) presented apossibility of developing a new imaging platform—known asautomatic serial-sectioning PS-OCT (as-PSOCT) for ex vivohuman brain imaging, with which it is possible to resolvehuman neuronal fiber projections and orientations, with3.5 𝜇m in-plane resolution [46]. Though this novel techniquerequires further improvements in image acquisition rate, themethod holds promise to give an improved understanding ofnormal human brain structure and function and of the effectsof neurological disorders at cellular resolution.However, OCT can image only up to a depth of 2-3 mm.As a result, in vivo noninvasive structural imaging of humanbrain is still not possible. It should be remembered that OCTcannot fully substitute MRI or other established techniques

Journal of Medical Engineering5Baseline10 minutes after cocaine21XXZZY500 mFlow velocity (mm/s)40Y500 m(a)4Y651 236 510 GCH20 GCH1310 GCH20 GCHBaseline 5 GCH1 2450ΔCBF (%)Y100X5 GCHBaselineX3054 50604 GG/sEn face ODT04 GG/s4 GG/s 4Side-view ODT(b) 100204812162024Time (min)(c)Figure 3: 3D ODT images of CBFv in mouse somatosensory cortex due to acute cocaine exposure. (a) Dynamic changes of 3D CBFnetworks (FOV: 3 3 1.8 mm3 ) in mouse somatosensory cortex in response to acute cocaine (30 mg/kg, i.p.). (b) En face and cross-sectionalprojections to show the flow dynamics in different vessels (e.g., 1–6) after cocaine. (c) Time-lapse CBF change (ΔCBF%) to track the dynamicsof different vascular compartments (e.g., arterioles and venules) in response to cocaine (reprinted from [47]).but can serve as a supportive tool only in experimental studiesof small animal models.3.2. Neurophysiological Imaging. In experimental settings,OCT neuroimaging has become crucial in studying cerebralblood flow (CBF), cortical hyperemia, capillary perfusion,intracellular motility, oxygen saturation, and other structural and functional changes within intrinsic contrast inliving rodents [48–50]. OCT is the first accepted imagingmethod for in vivo longitudinal monitoring of CBF withhigh resolution in rats and mice [45]. Doppler OCT (DOCT), which is also known as optical coherence Dopplertomography (ODT), has shown great promise in noninvasivemicrovascular imaging and is being widely used to investigateabsolute CBF measurements in the rodent brain [34, 45]. DOCT or ODT derived data offer great leverage in studyingbrain functional activation and cerebrovascular physiology[34, 51]. Moreover, D-OCT also has potentials to assist inthe testing of pharmacological agents in animal models [45].However, high-speed microcirculatory imaging in deep brainwith D-OCT or ODT remained an open quest. Recently,Chen et al. (2016) have developed a 1.3 𝜇m high-speed sweptsource ODT (SS-ODT) system that was capable of detectinghigh-speed microcirculatory blood flow elucidated by acutecocaine in deep brain (see Figure 3) [47]. Figure 3 shows highspeed SS-ODT images for functional imaging of the CBFnetwork dynamics in response to an acute cocaine challenge.Such imaging ability to differentiate CBF dynamics can beof interest for understanding complex relationship betweenbrain function, behavior, and CBF dynamics across differentcortical layers and regions as well as in different vascular trees.Chong et al. (2015) presented a method of measuringcerebral metabolic rate of oxygen (CMRO2 ) by combined DOCT and S-OCT [52]. Park et al. (2015) presented ODT’s usein high-resolution angiography of the cerebral vasculatureand quantitative CBF velocity (CBFv) in order to in vivomonitor neurovascular changes through cranial window dueto chronic cocaine exposure [53]. This methodology canbe used on animal models to explore the neurovascularfunctional changes induced by the brain diseases such as drug

6addiction. Optical coherence microangiography (OMAG)has been used to image label-free in vivo imaging of capillarylevel microcirculation in the meninges in mice with thecranium left intact [54]. Besides, OCT is also being widelyused in studying brain functional activation by some researchgroups [55, 56].Other neurophysiological parameters such as oxygen saturation, hemoglobin concentration, cerebral oxygen delivery,energy metabolism, and red blood cell (RBC) flux are studiedusing OCT [20, 57, 58]. Another important neurophysiological parameter, capillary transit time distribution, waschallenging to quantify comprehensively and efficiently atthe microscopic level in the past [35]. Recently Merkle andSrinivasan (2016) have used dynamic OCT (dyc-OCT) toinvestigate capillary transit time distribution in microvasculature across the entire depth of the mouse somatosensorycortex [35]. The findings may aid in explaining the time kinetics of the blood-oxygen-level-dependent functional magneticresonance imaging (BOLD fMRI) response.Nevertheless, there are some limitations as well in OCTneurophysiological imaging. OCT angiography cannot makeaccurate measurements for those vessels smaller than 20 𝜇m[3]. This problem may be mitigated by a cost-effective higherresolution system with sufficient depth of focus to coverthe entire cortical layer. But this is only the current limit,and different OCT setups are under development whichcan reach a resolution up to 1 𝜇m. Again, in experimentalsettings, thinned skull technique for OCT studies createssome subdural hemorrhage due to vibration of drilling andinterferes from time to time [54]. The remaining thinned skulllacks vasculature, it starts to become opaque within hours,and thinning needs to be repeated if more imaging sessionsare followed days after. To remove this limitation, cranialwindow and catheter probes can be used. In addition, DOCT and other OCT angiographic methods (e.g., OMAG)can measure only axial velocity and typically fail to detect theRBC velocities [3].3.3. Neural Activity Imaging. Neural activity in a neuralnetwork is mostly characterized by action potential (AP)propagation and generation through nerves [39]. APs aregenerated when the nerves are excited by a stimulus eitheras an external input or as a means of internal communicationbetween nerves. Neural probes with high spatial resolutionare needed for both neural recording and stimulating specificfunctional areas of the brain with precision. With multipleadvantages, existing neural recording methods have somelimitations which are shortly mentioned in Table 3 [59].Therefore, there has been a budding need for high spatiotemporal imaging technique for the functional imaging of brainactivity especially from individual neurons with miniaturizedless expensive detection systems.The utility of optical instrumentation to study neural activity dates to the late 1940s [60]. However, Cohen(1973) first pioneered the investigation of optically detectingbirefringence, fluorescence, light scattering, and structuralchanges during AP propagation [61]. These intrinsic opticalsignals can be observed with optical methods such as DopplerJournal of Medical EngineeringTable 3: Disadvantages of some current neural recording , MEG,thermal ImagingPET, fMRI, diffuseopticaltomography(DOT)LimitationsVulnerable to environmental electricalnoises and artifacts caused by electricalstimulation and neural recording and unableto reliably record chronic neural activity inmost casesLimited spatial resolution and/or temporalresolutionLow temporal resolution, huge size, andexpensiveflowmetry (LDF), near-infrared (NIR) spectrometer, functional optical coherence tomography (fOCT), and surfaceplasmon resonance (SPR) [59]. However, intrinsic opticalsignals are very small most often, which has entailed the useof molecular probes [62]. Consequently, fast voltage-sensitivedyes are being widely used to enhance the signal-to-noiseratio (SNR). For this reason, though OCT can render labelfree imaging of neural activity [39, 60, 62], voltage-sensitivedyes are also used in most cases.Akkin et al. (2010) have reported an SD-OCT intensitymeasurement on a squid giant axon with and without beingstained with voltage-sensitive dye to localize neural activityin depth [60]. Yeh et al. (2015) have proposed a functionalOCT scanner to detect cross-sectional neural activity inunmyelinated nerves dissected from squid (see Figures 4and 5) [62]. They conducted the study on both stained andunstained nerves and detected transient phase changes frombackscattered light during AP propagation. Figures 4 and5 show action-potential-related optical path length changes(Δ𝑝 response) in stained and unstained nerves. Their imagingmethod increased the number of recording sites to yieldneural activity in optical cross sections at high resolution,which may support neurophysiological studies in the future.Watanabe et al. (2011) used SS-OCT to guide electrodepenetration in neural tissue for in vivo neural recording [63].This also suggested that the SS-OCT penetration system mayaid future in vivo microinjection studies in neural tissue.OCT neural recording may have a significant impacton functional neuroimaging in near future [39, 60]. It canbe foreseen that OCT would enable the investigators tocompare the local structural and functional changes with ahigh spatiotemporal resolution during AP propagation, andbe used as an alternative or supportive tool to electrophysiology. It has the potential to produce critical data, whichcould increase the understanding of functioning nerve andaid future diagnostic applications [60]. However, OCT isunable to detect functional changes or neural activity in thefreely moving animal because of its bulky system. Furtherdevelopment is required in miniaturization of OCT systemalong with portability for neural recording and improvementof sensitivity.

10.50 0.5048Time (ms)712162020404015158010120160 Δp (nm)80510120160 Δp (nm)AP (mV)Journal of Medical Engineering52002001020(N 90)0301020(N 10)030(8, 41)(8, 41)5 HG5 HG(8, 141)ΔpΔp(8, 141)0246810Time (ms)1214(25, 141)(25, 141)(20, 123)(20, 123)160246810Time (ms)121416Figure 4: Details of the Δ𝑝 response in a stained squid nerve. (a) Action potential; (b) Δ𝑝 response at 8 ms is given by averaging 90 trials(𝑁 90) and (c) 10 trials (𝑁 10). In (b) and (c), arrow indicates the turning point of the galvanometer, and pixel numbers are given on the𝑥-axis and 𝑦-axis. Scale bars: horizontal, 10 𝜇m; vertical, 100 𝜇m. Signal traces in time (d, e) are given for selected pixels (lateral index, depthindex), which are marked by the blue circles in (b), with averaging 90 and 10 trials. Action potential traces in blue are for guidance (reprintedwith permission from [62]).

Journal of Medical EngineeringAP (mV)810.50 0.5048Time (ms)1216540(12, 122)48031202 Δp (nm)Δp(21, 126)(15, 141)1605 HG120010203000246810Time (ms)121416Figure 5: Details of the Δ𝑝 response in an unstained squid nerve. (a) Action potential recording; (b) Δ𝑝 image at 10.5 ms and (c) Δ𝑝 tracesof selected pixels from an unstained nerve with an averaging of 90 trials. Arrow in (b) indicates the turning point of the galvanometer mirror;scale bars: horizontal, 10 𝜇m; vertical, 100 𝜇m. Pixel coordinates in (c) are in the form of (lateral index, depth index), and the locations aremarked by blue circles in (b). The blue trace is the action potential recording for the registering time (reprinted with permission from [62]).4. OCT in NeurologyOCT has been used in answering several clinical questionsof neurology. Apart from experimental neuroimaging studiesmentioned above, recent innovations in establishing retinaas a biomarker to several neurologic disorders have enabledOCT to contribute bravely to clinical neurology too. Earlystudies suggested that several neurologic conditions havepathologic changes in the retinal nerve fiber layer (RNFL) ofthe eye, creating a potential biomarker for neurodegeneration[17]. Utilizing data that can be gathered from examinationsof the eye has allowed novel insights into the neurologicdisease to be garnered and modeling systems to be developed.Thus, OCT has the potential to become a noninvasive,reproducible test for axonal degeneration and could becomean invaluable tool for measuring the efficacy and safety ofpotential neuroprotective agents. Future neurologic clinicaltrials may incorporate OCT data in the outcome measuresfor drug validation. Apart from retinal imaging of neurologicdisorders, OCT is also being used in other subbranchesof neurology and even in neurosurgery which is discussedbelow.4.1. Neurological Disorders. In clinical settings, the majorusers of OCT technology over the last 20 years have beenmostly ophthalmologists, but in these days, it is also beingused by neurologists on patients with neurologic disorders[17]. An early review by Greenberg and Frohman (2010) hasexcellently summarized why and how OCT is contributingto clinical neurology [17]. A number of neurologic diseasesfollow a degenerative course, and neurological diagnosisis dependent on MRI technology in this regard, but itsrepr

optical tomography (DOT) Lowtemporalresolution,hugesize,and expensive flowmetry (LDF), near-infrared (NIR) spectrometer, func-tional optical coherence tomography (fOCT), and surface plasmon resonance (SPR) [59]. However, intrinsic optical e

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