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Abstract
Optical coherence tomography (OCT) is one of the most successful technologies in the history of biomedical optics. Optics Express played an important role in communicating groundbreaking technological achievements in the field of OCT, and, conversely, OCT papers are among the most frequently cited papers published in Optics Express. On the occasion of the 20th anniversary of the journal, this review analyzes the reasons for the success of OCT papers in Optics Express and discusses possible motivations for researchers to submit some of their best OCT papers to the journal.
© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
1. Introduction
Optical coherence tomography (OCT) was introduced as a new modality for high-resolution cross-sectional imaging of transparent and translucent samples and tissues in 1991 [1]. Based on low-coherence interferometric ranging [2] in combination with heterodyne detection [3], it can be regarded as a genuinely new optical imaging technology whose image formation process is very different from classical optical imaging approaches, but also from other tomographic imaging techniques like X-ray computed tomography (CT) or magnetic resonance imaging (MRI). OCT has found many fields of application [4], but its dominating applications are certainly in biomedicine, with ophthalmology being the first and still dominating application field, where OCT has revolutionized retinal diagnostics and is now the gold standard imaging modality [5].
On the occasion of the recent 25th anniversary of OCT, several reviews have been published on various aspects of OCT technology, applications, and history (see, e.g [6–27]; this list is, of course, not exhaustive). However, there seems to be no study yet that analyses the role that specific journals played in the history of communicating OCT technology and applications. While a comprehensive study on publication history for the field of OCT is beyond the scope of this review, the goal of this article is to start shedding some light into OCT publication history by analyzing, on occasion of the 20th anniversary of Optics Express (OpEx), the role that this journal has played, in comparison with competing optics journals.
Founded in 1997, several years after the introduction of OCT, OpEx has, nevertheless, played an important role for communicating groundbreaking technological achievements and applications in the field of OCT. Conversely, OCT has played an important role in establishing OpEx as a major publication organ for the biomedical optics community, which eventually led to the spin-off of Biomedical Optics Express (BOEx) in 2010. The following figures highlight the importance of the interplay between OpEx and OCT: two of the three most frequently cited papers of OpEx are OCT papers [28,29], as well as 16 of the top 100 cited ones (the total fraction of papers with OCT content in OpEx is just 2.4%).
This article first provides a quantitative overview of the development of papers published on OCT in various optics journals. In a next step, an analysis of the reasons for the success of OCT papers in OpEx will be provided, discussing possible motivations for researchers to publish some of their best work on OCT in OpEx. This overview will be accompanied by the presentation of several examples of groundbreaking OCT papers published in OpEx. It should be pointed out that this paper is not intended as a comprehensive review of the history of OCT but is limited to the history of OCT in OpEx. Therefore, several important papers on OCT that were published in other journals are not included here, e.g., several papers on ultrahigh resolution or endoscopic OCT, but also some early papers on functional extensions like Doppler or polarization sensitive OCT. Readers interested in a comprehensive history of OCT and its various subfields are referred to several other review papers (e.g., [6–27]) that cover the various aspects of OCT technology and applications. Furthermore, it should be mentioned that some of the methods used in OCT have relations to technology initially developed for the field of telecommunications, as explained, e.g., in refs [6,30].
2. Methods
2.1 Hypotheses
Optics Express was founded in 1997 as an electronic online-only journal that incorporates several features that were either not available or only available at extra costs in other optics journals at that time [31,32]. Among the attractive features were, e.g., its open access policy, free color images, multimedia content, and rapid time-to-publication. While all of these features were attractive for the OCT community (and also for the biomedical optics community in general), two of these features seem to be of special importance for the success of OCT papers in OpEx: the ability to publish multimedia content and the rapid time-to-publication.
2.2 Data analysis
For the analysis of papers with OCT content, the ISI Web of Science Core Collection database was used. The search was restricted to journals of the “Optics” category since an inclusion of other journals (e.g., medical journals) would be beyond the scope of this work. As search term, “optical coherence tomography” was used in the “topic” category, and the search was limited to the years 1991 – 2009 (in 1991, the term “optical coherence tomography” was introduced [1]; 2009 was chosen as the final year of this analysis since in 2010 the spin-off journal BOEx was founded [33] which drew an increasing number of OCT papers from OpEx; an analysis of the years after the introduction of BOEx is beyond the scope of this work).
The search brought a total of 1718 papers in peer-reviewed journals. For further analysis of papers published per year, and of their citation numbers, the following journals were selected: OpEx, Journal of Biomedical Optics, Optics Letters, Applied Optics, Optics Communications, Journal of the Optical Society of America A, IEEE Journal of Selected Topics in Quantum Electronics (more than 80% of OCT papers in optics journals were published in these journals).
To support the hypothesis that multimedia content played a key role, OpEx papers were analyzed for their multimedia content, comparing papers with OCT content to averages over all OpEx content. For this analysis, the publication years 1997 – 2009 were considered. Again, the ISI Web of Science Core Collection was used. The papers found under topic “Optical Coherence Tomography” were manually checked for misclassifications (e.g. papers that mention OCT in their discussion, thereby citing several other OCT papers, but without having actual OCT content) and misclassified papers were excluded. Each of the papers that passed the content check was manually checked for multimedia content. The results were compared to statistical data on multimedia content across all topic categories in OpEx, per year (these data were provided by OSA Publishing).
For the discussion on the role TTP may have played for the decision of authors to publish in OpEx, TTP data for OpEx and other OSA journals were provided by OSA Publishing for the years 1997 – 2009. Since TTP data for competing journals from other publishers are not directly available, such data were manually collected for the journals: Journal of Biomedical Optics, Optics Communications, and IEEE Journal of Selected Topics in Quantum Electronics by analyzing the submission and publication dates of 10 papers randomly selected from 3 issues, each, of these journals, for the publication years 1997, 2000, 2005, 2009 (i.e., 30 papers for each journal and each year were analyzed for these data by OSA Publishing staff).
3. Results
3.1 Distribution of OCT papers and their citations in optics journals
The search for papers with the topic “Optical Coherence Tomography” in optics journals returned a total of 1718 papers within the years 1991 – 2009 (since the first two volumes of Journal of Biomedical Optics (1996 and 1997) are not covered by the ISI Web of Science Core Collection, these volumes were manually searched for OCT content). Table 1 shows the total number of OCT papers per journal, together with the total number of citations to these papers (as of May 2018), the citations per paper, and the numbers of highly cited papers for each journal. Figure 1 shows the distribution of OCT papers among the 4 strongest journals over the years.
Table 1. Statistical data on OCT papers in optics journals
Fig. 1 Number of OCT papers published per year in four optics journals. AO, Applied Optics; JBO, Journal of Biomedical Optics; OpEx, Optics Express; OL, Optics Letters.
As can be seen in Fig. 1, the first OCT papers were published in optics journals in 1993 (the paper introducing the term in 1991 was published in Science [1] which is a general journal with broad coverage of topics across all fields of science and therefore not counted here). In the first years, until 1996, only 25 papers on OCT were published in optics journals. (Since the term OCT was rather new at that time, it was not exclusively used in the first years, so some OCT related papers that used other terminology like low coherence interferometry, partial coherence interferometry, etc., might have been missed here). The dominating optics journal for OCT papers in the first years was clearly Optics Letters, publishing 13 of the 25 papers from 1993 – 1996 (before the foundation of OpEx). Optics Letters dominated until 2003. Publication numbers of OCT papers in OpEx increased slowly until 2002, drawing nearly equal with Optics Letters in 2003 (24 vs. 29 papers). In 2004, OpEx surpassed Optics Letters in paper count and remained the leading journal until 2009 (the end of the period of this analysis).
As can be seen in Table 1, Optics Letters and OpEx are also dominating in terms of impact of their OCT papers. Not only the total numbers of citations to their OCT papers is stronger, but also the citations per paper, and the number of highly cited papers. OpEx is the only optics journal that has OCT papers with more than 1000 citations (2 papers [28,29]), and OpEx and Optics Letters have a considerable majority of papers with more than 500, 300, and 100 citations, with the third ranked journal in this respect being Journal of Biomedical Optics.
3.2 Multimedia content
The option to publish multimedia content was one of the most attractive features of OpEx, especially in the early days of the journal when this type of content was unique among optics journals. Most of the multimedia content in OpEx were short video clips that were used by the OCT community to demonstrate time series of OCT images, fly-through movies to present serial sections of 3D data sets, or animated (e.g., rotating) volume renderings as another way to visualize 3D data sets.
From 1997 to 2009, a total of 10182 papers were published in OpEx. 1454 (14.3%) of them had multimedia content. The search for papers with topic “optical coherence tomography” provided 414 hits for that time frame, after manual correction for misclassifications, 338 papers remained. 129 of them (38.2%) had multimedia content. Figures 2 and 3 compare these data in more detail.
Fig. 2 Papers published in OpEx per year (blue: total; red: with multimedia (MM) content). (a) all papers; (b) OCT papers.
Figure 2(a) shows the total number of papers per year published in OpEx, together with the number of papers with multimedia content, while Fig. 2(b) displays the OCT papers per year, together with the OCT papers that contain multimedia files. While multimedia papers make up only a small fraction of total papers in OpEx, the OCT papers have a considerably larger fraction of multimedia content. This fact is also clearly visible in Fig. 3, which shows the percentage of multimedia papers across all content (blue bars) and for OCT papers (red bars). Especially since 2003, multimedia content in OCT papers is consistently higher than in the general case (data for the early years suffer from statistical fluctuations associated with the low OCT paper counts in these years).
Another interesting observation is that OCT papers with the highest citation frequencies are likely to have multimedia content. For the publication years 2003 – 2009, at least 2 of the 3 most frequently cited OCT papers per year have multimedia content. The striking exception is 2003, where none of the top 3 cited papers has multimedia content – this will be discussed in chapter 4.2.
3.3 Time to publication
Table 2 summarizes TTP data for various optics journals in the years 1997, 2000, 2003, 2005, and 2009. The data are median times from receipt of submission to publication. For 2003, only data from OSA journals were available (because of the special importance of TTP data in this year, cf. section 4.2, I decided to include these data even though they are not available for all journals). As can be seen, TTP for OpEx ranges from 46 to 65 days, by far the shortest time among all compared journals.
Table 2. Time to publication of various optics journals
4. Discussion
In this chapter, I strive to interpret and discuss the data on development of OCT publications in OpEx over the years, and the possible motivations of authors to publish in the journal. I shall divide this discussion into three sub-chapters, discussing three phases of OCT technology development: (1) the early phase (1997 – 2002); (2) the year of the OCT technology paradigm change from time domain to spectral (or Fourier) domain (2003); and the later phase (2003 – 2009). For each phase, I will briefly present some of the high-impact (highly cited) OCT papers and discuss their relevance to the field as well as the relevance of OpEx features like multimedia and time-to-publication.
4.1 The early phase: 1997–2002
OpEx was founded in 1997 and received its first Journal Impact Factor (JIF = 1.811) from the ISI Web of Science in 2001 for the year 2000 (considering all citations made in papers included in the ISI Web of Science in the year 2000 to papers published in OpEx in the two previous years: 1998 and 1999). In this early phase, a total of 25 OCT papers were published in OpEx, two already in the first year [34,35], as part of a focus issue on biomedical optics [36]. The first of these two papers [34] is the first ever OCT paper in OpEx with multimedia content, featuring two video clips that demonstrate high-resolution color Dopper OCT of a beating Xenopus laevis heart. Imaging technology at that time was still slow (8 A-scans/s), so a special gating method had to be used to reconstruct a video clip showing a cross sectional movie covering one heart beat cycle (cf. Figure 4). The video clip was extracted from a longer data acquisition sequence by gating A-scans corresponding to the same phases of the heart beat cycle and re-ordering all scans to generate the movie.
Fig. 4 Reconstruction of a beating Xenopus heart using frame gating technique, played back at 0.75 times real-time (Visualization 1). Doppler processing is restricted to region indicated by rectangle. v, ventricle; a, atrium; ta, truncus arteriosus; p, pericardium; bv, branched vessels; d, diaphragm. Reprinted from Ref [34].
The second paper [35] demonstrates an in-vivo endoscopic application of OCT imaging to differentiate normal from cancerous mucosa in various internal organs. Both papers are heavily cited, the latter one being, with nearly 300 citations, the most frequently cited paper in its focus issue.
To raise the awareness for the new journal and its possibilities in the OCT community, a focus issue on OCT was organized in the following year by guest editor B. Bouma [37]. Four of the seven papers included in this focus issue contain multimedia files, and 6 of the seven papers are highly cited (> 100 citations), with the four having multimedia files being the most frequently cited papers of the focus issue. Rollins et al. [38] used the shortly before developed rapid scanning optical delay line [39] to demonstrate video rate OCT imaging (up to 32 frames/s at 4 kHz A-scan rate) of a beating Xenopus laevis embryo heart, the fastest OCT imaging demonstrated so far. J.M. Schmitt [40] demonstrated a new functional extension of OCT: OCT elastography, enabling the imaging of microscopic deformation and strain in tissue by 2D cross-correlation speckle tracking. Two movie clips in the paper demonstrate the method in a phantom and in tissue (pork muscle). Optical coherence elastography is now a rapidly expanding functional extension of OCT that has found many application fields [17]. Another functional extension of OCT published in this focus issue is polarization sensitive (PS) OCT that was used by de Boer et al. for the first time to image thermal damage in tissue via the reduction of birefringence in collagen [41].
In addition to functional extensions, also new application fields of OCT were demonstrated in the 1998 focus issue, e.g. imaging in dentistry [42] and in the oral cavity [43]. A non-biomedical OCT paper published not as part of the focus issue in 1998 should also be mentioned here: Duncan et al. published one of the first applications of OCT to non-destructive materials characterization [44], a field that later gained considerable interest [45].
After the “high” of nine OCT papers in 1998, publication numbers dropped in the following year to zero, followed by a slow rise to seven in 2002. For the year 2000, two papers that explored new ways of recording 3D data sets should be mentioned. Podoleanu et al. used an en face OCT scheme based on transverse scan priority, generating en face scans at successive imaging depths, and mounting these scans to 3D data sets [46]. Several video clips illustrated the method in retina and skin. M.K. Kim used a digital interference holography technique in combination with wavelength scanning to create 3D data sets of an insect which was also illustrated with a fly-through movie [47]. Although the depth resolution was rather limited, the paper is remarkable since the method has relations to recent developments of ultra-high-speed full-field swept source OCT [48].
In the following two years that mark the end of the “early phase” of OCT in OpEx, increasing interest in exploiting phase information from OCT signals and using it for various purposes led to some of the most frequently cited OCT papers of that period in the journal. Hitzenberger et al. expanded PS-OCT by using the phase information of the OCT signal to measure and image the optic axis orientation of birefringent samples [49], while Fercher et al. employed the phase for numerical dispersion compensation [50], and Ding et al. developed an improved high speed Doppler OCT method for blood flow imaging based on phase measurements [51].
Phase measurement from time domain OCT signals was complicated in these times, typically employing numerical [49] or optical [51] Hilbert transforms. The procedure of phase extraction from OCT signals was greatly simplified in later years by a new generation of OCT technology: Fourier domain (FD; or spectral domain: SD) OCT. This technology had its break-through in 2003, when it led to a paradigm change in OCT technology.
4.2 2003: the year of OCT paradigm change
The year 2003 marks the transition from TD to FD-OCT. Of course, this transition was not abrupt, and several interesting OCT concepts were still demonstrated with TD technology in 2003 and later. Povazay et al. [52] were the first to demonstrate, still with a TD technology setup, that OCT at ~1050 nm center wavelength has a better penetration through the highly scattering retinal pigment epithelium than OCT in the 800 nm regime which was the dominating wavelength for retinal imaging at that time (and still is the most frequently used wavelength in commercial ophthalmic OCT systems). This longer wavelength is therefore better suited for imaging deeper layers like the choroid, and more and more instruments operating at that wavelength are now being commercialized.
Other groups strived to improve functionality and speed of TD-OCT systems. Park et al. demonstrated a multi-functional high-speed TD-OCT system, employing a rapid scanning optical delay line operating at 2 kHz A-scan rate, for simultaneous imaging of intensity, polarization, and flow data [53]. Hitzenberger et al. developed a TD-OCT system based on en-face scanning in combination with an acousto-optic modulator that allowed recording of a 3D retinal data set in 1.2 seconds, the fastest TD-OCT retinal scanner so far [54]. This paper stretched TD-OCT to its limits in terms of speed and sensitivity. While the transversal scanning scheme allowed a somewhat higher illumination power because of the very high raster scan speed, thereby coming close to a speed of 1 volume/s, this came at the cost of reduced sensitivity and resolution. To overcome the limits of TD-OCT, a completely new technology was required [12].
Fourier domain OCT replaces the PIN diode in the interferometer’s detection arm by a spectrometer, and the depth information is retrieved by a Fourier transform of the detected spectral interferometric signal (this version is commonly called spectral domain (SD) OCT; another option is to record the spectral information over time using a laser that can be tuned in wavenumber, now commonly called swept source (SS) OCT). While the idea to use this method for intraocular ranging was already mentioned briefly by Fercher et al. in 1991 [55], its first demonstration for one-dimensional measurements (measuring the thickness of a human cornea in vivo) had to wait until 1995 [56], and first OCT images were presented by Haberland et al. in 1996 [57], Chinn et al. 1997 [58] (both using SS-OCT), and by Häusler and Lindner in 1998 [59] (SD-OCT). The early work on FD-OCT suffered from technology shortcomings (line scan cameras, tunable lasers) at that time. The situation improved with the advent of fast, sensitive, and high-resolution line scan cameras at the turn of the millennium. In early 2002, Leitgeb et al. first presented preliminary equations for the shot noise limit of SD OCT and predicted a huge sensitivity advantage over TD OCT [60]. In the same year, Wojtkowski et al. demonstrated first in vivo images of a human retina by SD OCT that clearly indicated a superior sensitivity over TD OCT [61].
At this point, end 2002/early 2003, indications were clear that FD OCT was potentially superior to TD OCT. Different groups were now independently striving to quantify and demonstrate this advantage. Leitgeb et al. were the first to succeed in publishing a comprehensive theoretic derivation of the FD OCT sensitivity advantage, including shot noise, excess noise, and receiver noise terms, together with an experimental demonstration of the theoretic results [28]. Figure 5 shows the theoretic sensitivity curves, calculated for FD and TD OCT, together with experimental results for the experimental conditions of that work, that are in good agreement with theory. The parallel detection scheme of FD OCT improves the sensitivity of FD OCT over TD OCT by a factor proportional to the number of detector elements of the line scan camera (2-3 orders of magnitude improvement are nowadays achievable). These results were confirmed shortly thereafter by de Boer et al. [62], who independently arrived at the same results by a different theoretic approach, and expanded by Choma et al. to swept source OCT [29], demonstrating theoretical equivalence of the two methods. Together, these three papers are now regarded as the basis of the paradigm change in OCT from TD to FD OCT which has since largely replaced the first generation TD technique.
Fig. 5 Sensitivity advantage of FD OCT versus TD OCT. Plot of sensitivity as a function of reference arm reflectivity. Red curve: theoretic plot of FD OCT sensitivity; blue curve: theoretic plot of TD OCT sensitivity; Σ excess: theoretic excess noise limit; Σ rec: theoretic receiver noise limit; Σ shot: theoretic shot noise limit; and squares: measured sensitivity with an FD OCT setup. Reprinted from Ref [28].
Two of these three papers [28], and [29], were published in OpEx, one [62] in Optics Letters. None of these papers contains multimedia files. The reason for submitting two of the papers to OpEx was clearly its rapid TTP. This was confirmed by the authors in private communication: suspecting that other groups were working on similar ideas, they wanted to have their papers published as soon as possible, so the choice was to publish in OpEx. Publishing in OpEx payed off, as can be seen from submission and publication dates: The first paper [28] was published 35 days after submission (submission date: March 17, 2003, publication date: April 21, 2003), the third paper [29] was published 49 days after submission (July 21 to Sept. 8). The second paper [62] took nearly seven months until publication (April 7 – Nov. 1); although being submitted only three weeks after the first paper, it was the last paper to be published. This reversed order of publication dates is reflected in citation counts: while the first paper [28] has a total of 1294 citations in the ISI Web of Science Core Collection as of the day of writing these lines (early June 2018), and the third paper [29] has 1123 citations, the second paper [62] has only 877 citations. The short TTP of OpEx was clearly an advantage.
After the demonstration of the FD OCT sensitivity advantage, the groups involved in this more theoretical work strived to capitalize on the new insights and rushed to experimental demonstrations of the technology and its advantages in real tissue. Yun et al. were the first to demonstrate high-speed FD OCT at speeds of 15 – 20 kHz A-scan rate in the wavelength regime of 1.3 µm in human skin. Within 2 months, they published two papers, demonstrating both versions of the technology, swept source [63] and spectrometer based [64] systems, both clearly benefiting from the FD advantage. Both papers are very highly cited; they don’t contain multimedia files but clearly drew advantage from rapid TTP (this group had previously suffered from the slower TTP of Optics Letters, now both papers were published within two months of submission).
Apart from the improved sensitivity, FD OCT has another advantage: the Fourier transform of the real-valued spectral interference data yields a complex depth scan signal from which the phase information can directly be extracted. This greatly simplifies velocity measurements by Doppler OCT: if two successive A-scans are recorded at the same position (or with sufficient spatial overlap), their phase difference can be directly calculated, and this phase difference is proportional to the velocity of the backscattering particles [60,65]. Although this method of FD Doppler OCT had been demonstrated before [60], the experimental equipment (CCD line scan camera) had not been sufficient to exploit the FD OCT sensitivity advantage. With new CCD camera technology available, the next goal of the involved research groups was demonstrating high-speed FD Doppler OCT to image blood flow in human retinal vessels. Leitgeb et al. were the first to submit and publish their paper [66], followed by White et al. a few weeks later [67]. The systems worked at speeds of 25 kHz and 29 kHz A-scan rate, respectively, and both papers demonstrated video clips of pulsatile bi-directional blood flow in human retinal vessels. Figure 6 shows a video clip recorded over ~3.3 seconds, illustrating structural and bi-directional flow information [67]. Both papers have more than 300 citations and are the first to demonstrate the benefit of high-speed FD OCT imaging to generate real-time high-resolution video clips of dynamic changes in the human retina. Both papers also drew advantage of rapid TTP, being published in less than two months after submission. This advantage is underlined by considering that another paper by Leigeb et al. that demonstrated FD Doppler OCT in a phantom measurement had been submitted to Optics Letters two months before the submission of their OpEx paper, but was published two months after the latter. Thereby, although submitted earlier, it was already outdated at the day of publication by the results published in the OpEx paper. The result, in terms of impact, is that the Optics Letters paper received less than half the citations of the OpEx paper, a striking demonstration of the advantage of fast publishing.
Fig. 6 Movie of structure (top panel) and bi-directional flow (bottom panel) acquired in vivo in the human eye at a rate of 29 frames per second (Visualization 2). The sequence contains 95 frames (totaling 3.28 seconds) played back at a rate of 10 frames per second. Image size is 1.6 mm wide by 580 μm deep. a: artery; v: vein; c: capillary; d: choroidal vessel. Reprinted from Ref [67].
4.3 The later phase: 2004–2009
After the year of the FD OCT break-through, OCT paper numbers in OpEx were strongly increasing, with constantly more than 30 papers per year and a peak of 76 papers (after correction for misclassifications) in 2009. Therefore, only a minor part of these papers can be discussed here. Rather than discussing these papers by year, I try to group them according to different topics. A general line of development in these years was that researchers rushed to convert the various OCT extensions that had been previously demonstrated with TD OCT into FD versions. It was clear that much was to win here in terms of impact and citation counts.
After the first demonstrations of 2D imaging, the natural next step was demonstration of high speed 3D imaging. Nassif et al. were the first to demonstrate volumetric imaging of the human retina with the new technique, demonstrating fly-through video clips of the macula and the optic nerve head [68]. Being published within less than two months after submission, this paper again demonstrates the advantages of fast publishing: the same group had submitted a paper on 2D retinal imaging with the new FD OCT technique to Optics Letters more than three months earlier [69] which was, however, outdated when it finally appeared about three weeks after the OpEx paper with its 3D results (however, both papers have nearly similar citation counts). Another attractive feature of the 3D OCT data sets was to generate en-face projection (pseudo SLO) images directly from them, as demonstrated by Jiao et al. [70] which were, of course, perfectly registered to the OCT B-scans, greatly helping with visual location of the cross sectional images on the ocular fundus.
Another step was the combination of a high-speed FD OCT retinal scanner with a broadband Ti:Sapphire laser, yielding the first ultra-high resolution (UHR) FD OCT images in the human retina by Leitgeb et al. [71]. Shortly thereafter, UHR OCT was extended to 3D imaging by Wojtkowski et al. [72] and Cense et al. [73], with both papers published in the same issue of OpEx. Figure 7 shows an UHR FD OCT image of a human retina in vivo, demonstrating the benefits of numerical dispersion compensation [72]. With the availability of even faster CMOS line scan cameras a few years later, imaging speed of retinal OCT scanners could be increased even further, into the multi-100 kHz regime [74].
Fig. 7 Ultrahigh-resolution SD OCT images of human macula. a) Image with unmatched dispersion. b) Same image with dispersion numerically corrected to second and third orders. These images consist of 3000 axial scans acquired in 150 ms. Adapted from Ref [72].
Not only axial but also transverse resolution was improved. This was achieved by combining OCT with adaptive optics (AO), a technology originally developed for astronomy and later extended to high-resolution imaging of the retina, correcting ocular aberrations by a deformable mirror [22]. Although first combinations of AO with OCT were demonstrated with TD technology [75–77], the improved imaging speed available by FD OCT triggered increased interest in this combination. Zhang et al. demonstrated short video bursts of 2D cross sectional B-scans, visualizing individual cone photoreceptor segments [78]; shortly thereafter first small 3D retinal volumes with resolution of the cone photoreceptor mosaic [79,80] were published. Both papers illustrated their results by video clips of volume rendered data sets. To push this technology to its resolution limit, a further aberration correction by an achromatizing lens is needed, as demonstrated by Zawadzki et al. [81] and Fernandez et al. [82].
While the high sensitivity and imaging speed achieved by FD OCT were huge advantages, the new method also suffered from a disadvantage: the imaging depth was limited by the spectrometer resolution and by mirror artifacts arising from the Fourier transform of the real-valued interference spectra to ~3 mm for most of the spectrometers used at that time. While this depth was sufficient for retinal imaging, other applications like anterior segment imaging demanded larger imaging depths. A solution to this problem was full range complex (FRC) OCT. By exploiting methods of phase shifting interferometry, the mirror artifacts could be eliminated and the measurement range doubled. For this method, two or more A-scans have to be recorded at the same sample position, with a sub-wavelength shift of the reference mirror in between them [83]. Initially, piezo actuators were used for these mirror shifts [83–85]. However, for the high scanning speeds available now, faster methods had to be developed, and most of them were first published in OpEx, e.g., the use of 3x3 fiber couplers by Sarunic et al. [86], electro-optic modulators by Götzinger et al. [87], or acousto-optic modulators by Bachmann et al. [88]. Finally, the use of an offset of the sample beam from the pivot point of the galvo scanning mirror in the sample arm by Baumann et al. [89] eliminated the need for additional phase modulators. For SS OCT, a similar problem exists; Yun et al. [90] demonstrated a solution by an additional frequency shift, introduced in the reference beam by an acousto-optic frequency shifter that eliminates the ambiguity between positive and negative path delays, thereby doubling the imaging range.
Apart from high speed and high resolution imaging, a main focus of OCT research was placed on exploring functional extensions of OCT. As mentioned in section 4.2, Doppler OCT was the first of the extensions combined with the new high speed FD OCT systems. While the measurement of blood flow was an attractive idea, the dependence of absolute flow speed measurement on the knowledge of the Doppler angle was problematic, and presently still considerable research efforts are going on to solve this problem. However, a simpler derivative of this technique is meanwhile commercially available and has found widespread applications in ophthalmic imaging: optical coherence angiography (OCT-A).
OCT-A does not quantitatively measure blood flow speed but just provides a binary information: is motion present in a given voxel: yes or no? For this purpose, various methods have been developed and demonstrated, probing a sample position twice (or multiple times), with a short time interval in between, and analyzing for differences in phase, intensity, or both. The resulting difference (or variance) images identify blood vessels by the varying contrast of the blood cells moving within them.
OCT-A was first demonstrated by Makita et al. who also introduced the term “optical coherence angiography” [91]. They used a phase based method and demonstrated depth resolved display of vessels in different vascular beds of the human ocular fundus (cf. Figure 8). Fly-through movies and video clips of animated volume renderings further illustrate the results. The method has two main advantages over conventional angiography: it is non-invasive, i.e., no contrast agents are needed, and it provides 3D information on the vascular structure. These advantages generated great interest in the new method and several research groups demonstrated further improvements [92–96] and extended applications to other tissues like the brain [97,98].
Fig. 8 Optical coherence angiography of the optic nerve head of the human eye. Each image is produced by the integration of (A) the entire depth, (C) tissue region, (D) retinal part, and (E) choroidal part of the power of Doppler shift images. And (F) is a combination of (D) and (E). In the cross-sectional flow image (B), each integration range is indicated. Reprinted from Ref [91].
Another functional extension of OCT adapted to the requirements of FD OCT was PS OCT [20]. In the spectrometer based version, two spectrometers were initially required to measure the horizontal and vertical polarization state simultaneously. Park et al. first demonstrated a multi-functional OCT at 1.3 µm wavelength that could measure backscattered intensity, retardation, and flow information [99]. For polarization sensitive measurements, the sample was illuminated, at alternating A-scans, with two polarization states that are orthogonal on the Poincaré sphere. Volumetric imaging in living human skin was demonstrated using fly-through video clips.
Götzinger et al. were the first to develop a high speed SD PS OCT retinal scanner at 840 nm [100]. This system illuminated the retina with a single, circular polarization state and provided reflectivity, retardation, and birefringent axis orientation. 3D data sets were demonstrated by fly-through and animated volume rendering video clips. Birefringence was observed in the retinal nerve fiber layer, Henle’s fiber layer, and at the rim of the scleral canal, while polarization scrambling (depolarization) was observed in the retinal pigment epithelium (RPE). The latter effect, that had already been observed with a TD PS OCT system based on en-face priority scanning [101], was later used to segment the RPE by its intrinsic, tissue specific depolarization contrast [102]. Figure 9 shows a video sequence of the segmentation of the RPE in a patient with age-related macular degeneration. Yamanari et al. developed a swept source based PS OCT system operating in the 1.3 µm wavelength regime and employing continuous source polarization modulation [103]. The two orthogonal polarization states were recorded simultaneously with two balanced detectors, and the method was demonstrated in chicken muscle and the human anterior eye segment in vivo.
Fig. 9 Frame no. 49 of an animation of a 3 dimensional volume rendered data set from a retina with age related macula degeneration. The gray value corresponds to the backscattered intensity, the red layer which appears during the movie corresponds to segmented RPE layer. Reprinted from Ref [102] (Visualization 3).
The highest OCT imaging speeds are nowadays achieved with SS OCT instruments. A key role for these systems played the development of suitable light sources with high tuning speed and range, operating at suitable wavelength ranges. Initial experiments to achieve high scanning speeds by Yun et al. used polygon scanner based wavelength filters [104]. Vakoc et al. from the same group later demonstrated Doppler OCT in human skin with an SS OCT system based on a polygon scanner [105]. In 2005, Huber et al. developed a tunable laser based on a compact fiber ring design, a semiconductor amplifier, and a tunable Fabry-Perot filter that achieved an output power of 45 mW and a scanning speed of 20 kHz [106]. This laser was demonstrated for SS OCT imaging of human skin. A year later, the same group published a groundbreaking new swept laser design, the Fourier domain mode locked (FDML) laser, achieving scan rates of 290 kHz, operating at a wavelength of ~1300 nm [107] and demonstrated 3D imaging of human skin with 3.5 volumes/s. With more than 500 citations, this paper is one of the most frequently cited OCT papers; the FDML design was constantly improved in the following years, boosting the sweep speed into the multi-MHz range [108].
Several groups worked on high speed 3D imaging by SS OCT technology, and only a few highly cited papers in OpEx can be mentioned here, all of them making use of multimedia content. Yasuno et al. used one of the first commercial high speed swept sources to image the anterior segment of the human eye in 3D [109]. The source operated at 20 kHz and was based on a fiber ring cavity and a polygon scanner for wavelength scanning. Lee et al. used a source centered at 1050 nm, also based on a polygon scanner and operating at ~19 kHz, to image the human ocular fundus [110]. They capitalized on the better penetration of 1050 nm light and were able to image down to the choroid (this advantage of 1050 nm radiation had been demonstrated the year before for the first time in human eyes in vivo by Unterhuber et al., using a TD OCT system [111]). Jenkins et al. demonstrated the use of the new FDML laser technology to image an embryonic avian heart at 100 kHz A-scan rate [112]. B-scans were recorded at 195 frames/s, and 3D data sets at rates of 10 volumes/s, enabling the detailed observation of morphologic heart dynamics without gating for the first time.
Finally, it should be mentioned that, in addition to technologies and methods discussed above, several more interesting extensions, applications, and methods of OCT were reported in OpEx that received high citation numbers and partly capitalized on the journal’s multimedia capabilities. For space limitations, I can just mention a few of them briefly.
Quantitative OCT measurements of optical properties of scattering phantoms and tissues like attenuation coefficient, scattering coefficient, and anisotropy factor were measured by Faber et al. [113] and Levitz et al. [114]. Such data can be useful for tissue differentiation and identification in clinical diagnosis. Another method that exploits intrinsic tissue properties is optical coherence elastography (OCE), a technique already mentioned previously in the context of TD OCT. This technique measures mechanical properties of tissue and was now combined with FD OCT technology to image tissue phantoms [115] and human skin in vivo [116], at that time still with a technique that combined a TD and an SS OCT system. OCE later evolved to an important subfield of functional OCT [17].
Other researchers used extrinsic contrast agents for a better visualization of tissues. E.g., Oldenburg et al. used magnetic nanoparticles under a modulated magnetic field to generate improved contrast in Xenopus laevis tadpoles [117]. The same group later used gold nanorods with low backscattering albedo as a contrast agent [118], while Adler et al. instead used highly absorbing gold nanorods for photothermal detection; illuminated by a laser beam, the absorbing nanorods generate local temperature oscillations that translate into slight path length variations measurable by OCT [119].
Another important extension of OCT comprises access to internal organs by coupling the sample arm to endoscopes or catheters. This work was continued and intensified in the years 2004 – 2009 (and later). Part of this research focused on improvement of resolution by employing broadband light sources. E.g., Herz et al. used a Cr4+:Forsterite laser and achieved a resolution of < 5 µm in the gastro-intestinal tract of rabits (still with a TD OCT system) [120]. However, the paradigm change to FD OCT also took place for endoscopic applications. Tumlinson et al. developed an endoscopic FD OCT system employing a broadband Ti:Sapphire laser and demonstrated imaging with 2.4 µm axial resolution in a mouse colon in vivo [121]. Further important developments comprised multifunctional endoscopic FD OCT, demonstrating reflectivity and birefringence imaging in the human oral cavity by Kim et al. [122], and ultrahigh speed endoscopic SS OCT, using an FDML laser at 62 kHz sweep rate, demonstrated by Adler et al. in human colon in vivo [123]. Endoscopic and catheter based OCT also evolved into broad research fields since, more information can be found in recent reviews [15,21].
4.4 Interactive science publishing
In 2008, OpEx explored new ways of presenting 3D data sets and large original data sets. In cooperation with the National Library of Medicine, The Optical Society (OSA) developed the concept of Interactive Science Publishing (ISP). Full 3D data sets could be published and viewed by special software that enabled interactive real time viewing and rendering. To demonstrate the capabilities of this new publishing paradigm, an ISP focus issue “Optical coherence tomography in ophthalmology” was published in OpEx [124]. This focus issue comprises 18 invited research papers that showcase methods and possibilities of ISP publishing in various fields, comprising OCT technology [125–128], functional extensions of OCT [129–131], visualization and image processing [132–134], as well as applications of OCT in imaging of glaucoma [135–138] and retinal disease [139–142]. A detailed discussion of these papers is beyond the scope of this review. While the concept of ISP attracted considerable interest, it should be mentioned that, in 2008–2009, it was probably ahead of its time and later discontinued. The main problem was that data sets could only be generated and viewed by special proprietary software which limited the flexibility of further developments. However, advanced and more flexible tools might revive this idea in coming years.
5. Outlook: 2010 and beyond
Because of the large increase in submissions from the biomedical optics community, OSA Publishing decided to start a spin-off journal of OpEx, Biomedical Optics Express, which had its inaugural issue published in August 2010. Over the following years, BOEx drew more and more biomedical optics papers, including OCT papers, from OpEx, and in 2011, BOEx already published more OCT papers than OpEx (80 vs. 62). Last year (2017), the number of OCT papers in BOEx was nearly three times higher than those in OpEx (145 vs. 54), however, OpEx still has a good fraction of OCT papers, comprising especially papers with pure technical content or with non-biomedical applications. In BOEx, the OCT papers remain to be one of the most successful categories of the journal, as recent download and citation statistics indicate.
Acknowledgments
The author acknowledges fruitful discussions with Rainer Leitgeb, Medical University of Vienna, and with Joe Izatt, Duke University, on the rationale for publishing papers in OpEx. Furthermore, the provision of statistical data on multimedia use in OpEx, and on TTP data of various journals by John Long (OSA Publishing) is gratefully acknowledged.
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94. L. An and R. K. Wang, “In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography,” Opt. Express 16, 11438–11452 (2008).
95. J. Fingler, R. J. Zawadzki, J. S. Werner, D. Schwartz, and S. E. Fraser, “Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique,” Opt. Express 17, 22190–22200 (2009).
96. A. Szkulmowska, M. Szkulmowski, D. Szlag, A. Kowalczyk, and M. Wojtkowski, “Three-dimensional quantitative imaging of retinal and choroidal blood flow velocity using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 17, 10584–10598 (2009).
97. R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15, 4083–4097 (2007).
98. R. K. Wang and S. Hurst, “Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3µm wavelength,” Opt. Express 15, 11402–11412 (2007).
99. B. H. Park, M. C. Pierce, B. Cense, S. H. Yun, M. Mujat, G. J. Tearney, B. E. Bouma, and J. F. de Boer, “Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 mu m,” Opt. Express 13, 3931–3944 (2005).
100. E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13, 10217–10229 (2005).
101. M. Pircher, E. Götzinger, R. Leitgeb, H. Sattmann, O. Findl, and C. K. Hitzenberger, “Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT,” Opt. Express 12, 5940–5951 (2004).
102. E. Götzinger, M. Pircher, W. Geitzenauer, C. Ahlers, B. Baumann, S. Michels, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography,” Opt. Express 16, 16410–16422 (2008).
103. M. Yamanari, S. Makita, and Y. Yasuno, “Polarization-sensitive swept-source optical coherence tomography with continuous source polarization modulation,” Opt. Express 16, 5892–5906 (2008).
104. S. H. Yun, C. Boudoux, G. J. Tearney, and B. E. Bouma, “High-speed wavelength-swept semiconductor laser with a polygon-scanner-based wavelength filter,” Opt. Lett. 28, 1981–1983 (2003).
105. B. J. Vakoc, S. H. Yun, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express 13, 5483–5493 (2005).
106. R. Huber, M. Wojtkowski, K. Taira, J. G. Fujimoto, and K. Hsu, “Amplified, frequency swept lasers for frequency domain reflectometry and OCT imaging: design and scaling principles,” Opt. Express 13, 3513–3528 (2005).
107. R. Huber, M. Wojtkowski, and J. G. Fujimoto, “Fourier Domain Mode Locking (FDML): A new laser operating regime and applications for optical coherence tomography,” Opt. Express 14, 3225–3237 (2006).
108. T. Klein, W. Wieser, L. Reznicek, A. Neubauer, A. Kampik, and R. Huber, “Multi-MHz retinal OCT,” Biomed. Opt. Express 4, 1890–1908 (2013).
109. Y. Yasuno, V. D. Madjarova, S. Makita, M. Akiba, A. Morosawa, C. Chong, T. Sakai, K. P. Chan, M. Itoh, and T. Yatagai, “Three-dimensional and high-speed swept-source optical coherence tomography for in vivo investigation of human anterior eye segments,” Opt. Express 13, 10652–10664 (2005).
110. E. C. W. Lee, J. F. de Boer, M. Mujat, H. Lim, and S. H. Yun, “In vivo optical frequency domain imaging of human retina and choroid,” Opt. Express 14, 4403–4411 (2006).
111. A. Unterhuber, B. Povazay, B. Hermann, H. Sattmann, A. Chavez-Pirson, and W. Drexler, “In vivo retinal optical coherence tomography at 1040 nm-enhanced penetration into the choroid,” Opt. Express 13, 3252–3258 (2005).
112. M. W. Jenkins, D. C. Adler, M. Gargesha, R. Huber, F. Rothenberg, J. Belding, M. Watanabe, D. L. Wilson, J. G. Fujimoto, and A. M. Rollins, “Ultrahigh-speed optical coherence tomography imaging and visualization of the embryonic avian heart using a buffered Fourier Domain Mode Locked laser,” Opt. Express 15, 6251–6267 (2007).
113. D. J. Faber, F. J. d. Meer, M. C. G. Aalders, and T. G. v. Leeuwen, “Quantitative measurement of attenuation coefficients of weakly scattering media using optical coherence tomography,” Opt. Express 12, 4353–4365 (2004).
114. D. Levitz, L. Thrane, M. H. Frosz, P. E. Andersen, C. B. Andersen, J. Valanciunaite, J. Swartling, S. Andersson-Engels, and P. R. Hansen, “Determination of optical scattering properties of highly-scattering media in optical coherence tomography images,” Opt. Express 12, 249–259 (2004).
115. S. J. Kirkpatrick, R. K. Wang, and D. D. Duncan, “OCT-based elastography for large and small deformations,” Opt. Express 14, 11585–11597 (2006).
116. B. F. Kennedy, T. R. Hillman, R. A. McLaughlin, B. C. Quirk, and D. D. Sampson, “In vivo dynamic optical coherence elastography using a ring actuator,” Opt. Express 17, 21762–21772 (2009).
117. A. L. Oldenburg, F. J.-J. Toublan, K. S. Suslick, A. Wei, and S. A. Boppart, “Magnetomotive contrast for in vivo optical coherence tomography,” Opt. Express 13, 6597–6614 (2005).
118. A. L. Oldenburg, M. N. Hansen, D. A. Zweifel, A. Wei, and S. A. Boppart, “Plasmon-resonant gold nanorods as low backscattering albedo contrast agents,” Opt. Express 14, 6724–6738 (2006).
119. D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express 16, 4376–4393 (2008).
120. P. R. Herz, Y. Chen, A. D. Aguirre, J. G. Fujimoto, H. Mashimo, J. Schmitt, A. Koski, J. Goodnow, and C. Petersen, “Ultrahigh resolution optical biopsy with endoscopic optical coherence tomography,” Opt. Express 12, 3532–3542 (2004).
121. A. R. Tumlinson, J. K. Barton, B. Povazay, H. Sattman, A. Unterhuber, R. A. Leitgeb, and W. Drexler, “Endoscope-tip interferometer for ultrahigh resolution frequency domain optical coherence tomography in mouse colon,” Opt. Express 14, 1878–1887 (2006).
122. K. H. Kim, B. H. Park, G. N. Maguluri, T. W. Lee, F. J. Rogomentich, M. G. Bancu, B. E. Bouma, J. F. de Boer, and J. J. Bernstein, “Two-axis magnetically-driven MEMS scanning catheter for endoscopic high-speed optical coherence tomography,” Opt. Express 15, 18130–18140 (2007).
123. D. C. Adler, C. Zhou, T.-H. Tsai, J. Schmitt, Q. Huang, H. Mashimo, and J. G. Fujimoto, “Three-dimensional endomicroscopy of the human colon using optical coherence tomography,” Opt. Express 17, 784–796 (2009).
124. J. G. Fujimoto, W. Drexler, J. S. Schuman, and C. K. Hitzenberger, “ISP Focus Issue: Optical Coherence Tomography (OCT) in Ophthalmology,” Opt. Express 17, 3978–3979 (2009).
125. R. J. Zawadzki, S. S. Choi, A. R. Fuller, J. W. Evans, B. Hamann, and J. S. Werner, “Cellular resolution volumetric in vivo retinal imaging with adaptive optics–optical coherence tomography,” Opt. Express 17, 4084–4094 (2009).
126. B. Cense, E. Koperda, J. M. Brown, O. P. Kocaoglu, W. Gao, R. S. Jonnal, and D. T. Miller, “Volumetric retinal imaging with ultrahigh-resolution spectral-domain optical coherence tomography and adaptive optics using two broadband light sources,” Opt. Express 17, 4095–4111 (2009).
127. R. B. Rosen, M. Hathaway, J. Rogers, J. Pedro, P. Garcia, P. Laissue, G. M. Dobre, and A. G. Podoleanu, “Multidimensional en-Face OCT imaging of the retina,” Opt. Express 17, 4112–4133 (2009).
128. B. Považay, B. Hofer, C. Torti, B. Hermann, A. R. Tumlinson, M. Esmaeelpour, C. A. Egan, A. C. Bird, and W. Drexler, “Impact of enhanced resolution, speed and penetration on three-dimensional retinal optical coherence tomography,” Opt. Express 17, 4134–4150 (2009).
129. E. Götzinger, M. Pircher, B. Baumann, C. Ahlers, W. Geitzenauer, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Three-dimensional polarization sensitive OCT imaging and interactive display of the human retina,” Opt. Express 17, 4151–4165 (2009).
130. T. Schmoll, C. Kolbitsch, and R. A. Leitgeb, “Ultra-high-speed volumetric tomography of human retinal blood flow,” Opt. Express 17, 4166–4176 (2009).
131. Y. K. Tao, K. M. Kennedy, and J. A. Izatt, “Velocity-resolved 3D retinal microvessel imaging using single-pass flow imaging spectral domain optical coherence tomography,” Opt. Express 17, 4177–4188 (2009).
132. M. Wojtkowski, B. L. Sikorski, I. Gorczynska, M. Gora, M. Szkulmowski, D. Bukowska, J. Kałuzny, J. G. Fujimoto, and A. Kowalczyk, “Comparison of reflectivity maps and outer retinal topography in retinal disease by 3-D Fourier domain optical coherence tomography,” Opt. Express 17, 4189–4207 (2009).
133. L. Kagemann, H. Isikawa, G. Wollstein, M. Gabriele, and J. S. Schuman, “Visualization of 3D high speed ultrahigh resolution optical coherence tomographic data identifies structures visible in 2D frames,” Opt. Express 17, 4208–4220 (2009).
134. M. Hangai, M. Yamamoto, A. Sakamoto, and N. Yoshimura, “Ultrahigh-resolution versus speckle noise-reduction in spectral-domain optical coherence tomography,” Opt. Express 17, 4221–4235 (2009).
135. Y. Yasuno, M. Yamanari, K. Kawana, T. Oshika, and M. Miura, “Investigation of post-glaucoma-surgery structures by three-dimensional and polarization sensitive anterior eye segment optical coherence tomography,” Opt. Express 17, 3980–3996 (2009).
136. D. C. Hood, A. S. Raza, K. Y. Kay, S. F. Sandler, D. Xin, R. Ritch, and J. M. Liebmann, “A comparison of retinal nerve fiber layer (RNFL) thickness obtained with frequency and time domain optical coherence tomography (OCT),” Opt. Express 17, 3997–4003 (2009).
137. G. Vizzeri, M. Balasubramanian, C. Bowd, R. N. Weinreb, F. A. Medeiros, and L. M. Zangwill, “Spectral domain-optical coherence tomography to detect localized retinal nerve fiber layer defects in glaucomatous eyes,” Opt. Express 17, 4004–4018 (2009).
138. M. Balasubramanian, C. Bowd, G. Vizzeri, R. N. Weinreb, and L. M. Zangwill, “Effect of image quality on tissue thickness measurements obtained with spectral domain-optical coherence tomography,” Opt. Express 17, 4019–4036 (2009).
139. C. Ahlers and U. Schmidt-Erfurth, “Three-dimensional high resolution OCT imaging of macular pathology,” Opt. Express 17, 4037–4045 (2009).
140. Y. Chen, L. N. Vuong, J. Liu, J. Ho, V. J. Srinivasan, I. Gorczynska, A. J. Witkin, J. S. Duker, J. Schuman, and J. G. Fujimoto, “Three-dimensional ultrahigh resolution optical coherence tomography imaging of age-related macular degeneration,” Opt. Express 17, 4046–4060 (2009).
141. Y. Wang, A. Fawzi, O. Tan, J. Gil-Flamer, and D. Huang, “Retinal blood flow detection in diabetic patients by Doppler Fourier domain optical coherence tomography,” Opt. Express 17, 4061–4073 (2009).
142. M. Ruggeri, G. Tsechpenakis, S. Jiao, M. E. Jockovich, C. Cebulla, E. Hernandez, T. G. Murray, and C. A. Puliafito, “Retinal tumor imaging and volume quantification in mouse model using spectraldomain optical coherence tomography,” Opt. Express 17, 4074–4083 (2009).
