Robert Huber

Bio: Robert Huber is an academic researcher from University of Lübeck. The author has contributed to research in topics: Optical coherence tomography & Laser. The author has an hindex of 54, co-authored 256 publications receiving 10655 citations. Previous affiliations of Robert Huber include Massachusetts Institute of Technology & Goethe University Frankfurt.

Fourier Domain Mode Locking (FDML): A new laser operating regime and applications for optical coherence tomography.

Abstract: We demonstrate a new technique for frequency-swept laser operation--Fourier domain mode locking (FDML)--and its application for swept-source optical coherence tomography (OCT) imaging. FDML is analogous to active laser mode locking for short pulse generation, except that the spectrum rather than the amplitude of the light field is modulated. High-speed, narrowband optical frequency sweeps are generated with a repetition period equal to the fundamental or a harmonic of cavity round-trip time. An FDML laser is constructed using a long fiber ring cavity, a semiconductor optical amplifier, and a tunable fiber Fabry-Perot filter. Effective sweep rates of up to 290 kHz are demonstrated with a 105 nm tuning range at 1300 nm center wavelength. The average output power is 3mW directly from the laser and 20 mW after post-amplification. Using the FDML laser for swept-source OCT, sensitivities of 108 dB are achieved and dynamic linewidths are narrow enough to enable imaging over a 7 mm depth with only a 7.5 dB decrease in sensitivity. We demonstrate swept-source OCT imaging with acquisition rates of up to 232,000 axial scans per second. This corresponds to 906 frames/second with 256 transverse pixel images, and 3.5 volumes/second with a 256x128x256 voxel element 3-DOCT data set. The FDML laser is ideal for swept-source OCT imaging, thus enabling high imaging speeds and large imaging depths.

Amplified, Frequency Swept Lasers for Frequency Domain Reflectometry and OCT Imaging : Design and Scaling Principles

Abstract: We demonstrate a high-speed, frequency swept, 1300 nm laser source for frequency domain reflectometry and OCT with Fourier domain/swept-source detection. The laser uses a fiber coupled, semiconductor amplifier and a tunable fiber Fabry-Perot filter. We present scaling principles which predict the maximum frequency sweep speed and trade offs in output power, noise and instantaneous linewidth performance. The use of an amplification stage for increasing output power and for spectral shaping is discussed in detail. The laser generates ~45 mW instantaneous peak power at 20 kHz sweep rates with a tuning range of ~120 nm full width. In frequency domain reflectometry and OCT applications the frequency swept laser achieves 108 dB sensitivity and ~10 mum axial resolution in tissue. We also present a fast algorithm for real time calibration of the fringe signal to equally spaced sampling in frequency for high speed OCT image preview.

Multi-megahertz OCT: High quality 3D imaging at 20 million A-scans and 4.5 GVoxels per second.

Abstract: We present ultra high speed optical coherence tomography (OCT) with multi-megahertz line rates and investigate the achievable image quality. The presented system is a swept source OCT setup using a Fourier domain mode locked (FDML) laser. Three different FDML-based swept laser sources with sweep rates of 1, 2.6 and 5.2MHz are compared. Imaging with 4 spots in parallel quadruples the effective speed, enabling depth scan rates as high as 20.8 million lines per second. Each setup provides at least 98dB sensitivity and approximately 10microm resolution in tissue. High quality 2D and 3D imaging of biological samples is demonstrated at full scan speed. A discussion about how to best specify OCT imaging speed is included. The connection between voxel rate, line rate, frame rate and hardware performance of the OCT setup such as sample rate, analog bandwidth, coherence length, acquisition dead-time and scanner duty cycle is provided. Finally, suitable averaging protocols to further increase image quality are discussed.

Buffered Fourier domain mode locking: Unidirectional swept laser sources for optical coherence tomography imaging at 370,000 lines/s.

Abstract: We describe buffered Fourier domain mode locking (FDML), a technique for tailoring the output and multiplying the sweep rate of FDML lasers. Buffered FDML can be used to create unidirectional wavelength sweeps from the normal bidirectional sweeps in an FDML laser without sacrificing sweep rate. We also investigate the role of the laser source in dynamic range versus sensitivity performance in optical coherence tomography (OCT) imaging. Unidirectional sweep rates of 370 kHz over a 100 nm range at a center wavelength of 1300 nm are achieved. High-speed, swept-source OCT is demonstrated at record speeds of up to 370,000 axial scans per second.

Megahertz OCT for ultrawide-field retinal imaging with a 1050nm Fourier domain mode-locked laser

Abstract: We demonstrate ultrahigh speed swept source retinal OCT imaging using a Fourier domain mode locked (FDML) laser. The laser uses a combination of a semiconductor optical amplifier and an ytterbium doped fiber amplifier to provide more than 50mW output power. The 1050nm FDML laser uses standard telecom fiber for the km long delay line instead of two orders of magnitude more expensive real single mode fiber. We investigate the influence of this “oligo-mode” fiber on the FDML laser performance. Two design configurations with 684,400 and 1,368,700 axial scans per second are investigated, 25x and 50x faster than current commercial instruments and more than 4x faster than previous single spot ophthalmic results. These high speeds enable the acquisition of densely sampled ultrawide-field data sets of the retina within a few seconds. Ultrawide-field data consisting of 1900 x 1900 A-scans with ~70° degrees angle of view are acquired within only 3 and 6 seconds using the different setups. Such OCT data sets, more than double as large as previously reported, are collapsed to a 4 megapixel high definition fundus image. We achieve good penetration into the choroid by hardware spectral shaping of the laser output. The axial resolution in tissue is 12µm (684kHz) and 19µm (1.37MHz). A series of new data processing and imaging extraction protocols, enabled by the ultrawide-field isotropic data sets, are presented. Dense isotropic sampling enables both, cross-sectional images along arbitrary coordinates and depth-resolved en-face fundus images. Additionally, we investigate how isotropic averaging compares to the averaging of cross-sections along the slow axis.

Imaging and photodynamic therapy: mechanisms, monitoring, and optimization.

Abstract: 1.1 Photodynamic Therapy and Imaging The purpose of this review is to present the current state of the role of imaging in photodynamic therapy (PDT). In order for the reader to fully appreciate the context of the discussions embodied in this article we begin with an overview of the PDT process, starting with a brief historical perspective followed by detailed discussions of specific applications of imaging in PDT. Each section starts with an overview of the specific topic and, where appropriate, ends with summary and future directions. The review closes with the authors’ perspective of the areas of future emphasis and promise. The basic premise of this review is that a combination of imaging and PDT will provide improved research and therapeutic strategies. PDT is a photochemistry-based approach that uses a light-activatable chemical, termed a photosensitizer (PS), and light of an appropriate wavelength, to impart cytotoxicity via the generation of reactive molecular species (Figure 1a). In clinical settings, the PS is typically administered intravenously or topically, followed by illumination using a light delivery system suitable for the anatomical site being treated (Figure 1b). The time delay, often referred to as drug-light interval, between PS administration and the start of illumination with currently used PSs varies from 5 minutes to 24 hours or more depending on the specific PS and the target disease. Strictly speaking, this should be referred to as the PS-light interval, as at the concentrations typically used the PS is not a drug, but the drug-light interval terminology seems to be used fairly frequently. Typically, the useful range of wavelengths for therapeutic activation of the PS is 600 to 800 nm, to avoid interference by endogenous chromophores within the body, and yet maintain the energetics necessary for the generation of cytotoxic species (as discussed below) such as singlet oxygen (1O2). However, it is important to note that photosensitizers can also serve as fluorescence imaging agents for which activation with light in the 400nm range is often used and has been extremely useful in diagnostic imaging applications as described extensively in Section 2 of this review. The obvious limitation of short wavelength excitation is the lack of tissue penetration so that the volumes that are probed under these conditions are relatively shallow. Open in a separate window Figure 1 (A) A schematic representation of PDT where PS is a photoactivatable multifunctional agent, which, upon light activation can serve as both an imaging agent and a therapeutic agent. (B) A schematic representation of the sequence of administration, localization and light activation of the PS for PDT or fluorescence imaging. Typically the PS is delivered systemically and allowed to circulate for an appropriate time interval (the “drug-light interval”), during which the PS accumulates preferentially in the target lesion(s) prior to light activation. In the idealized depiction here the PS is accumulation is shown to be entirely in the target tissue, however, even if this is not the case, light delivery confers a second layer of selectivity so that the cytotoxic effect will be generated only in regions where both drug and light are present. Upon localization of the PS, light activation will result in fluorescence emission which can be implemented for imaging applications, as well as generation cytotoxic species for therapy. In the former case light activation is achieved with a low fluence rate to generate fluorescence emission with little or no cytotoxic effect, while in the latter case a high fluence rate is used to generate a sufficient concentration of cytotoxic species to achieve biological effects.

HITEMP, the high-temperature molecular spectroscopic database

Abstract: A new molecular spectroscopic database for high-temperature modeling of the spectra of molecules in the gas phase is described. This database, called HITEMP, is analogous to the HITRAN database but encompasses many more bands and transitions than HITRAN for the absorbers H2O, CO2, CO, NO, and OH. HITEMP provides users with a powerful tool for a great many applications: astrophysics, planetary and stellar atmospheres, industrial processes, surveillance, non-local thermodynamic equilibrium problems, and investigating molecular interactions, to name a few. The sources and implementation of the spectroscopic parameters incorporated into HITEMP are discussed.

Gold nanoparticles in biomedical applications: recent advances and perspectives

Abstract: Gold nanoparticles (GNPs) with controlled geometrical, optical, and surface chemical properties are the subject of intensive studies and applications in biology and medicine. To date, the ever increasing diversity of published examples has included genomics and biosensorics, immunoassays and clinical chemistry, photothermolysis of cancer cells and tumors, targeted delivery of drugs and antigens, and optical bioimaging of cells and tissues with state-of-the-art nanophotonic detection systems. This critical review is focused on the application of GNP conjugates to biomedical diagnostics and analytics, photothermal and photodynamic therapies, and delivery of target molecules. Distinct from other published reviews, we present a summary of the immunological properties of GNPs. For each of the above topics, the basic principles, recent advances, and current challenges are discussed (508 references).

Evidence for lateral gene transfer between Archaea and Bacteria from genome sequence of Thermotoga maritima

Abstract: The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.