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Imaging needles consist of highly miniaturized focusing optics encased within a hypodermic needle. The needles may be inserted tens of millimeters into tissue and have the potential to visualize diseased cells well beyond the penetration depth of optical techniques applied externally. Multimodal imaging needles acquire multiple types of optical signals to differentiate cell types. However, their use has not previously been demonstrated with live cells.We demonstrate the ability of a multimodal imaging needle to differentiate cell types through simultaneous optical coherence tomography (OCT) and fluorescence imaging.We characterize the performance of a multimodal imaging needle. This is paired with a fluorescent analog of the therapeutic drug, tamoxifen, which enables cell-specific fluorescent labeling of estrogen receptor-positive (ER+) breast cancer cells. We perform simultaneous OCT and fluorescence in situ imaging on MCF-7 ER+ breast cancer cells and MDA-MB-231 ER- cells. Images are compared against unlabeled control samples and correlated with standard confocal microscopy images.We establish the feasibility of imaging live cells with these miniaturized imaging probes by showing clear differentiation between cancerous cells.Imaging needles have the potential to aid in the detection of specific cancer cells within solid tissue.

Miniaturised optical coherence tomography (OCT) fibre-optic probes have enabled high-resolution cross-sectional imaging deep within the body. However, existing OCT fibre-optic probe fabrication methods cannot generate miniaturised freeform optics, which limits our ability to fabricate probes with both complex optical function and dimensions comparable to the optical fibre diameter. Recently, major advances in two-photon direct laser writing have enabled 3D printing of arbitrary three-dimensional micro/nanostructures with a surface roughness acceptable for optical applications. Here, we demonstrate the feasibility of 3D printing of OCT probes. We evaluate the capability of this method based on a series of characterisation experiments. We report fabrication of a micro-optic containing an off-axis paraboloidal total internal reflecting surface, its integration as part of a common-path OCT probe, and demonstrate proof-of-principle imaging of biological samples.

We report the synthesis, characterisation and evaluation of the in vitro biocompatibility of polymeric nanoparticles with both magnetic and upconverting fluorescent properties. The particles consist of superparamagnetic iron oxide nanoparticles and upconverting NaYF4:Yb,Er nanoparticles co-encapsulated within a poly(glycidyl methacrylate) sphere. Two different upconverting nanoparticles (10 nm α-NaYF4:Yb,Er and 50 nm β-NaYF4:Yb,Er) were synthesised and the optical and magnetic properties of the composite polymeric nanoparticle systems assessed by near infra-red laser spectroscopy, SQUID magnetometry and proton relaxometry. A live-dead assay was used to assess the viability of PC-12 neural cells incubated with varying concentrations of the nanoparticles. The composite nanoparticles produced no observed impact on cellular viability even at concentrations as high as 1000 μg mL−1. Confocal microscopy revealed uptake of nanoparticles by PC-12 cells and peri-nuclear cytoplasmic localisation. Both particle systems show favourable magnetic properties. However, only the nanospheres containing 50 nm β-NaYF4:Yb,Er were suitable for optical tracking because the presence of iron oxide within the composites imparts a significant quenching of the upconversion emission. This study demonstrates the size and phase of the upconverting nanoparticles are important parameters that have to be taken into account in the design of multimodal nanoparticles using co-encapsulation strategies.

OCT imaging through miniature needle probes has extended the range of OCT and enabled structural imaging deep inside breast tissue, with the potential to assist in the intraoperative assessment of tumor margins. However, in many situations, scattering contrast alone is insufficient to clearly identify and delineate malignant areas. Here, we present a portable, depth-encoded polarization-sensitive OCT system, connected to a miniature needle probe. From the measured polarization states we constructed the tissue Mueller matrix at each sample location and improved the accuracy of the measured polarization states through incoherent averaging before retrieving the depth-resolved tissue birefringence. With the Mueller matrix at hand, additional polarization properties such as depolarization are readily available. We then imaged freshly excised breast tissue from a patient undergoing lumpectomy. The reconstructed local retardation highlighted regions of connective tissue, which exhibited birefringence due to the abundance of collagen fibers, and offered excellent contrast to areas of malignant tissue, which exhibited less birefringence due to their different tissue composition. Results were validated against co-located histology sections. The combination of needle-based imaging with the complementary contrast provided by polarization-sensitive analysis offers a powerful instrument for advanced tissue imaging and has potential to aid in the assessment of tumor margins during the resection of breast cancer.

Light scattered by turbid tissue is known to degrade optical coherence tomography (OCT) image contrast progressively with depth. Bessel beams have been proposed as an alternative to Gaussian beams to image deeper into turbid tissue. However, studies of turbid tissue comparing the image quality for different beam types are lacking. We present such a study, using numerically simulated beams and experimental OCT images formed by Bessel or Gaussian beams illuminating phantoms with optical properties spanning a range typical of soft tissue. We demonstrate that, for a given scattering parameter, the higher the scattering anisotropy the lower the OCT contrast, regardless of the beam type. When focusing both beams at the same depth in the sample, we show that, at focus and for equal input power and resolution, imaging with the Gaussian beam suffers less reduction of contrast. This suggests that, whilst Bessel beams offer extended depth of field in a single depth scan, for low numerical aperture (NA μs = 3.7 mm−1 and high scattering anisotropy, g > 0.95), superior contrast (by up to ~40%) may be obtained over an extended depth range by a Gaussian beam combined with dynamic focusing.

Visualizing stiffness within the local tissue environment at the cellular and sub-cellular level promises to provide insight into the genesis and progression of disease. In this paper, we propose ultrahigh-resolution optical coherence elastography, and demonstrate three-dimensional imaging of local axial strain of tissues undergoing compressive loading. The technique employs a dual-arm extended focus optical coherence microscope to measure tissue displacement under compression. The system uses a broad bandwidth supercontinuum source for ultrahigh axial resolution, Bessel beam illumination and Gaussian beam detection, maintaining sub-2 μm transverse resolution over nearly 100 μm depth of field, and spectral-domain detection allowing high displacement sensitivity. The system produces strain elastograms with a record resolution (x,y,z) of 2×2×15 μm. We benchmark the advances in terms of resolution and strain sensitivity by imaging a suitable inclusion phantom. We also demonstrate this performance on freshly excised mouse aorta and reveal the mechanical heterogeneity of vascular smooth muscle cells and elastin sheets, otherwise unresolved in a typical, lower resolution optical coherence elastography system.

We present a proof-of-concept experiment utilizing a novel “snap-shot” spectral domain OCT technique that captures a phase coherent volume in a single frame. The sample is illuminated with a collimated beam of 75 μm diameter and the back-reflected light is analyzed by a 2-D matrix of spectral interferograms. A key challenge that is addressed is simultaneously maintaining lateral and spectral phase coherence over the imaged volume in the presence of sample motion. Digital focusing is demonstrated for 5.0 μm lateral resolution over an 800 μm axial range.

Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins., National Institutes of Health (U.S.) (Grants P41 EB015903)

Synthetic multifunctional electrospun composites are a new class of hybrid materials with many potential applications. However, the lack of an efficient, reactive large-area substrate has been one of the major limitations in the development of these materials as advanced functional platforms. Herein, we demonstrate the utility of electrospun poly(glycidyl methacrylate) films as a highly versatile platform for the development of functional nanostructured materials anchored to a surface. The utility of this platform as a reactive substrate is demonstrated by grafting poly(N-isopropylacrylamide) to incorporate stimuli–responsive properties. Additionally, we demonstrate that functional nanocomposites can be fabricated using this platform with properties for sensing, fluorescence imaging, and magneto-responsiveness.

Optical coherence tomography (OCT) is a high-resolution imaging modality with the potential to provide in situ assessment to distinguish normal from cancerous tissue. However, limited image penetration depth has restricted its utility. This paper demonstrates the feasibility of an OCT needle probe to perform interstitial imaging deep below the tissue surface. The side-facing needle probe comprises miniaturized focusing optics consisting of no-core and GRIN fiber encased within either a 22- or 23-gauge needle. 3-D OCT volumetric data sets were acquired by rotating and retracting the probe during imaging. We present the first published image of a human breast cancer tumor margin, and of human axillary lymph nodes acquired with an OCT needle probe. Through accurate correlation with the histological gold standard, OCT is shown to enable a clear delineation of tumor boundary from surrounding adipose tissue, and identification of microarchitectural features.

We demonstrate polarization sensitive OCT using miniaturized needle probes. Employing the Mueller-formalism, we reconstruct tissue birefringence and retrieve the depolarization index of ex vivo tissue samples, providing contrast complementary to the structural intensity signal.

Applied Physics B, 79 (8), ISSN:0946-2171, ISSN:1432-0649, ISSN:0721-7269, ISSN:0340-3793

We report the synthesis, characterisation and evaluation of the in vitro biocompatibility of polymeric nanoparticles with both magnetic and upconverting fluorescent properties. The particles consist of superparamagnetic iron oxide nanoparticles and upconverting NaYF4:Yb,Er nanoparticles co-encapsulated within a poly(glycidyl methacrylate) sphere. Two different upconverting nanoparticles (10 nm α-NaYF4:Yb,Er and 50 nm β-NaYF4:Yb,Er) were synthesised and the optical and magnetic properties of the composite polymeric nanoparticle systems assessed by near infra-red laser spectroscopy, SQUID magnetometry and proton relaxometry. A live-dead assay was used to assess the viability of PC-12 neural cells incubated with varying concentrations of the nanoparticles. The composite nanoparticles produced no observed impact on cellular viability even at concentrations as high as 1000 μg mL(-1). Confocal microscopy revealed uptake of nanoparticles by PC-12 cells and peri-nuclear cytoplasmic localisation. Both particle systems show favourable magnetic properties. However, only the nanospheres containing 50 nm β-NaYF4:Yb,Er were suitable for optical tracking because the presence of iron oxide within the composites imparts a significant quenching of the upconversion emission. This study demonstrates the size and phase of the upconverting nanoparticles are important parameters that have to be taken into account in the design of multimodal nanoparticles using co-encapsulation strategies.

We report an optical imaging needle for simultaneous optical coherence tomography and fluorescence imaging of tissue labeled with bound fluorescent biomarkers. We demonstrate its performance by imaging antibody-labeled cells in human liver sections.

Multifunctional materials exhibiting photon upconversion show promising applications for biological imaging and sensing. In this study, we examine the solid-state upconversion emission of NaYF4:Yb,Er nanoparticles in the presence of iron oxide nanoparticles. Fe3O4 nanoparticles (6 nm) were mixed with NaYF4:Yb,Er nanoparticles (either 10 or 50 nm) in varying proportions by drying chloroform solutions of nanoparticles onto glass slides. Upconversion spectra were acquired, and a laser power-dependent emission was observed and correlated with the iron oxide content in the mixture. Changes in the lattice temperature of the upconverting particles were monitored by careful observation of the relative intensities of the (2)H11/2 and (4)S3/2 →( 4)I15/2 transitions. The emission characteristics observed are consistent with an iron oxide-induced thermal effect that is dependent on both the laser power and the proportion of iron oxide. The results highlight that the thermal effects of mixed nanoparticle systems should be considered in the design of luminescent upconverting hybrid materials.

Fiber-optic needle probes are highly miniaturized imaging devices that enable imaging deep inside the body. Utilizing optical coherence tomography (OCT), these devices replace the standard scanning mechanism of an OCT scanner with all-fiber focusing optics small enough to be encased within a hypodermic needle. We describe recent innovation in the design of these probes, including novel fiber-optic configurations to achieve extended depth of focus, and the use of double-clad fiber to enable the first dual-modality fiber-optic needle probe, simultaneously acquiring both OCT and fluorescence images.

We present a high-optical-quality imaging needle for optical coherence tomography (OCT) that achieves sensitivity and resolution comparable to conventional free-space OCT sample arms. The side-viewing needle design utilizes total internal reflection from an angle-polished fiber tip, encased in a glass microcapillary. Fusion of the capillary to the fiber provides a robust, optical-quality output window. The needle's focusing optics are based on an astigmatism-free design, which exploits the "focal shift" phenomenon for focused Gaussian beams to achieve equal working distances (WDs) for both axes. We present a fabricated needle with a WD ratio of 0.98 for imaging in an aqueous environment. Our needle achieves the highest sensitivity of currently reported OCT imaging needles (112 dB), and we demonstrate its performance by superficial imaging of human skin and 3D volumetric imaging within a biological sample.

The development and deployment of OCT needle-probe technologies are reviewed. Their use through several different clinical applications, including demarcation of breast cancer tumor margins and lung imaging, is demonstrated.

Fiber-optic probes for sensing and imaging applications often employ sections of graded-index (GRIN) fiber to refocus the diverging light from the delivery fiber. Such GRIN fiber microlenses possess aberrations which can cause significant distortions of the focused output beam. Using a numerical beam propagation method, we analyze the output beams resulting from index profiles that exhibit a central dip or a deviation from the ideal parabolic shape. Our method is in good agreement with experimental data and it enables the accurate simulation of fiber probes for biomedical applications using non-ideal or custom-engineered GRIN fibers with arbitrary refractive index profiles.

Imaging of alveoli in situ has for the most part been infeasible due to the high resolution required to discern individual alveoli and limited access to alveoli beneath the lung surface. In this study, we present a novel technique to image alveoli using optical coherence tomography (OCT). We propose the use of OCT needle probes, where the distal imaging probe has been miniaturized and encased within a hypodermic needle (as small as 30-gauge, outer diameter 310 μm), allowing insertion deep within the lung tissue with minimal tissue distortion. Such probes enable imaging at a resolution of ∼12 μm within a three-dimensional cylindrical field of view with diameter ∼1.5 mm centered on the needle tip. The imaging technique is demonstrated on excised lungs from three different species: adult rats, fetal sheep, and adult pigs. OCT needle probes were used to image alveoli, small bronchioles, and blood vessels, and results were matched to histological sections. We also present the first dynamic OCT images acquired with an OCT needle probe, allowing tracking of individual alveoli during simulated cyclical lung inflation and deflation.

We report on a novel scheme for extending the depth of focus (DOF) of ultrathin (125 μm diameter) fiber probes for optical coherence tomography (OCT) using a simple phase mask consisting of graded-index (GRIN) fiber. The technique is compatible with existing all-in-fiber probe fabrication techniques, and our simulations show that it can provide a DOF gain of ∼2 at a modest ∼5 dB reduction of peak sensitivity. In a prototype device using commercially available GRIN fiber, a DOF gain of 1.55 is obtained, validated by beam profiling and OCT imaging.

Visualizing stiffness within the local tissue environment at the cellular and subcellular level promises to provide insight into the genesis and progression of disease. In this Letter, we propose ultrahigh-resolution optical coherence elastography (UHROCE), and demonstrate 3D imaging of local axial strain of tissues undergoing compressive loading. We combine optical coherence microscopy (OCM) and phase-sensitive detection of local tissue displacement to produce strain elastograms with resolution (x,y,z) of 2×2×15 μm. We demonstrate this performance on a freshly excised mouse aorta and reveal the mechanical heterogeneity of vascular smooth muscle cells and elastin sheets, otherwise unresolved in a typical, lower resolution optical coherence elastography (OCE) system.

In situ imaging of alveoli and small airways with optical coherence tomography (OCT) needle probes has significant potential in the study and clinical assessment of lung disease. We present the smallest reported OCT needle probe capable of acquiring 3D volumetric data. The side-facing needle probe comprises miniaturized focusing optics consisting of no-core and GRIN fibre, terminated with a reflection-coated, fibre tip beam deflector. The optics are encased within a 30-gauge (outer diameter 310 µm) needle, and interfaced to a spectral-domain OCT scanner. Multiple 3D-OCT data sets were acquired on preterm lamb lungs (excised) filled with amniotic fluid and saline. Results demonstrated the ability of such a probe to image individual alveoli and bronchioles, and enabled the rendering of 3D volumetric visualisations of the data. We observed notably less tissue distortion than in earlier work with larger 23 gauge needle probes.

We present the smallest reported side-viewing needle probe for optical coherence tomography (OCT). Design, fabrication, optical characterization, and initial application of a 30-gauge (outer diameter 0.31 mm) needle probe are demonstrated. Extreme miniaturization is achieved by using a simple all-fiber probe design incorporating an angle-polished and reflection-coated fiber-tip beam deflector. When inserted into biological tissue, aqueous interstitial fluids reduce the probe's inherent astigmatism ratio to 1.8, resulting in a working distance of 300 μm and a depth-of-field of 550 μm with beam diameters below 30 μm. The needle probe was interfaced with an 840 nm spectral-domain OCT system and the measured sensitivity was shown to be only 7 dB lower than that of a comparable galvo-scanning sample arm configuration. 3D OCT images of lamb lungs were acquired over a depth range of ~600 μm, showing individual alveoli and bronchioles.

We report on the design and implementation of a 350 I¼m-diameter confocal imaging probe based on gradient-index (GRIN) optics and a fiber-based scanning arrangement. The form factor of the probe is such that it can potentially be inserted into a 22-gauge hypodermic needle to perform high-resolution confocal fluorescence imaging in solid tissues. We introduce a simple scanning arrangement based on lensed fiber, which eliminates off-axis aberrations induced by conventional scanning optics and is suitable for integration into a compact hand-held unit. We present the details of the optical design and experimental verification of the performance of the optical system. The measured lateral resolution of ~700 nm is in agreement with the optical design and is the highest resolution reported for a confocal fluorescence imaging probe of this size. Further, we demonstrate the imaging capability of the probe by obtaining high-resolution images of fluorescently labeled muscle fibers.

Practical micro-imaging deep in solid tissues will open up new avenues in research on clinical diagnosis and treatment of disease. We report on our recent advances in optical microscope-in-a-needle technology capable of 3D micro-imaging in situ.

We report on the design and implementation of a gradient-index microendoscope suitable for accessing tissues deep within the body using confocal fluorescence imaging. The 350-μm diameter microendoscope has a length of 27 mm, which enables it to be inserted through a 22-gauge hypodermic needle. A prototype imaging system is demonstrated to obtain images of tissue samples at depths of ~15 mm with a lateral resolution of ~700 nm. To the best of our knowledge, this is the highest resolution and imaging depth reported for a confocal probe of these dimensions. We employ a scanning arrangement using a lensed fiber that can conveniently control the input beam parameters without causing off-axis aberrations typically present in the optical relay lenses used in galvanometer-mirror scanning systems.

Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue.

We present high-repetition-rate passively mode-locked vertical-external-cavity surface-emitting semiconductor lasers in a 1:1 mode ratio configuration, achieving a record repetition rate of 50 GHz in 3.1-ps pulses with 42 mW average output power.

We demonstrate an optically pumped passively mode-locked external-cavity semiconductor laser generating 4.7-ps pulses at 957 nm with as much as 2.1 W of average output power and a 4-GHz repetition rate. Compared with earlier results, the chirp of the pulses has been greatly reduced by use of an intracavity etalon. Apart from restricting the bandwidth, the etalon also helps optimize wavelength-dependent gain parameters and dispersion.

We present high-repetition-rate passively mode-locked vertical external-cavity surface-emitting semiconductor lasers with average output powers of 1.4 W in 6.1-ps pulses at 10 GHz and 25 mW in 4.7-ps pulses at 30 GHz.

We review and compare several recently introduced approaches for the generation of picosecond pulse trains with multi-GHz repetition rates and relatively high average output power (up to several watts). Specifically, we consider passively mode-locked lasers with different gain media (Nd:YVO4, Er:Yb:glass, and surface-emitting semiconductor structures) as well as optical parametric oscillators., New Journal of Physics, 6, ISSN:1367-2630

We have recently introduced a novel kind of mode-locked semiconductor laser, based on an optically pumped surface-emitting semiconductor chip and a saturable semiconductor mirror in an external cavity. This type of laser offers unprecedented average output powers in the multi-watt range and multi-GHz pulse repetition rates. Latest results are reviewed.

Bessel beams feature a very large depth-of-focus (DOF) compared to conventional focusing schemes, but their central lobe carries only a small fraction of the total beam power, leading to a strongly reduced peak irradiance. This is problematic for power-limited applications, such as optical coherence tomography (OCT) or optical coherence microscopy, as it can result in a prohibitive reduction of the signal-to-noise ratio (SNR). Using scalar diffraction theory, we show that the trade-off between DOF and peak irradiance of Bessel beams depends solely on the Fresnel number N. We demonstrate the existence of a low-Fresnel-number regime, N

We have developed an extremely miniaturized optical coherence tomography (OCT) needle probe (outer diameter 310 µm) with high sensitivity (108 dB) to enable minimally invasive imaging of cellular structure deep within skeletal muscle. Three-dimensional volumetric images were acquired from ex vivo mouse tissue, examining both healthy and pathological dystrophic muscle. Individual myofibers were visualized as striations in the images. Degradation of cellular structure in necrotic regions was seen as a loss of these striations. Tendon and connective tissue were also visualized. The observed structures were validated against co-registered hematoxylin and eosin (H&E) histology sections. These images of internal cellular structure of skeletal muscle acquired with an OCT needle probe demonstrate the potential of this technique to visualize structure at the microscopic level deep in biological tissue in situ.

Fiber-optic probes for sensing and biomedical imaging applications such as optical coherence tomography (OCT) frequently employ sections of graded-index (GRIN) fiber to re-focus the diverging light from the delivery fiber. Such GRIN fiber microlenses often possess aberrations that cause significant distortions of the focused output beam. Current design methods based on ABCD matrix transformations of Gaussian beams cannot model such effects and are therefore inadequate for the analysis and design of high-performance probes that require diffraction-limited output beams. We demonstrate use of the beam propagation method (BPM) to analyze beam distortion in GRIN-lensed fibers resulting from index profiles that exhibit a deviation from the ideal parabolic shape or artifacts such as ripples or a central dip. Furthermore, we demonstrate the power of this method for exploring novel probe designs that incorporate GRIN phase masks to generate wavefront-shaped output beams with extended depth-of-focus (DOF). We present results using our method that are in good agreement with experimental data. The BPM enables accurate simulation of fiber probes using non-ideal or custom-engineered GRIN fibers with arbitrary refractive index profiles, which is important in the design of high-performance fiber-based micro-imaging systems for biomedical applications.

To the best of our knowledge, we present the first needle probe for combined optical coherence tomography (OCT), and fluorescence imaging. The probe uses double-clad fiber (DCF) that guides the OCT signal and fluorescence excitation light in the core and collects and guides the returning fluorescence in the large-diameter multimode inner cladding. It is interfaced to a 1310 nm swept-source OCT system that has been modified to enable simultaneous 488 nm fluorescence excitation and >500 nm emission detection by using a DCF coupler to extract the returning fluorescence signal in the inner cladding with high efficiency. We present imaging results from an excised sheep lung with fluorescein solution infused through the vasculature. We were able to identify alveoli, bronchioles, and blood vessels. The results demonstrate that the combined OCT plus fluorescence needle images provide improved tissue differentiation over OCT alone.

A microscope small enough to fit into a needle creates many new possibilities for optics in medicine. We have developed a range of optical coherence tomography (OCT) needle probes. Connected to an OCT scanner via a single mode fiber, the probes are constructed by fusing exact lengths of no-core fiber and graded-index fiber to focus a broadband light beam. We terminated the optics with anglepolished, gold-coated no-core fiber to deflect the beam. Encased in a needle (outer diameter 310 ?m), these probes are capable of 3-D imaging. However, the important developments of 2012 have been where we have taken these needle probes.

Evaluation of degradation in the structure of skeletal muscle is important for the assessment or diagnosis of many myopathies, such as Duchenne muscular dystrophy. Histological analysis is the gold standard to evaluate such degradation but requires excision and fixation of the tissue. This is undesirably invasive in patients and precludes longitudinal study of disease progression in patients or animal models. Optical coherence tomography (OCT) is a high-resolution (∼10 μm) imaging modality capable of visualising muscle structure and the morphological changes in muscular dystrophy. However, because of the limited image penetration of OCT (∼2 mm), previous studies have been restricted to imaging only superficial tissue. To overcome this limitation, we have developed a miniaturised OCT probe, in which the distal focusing optics are encased within a 30-gauge hypodermic needle and inserted deep within tissue. By rotating and translating the OCT needle probe, it is possible to acquire a 3D image volume of the internal structure of skeletal muscle. This is the smallest published OCT needle probe (outer diameter 310 μm) capable of acquiring a 3D image volume. We have tested this probe with ex vivo murine muscle tissue. We demonstrate the use of this probe with ex vivo murine muscle tissue (Tibialis anterior from 12-week-old male mouse). The acquired multiple 3D image volumes allow visualisation of individual myofibers. Structures such as fascicles, tendon and connective tissue were also detected within the muscle sample. Such miniaturised imaging probes have the potential to extend high resolution optical imaging techniques to in vivo imaging of muscle.

Synthesis of nanocrystals that exhibit strong upconversion (UC) luminescence upon infrared excitation has been challenging due to the stringent control needed over experimental variables. Herein, we report a method to synthesize nanocrystals demonstrating high UC at room temperature in aqueous solution on graphene.

We present a 10GHz passively mode-locked vertical external-cavity surface-emitting semiconductor laser (VECSEL) with 1.4W average output power in 6.1ps pulses. The output features a very good pulse quality with a time–bandwidth product of 0.42 in a nearly diffraction-limited beam. This demonstrates that passively mode-locked VECSELs are suitable for generating high powers in high-repetition-rate pulse trains.