Surgical treatment of cystic pituitary adenomas: literature-based definitions and postoperative outcomes.

BACKGROUND AND OBJECTIVES: To survey the applied definitions of 'cystic' among pituitary adenomas and evaluate whether postoperative outcomes differ relative to non-cystic counterparts. METHODS: A literature search and meta-analysis was performed using PRISMA guidelines. Studies were eligible if novel data were reported regarding the applied definition of 'cystic' and postoperative outcomes among cases of surgically treated pituitary adenomas. Data were pooled with random effects meta-analysis models into cohorts based on the applied definition of 'cystic'. Categorical meta-regressions were used to investigate differences between cohorts. Among studies comparing cystic and non-cystic pituitary adenomas, meta-analysis models were applied to determine the Odds Ratio [95% Confidence Interval]. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA, 4.0), with a priori significance defined as P < 0.05. RESULTS: Ten studies were eligible yielding 283 patients with cystic pituitary adenomas. The definitions of 'cystic' mainly varied between the visual appearance of cystic components on preoperative magnetic resonance imaging and a volumetric definition requiring 50% or greater of tumor volume exhibiting cystic components. Tumor diameter was seldom reported with an associated standard deviation/error, limiting meta-analyses. When the data were pooled in accordance with the definition applied, there were no significant differences in the rates of gross total resection (P = 0.830), endocrinologic remission (P = 0.563), and tumor recurrence (P = 0.320). Meta-analyses on studies comparing cystic versus non-cystic pituitary adenomas indicated no significant difference in the rates of gross total resection (P = 0.729), endocrinologic remission (P = 0.857), and tumor recurrence (P = 0.465). CONCLUSION: Despite some individual studies describing a significant influence of pituitary adenoma texture on postoperative outcomes, meta-analyses revealed no such differences between cystic and non-cystic pituitary adenomas. This discrepancy may be explained in part by the inconsistent definition of 'cystic' and between-group differences in tumor size. A notion of a field-standard definition of 'cystic' among pituitary adenomas should be established to facilitate inter-study comparisons.

Comparing the compensatory reserve metric obtained from invasive arterial measurements and photoplethysmographic volume-clamp during simulated hemorrhage.

PURPOSE: The compensatory reserve metric (CRM) is a novel tool to predict cardiovascular decompensation during hemorrhage. The CRM is traditionally computed using waveforms obtained from photoplethysmographic volume-clamp (PPGVC), yet invasive arterial pressures may be uniquely available. We aimed to examine the level of agreement of CRM values computed from invasive arterial-derived waveforms and values computed from PPGVC-derived waveforms. METHODS: Sixty-nine participants underwent graded lower body negative pressure to simulate hemorrhage. Waveform measurements from a brachial arterial catheter and PPGVC finger-cuff were collected. A PPGVC brachial waveform was reconstructed from the PPGVC finger waveform. Thereafter, CRM values were computed using a deep one-dimensional convolutional neural network for each of the following source waveforms; (1) invasive arterial, (2) PPGVC brachial, and (3) PPGVC finger. Bland-Altman analyses were used to determine the level of agreement between invasive arterial CRM values and PPGVC CRM values, with results presented as the Mean Bias [95% Limits of Agreement]. RESULTS: The mean bias between invasive arterial- and PPGVC brachial CRM values at rest, an applied pressure of -45mmHg, and at tolerance was 6% [-17%, 29%], 1% [-28%, 30%], and 0% [-25%, 25%], respectively. Additionally, the mean bias between invasive arterial- and PPGVC finger CRM values at rest, applied pressure of -45mmHg, and tolerance was 2% [-22%, 26%], 8% [-19%, 35%], and 5% [-15%, 25%], respectively. CONCLUSION: There is generally good agreement between CRM values obtained from invasive arterial waveforms and values obtained from PPGVC waveforms. Invasive arterial waveforms may serve as an alternative for computation of the CRM.

Determining optical material parameters with motion in structured illumination.

A set of power measurements as a function of controlled nanopositioner movement of a planar film arrangement in a standing wave field is presented as a means to obtain the thicknesses and the dielectric constants to a precision dictated by noise in an exciting laser beam and the positioning and detector process, all of which can be refined with averaging. From a mutual information perspective, knowing the set of positions at which measurements are performed adds information. While applicable to any arrangement of planar films, the implementation considered involves thin transmissive membranes, as are employed in applications such as optomechanics. We show that measured power data as a function of object position provides sensitivity to the film refractive index and far-subwavelength thickness. Use of a cost function allows iterative retrieval of the film parameters, and a multi-resolution framework is described as a computationally efficient procedure. The approach is complementary to ellipsometry and could play an important role in routine film characterization studies for fields involving solid state material processing, as is common in the semiconductor device field.

Muscle oxygenation during normoxic and hypoxic cycling exercise in humans with high-affinity haemoglobin.

NEW FINDINGS: What is the central question of this study? Do humans with high-affinity haemoglobin (HAH) demonstrate attenuated skeletal muscle deoxygenation during normoxic and hypoxic exercise? What is the main finding and its importance? Examination of near-infrared spectroscopy-derived muscle oxygenation profiles suggests that fractional oxygen extraction is blunted during hypoxic exercise in humans with HAH compared with control subjects. However, muscle tissue oxygen saturation levels were higher in humans with HAH during exercise in normoxia compared with control subjects. These alterations in fractional oxygen extraction in humans with HAH might influence blood flow regulation and exercise capacity during hypoxia. ABSTRACT: Recently, researchers in our laboratory have shown that humans with genetic mutations resulting in high-affinity haemoglobin (HAH) demonstrate better maintained aerobic capacity and peak power output during hypoxic exercise versus normoxic exercise in comparison to humans with normal-affinity haemoglobin. However, the influence of HAH on tissue oxygenation within exercising muscle during normoxia and hypoxia is unknown. Therefore, we examined near-infrared spectroscopy-derived oxygenation profiles of the vastus lateralis during graded cycling exercise in normoxia and hypoxia among humans with HAH (n = 5) and control subjects with normal-affinity haemoglobin (n = 12). The HAH group elicited a blunted increase of deoxygenated haemoglobin + myoglobin during hypoxic exercise compared with the control group (P = 0.03), suggesting reduced fractional oxygen extraction in the HAH group. In addition, the HAH group maintained a higher level of muscle tissue oxygen saturation during normoxic exercise (HAH, 75 ± 4% vs. controls, 65 ± 3%, P = 0.049) and there were no differences between groups in muscle tissue oxygen saturation during hypoxic exercise (HAH, 68 ± 3% vs. controls, 68 ± 2%, P = 0.943). Overall, our results suggest that humans with HAH might demonstrate divergent patterns of fractional oxygen extraction during hypoxic exercise and elevated muscle tissue oxygenation during normoxic exercise compared with control subjects.

Demonstration of Enhanced Optical Pressure on a Structured Surface.

The interaction of electromagnetic waves with condensed matter and the resultant force is fundamental in the physical sciences. The maximum pressure on a planar surface is understood to be twice the incident wave power density normalized by the background velocity. We demonstrate for the first time that this pressure can be exceeded by a substantial factor by structuring a surface. Experimental results for direct optomechanical deflection of a nanostructured gold film on a silicon nitride membrane illuminated by a laser beam are shown to significantly exceed those for the planar surface. This enhanced pressure can be understood as being associated with an asymmetric optical cavity array realized in the membrane film. The possible enhancement depends on the material properties and the geometrical parameters of the structured material. Such control and increase of optical pressure with nanostructured material should impact applications across the physical sciences.

Surface plasmon resonance imaging of excitable cells.

Surface plasmons (SPs) are surface charge density oscillations occuring at a metal/dieletric interface and are highly sensitive to refractive index variations adjacent to the surface. This sensitivity has been exploited successfully for chemical and biological assays. In these systems, a surface plasmon resonance (SPR)-based sensor detects temporal variations in the refractive index at a point. SPR has also been used in imaging systems where the spatial variations of refractive index in the sample provide the contrast mechanism. SPR imaging systems using high numerical aperture (NA) objective lenses have been designed to image adherent live cells with high magnification and near-diffraction limited spatial resolution. Addressing research questions in cell physiology and pharmacology often requires the development of a multimodal microscope where complementary information can be obtained. In this paper, we present the development of a multimodal microscope that combines SPR imaging with a number of additional imaging modalities including bright-field, epifluorescence, total internal reflection microscopy and SPR fluorescence microscopy. We used a high NA objective lens for SPR and TIR microscopy and the platform has been used to image live cell cultures demonstrating both fluorescent and label-free techniques. Both the SPR and TIR imaging systems feature a wide field of view (~300 µm) that allows measurements from multiple cells whilst maintaining a resolution sufficient to image fine cellular processes. The capability of the platform to perform label-free functional imaging of living cells was demonstrated by imaging the spatial variations in contractions from stem cell-derived cardiomyocytes. This technique shows promise for non-invasive imaging of cultured cells over very long periods of time during development.

Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells.

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex.

DRO1 influences root system architecture in Arabidopsis and Prunus species.

Roots provide essential uptake of water and nutrients from the soil, as well as anchorage and stability for the whole plant. Root orientation, or angle, is an important component of the overall architecture and depth of the root system; however, little is known about the genetic control of this trait. Recent reports in Oryza sativa (rice) identified a role for DEEPER ROOTING 1 (DRO1) in influencing the orientation of the root system, leading to positive changes in grain yields under water-limited conditions. Here we found that DRO1 and DRO1-related genes are present across diverse plant phyla, and fall within the IGT gene family. The IGT family also includes TAC1 and LAZY1, which are known to affect the orientation of lateral shoots. Consistent with a potential role in root development, DRO1 homologs in Arabidopsis and peach showed root-specific expression. Promoter-reporter constructs revealed that AtDRO1 is predominantly expressed in both the root vasculature and root tips, in a distinct developmental pattern. Mutation of AtDRO1 led to more horizontal lateral root angles. Overexpression of AtDRO1 under a constitutive promoter resulted in steeper lateral root angles, as well as shoot phenotypes including upward leaf curling, shortened siliques and narrow lateral branch angles. A conserved C-terminal EAR-like motif found in IGT genes was required for these ectopic phenotypes. Overexpression of PpeDRO1 in Prunus domestica (plum) led to deeper-rooting phenotypes. Collectively, these data indicate a potential application for DRO1-related genes to alter root architecture for drought avoidance and improved resource use.

Sensitive detection of voltage transients using differential intensity surface plasmon resonance system.

This paper describes theoretical and experimental study of the fundamentals of using surface plasmon resonance (SPR) for label-free detection of voltage. Plasmonic voltage sensing relies on the capacitive properties of metal-electrolyte interface that are governed by electrostatic interactions between charge carriers in both phases. Externally-applied voltage leads to changes in the free electron density in the surface of the metal, shifting the SPR position. The study shows the effects of the applied voltage on the shape of the SPR curve. It also provides a comparison between the theoretical and experimental response to the applied voltage. The response is presented in a universal term that can be used to assess the voltage sensitivity of different SPR instruments. Finally, it demonstrates the capacity of the SPR system in resolving dynamic voltage signals; a detection limit of 10mV with a temporal resolution of 5ms is achievable. These findings pave the way for the use of SPR systems in the detection of electrical activity of biological cells.

Diffuse optical localization of blood vessels and 3D printing for guiding oral surgery.

Diffuse optical imaging through centimeters of tissue has emerged as a powerful tool in biomedical research. However, applications in the operating theater have been limited in part due to data set requirements and computational burden. We present an approach that uses a small number of optical source-detector pairs that allows for the fast localization of arteries in the roof of the mouth and has the potential to reduce complications during oral surgery. The arteries are modeled as multiple-point absorbers, allowing localization of their complex shapes. The method is demonstrated using a printed tissue-simulating mouth phantom. Furthermore, we use the extracted position information to fabricate a custom surgical guide using 3D printing that could protect the arteries during surgery.

Printed optics: phantoms for quantitative deep tissue fluorescence imaging.

Three-dimensional (3D) printing allows for complex or physiologically realistic phantoms, useful, for example, in developing biomedical imaging methods and for calibrating measured data. However, available 3D printing materials provide a limited range of static optical properties. We overcome this limitation with a new method using stereolithography that allows tuning of the printed phantom's optical properties to match that of target tissues, accomplished by printing a mixture of polystyrene microspheres and clear photopolymer resin. We show that Mie theory can be used to design the optical properties, and demonstrate the method by fabricating a mouse phantom and imaging it using fluorescence optical diffusion tomography.

Printed optics: phantoms for quantitative deep tissue fluorescence imaging: publisher's note.

This note points out a number of corrections that were omitted from the published version of the article [Opt. Lett.41, 5230 (2016)OPLEDP0146-959210.1364/OL.41.005230].

Imaging Hidden Objects with Spatial Speckle Intensity Correlations over Object Position.

We present a coherent optical method for wavelength-resolution imaging of moving objects hidden within thick randomly scattering media. Spatial speckle intensity correlations as a function of object position are shown to provide access to the spatially dependent dielectric constant of the moving object. This speckle correlation imaging method yields field-based information previously inaccessible in heavily scattering environments. Proof of concept experimental results show excellent agreement with the theory. This new imaging approach will be valuable in high resolution imaging in tissue and other scattering environments where natural motion occurs or the object position can be controlled.

Fabrication and application of heterogeneous printed mouse phantoms for whole animal optical imaging.

This work demonstrates the usefulness of 3D printing for optical imaging applications. Progress in developing optical imaging for biomedical applications requires customizable and often complex objects for testing and evaluation. There is therefore high demand for what have become known as tissue-simulating "phantoms." We present a new optical phantom fabricated using inexpensive 3D printing methods with multiple materials, allowing for the placement of complex inhomogeneities in complex or anatomically realistic geometries, as opposed to previous phantoms, which were limited to simple shapes formed by molds or machining. We use diffuse optical imaging to reconstruct optical parameters in 3D space within a printed mouse to show the applicability of the phantoms for developing whole animal optical imaging methods. This phantom fabrication approach is versatile, can be applied to optical imaging methods besides diffusive imaging, and can be used in the calibration of live animal imaging data.

Thin-film optoacoustic transducers for subcellular Brillouin oscillation imaging of individual biological cells.

At low frequencies ultrasound is a valuable tool to mechanically characterize and image biological tissues. There is much interest in using high-frequency ultrasound to investigate single cells. Mechanical characterization of vegetal and biological cells by measurement of Brillouin oscillations has been demonstrated using ultrasound in the GHz range. This paper presents a method to extend this technique from the previously reported single-point measurements and line scans into a high-resolution acoustic imaging tool. Our technique uses a three-layered metal-dielectric-metal film as a transducer to launch acoustic waves into the cell we want to study. The design of this transducer and measuring system is optimized to overcome the vulnerability of a cell to the exposure of laser light and heat without sacrificing the signal-to-noise ratio. The transducer substrate shields the cell from the laser radiation, efficiently generates acoustic waves, facilitates optical detection in transmission, and aids with heat dissipation away from the cell. This paper discusses the design of the transducers and instrumentation and presents Brillouin frequency images on phantom, fixed, and living cells.

Optically excited nanoscale ultrasonic transducers.

In order to work at higher ultrasonic frequencies, for instance, to increase the resolution, it is necessary to fabricate smaller and higher frequency transducers. This paper presents an ultrasonic transducer capable of being made at a very small size and operated at GHz frequencies. The transducers are activated and read optically using pulsed lasers and without physical contact between the instrumentation and the transducer. This removes some of the practical impediments of traditional piezoelectric architectures (such as wiring) and allows the devices to be placed immediately on or within samples, reducing the significant effect of attenuation which is very strong at frequencies above 1 GHz. The transducers presented in this paper exploit simultaneous optical and mechanical resonances to couple the optical input into ultrasonic waves and vice versa. This paper discusses the mechanical and optical design of the devices at a modest scale (a few µm) and explores the scaling of the transducers toward the sub-micron scale. Results are presented that show how the transducers response changes depending on its local environment and how the resonant frequency shifts when the transducer is loaded by a printed protein sample.

Angle-insensitive and solar-blind ultraviolet bandpass filter.

We present a metal-dielectric stack ultraviolet (UV) bandpass filter that rejects the longer wavelength, visible spectrum and is thin and relatively insensitive to the angle of incidence. Parametric evaluations of the reflection phase shift at the metal-dielectric interface provide insight and design information. This nontrivial phase shift allows coupled Fabry-Perot resonances with subwavelength dielectric film thickness. Furthermore, the total phase shift, with contributions from wave propagation and nontrivial reflection phase shift, is insensitive to the angle of incidence. Filter passbands in the UV can be shifted to visible or longer wavelengths by engineering the dielectric thickness and selecting a metal with an appropriate plasma frequency.

Prediction of electric field frequency correlations for randomly scattering slabs in the nondiffusive regime with the scalar Bethe-Salpeter equation.

We show that a scalar Bethe-Salpeter equation model captures the measured copolarized electric field frequency correlation magnitude for randomly scattering slabs in the weakly scattering, nondiffusive regime. Consequently, the model could be used to form images of tissue on the millimeter and submillimeter length scale, and for environmental sensing with comparable scatter, as dictated by the optical scattering length in relation to the scattering domain size.