High Contrast Levels Research Articles

Imaging of adeno-associated viral capsids for purposes of gene editing using CEST NMR/MRI.

Gene therapy using adeno-associated virus (AAV) vector-mediated gene delivery has undergone substantial growth in recent years with promising results in both preclinical and clinical studies, as well as emerging regulatory approval. However, the inability to quantify the efficacy of gene therapy from cellular delivery of gene-editing technology to specific functional outcomes is an obstacle for efficient development of gene therapy treatments. Building on prior works that used the CEST reporter gene lysine rich protein, we hypothesized that AAV viral capsids may generate endogenous CEST contrast from an abundance of surface lysine residues. NMR experiments were performed on isolated solutions of AAV serotypes 1-9 on a Bruker 800-MHz vertical scanner. In vitro experiments were performed for testing of CEST-NMR contrast of AAV2 capsids under varying pH, density, biological transduction stage, and across multiple serotypes and mixed biological media. Reverse transcriptase-polymerase chain reaction was used to quantify virus concentration. Subsequent experiments at 7 T optimized CEST saturation schemes for AAV contrast detection and detected AAV2 particles encapsulated in a biocompatible hydrogel administered in the hind limb of mice. CEST-NMR experiments revealed CEST contrast up to 52% for AAV2 viral capsids between 0.6 and 0.8 ppm. CEST contrast generated by AAV2 demonstrated high levels of CEST contrast across a variety of chemical environments, concentrations, and saturation schemes. AAV2 CEST contrast displayed significant positive correlations with capsid density (R2 > 0.99, p < 0.001), pH (R2 = 0.97, p = 0.01), and viral titer per cell count (R2 = 0.92, p < 0.001). Transition to a preclinical field strength yielded up to 11.8% CEST contrast following optimization of saturation parameters. In vivo detection revealed statistically significant molecular contrast between viral and empty hydrogels using both mean values (4.67 ± 0.75% AAV2 vs. 3.47 ± 0.87% empty hydrogel, p = 0.02) and quantile analysis. AAV2 viral capsids exhibit strong capacity as an endogenous CEST contrast agent and can potentially be used for monitoring and evaluation of AAV vector-mediated gene therapy protocols.

ПРИМЕНЕНИЕ РАДАРНЫХ И ОПТИЧЕСКИХ ДАННЫХ ДЗЗ ДЛЯ ОЦЕНКИ КОЛИЧЕСТВА ПОСТРАДАВШИХ ДОМОВ, ПЛОЩАДИ И ГРАНИЦ ЗОН ЗАТОПЛЕНИЯ

The article presents the result of determining the flooding zone and the affected houses and buildings of the town of Atbasar from the spring floods of 2017. This result was obtained using three available remote sensing data Sentinel-2A, Landsat-8 and Sentinel-1B of medium spatial resolution. At the first stage, remote sensing data of the near, short-wave, thermal infrared (IR) range and polarization by contrast level were visually analyzed. Images were selected based on a high level of contrast between two classes: a water object and a non-water object (land). At the second stage, threshold values were calculated from a sample of pixels related to water bodies, and then binary images were created. In the third stage, binary images were logically summarized to eliminate the cloud effect and find the resulting binary image of the flood zone from spring floods. In the fourth stage, the resulting binary image was superimposed on the GIS data of the town of Atbasar, where the locations and the number of affected houses and buildings were located. According to this study, it was found that more than 200 country houses were flooded in the northern part, and 9 houses in the eastern part of the town of Atbasar. According to media reports and official bodies, the number of affected houses in Atbasar was about 400. The number of affected houses found by the method of logical summation with three remote sensing data was 52%. The accuracy of the location can be significantly improved by using high spatial resolution remote sensing data. The results of this study may be useful for the emergency service, local government agencies, and insurance companies in assessing damage from spring floods.

An optimized 3T MRI scan protocol to assess iris melanoma with subsequent histopathological verification – A prospective study

IntroductionMagnetic resonance imaging (MRI) has demonstrated high levels of tissue contrast, accuracy and reproducibility in evaluating posterior uveal melanoma. Owing to smaller size, the role of MRI in detecting and characterising iris melanoma has not yet been explored. Aims: To develop a protocol to image iris melanoma and describe the MRI characteristics of histopathological-confirmed iris melanoma. Materials and methodsAn optimised MRI protocol, using a 3T MRI scanner and a 32-channel head coil, was developed to image iris tumours. A prospective, single-centre, 12-month study was conducted on all patients with lesions suspicious for iris melanoma. All patients were offered an MRI scan in addition to the standardised clinical procedures. Image quality comparison was made with existing clinical investigations. Iris melanoma characteristics on MRI are described. ResultsA successful optimised MRI scan protocol was developed that was able to detect and characterise iris melanoma. One normal participant and five patients with subsequent histopathological-confirmed iris melanoma (n = 6) were recruited. Four patients completed the full MRI sequence. All iris melanoma were detected on at least one T1- or T2-weighted images. When compared to the vitreous, all iris melanomas demonstrated hyper-intensity on T1-weighted images and hypo-intensity on T2-weighted images. On T1-mapping, T1-values of iris melanoma demonstrated an inverse relationship with the degree of tumour pigmentation. ConclusionsThis study highlights an optimised, easily reproducible MRI scan protocol to image iris melanoma. Numerous MR imaging characteristics of iris melanoma are reported for the first time and a potential non-invasive tumour biomarker is described.

IMPLEMENTING THE NAXI ETHNIC CLOTHING ELEMENTS IN MODERN OUTFIT DESIGNS

ABSTRACT&#x0D; &#x0D; China's ancient ethnic minority clothes contain remarkable cultural elements, and among its treasures is the unique Naxi dress, the nation's oldest-standing traditional ethnic clothing. This study analyses the traditional Naxi clothing's structure, colour, fabric, motif characteristics, and accessories. These studies specify traditional Naxi clothing as the primary goal, which is fashioned in contemporary ways. Through an investigation of clothing composition and culture, the four main elements that constitute Naxi costumes should be applied to contemporary clothes. Firstly, the term "variability" designates a distinct style that differs in appearance depending on the way it is dressed. Secondly, the term 'colour contrast' denotes a high level of visual contrast. Third, material difference' integrates various materials into one. Fourth,' symbolic meaning' provides meaning to the wearer. As a consequence of this research, two modern clothing outfits were created with the implication of the unique character of Naxi costume clothes as a fashion design product, based on the traditional cultural characteristics of the Naxi people. By integrating components of traditional Naxi clothing and emphasising innovation, this study investigates and offers novel ideas for contemporary clothing design while simultaneously preserving traditional cultural elements for future generations.&#x0D; &#x0D; Keywords: Naxi people, Naxi traditional costumes, cultural elements, modern appeal

Three-dimensional X-ray microtomography of the heart of a chick embryo in the early period of embryogenesis

Relevance. The chicken embryo model is ideal for studying the development of the heart, which is the first functioning organ in embryogenesis. Particular attention is drawn to the embryonic period, when the embryonic heart is both functioning and forming, and small deviations in this process can lead to developmental anomalies. The current lack of results of accurate measurements of the morphology of the heart of a chicken embryo requires high-quality visualization, the complexity of which is determined by dynamic changes in the morphology of the heart, small size and complex spatial details of the organ. Threedimensional imaging methods are indispensable tools in this aspect, among which X-ray microtomography has special advantages.Methods. Embryo scanning (4–8 days, embryonic stages HH22–HH34) was performed using a highresolution X-ray microtomograph Skyscan 1176. A 1% solution of phosphoric-tungstic acid was used as a contrast. Post-processing, reconstruction, visualization of 3D-images, morphometry and X-ray density assessment were carried out using software packages DataViewer (1.5.6.2), CTvox (3.3.0r1403), CT-analyser (1.18.4.0).Results. The results obtained consist of three components: 1) general three-dimensional X-ray microtomographic visualization of chicken embryos in the early stages of embryogenesis with the designation of internal organs, allowing to determine the correct location of the heart; 2) microtomography of the heart with the designation of the main structures; 3) morphometric parameters of the embryo, heart and their X-ray density in units of the Hounsfield scale (HU). The methodological approach used has shown high efficiency. With an increase in the linear size of the chicken embryo and internal organs, including the heart, a high level of both general X-ray contrast and diffraction remains. At all the studied stages of the embryonic period of embryogenesis (4–8 days; HH22–HH34), the main visual and quantitative characteristics of cardiac morphogenesis were revealed.

Влияние мультифокальных ИОл на электрофизиологические параметры зрительного анализатора

The study of the electrophysiological parameters of the organ of vision before and after the implantation of multifocal intraocular lenses (mfIols) would provide new information about the effect of this type of lens on the processes of excitability and conduction of various parts of the visual analyzer as elements of the neuroadaptation process. Purpose of this study was to test the hypothesis about the effect of mfIol on the electrophysiological parameters of the organ of vision in the process of neuroadaptation of the central nervous system. Material and methods. The design is a prospective selective study. the total number of study participants was 48 patients. the object of the study were patients with a diagnosis of cataract. all patients underwent cataract surgery with mfIol implantation in one eye. the operation on the second eye was performed a month later. registration of visual evoked potentials (VEp) and electroretinography (Erg) were performed using the diopsys® noVa™ system. the diopsys® pErg-24 protocol was used to evaluate Erg. Functional Erg was also investigated using the diopsys® ffErg/Flash plus phnr protocol. VEp was assessed using the diopsys® VEp User-defined visual evoked potential protocol using 32×32 and 64×64 checkerboard pattern stimuli at low and high contrast levels. the number of analyzed features was — 122 units. Examination was carried out immediately before the first operation, the next day after the operation on the first eye, 1 month later (before and after the operation on the second eye), and after 3 months of observation. Results. Based on the results of the study, a quantitative characteristic was given to all evaluated features. the dynamics of indicators has been established. Significant differences were noted in some indicators, which may indicate the effect of the implanted mfIol on the electrophysiological parameters of the visual analyzer, indicating the presence of neuroadaptation process. Conclusion. 1. Implanted mfIols do not affect the function of ganglion cells and their axons. 2. the established changes in VEp are nonspecific, but the results obtained are statistically significant, which may indicate the effect of the implanted mfIol on the electrophysiological parameters of the visual analyzer. Keywords: neuroadaptation, electrophysiology of the organ of vision, multifocal intraocular lenses, cataract

Resonant Auger spectromicroscopy in ultrathin Fe films on W(110)

L3MM Auger transition is measured near the L3 resonance of ferromagnetic Fe films on W(110). The kinetic energies of the Auger peaks display the typical Raman behaviour for photon energies well below the absorption threshold, where the Auger energy follows the changes in the photon energy. Classical Auger behaviour with constant kinetic energy sets in at about 1.5 eV below the L3 resonance independently from the number of Fe layers down to the monolayer thickness. Strong x-ray circular magnetic dichroism is observed at the L3 edge in the entire L3MM Auger spectrum. Different Auger features originating from the final state with two 3p core holes show slight variations in the dichroic signal, which is attributed to the exchange interaction between the core holes and the valence band. Finally, XMCD-PEEM magnetic domain imaging using Auger electrons is demonstrated with a high level of contrast and lateral resolution approaching that of imaging with secondary photoelectrons.

Programmable Anisotropic Hydrogels with Localized Photothermal/Magnetic Responsive Properties.

Programmable smart materials that can respond locally to specific stimuli hold great potential for many applications, but controllable fabrication of these materials remains challenging. This work reports the development of novel programmable anisotropic materials with both magnetic and photothermal stimuli‐responsiveness, which are fabricated by anchoring thermosensitive poly(N‐isopropyl acrylamide) (PNIPAm) and magnetic Fe3O4 nanoparticles on the surface of MoS2 nanosheets. Further embedding PNIPAm‐MoS2/Fe3O4 into 3D‐printed hydrogel cubes results in stimuli‐responsive building blocks, and the magnetic field can precisely control their orientation and near‐infrared (NIR) light absorbing property. Particularly, the variation of the orientation of MoS2/Fe3O4 block results in obvious changes of their photothermal efficiency and optical property. By exploiting the anisotropy of MoS2/Fe3O4 and their NIR light responsiveness, thermally‐induced phase transitions in individual 3D printed hydrogel building block can be locally controlled for magnetic field‐assisted programming a quick response (QR) code. Alternatively, fluorescent QR code with high contrast and security level can be achieved by photothermal‐induced release of fluorescent dyes. These 3D printed magnetically programmed hydrogels hold great potential for application in information storage, intelligent materials, and precise therapy.

The Orientation Selectivity of Dichoptic Masking Suppression is Contrast Dependent in Amblyopia.

PurposeWe aimed to study the effect of stimulus contrast on the orientation selectivity of interocular interaction in amblyopia using a dichoptic masking paradigm.MethodsEight adults with anisometropic or mixed amblyopia and 10 control adults participated in our study. The contrast threshold in discriminating a target Gabor in the tested eye was measured with mean luminance in the untested eye, as well as with a bandpass oriented filtered noise in the other eye at low spatial frequency (0.25 c/d). Threshold elevation, which represents interocular suppression, was assessed using a the dichoptic masking paradigm (i.e. the contrast threshold difference between the target only and masked conditions), for each eye. Orientation selectivity of the interocular suppression as reflected by dichoptic masking was quantified by the difference between the parallel and orthogonal masking configurations. Two levels of mask's contrast (3 times or 10 times that of an individual's contrast threshold) were tested in this study.ResultsThe strength of dichoptic masking suppression was stronger at high, rather than low mask contrast in both amblyopic and control subjects. Normal controls showed orientation-dependent dichoptic masking suppression both under high and low contrast levels. However, amblyopes showed orientation-tuned dichoptic masking suppression only under the high contrast level, but untuned under the low contrast level.ConclusionsWe demonstrate that interocular suppression assessed by dichoptic masking is contrast-dependent in amblyopia, being orientation-tuned only at high suprathreshold contrast levels of the mask.

Measurement properties of electric field intensity distribution of whispering gallery mode with near-field optical probe

The distribution of the external electric field intensity of the whispering gallery mode (WGM) can be measured using a scanning near-field optical microscopy (SNOM) probe. As probing the resonator influences the optical resonance state, the measurement properties of the SNOM probe are worth studying. In this study, the measurement mechanism of WGMs using a glass SNOM probe was analyzed numerically. A probe with a nanometric-diameter is generally preferable. The results showed that the high-contrast measurement was possible; however, the signal was weak. Using a tip with a diameter equal to half the resonant wavelength, the signal strength was maximized with the same high contrast level as the nanoprobe. Interestingly, the measurement mechanism was different depending on tip size. With the nanoprobe, the interaction with the WGMs varied depending on the sensing locations; therefore, the resonant states were modulated during the measurements, which may have induced unexpected mode hopes. The resonance state was steady during measurements using a probe tip with a diameter of half the resonance wavelength. Although the mechanisms were different, the measured electric field intensity distributions were the same for both tip diameters.

Visual Function is Gradually Restored During Retina Regeneration in Adult Zebrafish.

In comparison to mammals, zebrafish are able to regenerate many organs and tissues, including the central nervous system (CNS). Within the CNS-derived neural retina, light lesions result in a loss of photoreceptors and the subsequent activation of Müller glia, the retinal stem cells. Müller glia-derived progenitors differentiate and eventually restore the anatomical tissue architecture within 4 weeks. However, little is known about how light lesions impair vision functionally, as well as how and to what extent visual function is restored during the course of regeneration, in particular in adult animals. Here, we applied quantitative behavioral assays to assess restoration of visual function during homeostasis and regeneration in adult zebrafish. We developed a novel vision-dependent social preference test, and show that vision is massively impaired early after lesion, but is restored to pre-lesion levels within 7 days after lesion. Furthermore, we employed a quantitative optokinetic response assay with different degrees of difficulty, similar to vision tests in humans. We found that vision for easy conditions with high contrast and low level of detail, as well as color vision, was restored around 7–10 days post lesion. Vision under more demanding conditions, with low contrast and high level of detail, was regained only later from 14 days post lesion onwards. Taken together, we conclude that vision based on contrast sensitivity, spatial resolution and the perception of colors is restored after light lesion in adult zebrafish in a gradual manner.

Narrow and Broad γ Bands Process Complementary Visual Information in Mouse Primary Visual Cortex.

γ Band plays a key role in the encoding of visual features in the primary visual cortex (V1). In rodents V1 two ranges within the γ band are sensitive to contrast: a broad γ band (BB) increasing with contrast, and a narrow γ band (NB), peaking at ∼60 Hz, decreasing with contrast. The functional roles of the two bands and the neural circuits originating them are not completely clear yet. Here, we show, combining experimental and simulated data, that in mice V1 (1) BB carries information about high contrast and NB about low contrast; (2) BB modulation depends on excitatory-inhibitory interplay in the cortex, while NB modulation is because of entrainment to the thalamic drive. In awake mice presented with alternating gratings, NB power progressively decreased from low to intermediate levels of contrast where it reached a plateau. Conversely, BB power was constant across low levels of contrast, but it progressively increased from intermediate to high levels of contrast. Furthermore, BB response was stronger immediately after contrast reversal, while the opposite held for NB. These complementary modulations were reproduced by a recurrent excitatory-inhibitory leaky integrate-and-fire network provided that the thalamic inputs were composed of a sustained and a periodic component having complementary sensitivity ranges. These results show that in rodents the thalamic-driven NB plays a specific key role in encoding visual contrast. Moreover, we propose a simple and effective network model of response to visual stimuli in rodents that might help in investigating network dysfunctions of pathologic visual information processing.

Highly Stable Indacenodithieno[3,2-b]thiophene-Based Donor-Acceptor Copolymers for Hybrid Electrochromic and Energy Storage Applications.

Stable doping of indacenodithieno[3,2-b]thiophene (IDTT) structures enables easy color tuning and significant improvement in the charge storage capacity of electrochromic polymers, making use of their full potential as electrochromic supercapacitors and in other emerging hybrid applications. Here, the IDTT structure is copolymerized with four different donor–acceptor–donor (DAD) units, with subtle changes in their electron-donating and electron-withdrawing characters, so as to obtain four different donor–acceptor copolymers. The polymers attain important form factor requirements for electrochromic supercapacitors: desired switching between achromatic black and transparent states (L*a*b* 45.9, −3.1, −4.2/86.7, −2.2, and −2.7 for PIDTT–TBT), high optical contrast (72% for PIDTT–TBzT), and excellent electrochemical redox stability (Ired/Ioxca. 1.0 for PIDTT–EBE). Poly[indacenodithieno[3,2-b]thiophene-2,8-diyl-alt-4,7-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-2-(2-hexyldecyl)-2H-benzo[d][1,2,3]triazole-7,7′-diyl] (PIDTT–EBzE) stands out as delivering simultaneously a high contrast (69%) and doping level (>100%) and specific capacitance (260 F g–1). This work introduces IDTT-based polymers as bifunctional electro-optical materials for potential use in color-tailored, color-indicating, and self-regulating smart energy systems.

Rapid Sonochemically-Assisted Synthesis of Highly Stable Gold Nanoparticles as Computed Tomography Contrast Agents

One of the most widely used modalities of clinical imaging is computed tomography (CT). Recent reports of new contrast agents toward CT imaging have been numerous. The production of gold nanoparticles (AuNPs) as contrast agents for CT is primarily a topic of intense interest. AuNPs have beneficial features for this application, including excellent X-ray attenuation, flexible sizes and shapes, tailorable surface chemistry, excellent biocompatibility and high levels of contrast generating matter. AuNPs with a size of about 18.5 nm and semi-spherical shape were synthesized using a sonochemical method. The attenuation rate of X-rays as measured in Hounsfield units per unit concentration (HU/mg) was measured. Ultrasound treatment for a duration of five min has been shown to produce highly stable AuNPs in different media (AuNPs in water and phosphate-buffered saline (PBS) was −42.1 mV and −39.5 mV, respectively). The CT value (HU = 395) of the AuNPs increased linearly with an increase in the AuNP dosage. The results confirm the use of ultrasonic treatment for the production of metal nanostructures, particularly highly stable non-toxic AuNPs, with good morphology and high-quality crystal structure using an easy and fast method. Synthesized AuNPs have the potential to be used as a CT contrast agent in medical imaging applications.

Motivation and Engagement during Visually Guided Behavior

SUMMARYAnimal behavior is motivated by internal drives, such as thirst and hunger, generated in hypothalamic neurons that project widely to many brain areas. We find that water-restricted mice maintain stable, high-level contrast sensitivity and brief reaction time while performing a visual task, but then abruptly stop and become disengaged. Mice consume a significant amount of water when freely provided in their home cage immediately after the task, indicating that disengagement does not reflect cessation of thirst. Neuronal responses of V1 neurons are reduced in the disengaged state, but pupil diameter does not decrease, suggesting that animals’ reduced level of arousal does not drive the transition to disengagement. Our findings indicate that satiation level alone does not have an instructive role in visually guided behavior and suggest that animals’ behavior is governed by cost-benefit analysis that can override thirst signals.

Extinguishing Exogenous Attention via Transcranial Magnetic Stimulation

Orienting covert exogenous (involuntary) attention to a target location improves performance in many visual tasks [1, 2]. It is unknown whether early visual cortical areas are necessary for this improvement. To establish a causal link between these areas and attentional modulations, we used transcranial magnetic stimulation (TMS) to briefly alter cortical excitability and determine whether early visual areas mediate the effect of exogenous attention on performance. Observers performed an orientation discrimination task. After a peripheral valid, neutral, or invalid cue, two cortically magnified gratings were presented, one in the stimulated region and the other in the symmetric region in the opposite hemifield. Observers received two successive TMS pulses around their occipital pole while the stimuli were presented. Shortly after, a response cue indicated the grating whose orientation observers had to discriminate. The response cue either matched-target stimulated-or did not match-distractor stimulated-the stimulated side. Grating contrast was varied to measure contrast response functions (CRF) for all combinations of attention and TMS conditions. When the distractor was stimulated, exogenous attention yielded response gain-performance benefits in the valid-cue condition and costs in the invalid-cue condition compared with the neutral condition at the high contrast levels. Crucially, when the target was stimulated, this response gain was eliminated. Therefore, TMS extinguished the effect of exogenous attention. These results establish a causal link between early visual areas and the modulatory effect of exogenous attention on performance.

Using machining force feedback to quantify grain size in beta titanium

The fluctuating forces on the cutting tool generated during machining of β processed Ti-17 alloy are shown to contain sufficient information to enable measurement of β grain size to an equivalent accuracy of standard etching methods. Three orthogonal forces were gathered, cutting force tangential to the rotation, the force in the feed (radial) direction, and the normal force in the longitudinal axis. Each individual force produced a microstructure image with a high level of contrast but in some cases did not fully highlight all features as shown in the optical image of the equivalent area. By normalising and combining the three forces into a vector, followed by noise reduction, a high-resolution image with sufficient detail to undertake grain size measurements using the linear intercept was produced. The measured grain size differed by no more than 5% with respect the grain size measured in the etched micrograph. It is believed that the forces which have a higher proportion of elastic response in their total values, i.e., the feed and normal forces, produced the higher contrast images, indicating that elastic stresses produce the highest contrast between grains and plastic strains smear out the grain to grain variation.

CONTROL OF THE CAUSES OF THE DAMPING OFF DISEASE ON PEPPER BY SOME BIOLOGICAL AGENTS IN BABYLON PROVINCE-IRAQ

The aim of the study was to isolate and diagnose the pathogens of the Damping off of pepper seedlings in Babylon province-Iraq and to evaluate the effectiveness of some biological control agents in disease control. 7 species of fungi associated with root rot and Damping off of pepper seedlings were diagnosed. Fusariumsolani was the most common fungus followed by Macrophominaphaseolina and Rhizoctoniasolani. The results showed that Trichodermaharzianium and Pseudomonas fluorescens have a high level of antagonistic contrast with pathogens. The results appeared the efficacy of the Black Cumin (Nigella sativa) extract in inhibiting the growth of pathogenic fungi. All the used treatments resulted in an increase in the percentage of pepper seed germination. A significant improvement in the biologic integration of T. harzianum and P. fluorescens and water extract of the Black Cumin increasing the percentage of germination of pepper seeds and provide good protection from the infection by pathogenic fungi causing Damping off disease, ranging between 62.5 - 87.5%. The conclusion of this study the effectiveness of the T. harzianum, P. fluorescens and the black cumin seed water extract in the protection of pepper seeds and seedlings from the infection by some pathogenic fungi Keywords: pepper; damping off, Biological control, Plant Extracts, Black Cumin.

Differential effects of antipsychotic drugs on contrast response functions of retinal ganglion cells in wild-type Sprague-Dawley rats and P23H retinitis pigmentosa rats.

Antipsychotic drugs haloperidol and clozapine have been reported to increase the sensitivity of retinal ganglion cells (RGCs) to flashes of light in the P23H rat model of retinitis pigmentosa. In order to better understand the effects of these antipsychotic drugs on the visual responses of P23H rat RGCs, I examined the responses of RGCs to a drifting sinusoidal grating of various contrasts. In-vitro multielectrode array recordings were made from P23H rat RGCs and healthy Sprague-Dawley (SD) rat RGCs. Retinas were stimulated with a drifting sinusoidal grating with eight values of contrast (0, 4, 6, 8.5, 13, 26, 51, and 83%). Contrast response functions based on response amplitudes were fitted with a hyperbolic ratio function and contrast thresholds were determined from the fitted curves. SD rat RGCs were divided into two categories, saturating and non-saturating cells, based on whether they showed saturation of responses at high contrast levels. Most SD rat RGCs (58%) were saturating cells. Haloperidol and clozapine decreased the responses of saturating SD rat RGCs to all grating contrasts, except for the highest contrast tested. Clozapine also decreased the responses of non-saturating SD rat RGCs to all grating contrasts, except for the highest contrast tested. Haloperidol did not however significantly affect the responses of non-saturating SD rat RGCs. Haloperidol and clozapine increased the contrast thresholds of both saturating and non-saturating cells in SD rat retinas. Most (73%) P23H rat RGCs could be categorized as either saturating or non-saturating cells. The remaining ‘uncategorized’ cells were poorly responsive to the drifting grating and were analyzed separately. Haloperidol and clozapine increased the responses of non-saturating and uncategorized P23H rat RGCs to most grating contrasts, including the highest contrast tested. Haloperidol and clozapine also increased the responses of saturating P23H rat RGCs to most grating contrasts but these increases were not statistically significant. Haloperidol and clozapine decreased the contrast thresholds of saturating cells, non-saturating cells and uncategorized cells in P23H rat retinas, although the decrease in contrast thresholds of saturating cells was not found to be statistically significant. Overall, the findings show that haloperidol and clozapine have differential effects on the contrast response functions of SD and P23H rat RGCs. In contrast to the effects observed on SD rat RGCs, both haloperidol and clozapine increased the responsiveness of P23H rat RGCs to both low and high contrast visual stimuli and decreased contrast thresholds.

Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging

Standard clinical X-ray contrast agents are small iodine-containing molecules that are rapidly cleared by the kidneys and provide robust imaging for only a few seconds, thereby limiting more extensive vascular and tissue biodistribution imaging as well as optimal tumor uptake. They are also not generally useful for preclinical microCT imaging where longer scan times are required for high resolution image acquisition. We here describe a new iodine nanoparticle contrast agent that has a unique combination of properties: 20 nm hydrodynamic diameter, covalent PEG coating, 40 hour blood half-life, 50% liver clearance after six months, accumulation in tumors, and well-tolerated to at least 4 g iodine/kg body weight after intravenous administration in mice. These characteristics are unique among the other iodine nanoparticles that have been previously reported and provide extended-time high contrast vascular imaging and tumor loading. As such, it is useful for preclinical MicroCT animal studies. Potential human applications might include X-ray radiation dose enhancement for cancer therapy and vascular imaging for life-threatening situations where high levels of contrast are needed for extended periods of time.