Preliminary Imaging Research Articles

Design, synthesis, in vitro characterization and preliminary imaging studies on fluorinated bile acid derivatives as PET tracers to study hepatic transporters

With the aim of identifying a fluorinated bile acid derivative that could be used as [18F]-labeled Positron Emission Tomography (PET) tracer for imaging the in vivo functioning of liver transporter proteins, and particularly of OATP1B1, three fluorinated bile acid triazole derivatives of cholic, deoxycholic and lithocholic acid (CATD, DCATD and LCATD 4a–c, respectively) were synthesized and labeled with tritium. In vitro transport properties were studied with cell-based assays to identify the best substrate for OATP1B1. In addition, the lead compound, LCATD (4c), was tested as a substrate of other liver uptake transporters OATP1B3, NTCP and efflux transporter BSEP to evaluate its specificity of liver transport. The results suggest that 4c is a good substrate of OATP1B1 and NTCP, whereas it is a poor substrate of OATP1B3. The efflux transporter BSEP also appears to be involved in the excretion of 4c from hepatocytes. The automated radiosynthesis of [18F]-4c was accomplished in a multi-GBq scale and a pilot imaging experiment in a wild type rat was performed after i.v. administration to assess the biodistribution and clearance of the tracer. PET imaging revealed that radioactivity was primarily located in the liver (tmax=75s) and cleared exclusively through the bile, thus allowing to image the hepatobiliary excretion of bile acids in the animal model. These findings suggest that [18F]-LCATD 4c is a promising PET probe for the evaluation of hepatic transporters OATP1B1, NTCP and BSEP activity with potential for studying drug-drug interactions and drug-induced toxicity involving these transporters.

Fluorescence imaging as a diagnostic of M-band x-ray drive condition in hohlraum with fluorescent Si targets

Fluorescence imaging of surrogate Si-doped CH targets has been used to provide a measurement for drive condition of high-energy x-ray (i.e. M-band x-ray) drive symmetry upon the capsule in hohlraum on Shenguang-II laser facility. A series of experiments dedicated to the study of photo-pumping and fluorescence effect in Si-plasma are presented. To investigate the feasibility of fluorescence imaging in Si-plasma, an silicon plasma in Si-foil target is pre-formed at ground state by the soft x-ray from a half-hohlraum, which is then photo-pumped by the K-shell lines from a spatially distinct laser-produced Si-plasma. The resonant Si photon pump is used to improve the fluorescence signal and cause visible image in the Si-foil. Preliminary fluorescence imaging of Si-ball target is performed in both Si-doped and pure Au hohlraum. The usual capsule at the center of the hohlraum is replaced with a solid Si-doped CH-ball (Si-ball). Since the fluorescence is proportional to the photon pump upon the Si-plasma, high-energy x-ray drive symmetry is equal to the fluorescence distribution of the Si-ball.

Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions.

The peripheral retina of the human eye offers a unique opportunity for assessment and monitoring of ocular diseases. We have developed a novel wide-field (>70°) optical coherence tomography system (WF-OCT) equipped with wavefront sensorless adaptive optics (WSAO) for enhancing the visualization of smaller (<25°) targeted regions in the peripheral retina. We iterated the WSAO algorithm at the speed of individual OCT B-scans (~20 ms) by using raw spectral interferograms to calculate the optimization metric. Our WSAO approach with a 3 mm beam diameter permitted primarily low- but also high- order peripheral wavefront correction in less than 10 seconds. In preliminary imaging studies in five normal human subjects, we quantified statistically significant changes with WSAO correction, corresponding to a 10.4% improvement in average pixel brightness (signal) and 7.0% improvement in high frequency content (resolution) when visualizing 1 mm (~3.5°) B-scans of the peripheral (>23°) retina. We demonstrated the ability of our WF-OCT system to acquire non wavefront-corrected wide-field images rapidly, which could then be used to locate regions of interest, zoom into targeted features, and visualize the same region at different time points. A pilot clinical study was conducted on seven healthy volunteers and two subjects with prodromal Alzheimer's disease which illustrated the capability to image Drusen-like pathologies as far as 32.5° from the fovea in un-averaged volume scans. This work suggests that the proposed combination of WF-OCT and WSAO may find applications in the diagnosis and treatment of ocular, and potentially neurodegenerative, diseases of the peripheral retina, including diabetes and Alzheimer's disease.

Towards a Reduced-Wire Interface for CMUT-Based Intravascular Ultrasound Imaging Systems.

Having intravascular ultrasound (IVUS) imaging capability on guide wires used in cardiovascular interventions may eliminate the need for separate IVUS catheters and expand the use of IVUS in a larger portion of the vasculature. High frequency capacitive micro machined ultrasonic transducer (CMUT) arrays should be integrated with interface electronics and placed on the guide wire for this purpose. Besides small size, this system-on-a-chip (SoC) front-end should connect to the back-end imaging system with a minimum number of wires to preserve the critical mechanical properties of the guide wire. We present a 40 MHz CMUT array interface SoC, which will eventually use only two wires for power delivery and transmits image data using a combination of analog-to-time conversion (ATC) and an impulse radio ultra-wideband (IR-UWB) wireless link. The proof-of-concept prototype ASIC consumes only 52.8 mW and occupies 4.07 [Formula: see text] in a 0.35- [Formula: see text] standard CMOS process. A rectifier and regulator power the rest of the SoC at 3.3 V from a 10 MHz power carrier that is supplied through a 2.4 m micro-coax cable with an overall efficiency of 49.1%. Echo signals from an 8-element CMUT array are amplified by a transimpedance amplifier (TIA) array and down-converted to baseband by quadrature sampling using a 40 MHz clock, derived from the power carrier. The ATC generates pulse-width-modulated (PWM) samples at 2 × 10 MS/s with 6 bit resolution, while the entire system achieved 5.1 ENOB. Preliminary images from the prototype system are presented, and alternative data transmission and possible future directions towards practical implementation are discussed.

World FDI, an 'Unequal Partners' and 'Concentric Circles' Design Part IV. Further on Regions, with Preliminary Images. South-East Europe, CIS Member Countries and near East

This article continues the previously promised series to focus on FDI & DIA, as unitary fluid substance world owned, and so flows and stocks and country actors carrying these, but respective amounts unevenly distribute on these country actors. Once more, our approach on FDI keeps on its unchanged paradigm, coordinates and criteria considered, i.e. dynamics mean individual country versus world speed difference along the 1994-2015 interval, in which the 1994 stocks cumulate FDI & DIA flows since 1990, and top countries range up to an important majority of stocks amounts in the total (85-95%) and so a relatively stable percentage, on the one hand, and down to 0.2% on FDI/inflows and to 0.1% of the same total world stocks on DIA/outflows, on the other. It will be this time for other three regions that are: South-East Europe, CIS and Near East countries.

Preliminary imaging results and SAR analysis of a microwave imaging system for early breast cancer detection.

Currently X-ray-based imaging systems suffer from low contrast between malignant and healthy fibrous tissues in breast. Microwave Near-field Radar Imaging (NRI) shows a higher contrast between the aforementioned tissues and therefore can enhance tumor detection and diagnosis accuracy. In this work, we present the first imaging results of our developed NRI system that is equipped with a pair of Antipodal Vivaldi Antennas. We used a metal bearing ball immersed in oil as our object of interest, to keep the first measurement configuration simple. Moreover, to demonstrate the safety of our system for human subject tests, we simulated the Specific Absorption Rate (SAR) in a realistic breast tissue model and compared the resulted values with both the USA and Europe standards. The results show that firstly the imaging results from the measurements and simulations are comparable, and secondly the antennas radiations meet the SAR criteria.

System Description and First Application of an FPGA-Based Simultaneous Multi-Frequency Electrical Impedance Tomography.

A new prototype of a multi-frequency electrical impedance tomography system is presented. The system uses a field-programmable gate array as a main controller and is configured to measure at different frequencies simultaneously through a composite waveform. Both real and imaginary components of the data are computed for each frequency and sent to the personal computer over an ethernet connection, where both time-difference imaging and frequency-difference imaging are reconstructed and visualized. The system has been tested for both time-difference and frequency-difference imaging for diverse sets of frequency pairs in a resistive/capacitive test unit and in self-experiments. To our knowledge, this is the first work that shows preliminary frequency-difference images of in-vivo experiments. Results of time-difference imaging were compared with simulation results and shown that the new prototype performs well at all frequencies in the tested range of 60 kHz–960 kHz. For frequency-difference images, further development of algorithms and an improved normalization process is required to correctly reconstruct and interpreted the resulting images.

Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging.

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology, and neurology. N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A (11) C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding.

Discovery of a Highly Selective Glycogen Synthase Kinase‐3 Inhibitor (PF‐04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging

AbstractGlycogen synthase kinase‐3 (GSK‐3) regulates multiple cellular processes in diabetes, oncology, and neurology. N‐(3‐(1H‐1,2,4‐triazol‐1‐yl)propyl)‐5‐(3‐chloro‐4‐methoxyphenyl)oxazole‐4‐carboxamide (PF‐04802367 or PF‐367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK‐3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF‐367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF‐367 is ideal for discovery of radiopharmaceuticals for GSK‐3 in the central nervous system. A 11C‐isotopologue of PF‐367 was synthesized and preliminary PET imaging studies in non‐human primates confirmed that we have overcome the two major obstacles for imaging GSK‐3, namely, reasonable brain permeability and displaceable binding.

Spectral-Domain Optical Coherence Tomography Angiography Findings in Multifocal Choroiditis With Active Lesions

To describe optical coherence tomography angiography (OCTA) findings in multifocal choroiditis (MFC) with active lesions and to characterize the concordance between the OCTA and other traditional imaging modalities. Reliability and validity analysis. Patients with suspected choroidal neovascularization (CNV) or acute inflammatory lesions associated with MFC were assessed in this study. All participants underwent preliminary traditional multimodal imaging including color fundus photography, fundus autofluorescence, near-infrared reflectance imaging, spectral-domain optical coherence tomography, and fluorescence angiography (FA). The participants were prospectively recruited to perform OCTA. OCTA findings of active lesions were compared with other traditional imaging results. Vascular flow signal representing CNV was identified, and a quantitative analysis of CNV size was performed on OCTA. Fifty-two eyes of 26 MFC patients (14 were bilaterally affected and 12 were unilaterally affected) wereincluded. Among the 23 active CNV cases, 20 were confirmed on OCTA while the other 3 were invalid owing to severe motion artifacts. OCTA of CNV showed a well-circumscribed vascular network (mean flow area, 0.271mm(2) [± 0.144mm(2)]). Among the 34 inflammatory lesions in 13 eyes, 32 showed no blood flow in the outer retina on OCTA while the other 2 showed blood flow signal. OCTA has a predominant advantage in differentiating CNV from inflammatory lesions. It also allows the visualization of detailed vascular structure of CNV and the function of flow area measurement realizes the quantitative analysis of CNV. Hence, it could be an alternative option for CNV identification and may better guide treatment.

MAPPING LANDSLIDES IN LUNAR IMPACT CRATERS USING CHEBYSHEV POLYNOMIALS AND DEM’S

Abstract. Geological slope failure processes have been observed on the Moon surface for decades, nevertheless a detailed and exhaustive lunar landslide inventory has not been produced yet. For a preliminary survey, WAC images and DEM maps from LROC at 100 m/pixels have been exploited in combination with the criteria applied by Brunetti et al. (2015) to detect the landslides. These criteria are based on the visual analysis of optical images to recognize mass wasting features. In the literature, Chebyshev polynomials have been applied to interpolate crater cross-sections in order to obtain a parametric characterization useful for classification into different morphological shapes. Here a new implementation of Chebyshev polynomial approximation is proposed, taking into account some statistical testing of the results obtained during Least-squares estimation. The presence of landslides in lunar craters is then investigated by analyzing the absolute values off odd coefficients of estimated Chebyshev polynomials. A case study on the Cassini A crater has demonstrated the key-points of the proposed methodology and outlined the required future development to carry out.

MAPPING LANDSLIDES IN LUNAR IMPACT CRATERS USING CHEBYSHEV POLYNOMIALS AND DEM’S

Geological slope failure processes have been observed on the Moon surface for decades, nevertheless a detailed and exhaustive lunar landslide inventory has not been produced yet. For a preliminary survey, WAC images and DEM maps from LROC at 100 m/pixels have been exploited in combination with the criteria applied by Brunetti et al. (2015) to detect the landslides. These criteria are based on the visual analysis of optical images to recognize mass wasting features. In the literature, Chebyshev polynomials have been applied to interpolate crater cross-sections in order to obtain a parametric characterization useful for classification into different morphological shapes. Here a new implementation of Chebyshev polynomial approximation is proposed, taking into account some statistical testing of the results obtained during Least-squares estimation. The presence of landslides in lunar craters is then investigated by analyzing the absolute values off odd coefficients of estimated Chebyshev polynomials. A case study on the Cassini A crater has demonstrated the key-points of the proposed methodology and outlined the required future development to carry out.

High energy X-ray photon counting imaging using linear accelerator and silicon strip detectors

A photon counting imaging detector system for high energy X-rays is developed for on-site non-destructive testing of thick objects. One-dimensional silicon strip (1mm pitch) detectors are stacked to form a two-dimensional edge-on module. Each detector is connected to a 48-channel application specific integrated circuit (ASIC). The threshold-triggered events are recorded by a field programmable gate array based counter in each channel. The detector prototype is tested using 950kV linear accelerator X-rays. The fast CR shaper (300ns pulse width) of the ASIC makes it possible to deal with the high instant count rate during the 2μs beam pulse. The preliminary imaging results of several metal and concrete samples are demonstrated.

Brain penetrant small molecule 18F-GnRH receptor (GnRH-R) antagonists: Synthesis and preliminary positron emission tomography imaging in rats

IntroductionThe gonadotropin releasing hormone receptor (GnRH-R) has a well-described neuroendocrine function in the anterior pituitary. However, little is known about its function in the central nervous system (CNS), where it is most abundantly expressed in hippocampus and amygdala. Since peptide ligands based upon the endogenous decapetide GnRH do not pass the blood–brain-barrier, we are seeking a high-affinity small molecule GnRH-R ligand suitable for brain imaging by positron emission tomography. We have previously reported the radiosynthesis and in vitro evaluation of two novel [18F]fluorinated GnRH-R ligands belonging to the furamide class of antagonists, with molecular weight less than 500 Da. We now extend this work using palladium coupling for the synthesis of four novel radioligands, with putatively reduced polar surface area and hydrophilicity relative to the two previously described compounds, and report the uptake of these 18F-labeled compounds in brain of living rats. MethodsWe synthesized reference standards of the small molecule GnRH-R antagonists as well as mesylate precursors for 18F-labeling. The antagonists were tested for binding affinity for both human and rat GnRH-R. Serum and blood stability in vitro and in vivo were studied. Biodistribution and PET imaging studies were performed in male rats in order to assess brain penetration in vivo. ResultsA palladium coupling methodology served for the synthesis of four novel fluorinated furamide GnRH receptor antagonists with reduced heteroatomic count. Radioligand binding assays in vitro revealed subnanomolar affinity of the new fluorinated compounds for both human and rat GnRH-R. The 18F-GnRH antagonists were synthesized from the corresponding mesylate precursors in 5–15% overall radiochemical yield. The radiolabeled compounds demonstrated good in vivo stability. PET imaging with the 18F-radiotracers in naive rats showed good permeability into brain and rapid washout, but absence of discernible specific binding in vivo. ConclusionsThe novel small molecule 18F-fluorinated GnRH-R antagonist compounds show high receptor affinity in vitro, and may prove useful for quantitative autoradiographic studies in vitro. The compounds were permeable to the blood–brain barrier, but nonetheless failed to reveal significant specific binding in brain of living rats. Nonetheless, our approach may serve as a foundation for designing PET ligands suitable to image the GnRH-R distribution in brain.

Preparation of 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS) and its biodistribution and preliminary imaging study in nude mice bearing human breast cancer

Objective To synthesize 99Tcm-(HYNIC-BMS-200261)(tricine)(trisodium triphenylphosphine-3, 3', 3″-trisulfonate)(99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS)) and evaluate its biodistribution and feasibility of imaging in nude mice bearing human breast cancer xenografts. Methods HYNIC was conjugated to BMS-200261, then tricine and TPPTS were used as coligands for 99Tcm-labeling. The radiochemical purity and stability of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) were measured with HPLC. Biodistribution in normal mice and imaging in nude mice bearing MDA-MB-435 breast cancer xenografts were performed respectively. Results The radiochemical purity of 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS) was over 90%, and remained over 85% after 4 h at room temperature. The biodistribution data in normal mice showed a rapid clearance from blood. The tracer uptake of blood was (0.08±0.02) %ID/g at 2 h postinjection. 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS) was excreted mainly via the liver and kidneys. There was little radioactivity accumulation in gastrointestinal tract. The tracer uptake of spleen, stomach and small intestine were (0.35±0.13), (0.27±0.11) and (0.25±0.07) %ID/g at 2 h postinjection. Gamma imaging showed the tumor tissue uptake was remarkable at 30 min postinjection, with the maximum T/NT ratio of 3.40±0.30 at 1 h postinjection. Conclusions 99Tcm-(HYNIC-BMS-200261)(tricine) (TPPTS) may be easily prepared with high radiochemical purity and stability. The imaging results and biodistribution characteristics suggest it may be promising for the detection of breast cancer. Key words: (HYNIC-BMS-200261)(tricine)-(TPPTS); Istope labeling; Technetium; Radionuclide imaging; Breast neoplasms; Mice

Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of [(11)C]CO2.

Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [(11)C]CO2 followed by an intermolecular cycloaddition between a [(11)C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [(11)C]ibrutinib (Bruton's tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [(11)C]acrylic acid (generated from [(11)C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully automated on commercial radiochemical synthesis modules and provide radiotracers in 1-5% radiochemical yield (noncorrected, based upon [(11)C]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported.

Excitation-Scanning Hyperspectral Imaging System for Microscopic and Endoscopic Applications.

Current microscopic and endoscopic technologies for cancer screening utilize white-light illumination sources. Hyper-spectral imaging has been shown to improve sensitivity while retaining specificity when compared to white-light imaging in both microscopy and in vivo imaging.1,2 However, hyperspectral imaging methods have historically suffered from slow acquisition times due to the narrow bandwidth of spectral filters. Often minutes are required to gather a full image stack. We have developed a novel approach called excitation-scanning hyperspectral imaging that provides 2-3 orders of magnitude increased signal strength. This reduces acquisition times significantly, allowing for live video acquisition. Here, we describe a preliminary prototype excitation-scanning hyperspectral imaging system that can be coupled with endoscopes or microscopes for hyperspectral imaging of tissues and cells. Our system is comprised of three subsystems: illumination, transmission, and imaging. The illumination subsystem employs light-emitting diode arrays to illuminate at different wavelengths. The transmission subsystem utilizes a unique geometry of optics and a liquid light guide. Software controls allow us to interface with and control the subsystems and components. Digital and analog signals are used to coordinate wavelength intensity, cycling and camera triggering. Testing of the system shows it can cycle 16 wavelengths at as fast as 1 ms per cycle. Additionally, more than 18% of the light transmits through the system. Our setup should allow for hyperspectral imaging of tissue and cells in real time.

Preliminary energy-filtering neutron imaging with time-of-flight method on PKUNIFTY: A compact accelerator based neutron imaging facility at Peking University

Peking University Neutron Imaging Facility (PKUNIFTY) works on an accelerator–based neutron source with a repetition period of 10ms and pulse duration of 0.4ms, which has a rather low Cd ratio. To improve the effective Cd ratio and thus improve the detection capability of the facility, energy-filtering neutron imaging was realized with the intensified CCD camera and time-of-flight (TOF) method. Time structure of the pulsed neutron source was firstly simulated with Geant4, and the simulation result was evaluated with experiment. Both simulation and experiment results indicated that fast neutrons and epithermal neutrons were concentrated in the first 0.8ms of each pulse period; meanwhile in the period of 0.8–2.0ms only thermal neutrons existed. Based on this result, neutron images with and without energy filtering were acquired respectively, and it showed that detection capability of PKUNIFTY was improved with setting the exposure interval as 0.8–2.0ms, especially for materials with strong moderating capability.

Decorporation of Iron Metal Using Dialdehyde Cellulose-Deferoxamine Microcarrier

Deferoxamine iron chelator has a limited therapeutic index due to rapid clearance from blood and possesses dose-limiting toxicity. Therefore, an intravenous deferoxamine delivery system based on dialdehyde cellulose (DAC) polymer was developed and its efficacy and toxicity were tested in iron-overloaded animals. The amino groups of deferoxamine were conjugated to free aldehyde moieties of dialdehyde cellulose via Schiff base reaction to form dialdehyde cellulose-deferoxamine (DAC-DFO) conjugate and characterized by Fourier transform infrared spectrophotometer, scanning electron microscope, and X-ray diffraction. The toxicity of prepared formulation was analyzed by XTT cell viability assay and LD50 study in mice. The change in serum iron levels, after intravenous administration of formulation, was observed in iron-overloaded rats. The DAC-DFO conjugate was tagged with Tc-99m to study the blood kinetics and observe change in blood circulation time. DAC-DFO conjugate was dispersible in water at concentration ∼75mg/ml. In vitro cytotoxicity assay and LD50 study in mice indicated significantly enhanced safety of covalently bound deferoxamine (at >1000mg/kg body weight compared to free drug at ∼270mg/kg dose). A preliminary scintigraphy imaging and blood clearance study, with technetium-99m, indicated prolonged circulation of conjugated DFO in rabbit blood. A single dose of formulation injected into iron overloaded animals was found to maintain the normal serum iron levels until 10days. The polymeric conjugate was effective in maintaining normal serum iron levels until 10days at a dose of 100mg/kg body weight.

Ion microscopy based on laser-cooled cesium atoms

We demonstrate a prototype of a Focused Ion Beam machine based on the ionization of a laser-cooled cesium beam and adapted for imaging and modifying different surfaces in the few-tens nanometer range. Efficient atomic ionization is obtained by laser promoting ground-state atoms into a target excited Rydberg state, then field-ionizing them in an electric field gradient. The method allows obtaining ion currents up to 130pA. Comparison with the standard direct photo-ionization of the atomic beam shows, in our conditions, a 40-times larger ion yield. Preliminary imaging results at ion energies in the 1–5keV range are obtained with a resolution around 40nm, in the present version of the prototype. Our ion beam is expected to be extremely monochromatic, with an energy spread of the order of the eV, offering great prospects for lithography, imaging and surface analysis.