Coronary artery stenosis quantification in patients with dense calcifications using ultra-high-resolution photon-counting-detector computed tomography.

BACKGROUND: To quantify differences in coronary artery stenosis severity in patients with calcified lesions between conventional energy-integrating detector (EID) CT and ultra-high-resolution (UHR) photon-counting-detector (PCD) CT. METHODS: Patients undergoing clinically indicated coronary CT angiography were prospectively recruited and scanned first on an EID-CT (SOMATOM Force, Siemens Healthineers) and then a PCD-CT (NAEOTOM Alpha, Siemens Healthineers) on the same day. EID-CT was performed with standard mode (192 â€‹× â€‹0.6 â€‹mm detector collimation) following our clinical protocol. PCD-CT scans were performed under UHR mode (120 â€‹× â€‹0.2 â€‹mm detector collimation). For each patient, left main, left anterior descending, right coronary artery, and circumflex were reviewed and the most severe stenosis from dense calcification for each coronary was quantified using commercial software. Additionally, each measured stenosis was assigned a severity category based on percent diameter stenosis, and changes in severity category across EID-CT and PCD-CT were assessed. RESULTS: A total of 23 patients were enrolled, with 34 coronary artery stenoses analyzed. Stenosis was significantly reduced in PCD-CT compared to EID-CT (p â€‹< â€‹0.001), resulting in an average of 11% (SD â€‹= â€‹11%) reduction in percent diameter stenosis. Among the 34 lesions, 15 changed in stenosis severity category: 3 went from moderate to minimal, 1 from moderate to mild, 9 from mild to minimal, and 2 from minimal to mild with the use of PCD-CT compared to EID-CT. CONCLUSION: Use of UHR PCD-CT decreased percent diameter stenosis by an average of 11% relative to EID-CT, resulting in 13 of 34 stenoses being downgraded in stenosis severity category, potentially sparing patients from unnecessary intervention.

Seeing More with Less: Clinical Benefits of Photon-counting Detector CT.

Photon-counting detector (PCD) CT is an emerging technology that has led to continued innovation and progress in diagnostic imaging after it was approved by the U.S. Food and Drug Administration for clinical use in September 2021. Conventional energy-integrating detector (EID) CT measures the total energy of x-rays by converting photons to visible light and subsequently using photodiodes to convert visible light to digital signals. In comparison, PCD CT directly records x-ray photons as electric signals, without intermediate conversion to visible light. The benefits of PCD CT systems include improved spatial resolution due to smaller detector pixels, higher iodine image contrast, increased geometric dose efficiency to allow high-resolution imaging, reduced radiation dose for all body parts, multienergy imaging capabilities, and reduced artifacts. To recognize these benefits, diagnostic applications of PCD CT in musculoskeletal, thoracic, neuroradiologic, cardiovascular, and abdominal imaging must be optimized and adapted for specific diagnostic tasks. The diagnostic benefits and clinical applications resulting from PCD CT in early studies have allowed improved visualization of key anatomic structures and radiologist confidence for some diagnostic tasks, which will continue as PCD CT evolves and clinical use and applications grow. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material. See the invited commentary by Ananthakrishnan in this issue.

Photon-counting Detector CT with Deep Learning Noise Reduction to Detect Multiple Myeloma.

Background Photon-counting detector (PCD) CT and deep learning noise reduction may improve spatial resolution at lower radiation doses compared with energy-integrating detector (EID) CT. Purpose To demonstrate the diagnostic impact of improved spatial resolution in whole-body low-dose CT scans for viewing multiple myeloma by using PCD CT with deep learning denoising compared with conventional EID CT. Materials and Methods Between April and July 2021, adult participants who underwent a whole-body EID CT scan were prospectively enrolled and scanned with a PCD CT system in ultra-high-resolution mode at matched radiation dose (8 mSv for an average adult) at an academic medical center. EID CT and PCD CT images were reconstructed with Br44 and Br64 kernels at 2-mm section thickness. PCD CT images were also reconstructed with Br44 and Br76 kernels at 0.6-mm section thickness. The thinner PCD CT images were denoised by using a convolutional neural network. Image quality was objectively quantified in two phantoms and a randomly selected subset of participants (10 participants; median age, 63.5 years; five men). Two radiologists scored PCD CT images relative to EID CT by using a five-point Likert scale to detect findings reflecting multiple myeloma. The scoring for the matched reconstruction series was blinded to scanner type. Reader-averaged scores were tested with the null hypothesis of equivalent visualization between EID and PCD. Results Twenty-seven participants (median age, 68 years; IQR, 61-72 years; 16 men) were included. The blinded assessment of 2-mm images demonstrated improvement in viewing lytic lesions, intramedullary lesions, fatty metamorphosis, and pathologic fractures for PCD CT versus EID CT (P < .05 for all comparisons). The 0.6-mm PCD CT images with convolutional neural network denoising also demonstrated improvement in viewing all four pathologic abnormalities and detected one or more lytic lesions in 21 of 27 participants compared with the 2-mm EID CT images (P < .001). Conclusion Ultra-high-resolution photon-counting detector CT improved the visibility of multiple myeloma lesions relative to energy-integrating detector CT. © RSNA, 2022 Online supplemental material is available for this article.

Estimating the Clinical Impact of Photon-Counting-Detector CT in Diagnosing Usual Interstitial Pneumonia.

OBJECTIVE: The aim of this study was to evaluate the clinical impact of a higher spatial resolution, full field-of-view investigational photon-counting detector computed tomography (PCD-CT) on radiologist confidence in imaging findings and diagnosis of usual interstitial pneumonia (UIP) compared with conventional energy-integrating detector CT (EID-CT). MATERIALS AND METHODS: Patients suspected of interstitial lung disease were scanned on a PCD-CT system after informed consent and a clinically indicated EID-CT. In 2 sessions, 3 thoracic radiologists blinded to clinical history and scanner type evaluated CT images of the right and left lungs separately on EID- or PCD-CT, reviewing each lung once/session, rating confidence in imaging findings of reticulation, traction bronchiectasis, honeycombing, ground-glass opacities (GGOs), mosaic pattern, and lower lobe predominance (100-point scale: 0-33, likely absent; 34-66, indeterminate; 67-100, likely present). Radiologists also rated confidence for the probability of UIP (0-20, normal; 21-40, inconsistent with UIP; 41-60, indeterminate UIP; 61-81; probable UIP; 81-100, definite UIP) and graded image quality. Because a confidence scale of 50 represented completely equivocal findings, magnitude score (the absolute value of confidence scores from 50) was used for analysis (higher scores were more confident). Image noise was measured for each modality. The magnitude score was compared using linear mixed effects regression. The consistency of findings and diagnosis between 2 scanners were evaluated using McNemar test and weighted κ statistics, respectively. RESULTS: A total of 30 patients (mean age, 68.8 ± 11.0 years; M:F = 18:12) underwent conventional EID-CT (median CTDI vol , 7.88 mGy) and research PCD-CT (median CTDI vol , 6.49 mGy). The magnitude scores in PCD-CT were significantly higher than EID-CT for imaging findings of reticulation (40.7 vs 38.3; P = 0.023), GGO (34.4 vs 31.7; P = 0.019), and mosaic pattern (38.6 vs 35.9; P = 0.013), but not for other imaging findings ( P ≥ 0.130) or confidence in UIP (34.1 vs 22.2; P < 0.059). Magnitude score of probability of UIP in PCD-CT was significantly higher than EID-CT in one reader (26.0 vs 21.5; P = 0.009). Photon-counting detector CT demonstrated a decreased number of indeterminate GGO (17 vs 26), an increased number of unlikely GGO (74 vs 50), and an increased number of likely reticulations (140 vs 130) relative to EID-CT. Interobserver agreements among 3 readers for imaging findings and probability of UIP were similar between PCD-CT and EID-CT (intraclass coefficient: 0.507-0.818 vs 0.601-0.848). Photon-counting detector CT had higher scores in overall image quality (4.84 ± 0.38) than those in EID-CT (4.02 ± 0.40; P < 0.001) despite increased image noise (mean 85.5 vs 36.1 HU). CONCLUSIONS: Photon-counting detector CT provided better image quality and improved the reader confidence for presence or absence of imaging findings of reticulation, GGO, and mosaic pattern with idiosyncratic improvement in confidence in UIP presence.

First Clinical Photon-counting Detector CT System: Technical Evaluation.

Background The first clinical CT system to use photon-counting detector (PCD) technology has become available for patient care. Purpose To assess the technical performance of the PCD CT system with use of phantoms and representative participant examinations. Materials and Methods Institutional review board approval and written informed consent from four participants were obtained. Technical performance of a dual-source PCD CT system was measured for standard and high-spatial-resolution (HR) collimations. Noise power spectrum, modulation transfer function, section sensitivity profile, iodine CT number accuracy in virtual monoenergetic images (VMIs), and iodine concentration accuracy were measured. Four participants were enrolled (between May 2021 and August 2021) in this prospective study and scanned using similar or lower radiation doses as their respective clinical examinations performed on the same day using energy-integrating detector (EID) CT. Image quality and findings from the participants' PCD CT and EID CT examinations were compared. Results All standard technical performance measures met accreditation and regulatory requirements. Relative to filtered back-projection reconstructions, images from iterative reconstruction had lower noise magnitude but preserved noise power spectrum shape and peak frequency. Maximum in-plane spatial resolutions of 125 and 208 µm were measured for HR and standard PCD CT scans, respectively. Minimum values for section sensitivity profile full width at half maximum measurements were 0.34 mm (0.2-mm nominal section thickness) and 0.64 mm (0.4-mm nominal section thickness) for HR and standard PCD CT scans, respectively. In a 120-kV standard PCD CT scan of a 40-cm phantom, VMI iodine CT numbers had a mean percentage error of 5.7%, and iodine concentration had root mean squared error of 0.5 mg/cm3, similar to previously reported values for EID CT. VMIs, iodine maps, and virtual noncontrast images were created for a coronary CT angiogram acquired with 66-msec temporal resolution. Participant PCD CT images showed up to 47% lower noise and/or improved spatial resolution compared with EID CT. Conclusion Technical performance of clinical photon-counting detector (PCD) CT is improved relative to that of a current state-of-the-art CT system. The dual-source PCD geometry facilitated 66-msec temporal resolution multienergy cardiac imaging. Study participant images illustrated the effect of the improved technical performance. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Willemink and Grist in this issue.

Full field-of-view, high-resolution, photon-counting detector CT: technical assessment and initial patient experience.

We report a comprehensive evaluation of a full field-of-view (FOV) photon-counting detector (PCD) computed tomography (CT) system using phantoms, and qualitatively assess image quality in patient examples. A whole-body PCD-CT system with 50 cm FOV, 5.76 cm z-detector coverage and two acquisition modes (standard: 144 × 0.4 mm collimation and ultra-high resolution (UHR): 120 × 0.2 mm collimation) was used in this study. Phantoms were scanned to assess image uniformity, CT number accuracy, noise power spectrum, spatial resolution, material decomposition and virtual monoenergetic imaging (VMI) performance. Four patients were scanned on the PCD-CT system with matched or lower radiation dose than their prior clinical CT scans performed using energy-integrating detector (EID) CT, and the potential clinical impact of PCD-CT was qualitatively evaluated. Phantom results showed water CT numbers within ±5 HU, and image uniformity measured between peripheral and central regions-of-interests to be within ±5 HU. For the UHR mode using a dedicated sharp kernel, the cut-off spatial frequency was 40 line-pairs cm-1, which corresponds to a 125µm limiting in-plane spatial resolution. The full-width-at-half-maximum for the section sensitivity profile was 0.33 mm for the smallest slice thickness (0.2 mm) using the UHR mode. Material decomposition in a multi-energy CT phantom showed accurate material classification, with a root-mean-squared-error of 0.3 mg cc-1for iodine concentrations (2-15 mg cc-1) and 14.2 mg cc-1for hydroxyapatite concentrations (200 and 400 mg cc-1). The average percent error for CT numbers corresponding to the iodine concentrations in VMI (40-70 keV) was 2.75%. Patient PCD-CT images demonstrated better delineation of anatomy for chest and temporal bone exams performed with the UHR mode, which allowed the use of very sharp kernels not possible with EID-CT. VMI and virtual non-contrast images generated from a patient head CT angiography exam using the standard acquisition mode demonstrated the multi-energy capability of the PCD-CT system.

Empirical beam hardening and ring artifact correction for x-ray grating interferometry (EBHC-GI).

PURPOSE: Talbot-Lau grating interferometry enables the use of polychromatic x-ray sources, extending the range of potential applications amenable to phase contrast imaging. However, these sources introduce beam hardening effects not only from the samples but also from the gratings. As a result, grating inhomogeneities due to manufacturing imperfections can cause spectral nonuniformity artifacts when used with polychromatic sources. Consequently, the different energy dependencies of absorption, phase, and visibility contrasts impose challenges that so far have limited the achievable image quality. The purpose of this work was to develop and validate a correction strategy for grating-based x-ray imaging that accounts for beam hardening generated from both the imaged object and the gratings. METHODS: The proposed two-variable polynomial expansion strategy was inspired by work performed to address beam hardening from a primary modulator. To account for the multicontrast nature of grating interferometry, this approach was extended to each contrast to obtain three sets of correction coefficients, which were determined empirically from a calibration scan. The method's feasibility was demonstrated using a tabletop Talbot-Lau grating interferometer micro-computed tomography (CT) system using CT acquisitions of a water sample and a silicon sample, representing low and high atomic number materials. Spectral artifacts such as cupping and ring artifacts were quantified using mean squared error (MSE) from the beam-hardening-free target image and standard deviation within a reconstructed image of the sample. Finally, the model developed using the water sample was applied to a fixated murine lung sample to demonstrate robustness for similar materials. RESULTS: The water sample's absorption CT image was most impacted by spectral artifacts, but following correction to decrease ring artifacts, an 80% reduction in MSE and 57% reduction in standard deviation was observed. The silicon sample created severe artifacts in all contrasts, but following correction, MSE was reduced by 94% in absorption, 96% in phase, and 90% in visibility images. These improvements were due to the removal of ring artifacts for all contrasts and reduced cupping in absorption and phase images and reduced capping in visibility images. When the water calibration coefficients were applied to the lung sample, ring artifacts most prominent in the absorption contrast were eliminated. CONCLUSIONS: The described method, which was developed to remove artifacts in absorption, phase, and normalized visibility micro-CT images due to beam hardening in the system gratings and imaged object, reduced the MSE by up to 96%. The method depends on calibrations that can be performed on any system and does not require detailed knowledge of the x-ray spectrum, detector energy response, grating attenuation properties and imperfections, or the geometry and composition of the imaged object.

High Resolution, Full Field-of-View, Whole Body Photon-Counting Detector CT: System Assessment and Initial Experience.

Computed tomography (CT) using photon-counting detectors (PCD) offers dose-efficient ultra-high-resolution imaging, high iodine contrast-to-noise ratio, multi-energy and material decomposition capabilities. We have previously demonstrated the potential benefits of PCD-CT using phantoms, cadavers, and human studies on a prototype PCD-CT system. This system, however, had several limitations in terms of scan field-of-view (FOV) and longitudinal coverage. Recently, a full FOV (50 cm) PCD-CT system with wider longitudinal coverage and higher spatial resolution (0.15 mm detector pixels) has been installed in our lab capable of human scanning at clinical dose and dose rate. In this work, we share our initial experience of the new PCD-CT system and compare its performance with a state-of-the-art 3rd generation dual-source CT scanner. Basic image quality was assessed using an ACR CT accreditation phantom, high-resolution performance using an anthropomorphic head phantom, and multi-energy and material decomposition performance using a multi-energy CT phantom containing various concentrations of iodine and hydroxyapatite. Finally, we demonstrate the feasibility of high-resolution, full FOV PCD-CT imaging for improved delineation of anatomical and pathological features in a patient with pulmonary nodules.

Wave optics simulation of grating-based X-ray phase-contrast imaging using 4D Mouse Whole Body (MOBY) phantom.

PURPOSE: Demonstrate realistic simulation of grating-based x-ray phase-contrast imaging (GB-XPCI) using wave optics and the four-dimensional Mouse Whole Body (MOBY) phantom defined with non-uniform rational B-splines (NURBS). METHODS: We use a full-wave approach, which uses wave optics for x-ray wave propagation from the source to the detector. This forward imaging model can be directly applied to NURBS-defined numerical phantoms such as MOBY. We assign the material properties (attenuation coefficient and electron density) of each model part using the data for adult human tissues. The Poisson noise is added to the simulated images based on the calculated photon flux at each pixel. RESULTS: We simulate the intensity images of the MOBY phantom for eight different grating positions. From the simulated images, we calculate the absorption, differential phase, and normalized visibility contrast images. We also predict how the image quality is affected by different exposure times. CONCLUSIONS: GB-XPCI can be simulated with the full-wave approach and a realistic numerical phantom defined with NURBS.

Forward model for propagation-based x-ray phase contrast imaging in parallel- and cone-beam geometry.

We demonstrate a fast, flexible, and accurate paraxial wave propagation model to serve as a forward model for propagation-based X-ray phase contrast imaging (XPCI) in parallel-beam or cone-beam geometry. This model incorporates geometric cone-beam effects into the multi-slice beam propagation method. It enables rapid prototyping and is well suited to serve as a forward model for propagation-based X-ray phase contrast tomographic reconstructions. Furthermore, it is capable of modeling arbitrary objects, including those that are strongly or multi-scattering. Simulation studies were conducted to compare our model to other forward models in the X-ray regime, such as the Mie and full-wave Rytov solutions.

Full-field imaging of thermal and acoustic dynamics in an individual nanostructure using tabletop high harmonic beams.

Imaging charge, spin, and energy flow in materials is a current grand challenge that is relevant to a host of nanoenhanced systems, including thermoelectric, photovoltaic, electronic, and spin devices. Ultrafast coherent x-ray sources enable functional imaging on nanometer length and femtosecond timescales particularly when combined with advances in coherent imaging techniques. Here, we combine ptychographic coherent diffractive imaging with an extreme ultraviolet high harmonic light source to directly visualize the complex thermal and acoustic response of an individual nanoscale antenna after impulsive heating by a femtosecond laser. We directly image the deformations induced in both the nickel tapered nanoantenna and the silicon substrate and see the lowest-order generalized Lamb wave that is partially confined to a uniform nanoantenna. The resolution achieved-sub-100 nm transverse and 0.5-Å axial spatial resolution, combined with ≈10-fs temporal resolution-represents a significant advance in full-field dynamic imaging capabilities. The tapered nanoantenna is sufficiently complex that a full simulation of the dynamic response would require enormous computational power. We therefore use our data to benchmark approximate models and achieve excellent agreement between theory and experiment. In the future, this work will enable three-dimensional functional imaging of opaque materials and nanostructures that are sufficiently complex that their functional properties cannot be predicted.

Colloidal crystal order and structure revealed by tabletop extreme ultraviolet scattering and coherent diffractive imaging.

Colloidal crystals with specific electronic, optical, magnetic, vibrational properties, can be rationally designed by controlling fundamental parameters such as chemical composition, scale, periodicity and lattice symmetry. In particular, silica nanospheres -which assemble to form colloidal crystals- are ideal for this purpose, because of the ability to infiltrate their templates with semiconductors or metals. However characterization of these crystals is often limited to techniques such as grazing incidence small-angle scattering that provide only global structural information and also often require synchrotron sources. Here we demonstrate small-angle Bragg scattering from nanostructured materials using a tabletop-scale setup based on high-harmonic generation, to reveal important information about the local order of nanosphere grains, separated by grain boundaries and discontinuities. We also apply full-field quantitative ptychographic imaging to visualize the extended structure of a silica close-packed nanosphere multilayer, with thickness information encoded in the phase. These combined techniques allow us to simultaneously characterize the silica nanospheres size, their symmetry and distribution within single colloidal crystal grains, the local arrangement of nearest-neighbor grains, as well as to quantitatively determine the number of layers within the sample. Key to this advance is the good match between the high harmonic wavelength used (13.5nm) and the high transmission, high scattering efficiency, and low sample damage of the silica colloidal crystal at this wavelength. As a result, the relevant distances in the sample - namely, the interparticle distance (≈124nm) and the colloidal grains local arrangement (≈1µm) - can be investigated with Bragg coherent EUV scatterometry and ptychographic imaging within the same experiment simply by tuning the EUV spot size at the sample plane (5µm and 15µm respectively). In addition, the high spatial coherence of high harmonics light, combined with advances in imaging techniques, makes it possible to image near-periodic structures quantitatively and nondestructively, and enables the observation of the extended order of quasi-periodic colloidal crystals, with a spatial resolution better than 20nm. In the future, by harnessing the high time-resolution of tabletop high harmonics, this technique can be extended to dynamically image the three-dimensional electronic, magnetic, and transport properties of functional nanosystems.

Multiple beam ptychography for large field-of-view, high throughput, quantitative phase contrast imaging.

The ability to record large field-of-view images without a loss in spatial resolution is of crucial importance for imaging science. For most imaging techniques however, an increase in field-of-view comes at the cost of decreased resolution. Here we present a novel extension to ptychographic coherent diffractive imaging that permits simultaneous full-field imaging of multiple locations by illuminating the sample with spatially separated, interfering probes. This technique allows for large field-of-view imaging in amplitude and phase while maintaining diffraction-limited resolution, without an increase in collected data i.e. diffraction patterns acquired.

Ptychographic hyperspectral spectromicroscopy with an extreme ultraviolet high harmonic comb.

We report a proof-of-principle demonstration of a new scheme of spectromicroscopy in the extreme ultraviolet (EUV) spectral range, where the spectral response of the sample at different wavelengths is imaged simultaneously. This scheme is enabled by combining ptychographic information multiplexing (PIM) with a tabletop EUV source based on high harmonic generation, where four spectrally narrow harmonics near 30 nm form a spectral comb structure. Extending PIM from previously demonstrated visible wavelengths to the EUV/X-ray wavelengths promises much higher spatial resolution and a more powerful spectral contrast mechanism, making PIM an attractive spectromicroscopy method in both microscopy and spectroscopy aspects. In addition to spectromicroscopy, this method images the multicolor EUV beam in situ, making this a powerful beam characterization technique. In contrast to other methods, the techniques described here use no hardware to separate wavelengths, leading to efficient use of the EUV radiation.

Quantitative Chemically Specific Coherent Diffractive Imaging of Reactions at Buried Interfaces with Few Nanometer Precision.

We demonstrate quantitative, chemically specific imaging of buried nanostructures, including oxidation and diffusion reactions at buried interfaces, using nondestructive tabletop extreme ultraviolet (EUV) coherent diffractive imaging (CDI). Copper nanostructures inlaid in SiO2 are coated with 100 nm of aluminum, which is opaque to visible light and thick enough that neither visible microscopy nor atomic force microscopy can image the buried interface. Short wavelength high harmonic beams can penetrate the aluminum layer, yielding high-contrast images of the buried structures. Quantitative analysis shows that the reflected EUV light is extremely sensitive to the formation of multiple oxide layers, as well as interdiffusion of materials occurring at the metal-metal and metal-insulator boundaries deep within the nanostructure with few nanometers precision.

Spatial, spectral, and polarization multiplexed ptychography.

We introduce a novel coherent diffraction imaging technique based on ptychography that enables simultaneous full-field imaging of multiple, spatially separate, sample locations. This technique only requires that diffracted light from spatially separated sample sites be mutually incoherent at the detector, which can be achieved using multiple probes that are separated either by wavelength or by orthogonal polarization states. This approach enables spatially resolved polarization spectroscopy from a single ptychography scan, as well as allowing a larger field of view to be imaged without loss in spatial resolution. Further, we compare the numerical efficiency of the multi-mode ptychography algorithm with a single mode algorithm.

High contrast 3D imaging of surfaces near the wavelength limit using tabletop EUV ptychography.

Scanning electron microscopy and atomic force microscopy are well-established techniques for imaging surfaces with nanometer resolution. Here we demonstrate a complementary and powerful approach based on tabletop extreme-ultraviolet ptychography that enables quantitative full field imaging with higher contrast than other techniques, and with compositional and topographical information. Using a high numerical aperture reflection-mode microscope illuminated by a tabletop 30 nm high harmonic source, we retrieve high quality, high contrast, full field images with 40 nm by 80 nm lateral resolution (≈1.3 λ), with a total exposure time of less than 1 min. Finally, quantitative phase information enables surface profilometry with ultra-high, 6 Å axial resolution. In the future, this work will enable dynamic imaging of functioning nanosystems with unprecedented combined spatial (<10 nm) and temporal (<10 fs) resolution, in thick opaque samples, with elemental, chemical and magnetic sensitivity.

Full field tabletop EUV coherent diffractive imaging in a transmission geometry.

We demonstrate the first general tabletop EUV coherent microscope that can image extended, non-isolated, non-periodic, objects. By implementing keyhole coherent diffractive imaging with curved mirrors and a tabletop high harmonic source, we achieve improved efficiency of the imaging system as well as more uniform illumination at the sample, when compared with what is possible using Fresnel zone plates. Moreover, we show that the unscattered light from a semi-transparent sample can be used as a holographic reference wave, allowing quantitative information about the thickness of the sample to be extracted from the retrieved image. Finally, we show that excellent tabletop image fidelity is achieved by comparing the retrieved images with scanning electron and atomic force microscopy images, and show superior capabilities in some cases.

Optimizing bead size reduces errors in force measurements in optical traps.

Optical traps are used to measure force (F) over a wide range (0.01 to 1,000 pN). Variations in bead radius (r) hinder force precision since trap stiffness (k(trap)) varies as r3 when r is small. Prior work has shown k(trap) is maximized when r is approximately equal to the beam waist (w0), which on our instrument was ~400 nm when trapping with a 1064-nm laser. In this work, we show that by choosing r ≈w0, we improved the force precision by 2.8-fold as compared to a smaller bead (250 nm). This improvement in force precision was verified by pulling on a canonical DNA hairpin. Thus, by using an optimum bead size, one can simultaneously maximize k(trap) while minimizing errors in F.