Clinical evaluation of deep learning-enhanced lymphoma pet imaging with accelerated acquisition.

PURPOSE: This study aims to evaluate the clinical performance of a deep learning (DL)-enhanced two-fold accelerated PET imaging method in patients with lymphoma. METHODS: A total of 123 cases devoid of lymphoma underwent whole-body 18F-FDG-PET/CT scans to facilitate the development of an advanced SAU2Net model, which combines the advantages of U2Net and attention mechanism. This model integrated inputs from simulated 1/2-dose (0.07 mCi/kg) PET acquisition across multiple slices to generate an estimated standard dose (0.14 mCi/kg) PET scan. Additional 39 cases with confirmed lymphoma pathology were utilized to evaluate the model's clinical performance. Assessment criteria encompassed peak-signal-to-noise ratio (PSNR), structural similarity index (SSIM), a 5-point Likert scale rated by two experienced physicians, SUV features, image noise in the liver, and contrast-to-noise ratio (CNR). Diagnostic outcomes, including lesion numbers and Deauville score, were also compared. RESULTS: Images enhanced by the proposed DL method exhibited superior image quality (P < 0.001) in comparison to low-dose acquisition. Moreover, they illustrated equivalent image quality in terms of subjective image analysis and lesion maximum standardized uptake value (SUVmax) as compared to the standard acquisition method. A linear regression model with y = 1.017x + 0.110 ( R 2 = 1.00 ${R^2} = \;1.00$ ) can be established between the enhanced scans and the standard acquisition for lesion SUVmax. With enhancement, increased signal-to-noise ratio (SNR), CNR, and reduced image noise were observed, surpassing those of the standard acquisition. DL-enhanced PET images got diagnostic results essentially equavalent to standard PET images according to two experienced readers. CONCLUSION: The proposed DL method could facilitate a 50% reduction in PET imaging duration for lymphoma patients, while concurrently preserving image quality and diagnostic accuracy.

Atomic Visualization of the 3D Charge Density Wave Stacking in 1T-TaS2 by Cryogenic Transmission Electron Microscopy.

Charge density waves (CDWs) in 1T-TaS2 maintain 2D ordering by forming periodic in-plane star-of-David (SOD) patterns, while they also intertwined with orbital order in the c axis. Recent theoretical calculations and surface measurements have explored 3D CDW configurations, but interlayer intertwining of a 2D CDW order remains elusive. Here, we investigate the in- and out-of-plane ordering of the commensurate CDW superstructure in a 1T-TaS2 thin flake in real space, using aberration-corrected cryogenic transmission electronic microscopy (cryo-TEM) in low-dose mode, far below the threshold dose for an electron-induced CDW phase transition. By scrutinizing the phase intensity variation of modulated Ta atoms, we visualize the penetrative 3D CDW stacking structure, revealing an intertwining multidomain structure with three types of vertical CDW stacking configurations. Our results provide microstructural evidence for the coexistence of local Mott insulation and metal phases and offer a paradigm for studying the CDW structure and correlation order in condensed-matter physics using cryo-TEM.

How Fast is Your Detector? The Effect of Temporal Response on Image Quality.

With increasing interest in high-speed imaging, there should be an increased interest in the response times of our scanning transmission electron microscope detectors. Previous works have highlighted and contrasted the performance of various detectors for quantitative compositional or structural studies, but here, we shift the focus to detector temporal response, and the effect this has on captured images. The rise and decay times of eight detectors' single-electron response are reported, as well as measurements of their flatness, roundness, smoothness, and ellipticity. We develop and apply a methodology for incorporating the temporal detector response into simulations, showing that a loss of resolution is apparent in both the images and their Fourier transforms. We conclude that the solid-state detector outperforms the photomultiplier tube-based detectors in all areas bar a slightly less elliptical central hole and is likely the best detector to use for the majority of applications. However, using the tools introduced here, we encourage users to effectively evaluate which detector is most suitable for their experimental needs.

An Innovative Low-dose CT Inpainting Algorithm based on Limited-angle Imaging Inpainting Model.

BACKGROUND: With the popularity of computed tomography (CT) technique, an increasing number of patients are receiving CT scans. Simultaneously, the public's attention to CT radiation dose is also increasing. How to obtain CT images suitable for clinical diagnosis while reducing the radiation dose has become the focus of researchers. OBJECTIVE: To demonstrate that limited-angle CT imaging technique can be used to acquire lower dose CT images, we propose a generative adversarial network-based image inpainting model-Low-dose imaging and Limited-angle imaging inpainting Model (LDLAIM), this method can effectively restore low-dose CT images with limited-angle imaging, which verifies that limited-angle CT imaging technique can be used to acquire low-dose CT images. METHODS: In this work, we used three datasets, including chest and abdomen dataset, head dataset and phantom dataset. They are used to synthesize low-dose and limited-angle CT images for network training. During training stage, we divide each dataset into training set, validation set and testing set according to the ratio of 8:1:1, and use the validation set to validate after finishing an epoch training, and use the testing set to test after finishing all the training. The proposed method is based on generative adversarial networks(GANs), which consists of a generator and a discriminator. The generator consists of residual blocks and encoder-decoder, and uses skip connection. RESULTS: We use SSIM, PSNR and RMSE to evaluate the performance of the proposed method. In the chest and abdomen dataset, the mean SSIM, PSNR and RMSE of the testing set are 0.984, 35.385 and 0.017, respectively. In the head dataset, the mean SSIM, PSNR and RMSE of the testing set are 0.981, 38.664 and 0.011, respectively. In the phantom dataset, the mean SSIM, PSNR and RMSE of the testing set are 0.977, 33.468 and 0.022, respectively. By comparing the experimental results of other algorithms in these three datasets, it can be found that the proposed method is superior to other algorithms in these indicators. Meanwhile, the proposed method also achieved the highest score in the subjective quality score. CONCLUSIONS: Experimental results show that the proposed method can effectively restore CT images when both low-dose CT imaging techniques and limited-angle CT imaging techniques are used simultaneously. This work proves that the limited-angle CT imaging technique can be used to reduce the CT radiation dose, and also provides a new idea for the research of low-dose CT imaging.

Real-Time Integration Center of Mass (riCOM) Reconstruction for 4D STEM.

A real-time image reconstruction method for scanning transmission electron microscopy (STEM) is proposed. With an algorithm requiring only the center of mass of the diffraction pattern at one probe position at a time, it is able to update the resulting image each time a new probe position is visited without storing any intermediate diffraction patterns. The results show clear features at high spatial frequency, such as atomic column positions. It is also demonstrated that some common post-processing methods, such as band-pass filtering, can be directly integrated in the real-time processing flow. Compared with other reconstruction methods, the proposed method produces high-quality reconstructions with good noise robustness at extremely low memory and computational requirements. An efficient, interactive open source implementation of the concept is further presented, which is compatible with frame-based, as well as event-based camera/file types. This method provides the attractive feature of immediate feedback that microscope operators have become used to, for example, conventional high-angle annular dark field STEM imaging, allowing for rapid decision-making and fine-tuning to obtain the best possible images for beam-sensitive samples at the lowest possible dose.

Evaluation of a High-Sensitivity Organ-Targeted PET Camera.

The aim of this study is to evaluate the performance of the Radialis organ-targeted positron emission tomography (PET) Camera with standardized tests and through assessment of clinical-imaging results. Sensitivity, count-rate performance, and spatial resolution were evaluated according to the National Electrical Manufacturers Association (NEMA) NU-4 standards, with necessary modifications to accommodate the planar detector design. The detectability of small objects was shown with micro hotspot phantom images. The clinical performance of the camera was also demonstrated through breast cancer images acquired with varying injected doses of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) and qualitatively compared with sample digital full-field mammography, magnetic resonance imaging (MRI), and whole-body (WB) PET images. Micro hotspot phantom sources were visualized down to 1.35 mm-diameter rods. Spatial resolution was calculated to be 2.3 ± 0.1 mm for the in-plane resolution and 6.8 ± 0.1 mm for the cross-plane resolution using maximum likelihood expectation maximization (MLEM) reconstruction. The system peak noise equivalent count rate was 17.8 kcps at a 18F-FDG concentration of 10.5 kBq/mL. System scatter fraction was 24%. The overall efficiency at the peak noise equivalent count rate was 5400 cps/MBq. The maximum axial sensitivity achieved was 3.5%, with an average system sensitivity of 2.4%. Selected results from clinical trials demonstrate capability of imaging lesions at the chest wall and identifying false-negative X-ray findings and false-positive MRI findings, even at up to a 10-fold dose reduction in comparison with standard 18F-FDG doses (i.e., at 37 MBq or 1 mCi). The evaluation of the organ-targeted Radialis PET Camera indicates that it is a promising technology for high-image-quality, low-dose PET imaging. High-efficiency radiotracer detection also opens an opportunity to reduce administered doses of radiopharmaceuticals and, therefore, patient exposure to radiation.

DeepTOFSino: A deep learning model for synthesizing full-dose time-of-flight bin sinograms from their corresponding low-dose sinograms.

PURPOSE: Reducing the injected activity and/or the scanning time is a desirable goal to minimize radiation exposure and maximize patients' comfort. To achieve this goal, we developed a deep neural network (DNN) model for synthesizing full-dose (FD) time-of-flight (TOF) bin sinograms from their corresponding fast/low-dose (LD) TOF bin sinograms. METHODS: Clinical brain PET/CT raw data of 140 normal and abnormal patients were employed to create LD and FD TOF bin sinograms. The LD TOF sinograms were created through 5% undersampling of FD list-mode PET data. The TOF sinograms were split into seven time bins (0, ±1, ±2, ±3). Residual network (ResNet) algorithms were trained separately to generate FD bins from LD bins. An extra ResNet model was trained to synthesize FD images from LD images to compare the performance of DNN in sinogram space (SS) vs implementation in image space (IS). Comprehensive quantitative and statistical analysis was performed to assess the performance of the proposed model using established quantitative metrics, including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM) region-wise standardized uptake value (SUV) bias and statistical analysis for 83 brain regions. RESULTS: SSIM and PSNR values of 0.97 ± 0.01, 0.98 ± 0.01 and 33.70 ± 0.32, 39.36 ± 0.21 were obtained for IS and SS, respectively, compared to 0.86 ± 0.02and 31.12 ± 0.22 for reference LD images. The absolute average SUV bias was 0.96 ± 0.95% and 1.40 ± 0.72% for SS and IS implementations, respectively. The joint histogram analysis revealed the lowest mean square error (MSE) and highest correlation (R2 = 0.99, MSE = 0.019) was achieved by SS compared to IS (R2 = 0.97, MSE= 0.028). The Bland & Altman analysis showed that the lowest SUV bias (-0.4%) and minimum variance (95% CI: -2.6%, +1.9%) were achieved by SS images. The voxel-wise t-test analysis revealed the presence of voxels with statistically significantly lower values in LD, IS, and SS images compared to FD images respectively. CONCLUSION: The results demonstrated that images reconstructed from the predicted TOF FD sinograms using the SS approach led to higher image quality and lower bias compared to images predicted from LD images.

Deep learning-assisted ultra-fast/low-dose whole-body PET/CT imaging.

PURPOSE: Tendency is to moderate the injected activity and/or reduce acquisition time in PET examinations to minimize potential radiation hazards and increase patient comfort. This work aims to assess the performance of regular full-dose (FD) synthesis from fast/low-dose (LD) whole-body (WB) PET images using deep learning techniques. METHODS: Instead of using synthetic LD scans, two separate clinical WB 18F-Fluorodeoxyglucose (18F-FDG) PET/CT studies of 100 patients were acquired: one regular FD (~ 27 min) and one fast or LD (~ 3 min) consisting of 1/8th of the standard acquisition time. A modified cycle-consistent generative adversarial network (CycleGAN) and residual neural network (ResNET) models, denoted as CGAN and RNET, respectively, were implemented to predict FD PET images. The quality of the predicted PET images was assessed by two nuclear medicine physicians. Moreover, the diagnostic quality of the predicted PET images was evaluated using a pass/fail scheme for lesion detectability task. Quantitative analysis using established metrics including standardized uptake value (SUV) bias was performed for the liver, left/right lung, brain, and 400 malignant lesions from the test and evaluation datasets. RESULTS: CGAN scored 4.92 and 3.88 (out of 5) (adequate to good) for brain and neck + trunk, respectively. The average SUV bias calculated over normal tissues was 3.39 ± 0.71% and - 3.83 ± 1.25% for CGAN and RNET, respectively. Bland-Altman analysis reported the lowest SUV bias (0.01%) and 95% confidence interval of - 0.36, + 0.47 for CGAN compared with the reference FD images for malignant lesions. CONCLUSION: CycleGAN is able to synthesize clinical FD WB PET images from LD images with 1/8th of standard injected activity or acquisition time. The predicted FD images present almost similar performance in terms of lesion detectability, qualitative scores, and quantification bias and variance.

Development of a Practicable Digital Pulse Read-Out for Dark-Field STEM.

When characterizing beam-sensitive materials in the scanning transmission electron microscope (STEM), low-dose techniques are essential for the reliable observation of samples in their true state. A simple route to minimize both the total electron-dose and the dose-rate is to reduce the electron beam-current and/or raster the probe at higher speeds. At the limit of these settings, and with current detectors, the resulting images suffer from unacceptable artifacts, including signal-streaking, detector-afterglow, and poor signal-to-noise ratios (SNRs). In this article, we present an alternative approach to capture dark-field STEM images by pulse-counting individual electrons as they are scattered to the annular dark-field (ADF) detector. Digital images formed in this way are immune from analog artifacts of streaking or afterglow and allow clean, high-SNR images to be obtained even at low beam-currents. We present results from both a ThermoFisher FEI Titan G2 operated at 300 kV and a Nion UltraSTEM200 operated at 200 kV, and compare the images to conventional analog recordings. ADF data are compared with analog counterparts for each instrument, a digital detector-response scan is performed on the Titan, and the overall rastering efficiency is evaluated for various scanning parameters.

Simulation-Trained Sparse Coding for High-Precision Phase Imaging in Low-Dose Electron Holography.

We broaden the applicability of sparse coding, a machine learning method, to low-dose electron holography by using simulated holograms for learning and validation processes. The holograms, with shot noise, are prepared to generate a model, or a dictionary, that includes basic features representing interference fringes. The dictionary is applied to sparse representations of other simulated holograms with various signal-to-noise ratios (SNRs). Results demonstrate that this approach successfully removes noise for holograms with an extremely small SNR of 0.10, and that the denoised holograms provide the accurate phase distribution. Furthermore, this study demonstrates that the dictionary learned from the simulated holograms can be applied to denoising of experimental holograms of a p-n junction specimen recorded with different exposure times. The results indicate that the simulation-trained sparse coding is suitable for use over a wide range of imaging conditions, in particular for observing electron beam-sensitive materials.

Stereoradiography imaging motion artifact: does it affect radiographic measures after spinal instrumentation?

PURPOSE: Stereoradiography imaging (SRI) is an accurate and reliable low-dose radiographic method. However, patients must remain motionless during image acquisition. Motion artifacts are frequently noted. The aims of the study were to determine the incidence of the SRI motion artifact and assess if motion during SRI acquisition affects radiographic measurements. METHODS: In this retrospective study, 198 patients with spinal instrumentation had biplanar SRI radiographs performed, of whom 39 had concomitant conventional radiographs. Eight coronal and sagittal spinal parameters were independently measured on SRI and conventional radiographs for the 39 patients by 2 observers. Inclusion criteria were: presence of spinal instrumentation of more than six levels and an SRI motion artifact identified on the coronal and/or the sagittal views on either the spinal rods or on the limbs. Means were compared between both types of radiographs using the Student's t test; intraclass correlation coefficients (ICCs) were used for intraobserver reproducibility and interrater reliability. RESULTS: A motion artifact was identified in 19.7 % (n = 39, mean age 19.5 ± 1.7 years) of the cases. There were no differences in any of the coronal or sagittal plane measurements between SRI and X-rays. Intraobserver reliability and interrater reproducibility was high (range 0.81-0.98). CONCLUSIONS: Motion artifact during full-spine stereoradiography imaging acquisition is frequent, but does not affect spinal measurements. SRI with a motion artifact can be used to produce reliable measurements of the sagittal and coronal parameters. Some SRI images with a motion artifact may suggest loss of fixation or bending of the rods. However, after becoming familiar with the appearance of the motion artifact, repeat radiographs are rarely indicated. IRB NUMBER: 14-004872. LEVEL OF EVIDENCE: Level IV.

Image Denoising of Low-Dose PET Mouse Scans with Deep Learning: Validation Study for Preclinical Imaging Applicability.

PURPOSE: Positron emission tomography (PET) image quality can be improved by higher injected activity and/or longer acquisition time, but both may often not be practical in preclinical imaging. Common preclinical radioactive doses (10 MBq) have been shown to cause deterministic changes in biological pathways. Reducing the injected tracer activity and/or shortening the scan time inevitably results in low-count acquisitions which poses a challenge because of the inherent noise introduction. We present an image-based deep learning (DL) framework for denoising lower count micro-PET images. PROCEDURES: For 36 mice, a 15-min [18F]FDG (8.15 ± 1.34 MBq) PET scan was acquired at 40 min post-injection on the Molecubes ß-CUBE (in list mode). The 15-min acquisition (high-count) was parsed into smaller time fractions of 7.50, 3.75, 1.50, and 0.75 min to emulate images reconstructed at 50, 25, 10, and 5% of the full counts, respectively. A 2D U-Net was trained with mean-squared-error loss on 28 high-low count image pairs. RESULTS: The DL algorithms were visually and quantitatively compared to spatial and edge-preserving denoising filters; the DL-based methods effectively removed image noise and recovered image details much better while keeping quantitative (SUV) accuracy. The largest improvement in image quality was seen in the images reconstructed with 10 and 5% of the counts (equivalent to sub-1 MBq or sub-1 min mouse imaging). The DL-based denoising framework was also successfully applied on the NEMA-NU4 phantom and different tracer studies ([18F]PSMA, [18F]FAPI, and [68 Ga]FAPI). CONCLUSION: Visual and quantitative results support the superior performance and robustness in image denoising of the implemented DL models for low statistics micro-PET. This offers much more flexibility in optimizing preclinical, longitudinal imaging protocols with reduced tracer doses or shorter durations.

Low-dose electron microscopy imaging for beam-sensitive metal-organic frameworks.

Metal-organic frameworks (MOFs) have garnered significant attention in recent years owing to their exceptional properties. Understanding the intricate relationship between the structure of a material and its properties is crucial for guiding the synthesis and application of these materials. (Scanning) Transmission electron microscopy (S)TEM imaging stands out as a powerful tool for structural characterization at the nanoscale, capable of detailing both periodic and aperiodic local structures. However, the high electron-beam sensitivity of MOFs presents substantial challenges in their structural characterization using (S)TEM. This paper summarizes the latest advancements in low-dose high-resolution (S)TEM imaging technology and its application in MOF material characterization. It covers aspects such as framework structure, defects, and surface and interface analysis, along with the distribution of guest molecules within MOFs. This review also discusses emerging technologies like electron ptychography and outlines several prospective research directions in this field.

PETformer network enables ultra-low-dose total-body PET imaging without structural prior.

Objective.Positron emission tomography (PET) is essential for non-invasive imaging of metabolic processes in healthcare applications. However, the use of radiolabeled tracers exposes patients to ionizing radiation, raising concerns about carcinogenic potential, and warranting efforts to minimize doses without sacrificing diagnostic quality.Approach.In this work, we present a novel neural network architecture, PETformer, designed for denoising ultra-low-dose PET images without requiring structural priors such as computed tomography (CT) or magnetic resonance imaging. The architecture utilizes a U-net backbone, synergistically combining multi-headed transposed attention blocks with kernel-basis attention and channel attention mechanisms for both short- and long-range dependencies and enhanced feature extraction. PETformer is trained and validated on a dataset of 317 patients imaged on a total-body uEXPLORER PET/CT scanner.Main results.Quantitative evaluations using structural similarity index measure and liver signal-to-noise ratio showed PETformer's significant superiority over other established denoising algorithms across different dose-reduction factors.Significance.Its ability to identify and recover intrinsic anatomical details from background noise with dose reductions as low as 2% and its capacity in maintaining high target-to-background ratios while preserving the integrity of uptake values of small lesions enables PET-only fast and accurate disease diagnosis. Furthermore, PETformer exhibits computational efficiency with only 37 M trainable parameters, making it well-suited for commercial integration.

On the temporal transfer function in STEM imaging from finite detector response time.

Faster scanning in scanning transmission electron microscopy has long been desired for the ability to better control dose, minimise effects of environmental distortions, and to capture the dynamics of in-situ experiments. Advances in scan controllers and scan deflection systems have enabled scanning with pixel dwell times on the order of tens of nanoseconds. At these speeds, the finite response time of the electron detector must be considered as the signal from one electron detection event can contribute to multiple pixels, blurring the features within the image. Here we introduce a temporal transfer function (TTF) to describe and model the effects of detector response time on imaging, as well as a framework for incorporating these effects into simulation.

Low-dose measurement of electric potential distribution in organic light-emitting diode by phase-shifting electron holography with 3D tensor decomposition.

To improve the performance of organic light-emitting diodes (OLEDs), it is essential to understand and control the electric potential in the organic semiconductor layers. Electron holography (EH) is a powerful technique for visualizing the potential distribution with a transmission electron microscope. However, it has a serious issue that high-energy electrons may damage the organic layers, meaning that a low-dose EH is required. Here, we used a machine learning technique, three-dimensional (3D) tensor decomposition, to denoise electron interference patterns (holograms) of bilayer OLEDs composed of N,N'-di-[(1-naphthyl)-N,N'-diphenyl]-(1,1'-biphenyl)-4,4'-diamine (α-NPD) and tris-(8-hydroxyquinoline)aluminum (Alq3), acquired under a low-dose rate of 130 e- nm-2 s-1. The effect of denoising on the phase images reconstructed from the holograms was evaluated in terms of both the phase measurement error and the peak signal-to-noise ratio. We achieved a precision equivalent to that of a conventional measurement that had an exposure time 60 times longer. The electric field within the Alq3 layer decreased as the cumulative dose increased, which indicates that the Alq3 layer was degraded by the electron irradiation. On the basis of the degradation of the electric field, we concluded that the tolerance dose without damaging the OLED sample is about 1.7 × 105 e- nm-2, which is about 0.6 times that of the conventional EH. The combination of EH and 3D tensor decomposition denoising is capable of making a time series measurement of an OLED sample without any effect from the electron irradiation.

Comparative study of the quantitative accuracy of oncological PET imaging based on deep learning methods.

Background: [18F] Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an important tool for tumor assessment. Shortening scanning time and reducing the amount of radioactive tracer remain the most difficult challenges. Deep learning methods have provided powerful solutions, thus making it important to choose an appropriate neural network architecture. Methods: A total of 311 tumor patients who underwent 18F-FDG PET/CT were retrospectively collected. The PET collection time was 3 min/bed. The first 15 and 30 s of each bed collection time were selected to simulate low-dose collection, and the pre-90s was used as the clinical standard protocol. Low-dose PET was used as input, convolutional neural network (CNN, 3D Unet as representative) and generative adversarial network (GAN, P2P as representative) were used to predict the full-dose images. The image visual scores, noise levels and quantitative parameters of tumor tissue were compared. Results: There was high consistency in image quality scores among all groups [Kappa =0.719, 95% confidence interval (CI): 0.697-0.741, P<0.001]. There were 264 cases (3D Unet-15s), 311 cases (3D Unet-30s), 89 cases (P2P-15s) and 247 cases (P2P-30s) with image quality score ≥3, respectively. There was significant difference in the score composition among all groups (χ2=1,325.46, P<0.001). Both deep learning models reduced the standard deviation (SD) of background, and increased the signal-to-noise ratio (SNR). When 8%PET images were used as input, P2P and 3D Unet had similar enhancement effect on SNR of tumor lesions, but 3D Unet could significantly improve the contrast-noise ratio (CNR) (P<0.05). There was no significant difference in SUVmean of tumor lesions compared with s-PET group (P>0.05). When 17%PET image was used as input, SNR, CNR and SUVmax of tumor lesion of 3D Unet group had no statistical difference with those of s-PET group (P>0.05). Conclusions: Both GAN and CNN can suppress image noise to varying degrees and improve image quality. However, when 3D Unet reduces the noise of tumor lesions, it can improve the CNR of tumor lesions. Moreover, quantitative parameters of tumor tissue are similar to those under the standard acquisition protocol, which can meet the needs of clinical diagnosis.

The thumb ossification composite index is the optimal intersection between Sanders and low-dose scoliosis sterioradiography.

PURPOSE: Skeletal maturity assessment may be performed using low-dose scoliosis radiographs (LDSS) with simultaneous imaging of the hand or proximal humerus. We sought to compare the practicality, reliability and validity of the Sanders skeletal maturity staging (SMSS), proximal humerus ossification system (PHOS) and the thumb ossification composite index (TOCI) as skeletal maturity assessment tools using LDSS. METHODS: A survey including 85 LDSS and 42 hand radiographs was administered to four orthopedic clinicians. Each rater assessed the TOCI, SMSS and PHOS stage for each image. Standing LDSS with hands at the patient's side were used for TOCI, SMSS, and PHOS measurements. SMSS and TOCI measurements on dedicated hand radiographs were assessed as a comparison. Interobserver reliability was calculated for each scale using Fleiss' kappa. For SMSS and TOCI, intraobserver correlation between measurements on LDSS and measurements on hand radiographs were also assessed. RESULTS: 472 TOCI measurements, 288 SMSS measurements, and 340 measurements were collected. Kappa interobserver reliability for TOCI was 0.79 (strong) using hand radiographs and 0.74 (strong) using LDSS. Kappa for SMSS was 0.66 (strong) using hand radiographs and 0.45 (moderate) using LDSS. Kappa for PHOS was 0.51 (moderate) using LDSS. Intraobserver agreement between LDSS and hand imaging averaged 0.78 (strong) for TOCI and 0.34 (weak) for SMSS. CONCLUSION: Skeletal maturity assessment with TOCI using LDSS demonstrates strong interobserver reliability when hands are placed at the patient's side and correlates well with assessment on hand radiographs. TOCI achieved better inter- and intraobserver reliability compared to SMSS and PHOS, likely because the thumb readily assumes a good position in standing scoliosis sterioradiographs. LEVEL OF EVIDENCE: Diagnostic-Level III.

TEM at millikelvin temperatures: Observing and utilizing superconducting qubits.

We present a case for developing a millikelvin-temperature transmission electron microscope (TEM). We start by reviewing known reasons for such development, then present new possibilities that have been opened up by recent progress in superconducting quantum circuitry, and finally report on our ongoing experimental effort. Specifically, we first review possibilities to observe a quantum mechanically superposed electromagnetic field around a superconducting qubit. This is followed by a new idea on TEM observation of microwave photons in an unusual quantum state in a resonator. We then proceed to review potential applications of these phenomena, which include low dose electron microscopy beyond the standard quantum limit. Finally, anticipated engineering challenges, as well as the authors' current ongoing experimental effort towards building a millikelvin TEM are described. In addition, we provide a brief introduction to superconducting circuitry in the Appendix for the interested reader who is not familiar with the subject.

Imaging biological macromolecules in thick specimens: The role of inelastic scattering in cryoEM.

We investigate potential improvements in using electron cryomicroscopy to image thick specimens with high-resolution phase contrast imaging. In particular, using model experiments, electron scattering theory, Monte Carlo and multislice simulations, we determine the potential for improving electron cryomicrographs of proteins within a cell using chromatic aberration (Cc) correction. We show that inelastically scattered electrons lose a quantifiable amount of spatial coherence as they transit the specimen, yet can be used to enhance the signal from thick biological specimens (in the 1000 to 5000 Å range) provided they are imaged close to focus with an achromatic lens. This loss of information quantified here, which we call "specimen induced decoherence", is a fundamental limit on imaging biological molecules in situ. We further show that with foreseeable advances in transmission electron microscope technology, it should be possible to directly locate and uniquely identify sub-100 kDa proteins without the need for labels, in a vitrified specimen taken from a cell.