The 4D Camera: An 87 kHz Direct Electron Detector for Scanning/Transmission Electron Microscopy.

We describe the development, operation, and application of the 4D Camera-a 576 by 576 pixel active pixel sensor for scanning/transmission electron microscopy which operates at 87,000 Hz. The detector generates data at ∼480 Gbit/s which is captured by dedicated receiver computers with a parallelized software infrastructure that has been implemented to process the resulting 10-700 Gigabyte-sized raw datasets. The back illuminated detector provides the ability to detect single electron events at accelerating voltages from 30 to 300 kV. Through electron counting, the resulting sparse data sets are reduced in size by 10--300× compared to the raw data, and open-source sparsity-based processing algorithms offer rapid data analysis. The high frame rate allows for large and complex scanning diffraction experiments to be accomplished with typical scanning transmission electron microscopy scanning parameters.

Screening chronic myeloid leukemia neutrophils using a novel 3-Dimensional Spectral Gradient Mapping algorithm on hyperspectral images.

Background and objective Early diagnosis of chronic myeloid leukemia (CML) is important for effective treatment. The high spectral and spatial resolution of hyperspectral cellular or tissue images coupled with image analysis algorithms may provide avenues to detect and diagnose diseases early. Many algorithms have been used to analyze medical hyperspectral image data, each having their own strengths and short-comings. We present a novel 3-Dimensional Spectral Gradient Mapping (3-D SGM) method to analyze hyperspectral image cubes of CML versus healthy blood smears. Methods In the present study, we analyzed 13 hyperspectral image cubes of CML and healthy neutrophils. The 3-D SGM algorithm was compared to the conventional Windowed Spectral Angle Mapping (Windowed SAM) method. The 3-D SGM exploited the spectral information of the image cube together with the inter-band and inter-pixel data by extracting the 3-D gradient vector from each pixel. The Windowed SAM determined the similarity between the averaged window of a 2×2 training pixel group and the test pixel, in the multidimensional spectral angle. Results The specificity measure of 3-D SGM (97.7%) was superior to Windowed SAM (72.7%) at ruling out the presence of the disease, making it potentially ideal for screening patients. The positive likelihood ratio value of 3-D SGM (16.70) was superior in diagnosing the presence of the disease (i.e., positive test for CML) versus Windowed SAM (2.26). An accuracy value of 84.2% was achieved with 3-D SGM versus only 70.2% for Windowed SAM. Conclusion The new method is efficient and robust for analyzing hyperspectral images of CML versus healthy neutrophils. It has the potential to be developed into an inexpensive, minimally invasive method for screening CML, and could directly facilitate early diagnosis and treatment of the disease.

Chronic neutrophilic leukemia presenting as secondary gout: Report of a rare myeloproliferative disorder.

Chronic neutrophilic leukemia is a rare leukemia seen in middle aged and elderly people, characterized by neutrophilic leukocytosis with no significant increase in granulocytic precursors. The chief criteria for diagnosis include total leukocyte count ≥25 × 109/L, >80% of white blood cells being mature neutrophils (segmented and band forms), immature granulocytic precursors ≥10% in the peripheral blood, and hypercellular marrow. In addition to this, there must be no evidence of dysplasia, monocytosis or BCR-ABL1, PDGFR-A, PDGFR-B, or FGRF-1 rearrangements. Moreover, the cause of neutrophilia should not be attributed to any other myeloproliferative disorders or to physiologic neutrophilia.We present two patients with this rare disorder who presented with gout as the initial symptom.

An ultrahigh-resolution soft x-ray microscope for quantitative analysis of chemically heterogeneous nanomaterials.

The analysis of chemical states and morphology in nanomaterials is central to many areas of science. We address this need with an ultrahigh-resolution scanning transmission soft x-ray microscope. Our instrument provides multiple analysis tools in a compact assembly and can achieve few-nanometer spatial resolution and high chemical sensitivity via x-ray ptychography and conventional scanning microscopy. A novel scanning mechanism, coupled to advanced x-ray detectors, a high-brightness x-ray source, and high-performance computing for analysis provide a revolutionary step forward in terms of imaging speed and resolution. We present x-ray microscopy with 8-nm full-period spatial resolution and use this capability in conjunction with operando sample environments and cryogenic imaging, which are now routinely available. Our multimodal approach will find wide use across many fields of science and facilitate correlative analysis of materials with other types of probes.