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Ultramicroscopy Jan 2022Electron crystallography has recently gained attentions in multiple fields of research, as it has been demonstrated to determine atomic structures for inorganic,...
Electron crystallography has recently gained attentions in multiple fields of research, as it has been demonstrated to determine atomic structures for inorganic, organic, and macromolecular materials from nano-sized crystals that were not amenable to conventional X-ray crystallography. Here, we demonstrate continuous-rotation microcrystal electron diffraction (microED) in a 200 kV transmission electron microscope using a DE-64 camera-a low-noise direct electron detector that can accommodate a linear response up to ∼1200 electrons per pixel per second at 20 fps with 2x-hardware-binning, making it ideal for acquisition of high-quality diffraction patterns. We have used this method and camera to determine a 0.75 Å structure of an organic molecule, biotin, with an exceptional goodness-of-fit, as well as a 0.88 Å structure of a chiral molecule, L-serine.
Topics: Crystallography; Crystallography, X-Ray; Electrons; Macromolecular Substances; Models, Molecular
PubMed: 34695647
DOI: 10.1016/j.ultramic.2021.113417 -
Journal of Nuclear Medicine : Official... Mar 2018The advent of hybrid cameras that combine MRI with either SPECT or PET has stimulated growing interest in developing multimodality imaging probes. Countless options are... (Review)
Review
The advent of hybrid cameras that combine MRI with either SPECT or PET has stimulated growing interest in developing multimodality imaging probes. Countless options are available for fusing magnetically active species with positron- or γ-ray-emitting radionuclides. The initial problem is one of choice: which chemical systems are a suitable basis for developing hybrid imaging agents? Any attempt to answer this question must also address how the physical, chemical, and biologic properties of a unified imaging agent can be tailored to ensure that optimum specificity and contrast are achieved simultaneously for both imaging modalities. Nanoparticles have emerged as attractive platforms for building multimodality radiotracers for SPECT/MRI and PET/MRI. A wide variety of nanoparticle constructs have been utilized as radiotracers, but irrespective of the particle class, radiolabeling remains a key step. Classic methods for radiolabeling nanoparticles involve functionalization of the particle surface, core, or coating. These modifications typically rely on using traditional metal ion chelate or prosthetic group chemistries. Though seemingly innocuous, appending nanoparticles with these radiolabeling handles can have dramatic effects on important properties such as particle size, charge, and solubility. In turn, alterations in the chemical and physical properties of the nanoparticle often have a negative impact on their pharmacologic profile. A central challenge in radiolabeling nanoparticles is to identify alternative chemical methods that facilitate the introduction of a radioactive nuclide without detrimental effects on the pharmacokinetic and toxicologic properties of the construct. Efforts to solve this challenge have generated a range of innovative chelate-free radiolabeling methods that exploit intrinsic chemical features of nanoparticles. Here, the chemistry of 9 mechanistically distinct methods for radiolabeling nanoparticles is presented. This discourse illustrates the evolution of nanoparticle radiochemistry from classic approaches to modern chelate-free or intrinsic methods.
Topics: Isotope Labeling; Magnetic Resonance Imaging; Multimodal Imaging; Nanomedicine; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon
PubMed: 29025988
DOI: 10.2967/jnumed.116.187419 -
Accounts of Chemical Research Oct 2014Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in... (Review)
Review
Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test-retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available to predict bioavailability, blood-brain barrier (BBB) permeability, and the associated issues of nonspecific binding and metabolic stability. To evaluate the synthesized chemical library, researchers need to consider high-throughput affinity assays, the analysis of specific binding, and the importance of fast binding kinetics. Finally, we describe how we initially assess preclinical radiotracer imaging, using brain uptake, specific binding, and preliminary kinetic analysis to identify promising radiotracers that may be useful for human brain imaging. Although we discuss these five design components separately and linearly in this Account, in practice we develop new PET-based radiotracers using these design components nonlinearly and iteratively to develop new compounds in the most efficient way possible.
Topics: Central Nervous System; Humans; Positron-Emission Tomography; Radioactive Tracers
PubMed: 25272291
DOI: 10.1021/ar500233s -
Circulation. Cardiovascular Imaging Jun 2022Single photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc...
Accuracy and Reproducibility of Myocardial Blood Flow Quantification by Single Photon Emission Computed Tomography Imaging in Patients With Known or Suspected Coronary Artery Disease.
BACKGROUND
Single photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate Tc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique.
METHODS
Accuracy was assessed in 34 participants who underwent dynamic Tc-sestamibi SPECT and N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 Tc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model' and MFR was derived as the stress/rest MBF ratio.
RESULTS
SPECT global MBF with splines showed good correlation with N-ammonia positron emission tomography (r=0.81, <0.001) and MFR estimates (r=0.74, <0.001). Correlations were substantially weaker for standard reconstruction without splines (r=0.61, <0.001 and r=0.34, =0.07, for MBF and MFR, respectively). Reproducibility of global MBF estimates with splines in paired SPECT scans was good (r=0.77, <0.001), while ordered subset expectation maximization without splines led to decreased MBF (r=0.68, <0.001) and MFR correlations (r=0.33, =0.3). There were no significant differences in MBF or MFR between the 2 reproducibility scans independently of the reconstruction algorithm (>0.05 for all).
CONCLUSIONS
MBF and MFR quantification using Tc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation.
Topics: Ammonia; Cadmium; Coronary Artery Disease; Coronary Circulation; Humans; Myocardial Perfusion Imaging; Positron-Emission Tomography; Reproducibility of Results; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon; Zinc
PubMed: 35674051
DOI: 10.1161/CIRCIMAGING.122.013987 -
Circulation. Cardiovascular Imaging May 2024
Review
Topics: Humans; Cardiology; Nuclear Medicine; History, 21st Century; Forecasting; History, 20th Century; Cardiovascular Diseases; Predictive Value of Tests; Myocardial Perfusion Imaging
PubMed: 38771905
DOI: 10.1161/CIRCIMAGING.124.016875 -
Microscopy Research and Technique Feb 2023The achievement of this work is that fine tuning of experimental and evaluation parameters can improve the absolute accuracy and reproducibility of selected area...
The achievement of this work is that fine tuning of experimental and evaluation parameters can improve the absolute accuracy and reproducibility of selected area electron diffraction (SAED) to 0.1% without using internal standard. Due to the proposed procedure it was possible to reach a reproducibility better than 0.03% for camera length between sessions by careful control of specimen height and illumination conditions by monitoring lens currents. We applied a calibration specimen composed of nanocrystalline grains free of texture and providing narrow diffraction rings. Refinements of the centre of the diffraction pattern and corrections for elliptic ring distortions allowed for determining the ring diameters with an accuracy of 0.1%. We analyze the effect of different error sources and reason the achieved absolute accuracy of the measurement. Application of the proposed evaluation procedure is inevitable in case of multicomponent nanocomposites or textured materials and/or having close diffraction rings where application of automated procedures is limited. The achieved accuracy of 0.1% without internal standard is approaching that of routine laboratory XRD, and reduction of instrumental broadening due to the elaborated evaluation procedure allows for separation of close reflections, provides more reliable ring width and thus improved input parameters for further nanostructure analysis as demonstrated on dental enamel bioapatite.
Topics: Electrons; Reproducibility of Results; Nanocomposites
PubMed: 36069159
DOI: 10.1002/jemt.24229 -
Journal of Nuclear Cardiology :... Aug 2022With the appearance of cadmium-zinc-telluride (CZT) cameras, dynamic myocardial perfusion imaging (MPI) has been introduced, but comparable data to other MPI modalities,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the appearance of cadmium-zinc-telluride (CZT) cameras, dynamic myocardial perfusion imaging (MPI) has been introduced, but comparable data to other MPI modalities, such as quantitative coronary angiography (CAG) with fractional flow reserve (FFR) and positron emission tomography (PET), are lacking. This study aimed to evaluate the diagnostic accuracy of dynamic CZT single-photon emission tomography (SPECT) in coronary artery disease compared to quantitative CAG, FFR, and PET as reference.
MATERIALS AND METHODS
Different databases were screened for eligible citations performing dynamic CZT-SPECT against CAG, FFR, or PET. PubMed, OvidSP (Medline), Web of Science, the Cochrane Library, and EMBASE were searched on the 5th of July 2020. Studies had to meet the following pre-established inclusion criteria: randomized controlled trials, retrospective trails or observational studies relevant for the diagnosis of coronary artery disease, and performing CZT-SPECT and within half a year the methodological references. Studies which considered coronary stenosis between 50% and 70% as significant based only on CAG were excluded. Data extracted were sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Quality was assessed with QUADAS-2 and statistical analysis was performed using a bivariate model.
RESULTS
Based on our criteria, a total of 9 studies containing 421 patients were included. For the assessment of CZT-SPECT, the diagnostic value pooled analysis with a bivariate model was calculated and yielded a sensitivity of 0.79 (% CI 0.73 to 0.85) and a specificity of 0.85 (95% CI 0.74 to 0.92). Diagnostic odds ratio (DOR) was 17.82 (95% CI 8.80 to 36.08, P < 0.001). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.86 (95% CI 2.76 to 5.38, P < 0.001) and 0.21 (95% CI 0.13 to 0.33, P < 0.001), respectively.
CONCLUSION
Based on the results of the current systematic review and meta-analysis, dynamic CZT-SPECT MPI demonstrated a good sensitivity and specificity to diagnose CAD as compared to the gold standards. However, due to the heterogeneity of the methodologies between the CZT-SPECT MPI studies and the relatively small number of included studies, it warrants further well-defined study protocols.
Topics: Cadmium; Coronary Angiography; Coronary Artery Disease; Fractional Flow Reserve, Myocardial; Humans; Myocardial Perfusion Imaging; Retrospective Studies; Tellurium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Zinc
PubMed: 34350553
DOI: 10.1007/s12350-021-02721-8 -
Nuclear Medicine and Molecular Imaging Dec 2021We review the history of nuclear medicine physics, instrumentation, and data sciences in Korea to commemorate the 60 anniversary of the Korean Society of Nuclear... (Review)
Review
We review the history of nuclear medicine physics, instrumentation, and data sciences in Korea to commemorate the 60 anniversary of the Korean Society of Nuclear Medicine. In the 1970s and 1980s, the development of SPECT, nuclear stethoscope, and bone densitometry systems, as well as kidney and cardiac image analysis technology, marked the beginning of nuclear medicine physics and engineering in Korea. With the introduction of PET and cyclotron in Korea in 1994, nuclear medicine imaging research was further activated. With the support of large-scale government projects, the development of gamma camera, SPECT, and PET systems was carried out. Exploiting the use of PET scanners in conjunction with cyclotrons, extensive studies on myocardial blood flow quantification and brain image analysis were also actively pursued. In 2005, Korea's first domestic cyclotron succeeded in producing radioactive isotopes, and the cyclotron was provided to six universities and university hospitals, thereby facilitating the nationwide supply of PET radiopharmaceuticals. Since the late 2000s, research on PET/MRI has been actively conducted, and the advanced research results of Korean scientists in the fields of silicon photomultiplier PET and simultaneous PET/MRI have attracted significant attention from the academic community. Currently, Korean researchers are actively involved in endeavors to solve a variety of complex problems in nuclear medicine using artificial intelligence and deep learning technologies.
PubMed: 34868376
DOI: 10.1007/s13139-021-00721-7 -
PloS One 2018Imaging was conducted using an electron tracking-Compton camera (ETCC), which measures γ-rays with energies in the range of 200-900 keV from 95mTc. 95mTc was produced...
Imaging was conducted using an electron tracking-Compton camera (ETCC), which measures γ-rays with energies in the range of 200-900 keV from 95mTc. 95mTc was produced by the 95Mo(p, n)95mTc reaction on a 95Mo-enriched target. A method for recycling 95Mo-enriched molybdenum trioxide was employed, and the recycled yield of 95Mo was 70%-90%. Images were obtained with the gate of three energies. The results showed that the spatial resolution increases with increasing γ-ray energy, and suggested that the ETCC with high-energy γ-ray emitters such as 95mTc is useful for the medical imaging of deep tissue and organs in the human body.
Topics: Algorithms; Diagnostic Imaging; Electrons; Gamma Cameras; Gamma Rays; Humans; Molybdenum; Monte Carlo Method; Oxides; Phantoms, Imaging; Photons; Radioisotopes; Scattering, Radiation; Technetium
PubMed: 30532248
DOI: 10.1371/journal.pone.0208909 -
Journal of Nuclear Medicine Technology Mar 2014Combined PET and SPECT scanning can give supplementary information. However, activity from PET radionuclides can cause background counts and increased dead time in γ...
UNLABELLED
Combined PET and SPECT scanning can give supplementary information. However, activity from PET radionuclides can cause background counts and increased dead time in γ camera imaging (SPECT or planar) because the 511-keV photons can penetrate collimators designed for lower energies. This study investigated how to manage this issue, including what levels of PET radionuclides can be tolerated when a γ-camera investigation is performed.
METHODS
Different combinations of (68)Ga (PET radionuclide), (99m)Tc (low-energy radionuclide), and (111)In (medium-energy radionuclide) were scanned by a γ camera. Standard low-, medium-, and high-energy collimators were used with the γ camera. Dead time and counts near and distant from the sources were recorded.
RESULTS
Down scatter from 511 keV can give rise to a considerable number of counts within the (99m)Tc or (111)In energy windows, especially when the PET source is close to the camera head. Over the full camera head, the PET source can result in more counts per megabecquerel than the SPECT source ((99m)Tc or (111)In). Counts from the PET source were distributed over a large region of the camera head. With medium- and high-energy collimators, the sensitivity to the PET radionuclide was found to be about 10% of the sensitivity to (99m)Tc and about 20% of the sensitivity to (111)In, as measured within a 3-cm-radius region of interest.
CONCLUSION
If PET radionuclides of activity 1 MBq or higher are present in the patient at the time of SPECT, a medium-energy collimator should be used. Counts from PET sources will in SPECT usually be seen as a diffuse background rather than as foci. The thick septa of high-energy collimators may result in structure in the image, and a high-energy collimator is recommended only if PET activity is greater than 10 MBq.
Topics: Half-Life; Positron-Emission Tomography; Reference Standards; Tomography, Emission-Computed, Single-Photon
PubMed: 24470597
DOI: 10.2967/jnmt.113.131003