Development, validation, and relevance of in vivo low‐contrast task transfer function to estimate detectability in clinical CT images

The purpose of image reconstruction is to determine the mass densities within molecules by analysis of the intensities within images. Cryo-EM offers this possibility by virtue of the excellent preservation of internal structure without heavy atom staining. Cryo-EM images, however, have low contrast because of the similarity between the density of biological material and the density of vitreous ice. The images also contain a high background of inelastic scattering. To overcome the low signal and high background, cryo-images are typically recorded 1-3 μm underfocus to maximize phase contrast. Under those conditions the image intensities bear little resemblance to the object, due to the dependence of the contrast transfer function (CTF) upon spatial frequency. Compensation (i.e., correction) for the CTF is theoretically possible, but implementation has been rare. Despite numerous studies of molecules in ice, there has never been a quantitative evaluation of compensated images of biological molecules of known structure.

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Increased [18F]FMISO accumulation under hypoxia by multidrug-resistant protein 1 inhibitors

EJNMMI Research ◽

10.1186/s13550-021-00752-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoichi Shimizu ◽

Yukihiro Nakai ◽

Hiroyuki Watanabe ◽

Shimpei Iikuni ◽

Masahiro Ono ◽

...

Keyword(s):

Cyclosporine A ◽

Pet Imaging ◽

Multidrug Resistant ◽

Ct Images ◽

Pet Scan ◽

Reduced Form ◽

Pet Ct ◽

Fadu Cells ◽

Hypoxic State

Abstract Background [18F]Fluoromisonidazole ([18F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [18F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [18F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [18F]FMISO PET imaging. Methods FaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [18F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [18F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan). Results FaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p < 0.01). In the in vivo PET study, the SUVmean ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p < 0.05). Conclusion In this study, we revealed that MRP1 inhibitors increase [18F]FMISO accumulation in hypoxic cells. This suggests that [18F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state.

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Comparative Evaluation of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using a Sheep Model

Journal of Functional Biomaterials ◽

10.3390/jfb12030044 ◽

2021 ◽

Vol 12 (3) ◽

pp. 44

Author(s):

Leyla Hasandoost ◽

Daniella Marx ◽

Paul Zalzal ◽

Oleg Safir ◽

Mark Hurtig ◽

...

Keyword(s):

Bone Resorption ◽

Ct Images ◽

Revision Total Knee Arthroplasty ◽

Volumetric Shrinkage ◽

Ion Release ◽

Sheep Model ◽

Cement Interface ◽

Setting Times ◽

Varied Response

Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO2-CaO-SrO-P2O5-Ta2O5, were investigated. Working and setting times, pH, ion release, compressive strength, and cytotoxicity of each composition were assessed, and based on the results of these tests, three sets of samples from GPCA were implanted into the distal femur and proximal tibia of three sheep (alongside PMMA as control). Clinical CT scans and micro-CT images obtained at 0, 6, and 12 weeks revealed the varied radiological responses of sheep bone to GPCA. One GPCA sample (implanted in the sheep for 12 weeks) was characterized with no bone resorption. Furthermore, a continuous bone–cement interface was observed in the CT images of this sample. The other implanted GPCA showed a thin radiolucent border at six weeks, indicating some bone resorption occurred. The third sample showed extensive bone resorption at both six and 12 weeks. Possible speculative factors that might be involved in the varied response can be: excessive Zn2+ ion release, low pH, mixing variability, and difficulty in inserting the samples into different parts of the sheep bone.

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Dynamic Quantitative Iodine Myocardial Perfusion Imaging with Dual-Layer CT using a Porcine Model

Scientific Reports ◽

10.1038/s41598-019-52458-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Kai Scherer ◽

Johannes Hammel ◽

Thorsten Sellerer ◽

Korbinian Mechlem ◽

Bernhard Renger ◽

...

Keyword(s):

Contrast Agent ◽

Perfusion Imaging ◽

Porcine Model ◽

Ct Perfusion ◽

Dual Energy Ct ◽

Beam Hardening ◽

Low Contrast ◽

Time To Peak ◽

Coronary Ct

Abstract Ischemic heart disease is the globally leading cause of death. When using coronary CT angiography, the functional hemodynamics within the myocardium remain uncertain. In this study myocardial CT perfusion imaging using iodine contrast agent demonstrated to strongly improve the assessment of myocardial disorders. However, a retrieval of such dynamics using Hounsfield units from conventional CT poses concerns with respect to beam-hardening effects and low contrast-to-noise ratio (CNR). Dual-energy CT offers novel approaches to overcome aforementioned limitations. Quantitative peak enhancement, perfusion, time to peak and iodine volume measurements inside the myocardium were determined resulting in 0.92 mg/ml, 0.085 mg/ml/s 17.12 s and 29.89 mg/ml*s, respectively. We report on the first extensive quantitative and iodine-based analysis of myocardial dynamics in a healthy porcine model using a dual-layer spectral CT. We further elucidate on the potential of reducing the radiation dose from 135 to 18 mGy and the contrast agent volume from 60 to 30 mL by presenting a two-shot acquisition approach and measuring iodine concentrations in the myocardium in-vivo down to 1 mg/ml, respectively. We believe that dynamic quantitative iodine perfusion imaging may be a highly sensitive tool for the precise functional assessment and monitoring of early myocardial ischemia.

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