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1.
Proc Natl Acad Sci U S A ; 120(27): e2301549120, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37364114

RESUMO

Modern infectious disease outbreaks often involve changes in host tropism, the preferential adaptation of pathogens to specific hosts. The Lyme disease-causing bacterium Borrelia burgdorferi (Bb) is an ideal model to investigate the molecular mechanisms of host tropism, because different variants of these tick-transmitted bacteria are distinctly maintained in rodents or bird reservoir hosts. To survive in hosts and escape complement-mediated immune clearance, Bb produces the outer surface protein CspZ that binds the complement inhibitor factor H (FH) to facilitate bacterial dissemination in vertebrates. Despite high sequence conservation, CspZ variants differ in human FH-binding ability. Together with the FH polymorphisms between vertebrate hosts, these findings suggest that minor sequence variation in this bacterial outer surface protein may confer dramatic differences in host-specific, FH-binding-mediated infectivity. We tested this hypothesis by determining the crystal structure of the CspZ-human FH complex, and identifying minor variation localized in the FH-binding interface yielding bird and rodent FH-specific binding activity that impacts infectivity. Swapping the divergent region in the FH-binding interface between rodent- and bird-associated CspZ variants alters the ability to promote rodent- and bird-specific early-onset dissemination. We further linked these loops and respective host-specific, complement-dependent phenotypes with distinct CspZ phylogenetic lineages, elucidating evolutionary mechanisms driving host tropism emergence. Our multidisciplinary work provides a novel molecular basis for how a single, short protein motif could greatly modulate pathogen host tropism.


Assuntos
Borrelia burgdorferi , Doença de Lyme , Animais , Humanos , Evasão da Resposta Imune/genética , Filogenia , Tropismo Viral , Doença de Lyme/microbiologia , Proteínas de Bactérias/metabolismo , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Proteínas do Sistema Complemento/genética , Proteínas de Membrana/metabolismo
2.
Mol Microbiol ; 121(6): 1262-1272, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38830767

RESUMO

Emerging and re-emerging pathogens often stem from zoonotic origins, cycling between humans and animals, and are frequently vectored and maintained by hematophagous arthropod vectors. The efficiency by which these disease agents are successfully transmitted between vertebrate hosts is influenced by many factors, including the host on which a vector feeds. The Lyme disease bacterium Borrelia burgdorferi sensu lato has adapted to survive in complex host environments, vectored by Ixodes ticks, and maintained in multiple vertebrate hosts. The versatility of Lyme borreliae in disparate host milieus is a compelling platform to investigate mechanisms dictating pathogen transmission through complex networks of vertebrates and ticks. Squamata, one of the most diverse clade of extant reptiles, is comprised primarily of lizards, many of which are readily fed upon by Ixodes ticks. Yet, lizards are one of the least studied taxa at risk of contributing to the transmission and life cycle maintenance of Lyme borreliae. In this review, we summarize the current evidence, spanning from field surveillance to laboratory infection studies, supporting their contributions to Lyme borreliae circulation. We also summarize the current understanding of divergent lizard immune responses that may explain the underlying molecular mechanisms to confer Lyme spirochete survival in vertebrate hosts. This review offers a critical perspective on potential enzootic cycles existing between lizard-tick-Borrelia interactions and highlights the importance of an eco-immunology lens for zoonotic pathogen transmission studies.


Assuntos
Ixodes , Lagartos , Doença de Lyme , Animais , Lagartos/microbiologia , Doença de Lyme/microbiologia , Doença de Lyme/transmissão , Ixodes/microbiologia , Humanos , Grupo Borrelia Burgdorferi/fisiologia , Grupo Borrelia Burgdorferi/genética , Borrelia burgdorferi/genética , Borrelia burgdorferi/fisiologia
3.
Infect Immun ; 90(7): e0006222, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35861564

RESUMO

Transmitted by ticks, the bacterium Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD), the most common vector-borne disease in the Northern hemisphere. No effective vaccines are currently available. B. burgdorferi sensu lato produces the CspZ protein that binds to the complement inhibitor, factor H (FH), promoting evasion of the host complement system. We previously showed that while vaccination with CspZ did not protect mice from B. burgdorferi infection, mice can be protected after immunization with CspZ-Y207A/Y211A (CspZ-YA), a CspZ mutant protein without FH-binding activity. To further study the mechanism of this protection, herein we evaluated both poly- and monoclonal antibodies recognizing CspZ FH-binding or non-FH-binding sites. We found that the anti-CspZ antibodies that recognize the FH-binding sites (i.e., block FH-binding activity) eliminate B. burgdorferi sensu lato in vitro more efficiently than those that bind to the non-FH-binding sites, and passive inoculation with anti-FH-binding site antibodies eradicated B. burgdorferi sensu lato in vivo. Antibodies against non-FH-binding sites did not have the same effect. These results emphasize the importance of CspZ FH-binding sites in triggering a protective antibody response against B. burgdorferi sensu lato in future LD vaccines.


Assuntos
Grupo Borrelia Burgdorferi , Borrelia , Ixodes , Doença de Lyme , Animais , Anticorpos , Sítios de Ligação , Fator H do Complemento , Epitopos , Ixodes/microbiologia , Doença de Lyme/microbiologia , Camundongos
4.
Appl Environ Microbiol ; 88(5): e0155521, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-34986011

RESUMO

Lyme borreliosis is the most common vector-borne disease in the Northern Hemisphere, caused by spirochetes belonging to the Borrelia burgdorferi sensu lato species complex, which are transmitted by ixodid ticks. B. burgdorferi sensu lato species produce a family of proteins on the linear plasmid 54 (PFam54), some of which confer the functions of cell adhesion and inactivation of complement, the first line of host defense. However, the impact of PFam54 in promoting B. burgdorferi sensu lato pathogenesis remains unclear because of the hurdles to simultaneously knock out all PFam54 proteins in a spirochete. Here, we describe two Borrelia bavariensis strains, PBN and PNi, isolated from patients naturally lacking PFam54 but maintaining the rest of the genome with greater than 95% identity to the reference B. bavariensis strain, PBi. We found that PBN and PNi less efficiently survive in human serum than PBi. Such defects were restored by introducing two B. bavariensis PFam54 recombinant proteins, BGA66 and BGA71, confirming the role of these proteins in providing complement evasion of B. bavariensis. Further, we found that all three strains remain detectable in various murine tissues 21 days post-subcutaneous infection, supporting the nonessential role of B. bavariensis PFam54 in promoting spirochete persistence. This study identified and utilized isolates deficient in PFam54 to associate the defects with the absence of these proteins, building the foundation to further study the role of each PFam54 protein in contributing to B. burgdorferi sensu lato pathogenesis. IMPORTANCE To establish infections, Lyme borreliae utilize various means to overcome the host's immune system. Proteins encoded by the PFam54 gene array play a role in spirochete survival in vitro and in vivo. Moreover, this gene array has been described in all currently available Lyme borreliae genomes. By investigating the first two Borrelia bavariensis isolates naturally lacking the entire PFam54 gene array, we showed that both patient isolates display an increased susceptibility to human serum, which can be rescued in the presence of two PFam54 recombinant proteins. However, both isolates remain infectious to mice after intradermal inoculation, suggesting the nonessential role of PFam54 during the long-term, but may differ slightly in the colonization of specific tissues. Furthermore, these isolates show high genomic similarity to type strain PBi (>95%) and could be used in future studies investigating the role of each PFam54 protein in Lyme borreliosis pathogenesis.


Assuntos
Grupo Borrelia Burgdorferi , Borrelia , Ixodes , Doença de Lyme , Animais , Borrelia/genética , Grupo Borrelia Burgdorferi/genética , Humanos , Camundongos , Plasmídeos , Spirochaetales
5.
Radiology ; 298(1): 147-152, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33141002

RESUMO

Background Bone mineral density (BMD) could be derived from CT localizer radiographs and could potentially enable opportunistic osteoporosis screening. Purpose To assess the accuracy and precision of BMD measurement using two localizer radiographs obtained with energy-integrating detector CT and a single localizer radiograph obtained with photon-counting detector CT. Materials and Methods A calibration phantom and a porcine phantom with lumbar vertebrae were imaged with a dual-energy x-ray absorptiometry (DXA) scanner, a clinical energy-integrating detector CT scanner, and a prototype photon-counting detector CT scanner. Two localizer radiographs at different combinations of tube voltages were obtained with energy-integrating detector CT, and one localizer radiograph was obtained with photon-counting detector CT using different energy thresholds. BMD was calculated for all three approaches and compared with the known specifications in the calibration phantom. In the animal phantom, BMDs from both CT systems were compared with those from the DXA scanner (the reference standard). Accuracy was defined as the measurement error of BMD (ΔBMD), and precision was defined as the coefficient of variation (in percentage). Radiation doses were estimated. Nonparametric tests were applied. Results In the calibration phantom, ΔBMD was smaller with both CT systems compared with the DXA scanner (both P < .05). ΔBMD ranged from -5% to -1.8% for DXA, from -2.3% to -1.7% for energy-integrating detector CT, and from -1.6% to 1.6% for photon-counting detector CT. Precision (range, 0.3%-2.8%) was high for both CT systems. In the animal phantom, ΔBMD ranged from -0.6% to 0.1% for energy-integrating detector CT and from -0.1% to 0.6% for photon-counting detector CT, with no significant differences between CT systems (P = .65). The dose-area product in the animal phantom was 4.6 cGy ∙ cm2 for DXA, 3.5-11.5 cGy ∙ cm2 for energy-integrating detector CT, and 7.2-11.2 cGy ∙ cm2 for photon-counting detector CT, depending on tube voltage and energy threshold combination. Conclusion Experimental evidence suggests that bone mineral density measurements are accurate and precise using two localizer radiographs at different tube voltages from energy-integrating detector CT and a single localizer radiograph with different energy thresholds from photon-counting detector CT. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Pourmorteza in this issue.


Assuntos
Densidade Óssea/fisiologia , Vértebras Lombares/anatomia & histologia , Tomografia Computadorizada por Raios X/métodos , Absorciometria de Fóton , Animais , Modelos Animais , Imagens de Fantasmas , Fótons , Reprodutibilidade dos Testes , Suínos
7.
Diagnostics (Basel) ; 14(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38928677

RESUMO

Photon-counting CT systems generally allow for acquiring multiple spectral datasets and thus for decomposing CT images into multiple materials. We introduce a prior knowledge-free deterministic material decomposition approach for quantifying three material concentrations on a commercial photon-counting CT system based on a single CT scan. We acquired two phantom measurement series: one to calibrate and one to test the algorithm. For evaluation, we used an anthropomorphic abdominal phantom with inserts of either aqueous iodine solution, aqueous tungsten solution, or water. Material CT numbers were predicted based on a polynomial in the following parameters: Water-equivalent object diameter, object center-to-isocenter distance, voxel-to-isocenter distance, voxel-to-object center distance, and X-ray tube current. The material decomposition was performed as a generalized least-squares estimation. The algorithm provided material maps of iodine, tungsten, and water with average estimation errors of 4% in the contrast agent maps and 1% in the water map with respect to the material concentrations in the inserts. The contrast-to-noise ratio in the iodine and tungsten map was 36% and 16% compared to the noise-minimal threshold image. We were able to decompose four spectral images into iodine, tungsten, and water.

8.
Invest Radiol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526041

RESUMO

OBJECTIVES: Calcified plaques induce blooming artifacts in coronary computed tomography angiography (CCTA) potentially leading to inaccurate stenosis evaluation. Tungsten represents a high atomic number, experimental contrast agent with different physical properties than iodine. We explored the potential of a tungsten-based contrast agent for photon-counting detector (PCD) CCTA in heavily calcified coronary vessels. MATERIALS AND METHODS: A cardiovascular phantom exhibiting coronaries with calcified plaques was imaged on a first-generation dual-source PCD-CT. The coronaries with 3 different calcified plaques were filled with iodine and tungsten contrast media solutions equating to iodine and tungsten delivery rates (IDR and TDR) of 0.3, 0.5, 0.7, 1.0, 1.5, 2.0, 2.5, and 3.0 g/s, respectively. Electrocardiogram-triggered sequential acquisitions were performed in the spectral mode (QuantumPlus). Virtual monoenergetic images (VMIs) were reconstructed from 40 to 190 keV in 1 keV increments. Blooming artifacts and percentage error stenoses from calcified plaques were quantified, and attenuation characteristics of both contrast media were recorded. RESULTS: Blooming artifacts from calcified plaques were most pronounced at 40 keV (78%) and least pronounced at 190 keV (58%). Similarly, percentage error stenoses were highest at 40 keV (48%) and lowest at 190 keV (2%), respectively. Attenuation of iodine decreased monotonically in VMIs from low to high keV, with the strongest decrease from 40 keV to 100 keV (IDR of 2.5 g/s: 1279 HU at 40 keV, 187 HU at 100 kV, and 35 HU at 190 keV). The attenuation of tungsten, on the other hand, increased monotonically as a function of VMI energy, with the strongest increase between 40 and 100 keV (TDR of 2.5 g/s: 202 HU at 40 keV, 661 HU at 100 kV, and 717 HU at 190 keV). For each keV level, the relationship between attenuation and IDR/TDR could be described by linear regressions (R2 ≥ 0.88, P < 0.001). Specifically, attenuation increased linearly when increasing the delivery rate irrespective of keV level or contrast medium. Iodine exhibited the highest relative increase in attenuation values at lower keV levels when increasing the IDR. Conversely, for tungsten, the greatest relative increase in attenuation values occurred at higher keV levels when increasing the TDR. When high keV imaging is desirable to reduce blooming artifacts from calcified plaques, IDR has to be increased at higher keV levels to maintain diagnostic vessel attenuation (ie, 300 HU), whereas for tungsten, TDR can be kept constant or can be even reduced at high keV energy levels. CONCLUSIONS: Tungsten's attenuation characteristics in relation to VMI energy levels are reversed to those of iodine, with tungsten exhibiting high attenuation values at high keV levels and vice versa. Thus, tungsten shows promise for high keV imaging CCTA with PCD-CT as-in distinction to iodine-both high vessel attenuation and low blooming artifacts from calcified plaques can be achieved.

9.
Invest Radiol ; 58(7): 515-522, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37068840

RESUMO

ABSTRACT: The recent technological developments in photon-counting detector computed tomography (PCD-CT) and the introduction of the first commercially available clinical PCD-CT unit open up new exciting opportunities for contrast media research. With PCD-CT, the efficacy of available iodine-based contrast media improves, allowing for a reduction of iodine dosage or, on the other hand, an improvement of image quality in low contrast indications. Virtual monoenergetic image reconstructions are routinely available and enable the virtual monoenergetic image energy to be adapted to the diagnostic task.A key property of PCD-CT is the ability of spectral separation in combination with improved material decomposition. Thus, the discrimination of contrast media from intrinsic or pathological tissues and the discrimination of 2 or more contrasting elements that characterize different tissues are attractive fields for contrast media research. For these approaches, K-edge imaging in combination with high atomic number elements such as the lanthanides, tungsten, tantalum, or bismuth plays a central role.The purpose of this article is to present an overview of innovative contrast media concepts that use high atomic number elements. The emphasis is on improving contrast enhancement for cardiovascular plaque imaging, stent visualization, and exploring new approaches using 2 contrasting elements. Along with the published research, new experimental findings with a contrast medium that incorporates tungsten are included.Both the literature review and the new experimental data demonstrate the great potential and feasibility for new contrast media to significantly increase diagnostic performance and to enable new clinical fields and indications in combination with PCD-CT.


Assuntos
Meios de Contraste , Iodo , Imagens de Fantasmas , Fótons , Tomografia Computadorizada por Raios X/métodos , Tungstênio
10.
Ticks Tick Borne Dis ; 14(1): 102081, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36403322

RESUMO

In North America, Lyme disease is primarily caused by the spirochetal bacterium Borrelia burgdorferi sensu stricto (Bb), which is transmitted between multiple vertebrate hosts and ixodid ticks, and is a model commonly used to study host-pathogen interactions. While Bb is consistently observed in its mammalian and avian reservoirs, the bacterium is rarely isolated from North American reptiles. Two closely related lizard species, the eastern fence lizard (Sceloporus undulatus) and the western fence lizard (Sceloporus occidentalis), are examples of reptiles parasitized by Ixodes ticks. Vertebrates are known to generate complement as an innate defense mechanism, which can be activated before Bb disseminate to distal tissues. Complement from western fence lizards has proven lethal against one Bb strain, implying the role of complement in making those lizards unable to serve as hosts to Bb. However, Bb DNA is occasionally identified in distal tissues of field-collected eastern fence lizards, suggesting some Bb strains may overcome complement-mediated clearance in these lizards. These findings raise questions regarding the role of complement and its impact on Bb interactions with North American lizards. In this study, we found Bb seropositivity in a small population of wild-caught eastern fence lizards and observed Bb strain-specific survivability in lizard sera. We also found that a Bb outer surface protein, OspE, from Bb strains viable in sera, promotes lizard serum survivability and binds to a complement inhibitor, factor H, from eastern fence lizards. Our data thus identify bacterial and host determinants of eastern fence lizard complement evasion, providing insights into the role of complement influencing Bb interactions with North American lizards.


Assuntos
Antígenos de Bactérias , Proteínas da Membrana Bacteriana Externa , Borrelia burgdorferi , Proteínas do Sistema Complemento , Evasão da Resposta Imune , Lipoproteínas , Lagartos , Doença de Lyme , Animais , Borrelia burgdorferi/imunologia , Lagartos/sangue , Lagartos/imunologia , Lagartos/microbiologia , América do Norte , Antígenos de Bactérias/sangue , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/sangue , Proteínas da Membrana Bacteriana Externa/imunologia , Lipoproteínas/sangue , Lipoproteínas/imunologia , Proteínas do Sistema Complemento/imunologia , Doença de Lyme/sangue , Doença de Lyme/imunologia , Doença de Lyme/microbiologia , Doença de Lyme/virologia
11.
Eur Radiol ; 22(4): 900-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22071777

RESUMO

OBJECTIVE: To evaluate the potential of in vivo dynamic contrast-enhanced micro-computed tomography (DCE micro-CT) for the assessment of antiangiogenic drug therapy response of mice with mammary carcinoma. METHODS: 20 female mice with implanted MCF7 tumours were split into control group and therapy group treated with a known effective antiangiogenic drug. All mice underwent DCE micro-CT for the 3D analysis of functional parameters (relative blood volume [rBV], vascular permeability [K], area under the time-enhancement curve [AUC]) and morphology. All parameters were determined for total, peripheral and central tumour volumes of interest (VOIs). Immunohistochemistry was performed to characterise tumour vascularisation. 3D dose distributions were determined. RESULTS: The mean AUCs were significantly lower in therapy with P values of 0.012, 0.007 and 0.023 for total, peripheral and central tumour VOIs. K and rBV showed significant differences for the peripheral (P(per)(K) = 0.032, P(per) (rBV) = 0.029), but not for the total and central tumour VOIs (P(total)(K) = 0.108, P(central)(K) = 0.246, P(total) (rBV) = 0.093, P(central) (rBV) = 0.136). Mean tumour volume was significantly smaller in therapy (P (in vivo) = 0.001, P (ex vivo) = 0.005). Histology revealed greater vascularisation in the controls and central tumour necrosis. Doses ranged from 150 to 300 mGy. CONCLUSIONS: This study indicates the great potential of DCE micro-CT for early in vivo assessment of antiangiogenic drug therapy response. KEY POINTS: Dynamic contrast enhanced micro-CT (computed tomography) is a new experimental laboratory technique. DCE micro-CT allows early in vivo assessment of antiangiogenic drug therapy response. Pharmaceutical drugs can be tested before translation to clinical practice. Both morphological and functional parameters can be obtained using DCE micro-CT. Antiangiogenic effects can be visualised with DCE micro-CT.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Imageamento Tridimensional/veterinária , Iohexol/análogos & derivados , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Sirolimo/análogos & derivados , Tomografia Computadorizada por Raios X/veterinária , Animais , Linhagem Celular Tumoral , Meios de Contraste , Everolimo , Feminino , Camundongos , Camundongos Nus , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sirolimo/administração & dosagem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
12.
Med Phys ; 39(6): 3229-39, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22755706

RESUMO

PURPOSE: To optimize micro-CT protocols with respect to x-ray spectra and thereby reduce radiation dose at unimpaired image quality. METHODS: Simulations were performed to assess image contrast, noise, and radiation dose for different imaging tasks. The figure of merit used to determine the optimal spectrum was the dose-weighted contrast-to-noise ratio (CNRD). Both optimal photon energy and tube voltage were considered. Three different types of filtration were investigated for polychromatic x-ray spectra: 0.5 mm Al, 3.0 mm Al, and 0.2 mm Cu. Phantoms consisted of water cylinders of 20, 32, and 50 mm in diameter with a central insert of 9 mm which was filled with different contrast materials: an iodine-based contrast medium (CM) to mimic contrast-enhanced (CE) imaging, hydroxyapatite to mimic bone structures, and water with reduced density to mimic soft tissue contrast. Validation measurements were conducted on a commercially available micro-CT scanner using phantoms consisting of water-equivalent plastics. Measurements on a mouse cadaver were performed to assess potential artifacts like beam hardening and to further validate simulation results. RESULTS: The optimal photon energy for CE imaging was found at 34 keV. For bone imaging, optimal energies were 17, 20, and 23 keV for the 20, 32, and 50 mm phantom, respectively. For density differences, optimal energies varied between 18 and 50 keV for the 20 and 50 mm phantom, respectively. For the 32 mm phantom and density differences, CNRD was found to be constant within 2.5% for the energy range of 21-60 keV. For polychromatic spectra and CMs, optimal settings were 50 kV with 0.2 mm Cu filtration, allowing for a dose reduction of 58% compared to the optimal setting for 0.5 mm Al filtration. For bone imaging, optimal tube voltages were below 35 kV. For soft tissue imaging, optimal tube settings strongly depended on phantom size. For 20 mm, low voltages were preferred. For 32 mm, CNRD was found to be almost independent of tube voltage. For 50 mm, voltages larger than 50 kV were preferred. For all three phantom sizes stronger filtration led to notable dose reduction for soft tissue imaging. Validation measurements were found to match simulations well, with deviations being less than 10%. Mouse measurements confirmed simulation results. CONCLUSIONS: Optimal photon energies and tube settings strongly depend on both phantom size and imaging task at hand. For in vivo CE imaging and density differences, strong filtration and voltages of 50-65 kV showed good overall results. For soft tissue imaging of animals the size of a rat or larger, voltages higher than 65 kV allow to greatly reduce scan times while maintaining dose efficiency. For imaging of bone structures, usage of only minimum filtration and low tube voltages of 40 kV and below allow exploiting the high contrast of bone at very low energies. Therefore, a combination of two filtrations could prove beneficial for micro-CT: a soft filtration allowing for bone imaging at low voltages, and a variable stronger filtration (e.g., 0.2 mm Cu) for soft tissue and contrast-enhanced imaging.


Assuntos
Microtomografia por Raio-X/métodos , Animais , Cor , Processamento de Imagem Assistida por Computador , Camundongos , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Doses de Radiação , Análise Espectral
13.
Med Phys ; 39(2): 658-70, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22320775

RESUMO

PURPOSE: At present, no established methods exist for dosimetry in micro computed tomography (micro-CT). The purpose of this study was therefore to investigate practical concepts for both dosimetric scanner quality assurance and tissue dose assessment for micro-CT. METHODS: The computed tomography dose index (CTDI) was adapted to micro-CT and measurements of the CTDI both free in air and in the center of cylindrical polymethyl methacrylate (PMMA) phantoms of 20 and 32 mm diameter were performed in a 6 month interval with a 100 mm pencil ionization chamber calibrated for low tube voltages. For tissue dose assessment, z-profile measurements using thermoluminescence dosimeters (TLDs) were performed and both profile and CTDI measurements were compared to Monte Carlo (MC) dose calculations to validate an existing MC tool for use in micro-CT. The consistency of MC calculations and TLD measurements was further investigated in two mice cadavers. RESULTS: CTDI was found to be a reproducible quantity for constancy tests on the micro-CT system under study, showing a linear dependence on tube voltage and being by definition proportional to mAs setting and z-collimation. The CTDI measured free in air showed larger systematic deviations after the 6 month interval compared to the CTDI measured in PMMA phantoms. MC calculations were found to match CTDI measurements within 3% when using x-ray spectra measured at our micro-CT installation and better than 10% when using x-ray spectra calculated from semi-empirical models. Visual inspection revealed good agreement for all z-profiles. The consistency of MC calculations and TLD measurements in mice was found to be better than 10% with a mean deviation of 4.5%. CONCLUSIONS: Our results show the CTDI implemented for micro-CT to be a promising candidate for dosimetric quality assurance measurements as it linearly reflects changes in tube voltage, mAs setting, and collimation used during the scan, encouraging further studies on a variety of systems. For tissue dose assessment, MC calculations offer an accurate and fast alternative to TLD measurements allowing for dose calculations specific to any geometry and scan protocol.


Assuntos
Modelos Biológicos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Doses de Radiação , Radiometria/métodos , Radiometria/normas , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas , Animais , Simulação por Computador , Alemanha , Camundongos , Garantia da Qualidade dos Cuidados de Saúde/normas
14.
Med Phys ; 39(4): 2249-60, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22482646

RESUMO

PURPOSE: Modern computed tomography (CT) systems are supporting increasingly fast rotation speeds, which are a prerequisite for fast dynamic acquisition, e.g. in perfusion imaging, and for new modalities such as dedicated breast CT, where breathhold scanning is indicated. However, not all detector technologies are supporting the high frame rates that are necessary to retain high resolution for objects far away from the isocenter. Even on systems that would support a sufficiently high frame rate, the necessary bandwidth of the data transfer from the rotating gantry stills remains challenging. The authors evaluated a pixel shifting technique termed time-delayed summation (TDS) as a method of increasing resolution on fast rotating CT systems without the need to increase the frame rate. METHODS: In TDS mode, detector pixel values are shifted along rows during image acquisition to compensate for detector motion. In order to fully exploit TDS, focal spot position control (FSC) was used in combination with TDS. FSC applies a counter movement to the x-ray focal spot during image acquisition such that it is kept fixed in space. As a proof of concept, measurements were performed on a prototype photon counting detector capable of TDS. The detector was mounted on a movable table and a gold wire phantom was imaged with different TDS settings and detector velocities. Additionally, simulations of a broad range of TDS and FSC settings on two different modalities, a clinical CT scanner and a breast CT scanner, and two different detector geometries, flat and cylindrical, were performed to assess the gain in resolution and contrast in cylindrical water phantoms containing a small wire at distances from the phantom center varied from 5% to 90% of the phantom radius. As figures of merit, the modulation transfer function (MTF) at 10% and the maximum contrast were used and compared against the respective values when using step-and-shoot acquisition, which means stopping the rotation when a projection image is acquired. RESULTS: Measurements showed that detector movement and the resulting blurring of the wire projections were compensated to the expected degree when using the appropriate number of TDS shifts per frame (TDS factor). Using simulations it was found that when using the optimal TDS factor, over 90% of the resolution achieved in step-and-shot mode was reached for all investigated wire positions. TDS showed better performance on a cylindrical detector that on the same system with a flat detector. TDS factors that were deviating from the optimum by more than 1 shift led to a performance below that of standard continuous acquisition. CONCLUSIONS: The findings of this study encourage the combined usage of TDS and FSC in systems that require fast rotation. The integration of TDS in state-of-the-art x-ray detectors is feasible.


Assuntos
Algoritmos , Imageamento Tridimensional/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Imagens de Fantasmas , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Rotação , Sensibilidade e Especificidade , Fatores de Tempo , Tomografia Computadorizada por Raios X/instrumentação
15.
Invest Radiol ; 57(6): 399-405, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35025834

RESUMO

OBJECTIVES: The diagnostic performance of coronary computed tomography angiography is known to be negatively affected by the presence of severely calcified plaques in the coronary arteries. In this article, the performance of a novel image reconstruction algorithm (PureLumen) based on spectral CT data of a first-generation dual-source photon-counting detector computed tomography (PCD-CT) system was assessed in a phantom study. PureLumen tries to remove only the calcified contributions from the image while leaving the rest unmodified. MATERIALS AND METHODS: The study uses 2 iodine contrast filled vessel phantoms (diameter 4 mm) filled with different concentrations of iodine and equipped with calcified stenosis inserts. Each phantom features 2 separate calcified lesions of 25% and 50% percentage diameter stenosis (PDS) size. The vessel phantoms were mounted inside an anthropomorphic thorax phantom attached to an artificial motion device, simulating realistic cardiac motion at heart rates between 50 beats per minute and 100 beats per minute. Acquisitions were performed using a prospectively electrocardiogram triggered dual-source sequence mode on a PCD-CT system (NAEOTOM Alpha, Siemens Healthineers). Images were reconstructed at 80% of the RR interval with virtual monoenergetic images (Mono) and with additional calcium-removal (PureLumen), both at 65 keV. PureLumen is based on a spectral base material decomposition into iodine and calcium, which aims to reconstruct images without calcium contributions, while leaving all other material contribution unchanged. Stenosis grade was assessed individually for each vessel insert in all reconstructed image series by 2 readers. RESULTS: The measured median PDS values for the 50% lesion were 56.0% (52.0%, 57.0%) for the Mono case and 50.0% (48.5%, 51.0%) for PureLumen. The 25% lesion median PDS values were 36.0% (29.5%, 39.5%) for Mono and 31.5% (30.5%, 34.0%) for PureLumen. Both lesion sizes demonstrate a significant difference between Mono and PureLumen in their result (P < 0.05) with PureLumen median values being closer to the actual true stenosis size for the 50% and 25% lesion. A visual assessment of the image quality depending on the heart rate yielded good image quality up to a heart rate of 80 beats per minute in the PureLumen case. CONCLUSIONS: This phantom study shows that a novel calcium-removal image reconstruction algorithm (PureLumen) using a first-generation dual-source PCD-CT effectively decreases blooming artifacts caused by heavily calcified plaques and improves image interpretability. It also shows that PureLumen retains its performance in the presence of motion with simulated heart rates up to 80 beats per minute. Future in vivo clinical studies are needed to confirm the benefits of this type of reconstruction in terms of coronary computed tomography angiography quality and accuracy.


Assuntos
Cálcio , Iodo , Algoritmos , Constrição Patológica , Humanos , Imagens de Fantasmas , Tomografia Computadorizada por Raios X/métodos
16.
mSystems ; 7(4): e0048822, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35938719

RESUMO

Host association-the selective adaptation of pathogens to specific host species-evolves through constant interactions between host and pathogens, leaving a lot yet to be discovered on immunological mechanisms and genomic determinants. The causative agents of Lyme disease (LD) are spirochete bacteria composed of multiple species of the Borrelia burgdorferi sensu lato complex, including B. burgdorferi (Bb), the main LD pathogen in North America-a useful model for the study of mechanisms underlying host-pathogen association. Host adaptation requires pathogens' ability to evade host immune responses, such as complement, the first-line innate immune defense mechanism. We tested the hypothesis that different host-adapted phenotypes among Bb strains are linked to polymorphic loci that confer complement evasion traits in a host-specific manner. We first examined the survivability of 20 Bb strains in sera in vitro and/or bloodstream and tissues in vivo from rodent and avian LD models. Three groups of complement-dependent host-association phenotypes emerged. We analyzed complement-evasion genes, identified a priori among all strains and sequenced and compared genomes for individual strains representing each phenotype. The evolutionary history of ospC loci is correlated with host-specific complement-evasion phenotypes, while comparative genomics suggests that several gene families and loci are potentially involved in host association. This multidisciplinary work provides novel insights into the functional evolution of host-adapted phenotypes, building a foundation for further investigation of the immunological and genomic determinants of host association. IMPORTANCE Host association is the phenotype that is commonly found in many pathogens that preferential survive in particular hosts. The Lyme disease (LD)-causing agent, B. burgdorferi (Bb), is an ideal model to study host association, as Bb is mainly maintained in nature through rodent and avian hosts. A widespread yet untested concept posits that host association in Bb strains is linked to Bb functional genetic variation conferring evasion to complement, an innate defense mechanism in vertebrate sera. Here, we tested this concept by grouping 20 Bb strains into three complement-dependent host-association phenotypes based on their survivability in sera and/or bloodstream and distal tissues in rodent and avian LD models. Phylogenomic analysis of these strains further correlated several gene families and loci, including ospC, with host-specific complement-evasion phenotypes. Such multifaceted studies thus pave the road to further identify the determinants of host association, providing mechanistic insights into host-pathogen interaction.


Assuntos
Borrelia burgdorferi , Borrelia , Doença de Lyme , Humanos , Filogenia , Doença de Lyme/genética , Borrelia burgdorferi/genética , Proteínas do Sistema Complemento/genética
17.
Invest Radiol ; 57(8): 536-543, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35318969

RESUMO

PURPOSE: The aim of this study was to evaluate coronary computed tomography angiography (CCTA)-based in vitro and in vivo coronary artery calcium scoring (CACS) using a novel virtual noniodine reconstruction (PureCalcium) on a clinical first-generation photon-counting detector-computed tomography system compared with virtual noncontrast (VNC) reconstructions and true noncontrast (TNC) acquisitions. MATERIALS AND METHODS: Although CACS and CCTA are well-established techniques for the assessment of coronary artery disease, they are complementary acquisitions, translating into increased scan time and patient radiation dose. Hence, accurate CACS derived from a single CCTA acquisition would be highly desirable. In this study, CACS based on PureCalcium, VNC, and TNC, reconstructions was evaluated in a CACS phantom and in 67 patients (70 [59/80] years, 58.2% male) undergoing CCTA on a first-generation photon counting detector-computed tomography system. Coronary artery calcium scores were quantified for the 3 reconstructions and compared using Wilcoxon test. Agreement was evaluated by Pearson and Spearman correlation and Bland-Altman analysis. Classification of coronary artery calcium score categories (0, 1-10, 11-100, 101-400, and >400) was compared using Cohen κ . RESULTS: Phantom studies demonstrated strong agreement between CACS PureCalcium and CACS TNC (60.7 ± 90.6 vs 67.3 ± 88.3, P = 0.01, r = 0.98, intraclass correlation [ICC] = 0.98; mean bias, 6.6; limits of agreement [LoA], -39.8/26.6), whereas CACS VNC showed a significant underestimation (42.4 ± 75.3 vs 67.3 ± 88.3, P < 0.001, r = 0.94, ICC = 0.89; mean bias, 24.9; LoA, -87.1/37.2). In vivo comparison confirmed a high correlation but revealed an underestimation of CACS PureCalcium (169.3 [0.7/969.4] vs 232.2 [26.5/1112.2], P < 0.001, r = 0.97, ICC = 0.98; mean bias, -113.5; LoA, -470.2/243.2). In comparison, CACS VNC showed a similarly high correlation, but a substantially larger underestimation (24.3 [0/272.3] vs 232.2 [26.5/1112.2], P < 0.001, r = 0.97, ICC = 0.54; mean bias, -551.6; LoA, -2037.5/934.4). CACS PureCalcium showed superior agreement of CACS classification ( κ = 0.88) than CACS VNC ( κ = 0.60). CONCLUSIONS: The accuracy of CACS quantification and classification based on PureCalcium reconstructions of CCTA outperforms CACS derived from VNC reconstructions.


Assuntos
Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana , Algoritmos , Cálcio , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Tomografia Computadorizada por Raios X/métodos
18.
Med Phys ; 38(12): 6469-82, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22149830

RESUMO

PURPOSE: Currently, only iodine- and barium-based contrast media (CM) are used in clinical contrast-enhanced computed tomography (CE-CT). High-Z metals would produce a higher contrast at equal mass density for the x-ray spectra used in clinical CT. Using such materials might allow for significant dose reductions in CE-CT. The purpose of this study was to quantify the potential for dose reduction when using CM based on heavy metals. METHODS: The contrast-to-noise ratio weighted by dose (CNRD) was determined as a function of scan protocol by means of measurements and simulations on a clinical CT scanner. For simulations, water cylinders with diameters 160, 320, 480, and 640 mm were used to cover a broad range of patient sizes. Measurements were conducted with 160 and 320 mm water-equivalent plastic cylinders. A central bore of 13 mm diameter was present in all phantoms. The tube voltage was varied from 80 to 140 kV for measurements and from 60 to 180 kV for simulations. Additional tin filtration of thicknesses 0.4, 0.8, and 1.2 mm was applied in the simulation to evaluate a range of spectral hardness. The bore was filled with a mixture of water and 10 mg/ml of pure iodine, holmium, gadolinium, ytterbium, osmium, tungsten, gold, and bismuth for the simulations and with aqueous solutions of ytterbium, tungsten, gold, and bismuth salts as well as Iopromid containing 10 mg/ml of the pure materials for the measurements. CNRDs were compared to iodine at phantom size-dependent reference voltages for all high-Z materials and the resulting dose reduction was calculated for equal contrast-to-noise ratio. RESULTS: Dose reduction potentials strongly depended on phantom size, spectral hardness, and tube voltage. Depending on the added filtration, a dose reduction of 19%-60% could be reached at 80 kV with gadolinium for the 160 mm phantom, 52%-69% at 100 kV with holmium for the 320 mm phantom, 62%-78% with 120 kV for hafnium and the 480 mm phantom and 74%-86% with 140 kV for gold and the 640 mm phantom. While gadolinium might be considered at 160 mm diameter, hafnium showed the best overall performance for phantom sizes of 320 mm and above. The measurements conducted on the clinical CT scanner showed very good agreement with simulations with deviations in the order of 5 to 10%. CONCLUSIONS: The results of this study encourage the development and use of CM based on high-Z materials, especially for adipose patients, where high tube voltages are necessary to reach sufficiently short scan times. Hafnium proved to be the best compromise for average-size and for adipose patients. Even higher-Z materials such as gold and bismuth showed a good overall performance in conjunction with high tube voltage, large patients or strong added filtration and may be recommended for scans under these conditions.


Assuntos
Aumento da Imagem/métodos , Metais , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste/química , Estudos de Viabilidade , Metais/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Invest Radiol ; 56(10): 614-620, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33787538

RESUMO

PURPOSE: The aim of this study was to assess the accuracy and impact of different sizes and tube voltages on bone mineral density (BMD) assessment using a computed tomography (CT) topogram acquired with photon-counting detector CT in an osteopenic ex vivo animal spine. MATERIALS AND METHODS: The lumbar back of a piglet was used to simulate osteopenia of the lumbar spine. Five fat layers (each with a thickness of 3 cm) were consecutively placed on top of the excised spine to emulate a total of 5 different sizes. Each size was repeatedly imaged on (A) a conventional dual-energy x-ray absorptiometry scanner as the reference standard, (B) a prototype photon-counting detector CT system at 120 kVp with energy thresholds at 20 and 70 keV, and (C) the same prototype system at 140 kVp with thresholds at 20 and 75 keV. Material-specific data were reconstructed from spectral topograms for B and C. Bone mineral density was measured for 3 lumbar vertebrae (L2-L4). A linear mixed-effects model was used to estimate the impact of vertebra, imaging setup, size, and their interaction term on BMD. RESULTS: The BMD of the lumbar spine corresponded to a T score in humans between -4.2 and -4.8, which is seen in osteoporosis. Averaged across the 3 vertebrae and 5 sizes, mean BMD was 0.56 ± 0.03, 0.55 ± 0.02, and 0.55 ± 0.02 g/cm2 for setup A, B, and C, respectively. There was no significant influence of imaging setup (P = 0.7), simulated size (P = 0.67), and their interaction term (both P > 0.2) on BMD. Bone mineral density decreased significantly from L2 to L4 for all 3 setups (all P < 0.0001). Bone mineral density was 0.59 ± 0.01, 0.57 ± 0.01, and 0.52 ± 0.02 g/cm2 for L2, L3, and L4, respectively, for setup A; 0.57 ± 0.02, 0.55 ± 0.01, and 0.53 ± 0.01 g/cm2 for setup B; and 0.57 ± 0.01, 0.55 ± 0.01, and 0.53 ± 0.01 g/cm2 for setup C. CONCLUSION: A single CT topogram acquired on photon-counting detector CT with 2 energy thresholds enabled BMD quantification with similar accuracy compared with dual-energy x-ray absorptiometry over a range of simulated sizes and tube voltages in an osteopenic ex vivo animal spine.


Assuntos
Densidade Óssea , Osteoporose , Absorciometria de Fóton , Animais , Humanos , Vértebras Lombares/diagnóstico por imagem , Suínos , Tomografia Computadorizada por Raios X
20.
Invest Radiol ; 56(9): 563-570, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33660630

RESUMO

PURPOSE: The aim of this study was to systematically evaluate the potential to combine investigational contrast media with spectrally optimized energy-thresholding of photon-counting detector computed tomography (PCCT) for subtraction of calcified plaques in a coronary artery stenosis phantom. METHODS: A small vessel phantom containing 3 fillable tubes (diameter, 3 mm each) with calcified plaques was placed into an anthropomorphic chest phantom. The plaques had incremental thicknesses ranging from 0.3 to 2.7 mm, simulating vessel stenoses ranging from 10% to 90% of the lumen diameter. The phantom was filled with 5 different investigational contrast media (iodine, bismuth, hafnium, holmium, and tungsten) at equal mass concentrations (15 mg/mL) and was imaged on a prototype PCCT at 140 kVp using optimized, contrast media-dependent energy thresholds. Contrast maps (CMs) were reconstructed for each contrast medium by applying a linear 2-material decomposition algorithm. Image noise magnitude and noise texture of CM were compared among the contrast media using the noise power spectrum. Two blinded readers independently rated the vessel lumen visualization on short-axis and the overall subjective image quality on long-axis CM relative to iodine as the reference standard. Four readers determined the highest degree of stenosis that could be assessed with high diagnostic confidence on long-axis CM. RESULTS: Average image noise on CM was lower for tungsten (49 HU) and hafnium (62 HU) and higher for bismuth (81 HU) and holmium (165 HU) compared with iodine (78 HU). Noise texture of CM was similar among the contrast media. Interreader agreement for vessel lumen visualization on short-axis CM ranged from moderate to excellent (k = 0.567-0.814). Compared with iodine, lumen visualization of each reader was improved using tungsten (P < 0.001 for both readers), similar to improved using hafnium (P = 0.008, P = 0.29), similar using bismuth (P = 0.38, P = 0.69), and decreased using holmium (both, P < 0.001). Overall subjective image quality was similar for holmium and superior for tungsten, hafnium, and bismuth as compared with iodine. Higher-degree stenoses were evaluable with high confidence using tungsten (mean, 70%; interquartile range, 70%-70%), bismuth (70%; 60%-70%), and hafnium (75%; 70%-80%) compared with iodine (50%; 50%-60%) and holmium (50%; 50%-60%). CONCLUSIONS: Spectral optimization in PCCT combined with investigational contrast media can improve calcium subtraction and stenosis assessment in small vessels. Contrast maps of tungsten and, to a lesser extent, hafnium as contrast media yielded superior image noise properties and improved vessel lumen visualization, along with a higher subjective image quality compared with the reference standard iodine.


Assuntos
Meios de Contraste , Iodo , Constrição Patológica , Humanos , Imagens de Fantasmas , Fótons , Tomografia Computadorizada por Raios X
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