Artículos de revistas: "Postmortem micro-CT"

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de Crespigny, Alex, Hani Bou-Reslan, Merry C. Nishimura, Heidi Phillips, Richard A. D. Carano y Helen E. D’Arceuil. "3D micro-CT imaging of the postmortem brain". Journal of Neuroscience Methods 171, n.º 2 (junio de 2008): 207–13. http://dx.doi.org/10.1016/j.jneumeth.2008.03.006.

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Dawood, Y., G. J. Strijkers, J. Limpens, R. J. Oostra y B. S. de Bakker. "Novel imaging techniques to study postmortem human fetal anatomy: a systematic review on microfocus-CT and ultra-high-field MRI". European Radiology 30, n.º 4 (13 de diciembre de 2019): 2280–92. http://dx.doi.org/10.1007/s00330-019-06543-8.

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Abstract Background MRI and CT have been extensively used to study fetal anatomy for research and diagnostic purposes, enabling minimally invasive autopsy and giving insight in human fetal development. Novel (contrast-enhanced) microfocus CT (micro-CT) and ultra-high-field (≥ 7.0 T) MRI (UHF-MRI) techniques now enable micron-level resolution that combats the disadvantages of low-field MRI and conventional CT. Thereby, they might be suitable to study fetal anatomy in high detail and, in time, contribute to the postmortem diagnosis of fetal conditions. Objectives (1) To systematically examine the usability of micro-CT and UHF-MRI to study postmortem human fetal anatomy, and (2) to analyze factors that govern success at each step of the specimen preparation and imaging. Method MEDLINE and EMBASE were systematically searched to identify publications on fetal imaging by micro-CT or UHF-MRI. Scanning protocols were summarized and best practices concerning specimen preparation and imaging were enumerated. Results Thirty-two publications reporting on micro-CT and UHF-MRI were included. The majority of the publications focused on imaging organs separately and seven publications focused on whole body imaging, demonstrating the possibility of visualization of small anatomical structures with a resolution well below 100 μm. When imaging soft tissues by micro-CT, the fetus should be stained by immersion in Lugol’s staining solution. Conclusion Micro-CT and UHF-MRI are both excellent imaging techniques to provide detailed images of gross anatomy of human fetuses. The present study offers an overview of the current best practices when using micro-CT and/or UHF-MRI to study fetal anatomy for clinical and research purposes. Key Points • Micro-CT and UHF-MRI can both be used to study postmortem human fetal anatomy for clinical and research purposes. • Micro-CT enables high-resolution imaging of fetal specimens in relatively short scanning time. However, tissue staining using a contrast solution is necessary to enable soft-tissue visualization. • UHF-MRI enables high-resolution imaging of fetal specimens, without the necessity of prior staining, but with the drawback of long scanning time.

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Sandrini, Camilla, Simona Boito, Claudio M. Lombardi y Sophie Lombardi. "Postmortem Micro-CT of Human Fetal Heart—A Systematic Literature Review". Journal of Clinical Medicine 10, n.º 20 (15 de octubre de 2021): 4726. http://dx.doi.org/10.3390/jcm10204726.

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Micro-computed tomography (CT) is a non-invasive alternative to conventional macroscopic dissection for the evaluation of human fetal cardiac anatomy. This paper aims to systematically review the literature regarding the use of micro-CT to examine human fetal hearts, to illustrate its educational and research implications and to explain its possible directions for the future. A systematic literature review was conducted following the PRISMA statement to identify publications concerning micro-CT applications for the isolated human fetal heart. The search strategy identified nine eligible studies. Micro-CT is technically feasible for postmortem examination of the human fetal heart coming from early and late termination of pregnancy. It reaches high diagnostic accuracy, and it seems to perform better than autopsy in small samples or in the case of early termination of pregnancy. Applications derived from micro-CT allow multiple off-time evaluations and interdisciplinary comparisons for educational purposes and research perspectives in biological and bioengineering domains.

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Lombardi, C. M., V. Zambelli, G. Botta, G. Cattoretti, V. Fesslova, F. Moltrasio, S. Lombardi y S. Cuttin. "OP22.06: Postmortem micro-computed tomography (micro-CT) of small fetuses and hearts". Ultrasound in Obstetrics & Gynecology 44, S1 (septiembre de 2014): 165. http://dx.doi.org/10.1002/uog.13851.

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Lombardi, C. M., V. Zambelli, G. Botta, F. Moltrasio, G. Cattoretti, V. Lucchini, V. Fesslova y M. S. Cuttin. "Postmortem microcomputed tomography (micro-CT) of small fetuses and hearts". Ultrasound in Obstetrics & Gynecology 44, n.º 5 (13 de octubre de 2014): 600–609. http://dx.doi.org/10.1002/uog.13330.

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Foerst, Jason, Timothy Ball y Aaron V. Kaplan. "Postmortem in situ micro-ct evaluation of coronary stent fracture". Catheterization and Cardiovascular Interventions 76, n.º 4 (23 de febrero de 2010): 527–31. http://dx.doi.org/10.1002/ccd.22498.

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Shelmerdine, S. C., M. Singh, I. C. Simcock, A. D. Calder, M. Ashworth, A. Beleza, N. J. Sebire y O. J. Arthurs. "Characterization of Bardet–Biedl syndrome by postmortem microfocus computed tomography (micro‐CT)". Ultrasound in Obstetrics & Gynecology 53, n.º 1 (enero de 2019): 132–34. http://dx.doi.org/10.1002/uog.19190.

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Vande Velde, Greetje, Ellen De Langhe, Jennifer Poelmans, Peter Bruyndonckx, Emiliano d'Agostino, Erik Verbeken, Ria Bogaerts, Rik Lories y Uwe Himmelreich. "Longitudinal in vivo microcomputed tomography of mouse lungs: No evidence for radiotoxicity". American Journal of Physiology-Lung Cellular and Molecular Physiology 309, n.º 3 (1 de agosto de 2015): L271—L279. http://dx.doi.org/10.1152/ajplung.00098.2015.

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Before microcomputed tomography (micro-CT) can be exploited to its full potential for longitudinal monitoring of transgenic and experimental mouse models of lung diseases, radiotoxic side effects such as inflammation or fibrosis must be considered. We evaluated dose and potential radiotoxicity to the lungs for long-term respiratory-gated high-resolution micro-CT protocols. Free-breathing C57Bl/6 mice underwent four different retrospectively respiratory gated micro-CT imaging schedules of repeated scans during 5 or 12 wk, followed by ex vivo micro-CT and detailed histological and biochemical assessment of lung damage. Radiation exposure, dose, and absorbed dose were determined by ionization chamber, thermoluminescent dosimeter measurements and Monte Carlo calculations. Despite the relatively large radiation dose delivered per micro-CT acquisition, mice did not show any signs of radiation-induced lung damage or fibrosis when scanned weekly during 5 and up to 12 wk. Doubling the scanning frequency and once tripling the radiation dose as to mimic the instant repetition of a failed scan also stayed without detectable toxicity after 5 wk of scanning. Histological analyses confirmed the absence of radiotoxic damage to the lungs, thereby demonstrating that long-term monitoring of mouse lungs using high-resolution micro-CT is safe. This opens perspectives for longitudinal monitoring of (transgenic) mouse models of lung diseases and therapeutic response on an individual basis with high spatial and temporal resolution, without concerns for radiation toxicity that could potentially influence the readout of micro-CT-derived lung biomarkers. This work further supports the introduction of micro-CT for routine use in the preclinical pulmonary research field where postmortem histological approaches are still the gold standard.

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Tekus, Eva, Alexandra Miko, Nora Furedi, Ildiko Rostas, Judit Tenk, Tamas Kiss, Istvan Szitter et al. "Body fat of rats of different age groups and nutritional states: assessment by micro-CT and skinfold thickness". Journal of Applied Physiology 124, n.º 2 (1 de febrero de 2018): 268–75. http://dx.doi.org/10.1152/japplphysiol.00884.2016.

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Obesity presents a growing public health problem. Therefore the analysis of body composition is important in clinical practice as well as in animal research models of obesity; hence precise methods for the assessment of body fat would be essential. We aimed to evaluate in vivo abdominal microcomputed tomography scan restricted to the L1–L3 region [micro-CT(L1–L3)], a skinfold thickness-based method (STM), and postmortem body composition analysis (PMA) with regard to whole body micro-CT scan in rats. Male Wistar rats of different age groups (from 3 to 24 mo) and nutritional states (normally fed, high-fat diet-induced obese, and calorie-restricted) were used. The fat percentage was determined with micro-CT(L1–L3) and whole body scan in anesthetized rats. Their skinfold thickness was measured in five locations with a Lange caliper. Wet weights of epididymal and retroperitoneal fat pads were determined via PMA. With regard to fat mass, the strongest correlation was observed between abdominal and whole body micro-CT. The other methods showed weaker associations with whole body micro-CT and with each other. Micro-CT(L1–L3) and PMA showed similar age-associated increase in fat mass between 3 and 18 mo. Micro-CT(L1–L3), STM, and PMA were efficient to detect differences in fat mass values in groups of different nutritional states. Micro-CT(L1–L3) appears to be a useful method for body fat assessment in rats with reduced scanning time. In rats, STM may also be a useful, low priced, noninvasive, and simple in vivo technique to assess obesity. NEW & NOTEWORTHY Body fat of rats assessed by in vivo abdominal microcomputed tomography of the L1–L3 region strongly correlates with values determined by whole body scan. Therefore, it is a useful method for fat assessment with reduced scanning time. Skinfold thickness measurement is an in vivo technique to assess progression of obesity in rats.

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Lupariello, Francesco, Tullio Genova, Federico Mussano, Giancarlo Di Vella y Giovanni Botta. "Micro-CT to study and reconstruct fetal and infant coronary arteries: a pilot study on a novel post-mortem technique". European Journal of Anatomy 26, n.º 4 (julio de 2022): 443–47. http://dx.doi.org/10.52083/fcws3396.

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For a significant part of infant and fetal deaths, specific pathophysiologic processes cannot be recognized. Thus, the scientific community is called to identify novel post-mortem diagnostic tools. This manuscript proposes the results of a pilot study which reports a novel post-mortem technique to study and reconstruct fetal/ infant coronary arteries. The study included human fetuses characterized by the absence of macroscopic cardiac abnormalities at postmortem in situ examination. For the study of fetal hearts, it was used a curing radiopaque silicone rubber compound (which solidified after injection in the coronary arteries) and an X-Ray microtomography (micro-CT). After micro- CT scans, coronary arteries’ branches were reconstructed throughout a specific software. At injection, it was possible to macroscopically evaluate coronary arteries’ perfusion. The analysis of the three-dimensional reconstructions highlighted that the aforementioned compound reached deep branches too. This approach can be considered a novel post-mortem technique for fetal/infant hearts. Nevertheless, the manuscript also discussed the following limitations: in some spots, coronary arteries’ reconstruction appeared interrupted; the compound also perfused parts of internal cardiac chambers. Until now, in the literature there are not methods that allow study with reconstruction of fetal/infant coronary arteries throughout micro-CT. The present paper pointed out the first indications for the application of this technique in human samples.

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Counter, W. B., I. Q. Wang, T. H. Farncombe y N. R. Labiris. "Airway and pulmonary vascular measurements using contrast-enhanced micro-CT in rodents". American Journal of Physiology-Lung Cellular and Molecular Physiology 304, n.º 12 (15 de junio de 2013): L831—L843. http://dx.doi.org/10.1152/ajplung.00281.2012.

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Preclinical imaging allows pulmonary researchers to study lung disease and pulmonary drug delivery noninvasively and longitudinally in small animals. However, anatomically localizing a pathology or drug deposition to a particular lung region is not easily done. Thus, a detailed knowledge of the anatomical structure of small animal lungs is necessary for understanding disease progression and in addition would facilitate the analysis of the imaging data, mapping drug deposition and relating function to structure. In this study, contrast-enhanced micro-computed tomography (CT) of the lung produced high-resolution images that allowed for the characterization of the rodent airway and pulmonary vasculature. Contrast-enhanced micro-CT was used to visualize the airways and pulmonary vasculature in Sprague-Dawley rats (200–225 g) and BALB/c mice (20–25 g) postmortem. Segmented volumes from these images were processed to yield automated measurements of the airways and pulmonary vasculature. The diameters, lengths, and branching angles of the airway, arterial, and venous trees were measured and analyzed as a function of generation number and vessel diameter to establish rules that could be applied at all levels of tree hierarchy. In the rat, airway, arterial, and venous tress were measured down to the 20th, 16th, and 14th generation, respectively. In the mouse, airway, arterial, and venous trees were measured down to the 16th, 8th, and 7th generation, respectively. This structural information, catalogued in a rodent database, will increase our understanding of lung structure and will aid in future studies of the relationship between structure and function in animal models of disease.

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Tse, Justin J., P. Joy Dunmore-Buyze, Maria Drangova y David W. Holdsworth. "Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging". Contrast Media & Molecular Imaging 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/7368384.

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Micro-computed tomography (micro-CT) facilitates the visualization and quantification of contrast-enhanced microvessels within intact tissue specimens, but conventional preclinical vascular contrast agents may be inadequate near dense tissue (such as bone). Typical lead-based contrast agents do not exhibit optimal X-ray absorption properties when used with X-ray tube potentials below 90 kilo-electron volts (keV). We have developed a high-atomic number lanthanide (erbium) contrast agent, with a K-edge at 57.5 keV. This approach optimizes X-ray absorption in the output spectral band of conventional microfocal spot X-ray tubes. Erbium oxide nanoparticles (nominal diameter < 50 nm) suspended in a two-part silicone elastomer produce a perfusable fluid with viscosity of 19.2 mPa-s. Ultrasonic cavitation was used to reduce aggregate sizes to <70 nm. Postmortem intact mice were perfused to investigate the efficacy of contrast agent. The observed vessel contrast was >4000 Hounsfield units, and perfusion of vessels < 10 μm in diameter was demonstrated in kidney glomeruli. The described new contrast agent facilitated the visualization and quantification of vessel density and microarchitecture, even adjacent to dense bone. Erbium’s K-edge makes this contrast agent ideally suited for both single- and dual-energy micro-CT, expanding potential preclinical research applications in models of musculoskeletal, oncological, cardiovascular, and neurovascular diseases.

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Hadden, William J., Mazen Ibrahim, Mariam Taha, Kerstin Ure, Yun Liu, Adam D. M. Paish, David W. Holdsworth y Hesham Abdelbary. "2021 Frank Stinchfield Award: A novel cemented hip hemiarthroplasty infection model with real-time in vivo imaging in rats". Bone & Joint Journal 103-B, n.º 7 Supple B (1 de julio de 2021): 9–16. http://dx.doi.org/10.1302/0301-620x.103b7.bjj-2020-2435.r1.

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Aims The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16.

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Malyar, Nasser M., Mario Gössl, Patricia E. Beighley y Erik L. Ritman. "Relationship between arterial diameter and perfused tissue volume in myocardial microcirculation: a micro-CT-based analysis". American Journal of Physiology-Heart and Circulatory Physiology 286, n.º 6 (junio de 2004): H2386—H2392. http://dx.doi.org/10.1152/ajpheart.00682.2003.

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The volume of myocardial tissue that is perfused by an epicardial coronary artery has been shown to be predictably related to the diameter of the epicardial arterial lumen. However, to what extent the intramyocardial microvasculature follows the epicardial rules remains unclear. To explore the relationship between the diameter of coronary arterioles and their subsequent perfused myocardial volumes, we quantified the volume of nonperfused myocardium resulting from an embolized arteriole of a certain diameter. We injected a single dose of microspheres selected from one of nine possible microsphere combinations (10, 30, and 100 μm diameter, each at three possible doses) into the left anterior descending coronary and/or left circumflex arteries of seven anesthetized pigs. At postmortem, the coronary arteries were infused with a radiopaque silicon polymer. Embolized myocardium (1 cm3) was scanned with a microcomputerized tomography scanner and resulted in three-dimensional images that consisted of 20 μm/side cubic voxels and a subvolume of the specimen with 4 μm/side cubic voxels. Image analysis provided the number and volumes of myocardial perfusion defects for each size and dose of microspheres. The smallest individual myocardial perfusion defects, which correspond to the volume of myocardium perfused by a single embolized arteriole, were found to be 0.0004 ± 0.0002, 0.02 ± 0.004, and 0.62 ± 0.099 mm3 for the 10-, 30-, and 100-μm microspheres, respectively. The number of myocardial perfusion defects in the embolized myocardium was inversely related to the dose of the injected microspheres. This reflects a clustering behavior that is consistent with a random distribution process of the individual embolized perfusion defects.

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Odekerken, Jim C. E., Geert H. I. M. Walenkamp, Boudewijn T. Brans, Tim J. M. Welting y Jacobus J. C. Arts. "The Longitudinal Assessment of Osteomyelitis Development by Molecular Imaging in a Rabbit Model". BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/424652.

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Introduction. Osteomyelitis is a severe orthopaedic complication which is difficult to diagnose and treat. Previous experimental studies mainly focussed on evaluating osteomyelitis in the presence of an implant or used a sclerosing agent to promote infection onset. In contrast, we focused on the longitudinal assessment of a nonimplant related osteomyelitis.Methods. An intramedullary tibial infection withS. aureuswas established in NZW rabbits. Clinical and haematological infection status was evaluated weekly, combined with X-ray radiographs, biweekly injections of calcium binding fluorophores, and postmortem micro-CT. The development of the infection was assessed by micro-PET at consecutive time points using18F-FDG as an infection tracer.Results. The intramedullary contamination of the rabbit tibia resulted in an osteomyelitis. Haematological parameters confirmed infection in mainly the first postoperative weeks (CRP at the first 5 postoperative weeks, leucocyte differentiation at the second and sixth postoperative weeks, and ESR on the second postoperative week only), while micro-PET was able to detect the infection from the first post-operative week onward until the end of the study.Conclusions. This study shows that osteomyelitis in the rabbit can be induced without use of an implant or sclerosing agent. The sequential follow-up indicates that the diagnostic value of each infection parameter is time point dependant. Furthermore, from all parameters used, the diagnostic value of 18F-FDG micro-PET is the most versatile to assess the presence of an orthopaedic infection in this model.

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Sandrini, C., C. M. Lombardi, V. Zambelli, R. Zanarotti, R. Raffaelli, M. P. Franchi, N. Papadopoulos et al. "What can we learn from systematic segmental analysis of fetal heart by postmortem micro-CT: Is it time to change approach?" International Journal of Cardiology Congenital Heart Disease 7 (marzo de 2022): 100308. http://dx.doi.org/10.1016/j.ijcchd.2021.100308.

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Barbone, Giacomo E., Alberto Bravin, Alberto Mittone, Sergio Grosu, Jens Ricke, Guido Cavaletti, Valentin Djonov y Paola Coan. "High-Spatial-Resolution Three-dimensional Imaging of Human Spinal Cord and Column Anatomy with Postmortem X-ray Phase-Contrast Micro-CT". Radiology 298, n.º 1 (enero de 2021): 135–46. http://dx.doi.org/10.1148/radiol.2020201622.

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Akbulut, Nihat, Selçuk Çetin, Burak Bilecenoğlu, Ahmet Altan, Mert Ocak, Esengül Şen, Cemal Atakan y Kaan Orhan. "Evaluation of the detectability of early mandible fracture healing findings in terms of vitality aspect by using micro-CT technology in postmortem interval". Legal Medicine 52 (septiembre de 2021): 101914. http://dx.doi.org/10.1016/j.legalmed.2021.101914.

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Akbulut, Nihat, Selçuk Çetin, Burak Bilecenoğlu, Ahmet Altan, Sibel Akbulut, Mert Ocak y Kaan Orhan. "The micro-CT evaluation of enamel-cement thickness, abrasion, and mineral density in teeth in the postmortem interval (PMI): new parameters for the determination of PMI". International Journal of Legal Medicine 134, n.º 2 (3 de julio de 2019): 645–53. http://dx.doi.org/10.1007/s00414-019-02104-2.

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Li, Guanwu, Zheng Xu, Lingmi Hou, Xuefeng Li, Xin Li, Wei Yuan, Maki Polat y Shixin Chang. "Differential effects of bisphenol A diglicydyl ether on bone quality and marrow adiposity in ovary-intact and ovariectomized rats". American Journal of Physiology-Endocrinology and Metabolism 311, n.º 6 (1 de diciembre de 2016): E922—E927. http://dx.doi.org/10.1152/ajpendo.00267.2016.

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Bisphenol A diglycidyl ether (BADGE), a PPARγ2 antagonist, has been shown to inhibit marrow adipogenesis and promote bone formation in intact animals. We investigated the impact of BADGE on a new and more clinically relevant physiological model, the ovariectomized (OVX) rat model. Forty female Wistar rats were divided into four treatment groups for 12 wk ( n = 10/group): sham+vehicle, sham+BADGE, OVX+vehicle, and OVX+BADGE. Postmortem analyses included MRI, micro-CT, serological test, histomorphometry, biomechanical tests, RT-PCR, and Western blot. Overall, OVX induced a sequential marrow fat expansion accompanied by bone deterioration. Compared with OVX controls, BADGE reduced fat fraction of the distal femur by 36.3%, adipocyte density by 33.0%, adipocyte size by 28.6%, adipocyte volume percentage by 57.8%, and adipogenic markers PPARγ2 and C/EBPα by ∼50% in OVX rats. Similar results were observed in sham rats vs. vehicle. BADGE could promote bone quality in sham rats; however, BADGE did not significantly improve trabecular microarchitecture, biomechanical strength, and dynamic histomorphometric parameters except for trabecular separation in OVX rats. We concluded that early BADGE treatment at a dose of 30 mg/kg attenuates marrow adiposity in ovary-intact and OVX rats and stimulates bone formation in ovary-intact rats but does not significantly rescue bone quality in OVX rats.

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Lee, Jungwon, Yong-Moo Lee, Young-Jun Lim y Bongju Kim. "Ridge Augmentation Using β-Tricalcium Phosphate and Biphasic Calcium Phosphate Sphere with Collagen Membrane in Chronic Pathologic Extraction Sockets with Dehiscence Defect: A Pilot Study in Beagle Dogs". Materials 13, n.º 6 (23 de marzo de 2020): 1452. http://dx.doi.org/10.3390/ma13061452.

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This study was conducted to comparatively examine spontaneous healing versus ridge augmentation, in surgically-created dehiscence defects, associated with chronic pathology in dogs. Mandibular second, third and fourth premolars (P2, P3 and P4) were hemi-sectioned, and a dehiscence defect was created at the mesial root, while a groove was made on the buccal area from the top of the teeth to the bottom of the defect, exposing the dental pulp. The mesial roots of P2, P3 and P4 were extracted 1 month after the induction of the dehiscence defect with chronic pathology. Three teeth were randomly allocated to these experimental groups: (i) spontaneous healing without any bone graft (Control group: C); (ii) ridge augmentation with β-tricalcium phosphate (β-TCP) granules (Test 1 group: T1); and (iii) ridge augmentation with 60% hydroxyapatite (HA) and 40% β-TCP microspheres (Test 2 group: T2). Postmortem histopathologic examination showed significant between-group differences in C and T1 and C and T2 in bone volume/tissue volume in qualitative micro-computed tomography (CT) analysis, as well as significant intergroup differences in the coronal area at 4 and 12 weeks. The composition of connective tissue and mineralized bone in C and T1 were higher than in T2 at 4 weeks of healing, whereas the composition of mineralized bone was higher in T2 than in T1 at 12 weeks of healing. Biphasic calcium phosphate, composed of 60% HA and 40% β-TCP microsphere (i) potentially prevented marked osteoclastic resorption and (ii) promoted ridge preservation in the extraction socket with the dehiscence defect and chronic pathology.

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Mehdi, Syed, Maurizio Zangari y Donghoon Yong. "An Improved Animal Model of Multiple Myeloma Bone Disease". Blood 136, Supplement 1 (5 de noviembre de 2020): 31. http://dx.doi.org/10.1182/blood-2020-142928.

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Multiple myeloma (MM) is a plasma cell malignancy that represents an accumulation of terminally differentiated monoclonal plasma cells (PCs) in the bone marrow (BM), accompanied by increased osteoclasts and decreased osteoblasts in areas adjacent to myeloma cells, leading to MM associated bone disease (MMBD). Osteolytic bone disease is one of the defining features of MM. During the disease, over 90% of patients are developing MMBD. Many of MM animal models have been developed and enable us to interrogate the mechanisms of MM tumorigenesis. Most MMBD models were derived by intratibial injection of myeloma cells. In these models, osteolysis occurs locally at the site where myeloma cells were injected. Mouse myeloma cells, 5TGM1 transplanting C57BL/KaLwRij mouse via the tail vein develops and shows MMBD features close to human MMBD. Even in this model, the MMBD levels on each mouse are widely varied. Lack of appropriate in vivo MMBD model hampers our understanding of the disease and developing therapy. We try to establish a murine model for MMBD to study its pathophysiology and test a novel treatment. 1x106 luciferase-expressing 5TGM1 (5TGM1-Luc) cells were injected into 8-12 week old NOD SCID gamma mouse (NSG) and C57BL/KaLwRij mouse via the tail vein. Myeloma progression was weekly assessed by in vivo bioluminescence (BL) imaging using IVIS-200 (Perkin Elmer). Mice were sacrificed when they showed endpoint signals such as significant weight loss, hindlimb paralysis, etc.. At postmortem, the micro-computer tomography (micro-CT) was performed for bone histo-morphometric analyses using micro CT400, Scano medical, Inc. The median survival was 56 days in NSG, while 42 days in C57BL/KaLwRij. In vivo BL image analysis showed that myeloma slowly develops in NSG mouse in comparison to C57BL/KaLwRij mouse. Histomorphic analyses found that severe osteolytic lesions occur at the lumbar spine in NSG mouse compared to C57BL/KaLwRij mouse, but no significant difference at the femur of both strains. At the lumbar spine, trabecular thickness (p < 0.0004) and trabecular space (p < 0.0014) were significantly increased in NSG mouse compared to C57BL/KaLwRij mouse. On the contrary, trabecular number (p < 0.0002) and bone volume density (p < 0.0005) were significantly decreased in NSG mouse compared to C57BL/KaLwRij mouse. In conclusion, we found that the systemic 5TGM1 injected NSG mouse slowly progresses myeloma and develops more severe MMBD than C57BL/KaLwRij model. This model will serve a better MMBD model to evaluate the therapeutic effects of MMBD targeted drugs. Disclosures No relevant conflicts of interest to declare.

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Morris, Carol A., Syed Mehdi, Jenat Rahman, Pamela Rosales, Sun-Ok Lee, Dam Huh y Donghoon Yoon. "Herbal Extracts from Lycii Radicis Corex and Achyranthes japonica Prevent Multiple Myeloma". Blood 138, Supplement 1 (5 de noviembre de 2021): 4918. http://dx.doi.org/10.1182/blood-2021-153673.

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Abstract Introduction Multiple Myeloma (MM) is a plasma cell malignancy that, despite advances in treatment, remains incurable. In over 90% of MM patients, aberrant bone remodeling occurs and results in osteolytic lesions. It severely reduces the patient's quality of life and increases mortality. Korean traditional medicine has a long-standing interest in healthy foods to enhance the immune system, energy-boost, and Yin-and-Yang balance. A healthy diet in Tradition medicine is based on accumulated observations from countless cases over multi-centuries. Traditional medicine has used herbal extracts (HE) from natural plants with fewer side effects and long-term treatment tolerance. In earlier studies, lycii radices cortex (LRC) and achyranthes japonica (AJ) containing herbal extracts (HE) have demonstrated the ability to enhance cell growth and mineralization of osteoblast cells while also inhibiting osteoclast differentiation. Furthermore, a sesquiterpene glucoside, (1'R,3'S,5'R,8'S,2 Z,4 E)-dihydrophaseic acid 3'-O-β-d-glucopyranoside (DPA3G) were isolated from the LRC ethanol extract and shown to be a bioactive compound for enhancement of cell growth and bone anabolic activity (Park et al). The current study investigated the effects of LRC+AJ containing HE on murine 5TGM1 MM-bearing mice. Methods We transplanted 1x10 6 cells of the enforced luciferase-expressing 5TGM1 (5TGM1-Luc) into 8~12-week-old Nod-Scid-IL2Rg null (NSG) mice via tail vein (representing an equal number of each sex). For LRC+AJ containing HE treatment, mice were divided into three groups; i) PBS group; ii) treatment group at 300 mg/kg, gavage, TIW started two weeks before MM transplant (TbT); and iii) treatment group at 300 mg/kg, gavage, TIW two weeks after MM transplant (TaT). We assessed tumor burden by weekly bioluminescence imaging (IVIS 200 Imager, Perkin Elmer). The spine was extracted from carcass and scanned at postmortem by Dual Energy X-ray Absorptiometry using PIXImus Densitometer (G.E. Lunar, Madison, USA) and micro-computed tomography (microCT; Scanco Medical AG, Switzerland). HE effects in cell growth were tested in the myeloma cells (5TGM1 and U266) and preosteoblast cells (MC3T3-E1). The cells were grown in various concentrations (8, 80, 800 ug/ml) of HE up to 96 hours. In addition, Chromatogram and Mass Spectrometry were conducted to identify the DPA3G. Results As shown in Figure 1A, this HE significantly increased the mouse survivals of both TbT and TaT groups with median survivals of undetermined and 52.5 days, respectively, while MM control had a median survival of 42 days. The Mantel-Cox test found that TbT and TaT mice were significantly different from the control group (P=0.0014 and 0.0182, respectively). Furthermore, DEXA scans at postmortem showed a significant increase in bone mineral density (BMD) and bone mineral content (BMC) in TbT and TaT groups than control MM mice. For a histomorphometry analysis, the spines were scanned by micro-CT and revealed that TbT and TaT groups had significantly increased bone volume over total volume (BV/TV) than control. To see if HE affects cell growth of myeloma cells and osteoblast cells, we further investigated the HE on preosteoblast cell line MC3T3-E1, mouse MM cell line 5TGM1-Luc, and human MM cell line U-266. Cells were treated with HE in various concentrations, and viability was assessed at 48 and 96 hours post-treatment. Remarkably, LRC+AJ containing HE increased MC3T3-E1 cell growth while it decreased 5TGM1 and U-266 cell viability. We identified the DAP3G and many other compounds in HE used in this study. Conclusions Our results demonstrated that LRC+AJ HE prevents MM and promotes bone formation in 5TGM1 engrafted NSG mice. We also found that LRC+AJ HE suppresses myeloma cell growth and enhances osteoblast cell survival. Although it is yet to be defined, a correlation of osteoblast activity and myeloma cell inhibition suggests a potential mechanism of the HE action to prevent MM progression. 1. Park E, Kim J, Yeo S, Lim E, Choi CW, Choi S, Li WY, Lee JW, Park JH, Huh D, Jeong SY. Anti-Osteoporotic Effects of Combined Extract of Lycii Radicis Cortexand Achyranthes japonica in Osteoblast and Osteoclast Cells and Ovariectomized Mice. Nutrients. 2019 Nov 9;11(11):2716. doi: 10.3390/nu11112716. PMID: 31717518; PMCID: PMC6893723.' Figure 1 Figure 1. Disclosures Huh: Dongwoodang Pharmacy Company: Current Employment. OffLabel Disclosure: Herbal Extracts from Lycii Radicis Corex and Achyranthes Japonica

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Docter, Daniël, Yousif Dawood, Karl Jacobs, Jaco Hagoort, Roelof-Jan Oostra, Maurice J. B. van den Hoff, Owen J. Arthurs y Bernadette S. de Bakker. "Microfocus computed tomography for fetal postmortem imaging: an overview". Pediatric Radiology, 28 de septiembre de 2022. http://dx.doi.org/10.1007/s00247-022-05517-1.

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AbstractOver the last few years, fetal postmortem microfocus computed tomography (micro-CT) imaging has increased in popularity for both diagnostic and research purposes. Micro-CT imaging could be a substitute for autopsy, particularly in very early gestation fetuses for whom autopsy can be technically challenging and is often unaccepted by parents. This article provides an overview of the latest research in fetal postmortem micro-CT imaging with a focus on diagnostic accuracy, endovascular staining approaches, placental studies and the reversibility of staining. It also discusses new methods that could prove helpful for micro-CT of larger fetuses. While more research is needed, contrast-enhanced micro-CT has the potential to become a suitable alternative to fetal autopsy. Further research using this novel imaging tool could yield wider applications, such as its practise in imaging rare museum specimens.

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Ortega-Gil, Ana, Juan José Vaquero, Mario Gonzalez-Arjona, Joaquín Rullas y Arrate Muñoz-Barrutia. "X-ray-based virtual slicing of TB-infected lungs". Scientific Reports 9, n.º 1 (diciembre de 2019). http://dx.doi.org/10.1038/s41598-019-55986-y.

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AbstractHollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray–based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases.

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Barbone, Giacomo E., Alberto Bravin, Alberto Mittone, Alexandra Pacureanu, Giada Mascio, Paola Di Pietro, Markus J. Kraiger et al. "X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer’s disease". European Journal of Nuclear Medicine and Molecular Imaging, 19 de julio de 2022. http://dx.doi.org/10.1007/s00259-022-05896-5.

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Abstract Purpose Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease. Methods We report the postmortem application of multiscale X-ray phase-contrast computed tomography (X-PCI-CT) for the label-free and dissection-free organ-level to intracellular-level 3D visualization of distinct single neurons and glia. In deep neuronal populations in the brain of aged wild-type and of 3xTgAD mice (a triply-transgenic model of Alzheimer’s disease), we quantified intracellular hyperdensity, a manifestation of aging or neurodegeneration. Results In 3xTgAD mice, the observed hyperdensity was identified as amyloid-β and hyper-phosphorylated tau protein deposits with calcium and iron involvement, by correlating the X-PCI-CT data to immunohistochemistry, X-ray fluorescence microscopy, high-field MRI, and TEM. As a proof-of-concept, X-PCI-CT was used to analyze hippocampal and cortical brain regions of 3xTgAD mice treated with LY379268, selective agonist of group II metabotropic glutamate receptors (mGlu2/3 receptors). Chronic pharmacologic activation of mGlu2/3 receptors significantly reduced the hyperdensity particle load in the ventral cortical regions of 3xTgAD mice, suggesting a neuroprotective effect with locoregional efficacy. Conclusions This multiscale micro-to-nano 3D imaging method based on X-PCI-CT enabled identification and quantification of cellular and sub-cellular aging and neurodegeneration in deep neuronal and glial cell populations in a transgenic model of Alzheimer’s disease. This approach quantified the localized and intracellular neuroprotective effects of pharmacological activation of mGlu2/3 receptors.

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Keiler, Jonas, Felix G. Meinel, Jasmin Ortak, Marc-André Weber, Andreas Wree y Felix Streckenbach. "Morphometric Characterization of Human Coronary Veins and Subvenous Epicardial Adipose Tissue—Implications for Cardiac Resynchronization Therapy Leads". Frontiers in Cardiovascular Medicine 7 (8 de diciembre de 2020). http://dx.doi.org/10.3389/fcvm.2020.611160.

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Subvenous epicardial fat tissue (SEAT), which acts as an electrical insulation, and the venous diameter (VD) both constitute histomorphological challenges for optimal application and lead design in cardiac synchronization therapy (CRT). In this study, we characterized the morphology of human coronary veins to improve the technical design of future CRT systems and to optimize the application of CRT leads. We retrospectively analyzed data from cardiac computed tomography (CT) of 53 patients and did studies of 14 human hearts using the postmortem freeze section technique and micro CT. Morphometric parameters (tributary distances, offspring angles, luminal VD, and SEAT thickness) were assessed. The left posterior ventricular vein (VVSP) had a mean proximal VD of 4.0 ± 1.4 mm, the left marginal vein (VMS) of 3.2 ± 1.5 mm and the anterior interventricular vein (VIA) of 3.9 ± 1.3 mm. More distally (5 cm), VDs decreased to 2.4 ± 0.6 mm, 2.3 ± 0.7 mm, and 2.4 ± 0.6 mm, respectively. In their proximal portions (15 mm), veins possessed mean SEAT thicknesses of 3.2 ± 2.4 (VVSP), 3.4 ± 2.4 mm (VMS), and 4.2 ± 2.8 mm (VIA), respectively. More distally (20–70 mm), mean SEAT thicknesses decreased to alternating low levels of 1.3 ± 1.1 mm (VVSP), 1.7 ± 1.1 mm (VMS), and 4.3 ± 2.6 mm (VIA), respectively. In contrast to the VD, SEAT thicknesses alternated along the further distal vein course and did not display a continuous decrease. Besides the CRT responsiveness of different areas of the LV myocardium, SEAT is a relevant electrophysiological factor in CRT, potentially interfering with sensing and pacing. A sufficient VD is crucial for successful CRT lead placement. Measurements revealed a trend toward greater SEAT thickness for the VIA compared to VVSP and VMS, suggesting a superior signal-to-noise-ratio in VVSP and VMS.

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