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The development of new drugs in nuclear medicine for diagnosis or treatment (chemotherapy) of brain tumors, in particular gliomas, is inextricably linked with the use of tumor models in animals (usually rats)., Objective: To compare the widely used glioma cell model C6 and the new experimental tissue model of glioblastoma 101.8., Material and Methods: A comparison was made of the diagnostic and morphological characteristics of the presented glioma models in two groups of animals with intracranially implanted tissue strain of experimental glioblastoma 101.8 ( n =4) and the C6 glioma cell line ( n =4) throughout the tumor development cycle within the rat brain. To monitor the progress of tumor growth and development, each animal underwent repeated diagnostic studies using PET-CT with 18 F-FDG and 18 F-FET to assess the metabolic activity and volume of the tumor. Also MRI images were collected. After the end of data acquisition, a histological examination of the tumor was carried out., Results: The tissue model of glioblastoma 101.8 demonstrated rapid growth and pronounced accumulation of the tracers in all animals during the tumor observation cycle. Formation of intratumoral necrosis and signs of disruption of the blood-brain barrier (BBB) were detected. In PET-CT studies of animals with a transplanted C6 tumor, no visible necrosis in the tumor structure was observed. Tumor growth was less rapid than in the case of model 101.8. The obtained morphological characteristics of 101.8 tumors transplanted into the rat brain demonstrated similar properties observed in real clinical conditions in patients with glioblastoma of the brain (necrosis, neovascularization, multiple pseudopalisade structures)., Conclusions: Tumor model 101.8 can be recommended for scientific research as it most closely reproduces the diagnostic and morphological features of a human glioblastoma.

Modern methodology of PET/CT quantitative analysis in patients with glioblastomas is not strictly standardized in clinic settings and does not exclude the influence of the human factor. Methods of radiomics may facilitate unification, and improve objectivity and efficiency of the medical image analysis. The aim of the study is to evaluate the potential of radiomics in the analysis of PET/CT glioblastoma images identifying the relationship between the radiomic features and the 11 С-methionine tumor-to-normal brain uptake ratio (TNR) determined by an expert in routine., Materials and Methods: PET/CT data (2018-2020) from 40 patients (average age was 55±12 years; 77.5% were males) with a histologically confirmed diagnosis of "glioblastoma" were included in the analysis. TNR was calculated as a ratio of the standardized uptake value of 11 C-methionine measured in the tumor and intact tissue. Calculation of radiomic features for each PET was performed in the specified volumetric region of interest, capturing the tumor with the surrounding tissues. The relationship between TNR and the radiomic features was determined using the linear regression model. Predictors were included in the model following correlation analysis and LASSO regularization. The experiment with machine learning was repeated 300 times, splitting the training (70%) and test (30%) subsets randomly. The model quality metrics and predictor significance obtained in 300 tests were summarized., Results: Of 412 PET/CT radiomic parameters significantly correlated with TNR (p<0.05), the regularization procedure left no more than 30 in each model (the median number of predictors was 9 [7; 13]). The experiment has demonstrated a non-random linear correlation (the Spearman correlation coefficient was 0.58 [0.43; 0.74]) between TNR and separate radiomic features, primarily fractal dimensions, characterizing the geometrical properties of the image., Conclusion: Radiomics enabled an objective determination of PET/CT image texture features reflecting the biological activity of glioblastomas. Despite the existing limitations in the application, the first results provide a good perspective of these methods in neurooncology., Competing Interests: Conflicts of interest. The authors have no conflicts of interest to declare.

The most important objective of modern neuroimaging is comparison of data on genotype and phenotype of brain gliomas. Radiogenomics as a new branch of science is devoted to searching for such relationships based on MRI and PET/CT parameters. The 2021 WHO classification of tumors of the central nervous system poses the most important tasks for physicians in assessment of biological behavior of tumors and their response to combined treatment. The review demonstrates the possibilities and prospects of preoperative MRI and PET/CT with amino acids in assessing the genetic profile of brain gliomas.

Objective: To evaluate the possibilities of dynamic preoperative 11 C-methionine (MET) PET/CT in differential diagnosis of various types of brain gliomas in adults., Material and Methods: The study included 74 patients aged 48±14 years with supratentorial gliomas: Grade IV - glioblastoma (GB, n =33), Grade III - anaplastic oligodendroglioma (AOD, n =10) and anaplastic astrocytoma (AA, n =12), Grade II - diffuse astrocytoma (DA, n =13) and oligodendroglioma (OD, n =6). All patients underwent standard MRI and dynamic MET PET/CT within 20 minutes after intravenous injection of radiopharmaceutical. Then, we compared MRI and PET/CT data and comprehensively analyzed the early stages of time-activity curve using 2 parameters: the first pass peak (FPP) and the first peak of maximum uptake (Pmax)., Results: We have significantly distinguished high-grade tumors (GB and AA+AOD) and certain benign gliomas (DA and OD) ( p <0.05). AUC was over 0.7 and 0.8 for FPP and Pmax in differential diagnosis of various gliomas, respectively. We found that difficulties in differential diagnosis of gliomas arise mainly if oligodendrogliomas are included in the control group., Conclusion: Dynamic PET/CT with analysis of FPP and Pmax increases specificity of differential diagnosis of various gliomas compared to standard static imaging. These data are valuable for choice of optimal treatment strategy, as well as fundamental research of metabolic processes and vascularization of various tumors.

We investigate biodistribution of gallium-labeled hydroxyethylidenediphosphonic acid ( 68 Ga-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) ( 68 Ga-DTPMP) in intact Wistar rats. It was shown that 68 Ga-DTPMP accumulated mainly in the bone tissue providing high femur/blood and femur/muscle ratios and had high stability in vivo. In contrast, 68 Ga-HEDP was characterized by low stability and high uptake of radioactivity in blood throughout the study. So 68 Ga-DTPMP can be considered as a new prospective radiotracer in oncology for imaging bone tissue metastasis by positron emission tomography.

Objective: To investigate the variations in 11 C-methionine uptake in the intact brain tissue and in glial brain tumors of different types., Material and Methods: Forty patients (21 men, 19 women) with gliomas, Grade I-IV, underwent 11 C-methionine PET-CT and contrast-enhanced MRI. Standardized uptake value (SUV), tumor-to-normal (T/N) ratios and tumor volume were analyzed., Results: The high inter-subject variability was detected in the intact brain tissue (SUV in the frontal lobe (FL) varies from 0.47 to 1.73). Amino acid metabolism was more active in women than in men (FL SUV 1.32±0.22 and 1.05±0.24, respectively). T/N ratio better differentiates gliomas by the degree of anaplasia compared to SUV. Gliomas of Grade III (T/N=2.64±0.98) were significantly different ( p <0.05) from those of Grade IV (T/N=3.83±0.75). The lowest level of methionine uptake was detected in diffuse astrocytomas (T/N=1.52±0.57), which was lower than with anaplastic astrocytomas (T/N=2.34±0.77, p <0.05)., Conclusions: 11 C-methionine PET-CT was informative in the high/low degree of malignancy differentiation (T/N 1.66±0.71 for Grade I-II and 3.18±1.06 for Grade III-IV, p <0.05). The method was also useful in separating astrocytomas of Grade II and III. The considerable variation of SUV in the intact brain tissue as well as the difference in uptake between selected areas of the brain were revealed.

Objective: To analyze intracellular pH measurement with phosphorus-31 MR spectroscopy in glioblastoma cells and to compare these data with intracellular pH in healthy volunteers., Material and Methods: There were 10 patients aged 41 - 67 years with supratentorial glioblastomas. Intracellular pH in glioblastoma cells was compared with pH in healthy persons., Results: We found a tendency to increased intracellular pH in glioblastoma cells in comparison with pH in intact brain tissue., Conclusion: Intracellular pH in brain tissue can be used as a potential marker of early abnormalities which could not be detected by conventional MRI. Moreover, these data may be valuable to estimate the efficacy of chemotherapy. The study was supported by Russian Science Foundation (grant No. 18-15-00337).

Evaluation of brain metabolism is an important part in examination of brain lesions. Phosphorus magnetic resonance spectroscopy opens up great opportunities for studying the energy metabolism and allows noninvasive examination of metabolic processes occurring both in healthy and in pathologic brain tissue by obtaining a spectrum of phosphorus-containing metabolites involved in the turnover of cell membrane phospholipids. The technique presented in this paper was used to conduct 31 P MR spectroscopy and to estimate the ratio between the peaks of the main metabolites and intracellular pH of the healthy brain tissue of 23 volunteers in the age group under 30 years old in clinical settings. Based on the recorded stable phosphorus spectra of metabolites of the healthy brain tissue, the value of intracellular pH (6.963±0.044) and the ratio of the main PME/PDE peaks (1.17±0.20) were calculated. The database was created to subsequently analyze the metabolic changes in brain tissue spectra in norm and in pathology, as well as the intracellular pH variations that have diagnostic and prognostic value.

The article contains a review of the literature dedicated to a rare complication of an abdominal aortic aneurysm, i.e., an aortic-intestinal fistula, and a report of two clinical cases illustrating different tactical approaches to management of this pathology in the settings of a referral department.

The host response to spinal cord injury can lead to an ischemic environment that can induce cell death and limits cell transplantation approaches to promote spinal cord regeneration. Spinal cord bridges that provide a localized and sustained release of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were investigated for their ability to promote angiogenesis and nerve growth within the injury. Bridges were fabricated by fusion of poly(lactide-co-glycolide) microspheres using a gas foaming/particulate leaching technique, and proteins were incorporated by encapsulation into the microspheres and/or mixing with the microspheres before foaming. Compared to the mixing method, encapsulation reduced the losses during leaching and had a slower protein release, while VEGF was released more rapidly than FGF-2. In vivo implantation of bridges loaded with VEGF enhanced the levels of VEGF within the injury at 1 week, and bridges releasing VEGF and FGF-2 increased the infiltration of endothelial cells and the formation of blood vessel at 6 weeks postimplantation. Additionally, substantial neurofilament staining was observed within the bridge; however, no significant difference was observed between bridges with or without protein. Bridges releasing angiogenic factors may provide an approach to overcome an ischemic environment that limits regeneration and cell transplantation-based approaches., (Copyright © 2011 Wiley Periodicals, Inc.)

Creating hybrid operating rooms (OR) is a new stage of the development of present-day cardiovascular surgery, with the need for these operating suites having evolved resulting from rapid implementation of novel techniques of treating cardiovascular diseases, combining elements of «open» and endovascular surgery. Despite widespread interest in this problem, there are virtually no systematized works properly describing the specificity of designing and organization of the hybrid OR's work. The present work was aimed at compiling the literature data and sharing own experience gained in organization of the hybrid OR, designation of indispensable technical and organizational requirements for performing hybrid interventions, studying the basic problems related to designing and building such operating rooms, as well as organization and management of the personnel.

Background: Increased bone loss has been associated with the development of vascular calcification in patients with chronic renal failure (CRF). In this study, the effect of impaired bone metabolism on aortic calcifications was investigated in uremic rats with or without ovariectomy., Methods: CRF was induced by administration of a 0.75% adenine/2.5% protein diet for 4 weeks. In one group, osteoporosis was induced by ovariectomy (CRF-OVX), while the other group underwent a sham-operation instead (CRF). A third group consisted of ovariectomized rats with normal renal function (OVX). At regular time intervals throughout the study, bone status and aortic calcifications were evaluated by in vivo micro-CT. At sacrifice after 6 weeks of CRF, bone histomorphometry was performed and vascular calcification was assessed by bulk calcium analysis and Von Kossa staining., Results: Renal function was significantly impaired in the CRF-OVX and CRF groups. Trabecular bone loss was seen in all groups. In the CRF-OVX and CRF groups, trabecular bone density was restored after adenine withdrawal, which coincided with cortical bone loss and the development of medial calcifications in the aorta. No significant differences with regard to the degree of aortic calcifications were seen between the two CRF groups. Neither cortical bone loss nor calcifications were seen in the OVX group. Cortical bone loss significantly correlated with the severity of vascular calcification in the CRF-OVX and CRF groups, but no associations with trabecular bone changes were found., Conclusions: Cortical rather than trabecular bone loss is associated with the process of calcification in rats with adenine- induced CRF., (Copyright © 2011 S. Karger AG, Basel.)

Background: Estrogen deficiency induced by aromatase inhibitors may be a novel treatment modality for growth enhancement in short children, but may have adverse effects on bone, brain and reproduction., Aim: To assess growth effects and potential adverse effects of aromatase inhibition in male rats., Methods: 26-day-old prepubertal rats received intramuscular injections with placebo or the aromatase inhibitor exemestane at a dose of 10, 30 or 100 mg/kg/week [E10, E30, E100(6)] for 6 weeks, completely covering the sexual maturation phase, or with 3 weeks E100 followed by 3 weeks placebo [E100(3)]. Growth parameters and histology of the testis, seminal vesicle and brain were analyzed. Bone architecture was studied with X-ray microtomography., Results: Exemestane dose-dependently decreased body weight and tail length gain, as well as liver and seminal vesicle weights, but did not affect nose-anus length gain, growth plate width or radial growth. E100(6) decreased trabecular thickness (epiphysis and metaphysis) and number (metaphysis). Normal IGF-I levels and brain, testis and seminal vesicle morphology were observed. E100(3) resulted in decreased tail length gain only., Conclusion: Exemestane treatment during sexual maturation did not augment linear growth in male rats, but caused impaired body weight and tail length gain and osteopenia., (Copyright 2010 S. Karger AG, Basel.)

Background: Aromatase inhibition has been proposed as a potential approach for growth enhancement in children with short stature, but detailed animal studies are lacking., Aim: To assess the effect and potential adverse effects of aromatase inhibition on growth in female rats., Methods: Prepubertal Wistar rats received intramuscular injections with placebo or the aromatase inhibitor exemestane at a dose of 10, 30 or 100 mg/kg/week (E10, E30, E100) for 3 weeks. A control group was ovariectomized (OVX). Weight and length gain, tibia and femur length, growth plate width, organ weights, insulin-like growth factor I (IGF-I) levels, and histology of the ovaries, uterus and brain were analyzed. X-ray microtomography of femora was performed., Results: E100 significantly increased weight gain and growth plate width, but less prominently than OVX. Trabecular number and thickness were decreased in E100 and OVX in the metaphysis and epiphysis. E100 significantly decreased ovarian weight and multiple cysts were seen upon histological evaluation. No significant effects were found on IGF-I levels and brain morphology in E100. E10 and E30 had no effects on growth., Conclusion: A high dose of exemestane marginally increases axial and appendicular growth in female rats, at the expense of osteopenia and polycystic ovaries.

Multiple myeloma (MM) is an incurable B-cell neoplasia in which progressive skeletal lesions are a characteristic feature. Earlier we established an animal model for human MM in the immune-deficient RAG2(-/-)gammac(-/-) mouse, in which the growth of luciferase-transduced MM cells was visualized using noninvasive bioluminescence imaging (BLI). This model appeared well suited to study disease progression and response to therapy by identifying the location of various foci of MM tumor growth scattered throughout the skeleton and at subsequent time points the quantitative assessment of the tumor load by using BLI. We report here on the corresponding high-resolution X-ray micro-computed tomographic (micro-CT) analysis to study skeletal defects in the mice with full-blown MM. Several anatomical derangements were observed, including abnormalities in geometry and morphology, asymmetrical bone structures, decreased overall density in the remaining bone, loss of trabecular bone mass, destruction of the inner microarchitecture, as well as cortical perforations. Using the combination of BLI, micro-CT imaging, and immune-histopathological techniques, we found a high correlation between the micro-CT-identified lesions, exact tumor location, and infiltration leading to structural lesions and local bone deformation. This confirms that this animal model strongly resembles human MM and has the potential for studying the biology of MM growth and for preclinical testing of novel therapies for MM and for repair of MM-induced bone lesions.

In the present paper, vascular calcifications due to chronic renal failure in rats are studied by X-ray microtomography (micro-CT). Although micro-CT is traditionally used as an imaging technique, a quantitative analysis of data obtained by in vivo and ex vivo micro-CT is described and discussed. By comparison with traditional destructive methods, such as histomorphometry and atomic absorption, the detection limits for calcium were determined in living rats and in extracted aortas. micro-CT proved to be an effective non-invasive imaging technique allowing non-destructive quantification of ectopic calcifications.

The mouse mutant Ozzy, originating from an ENU-mutagenesis programme, displays a head bobbing phenotype. We report here that Ozzy mice show a clear deficit in vestibulo-ocular reflex (VOR). Micro-CT scanning of the inner ears showed narrowing and truncations of at least one of the semicircular canals and loss of the ampullae. Frequency-specific auditory-evoked brainstem response (ABR) tests revealed a slight threshold increase in the middle frequency range compared to wild-type littermates. Linkage analysis localised the gene in a 5.5-cM region on chromosome 2. Subsequently, a 499 T-->A missense mutation was identified in Jag1, leading to a substitution of an evolutionary conserved tryptophane (W167R). Mutations in the human homologue of Jag1 cause Alagille syndrome (AGS), an autosomal dominant disorder associated with liver, heart, eye and skeletal abnormalities, accompanied by a characteristic facies. In human patients, it occasionally affects other organ systems like the kidney or the inner ear. Liver disease is the main diagnostic factor for AGS. Ozzy mice showed significantly less intrahepatic bile ducts than wild-type littermates. Thirty-seven percent of Ozzy mice showed heart defects. No eye or vertebral abnormalities could be detected. In conclusion, Ozzy mice show two of the major and one minor characteristic of AGS.

High resolution X-ray microtomography (micro-CT) was used for the detection of emphysema in live mice. Emphysema was induced in C57BL/6 J mice by intratracheal instillation of different amounts of porcine pancreatic elastase. This emphysema could be clearly detected by micro-CT seven weeks post-treatment: analysis of the whole data set of virtual cross-sections showed the presence of a dose-dependent level of emphysema.

In the present study, the feasibility of applying high-resolution microtomography (micro-CT) for the detection of lung tumors was investigated in live mice at an early and more advanced stage of tumor development. The chest area of anesthesized mice was scanned by X-ray micro-CT. In mice with a minor and heavy tumor load, micro-CT proved to be a fast and noninvasive imaging device for the detection of lung tumors. After validation of the CT data by histologic sectioning, it was shown that the majority of tumors could be distinguished in the reconstructed virtual slices obtained by micro-CT. The data from micro-CT were also confirmed by visual inspection of the inflated and excised lungs postmortem. In vivo micro-CT opens broad perspectives for imaging tumor development and its progression in a noninvasive way. Micro-CT also allows for longitudinal evaluation of the treatment of lung cancer by drugs., (Copyright 2004 Neoplasia Press, Inc.)

The epiphysis is a gland containing firm extracellular bodies (brain sand) the number of which increases with age. Microscopy and roentgen microtomography showed that in some cases of schizophrenia the amount of brain sand decreases. In parallel, cytoplasm of pinealocytes appears to contain concrements of a new type--irregular hollow spheres of 0.1-1.5 microm in size. They may contain fluoride. Typical hydroxyapatite retaining organic stroma may dissolve starting from the center both in health and schizophrenia.

A new non-destructive method based on x-ray microtomography (micro-CT) was developed to measure calcium density in bone. X-ray micro-CT was used as a quantitative approach to acquire and reconstruct virtual cross-sections through the sample. Accurate beam-hardening correction was implemented. Grey values in the virtual cross-sections were calibrated as calcium mineral density in bone. From these cross-sections, three-dimensional models were created. Calcium content was calculated directly from images and expressed as percentage per volume and per weight. Calcium mineral density was studied by this method in a unique set of bones isolated from newts (Pleurodeles waltlii Michah) that had travelled into space. A demineralization of 10% was shown as a consequence of sustained micro-gravity.