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PubMed1999

[Micro-CT. Technology and application for assessing bone structure].

The strength and fracture resistance of bone is determined by the structure of the trabecular network and the cortical shell. While standard 2D techniques like histomorphometry are inadequate to assess the 3D nature of the trabecular network, isotropic 3D datasets of this network can be acquired with the new imaging modality of microCT. However, so far the quantitative analysis of the generated datasets, in particular the extraction of appropriate parameters describing the bone structure, has not been finally solved. In this article we describe the technology and applications of microCT systems relevant in the field of osteology. The most important technical features of current microCT systems in this context are: 1. A spatial resolution down to 5-10 microns can be achieved. 2. The maximum sample size is related to the desired resolution by a factor of approximately 1000, that is, a resolution of 10 microns limits the maximum sample size to approximately 1 cm. 3. Scan times for microCT systems vary between minutes and hours. Currently five areas for the application of microCT systems in osteology can be identified: 1. The search of parameters characterizing the 3D trabecular structure. 2. The application of finite element models to determine the biochemical competence of the structural parameters. 3. The use of microCT in preclinical trials to study drug effects in small animals. 4. The validation of analysis methods used in high-resolution in-vivo imaging systems. 5. The 3D quantification of modeling and remodeling processes.

Adult↗

PubMed2005

Mapping and characterization of new EST-derived microsatellites for potato (Solanum tuberosum L.).

Microsatellites, or simple sequence repeats (SSRs) are very useful molecular markers for a number of plant species. They are commonly used in cultivar identification, plant variety protection, as anchor markers in genetic mapping, and in marker-assisted breeding. Early development of SSRs was hampered by the high cost of library screening and clone sequencing. Currently, large public SSR datasets exist for many crop species, but the number of publicly available, mapped SSRs for potato is relatively low (approximately 100). We have utilized a database mining approach to identify SSR-containing sequences in The Institute For Genomic Research Potato Gene Index database (http://www.tigr.org), focusing on sequences with size polymorphisms present in this dataset. Ninety-four primer pairs flanking SSR sequences were synthesized and used to amplify potato DNA. This study rendered 61 useful SSRs that were located in pre-existing genetic maps, fingerprinted in a set of 30 cultivars from South America, North America, and Europe or a combination thereof. The high proportion of success (65%) of expressed sequence tag-derived SSRs obtained in this work validates the use of transcribed sequences as a source of markers. These markers will be useful for genetic mapping, taxonomic studies, marker-assisted selection, and cultivar identification.

Chromosome Mapping↗

PubMed1997

A quantitative property-property relationship (QPPR) approach to estimate in vitro tissue-blood partition coefficients of organic chemicals in rats and humans.

The present study describes quantitative property-property relationships (QPPRs) for the partitioning of organic chemicals between blood and tissue homogenates from both rats and humans. The n-octanol/water partition coefficient (K[ow]) is used as a non-biological descriptor. QPPRs for human tissue-blood partition coefficients (PCs) were derived from a dataset of 24 volatile organic compounds in blood, liver, muscle, fat, kidney and brain tissue homogenates. QPPRs were also derived for the PCs of rat tissues, using a dataset of 42 volatile organic compounds in blood, liver, muscle and fat tissue homogenates. These QPPRs were evaluated using a test set of 10 compounds for human tissues and a test set of 14 compounds for rat tissues. For both human and rat test sets, it was generally observed that most estimated PCs were within a range of 50-200% of their experimental values. The present approach is concluded to offer a rapid means for the estimation of tissue-blood PCs of compounds on the basis of K(ow) values. In addition, indications for a possible role of tissue components other than lipid and water in the tissue-blood partitioning process of compounds were observed from the calibration results of the model.

1-Octanol↗

PubMed2003

Interpretation of mass spectrometry data for high-throughput proteomics.

Recent developments in proteomics have revealed a bottleneck in bioinformatics: high-quality interpretation of acquired MS data. The ability to generate thousands of MS spectra per day, and the demand for this, makes manual methods inadequate for analysis and underlines the need to transfer the advanced capabilities of an expert human user into sophisticated MS interpretation algorithms. The identification rate in current high-throughput proteomics studies is not only a matter of instrumentation. We present software for high-throughput PMF identification, which enables robust and confident protein identification at higher rates. This has been achieved by automated calibration, peak rejection, and use of a meta search approach which employs various PMF search engines. The automatic calibration consists of a dynamic, spectral information-dependent algorithm, which combines various known calibration methods and iteratively establishes an optimised calibration. The peak rejection algorithm filters signals that are unrelated to the analysed protein by use of automatically generated and dataset-dependent exclusion lists. In the "meta search" several known PMF search engines are triggered and their results are merged by use of a meta score. The significance of the meta score was assessed by simulation of PMF identification with 10,000 artificial spectra resembling a data situation close to the measured dataset. By means of this simulation the meta score is linked to expectation values as a statistical measure. The presented software is part of the proteome database ProteinScape which links the information derived from MS data to other relevant proteomics data. We demonstrate the performance of the presented system with MS data from 1891 PMF spectra. As a result of automatic calibration and peak rejection the identification rate increased from 6% to 44%.

Algorithms↗

PubMed2004

Identification of the regulatory proteins in human pancreatic cancers treated with Trichostatin A by 2D-PAGE maps and multivariate statistical analysis.

In this paper, principal component analysis (PCA) is applied to a spot quantity dataset comprising 435 spots detected in 18 samples belonging to two different cell lines (Paca44 and T3M4) of control (untreated) and drug-treated pancreatic ductal carcinoma cells. The aim of the study was the identification of the differences occurring between the proteomic patterns of the two investigated cell lines and the evaluation of the effect of the drug Trichostatin A on the protein content of the cells. PCA turned out to be a successful tool for the identification of the classes of samples present in the dataset. Moreover, the loadings analysis allowed the identification of the differentially expressed spots, which characterise each group of samples. The treatment of both the cell lines with Trichostatin A therefore showed an appreciable effect on the proteomic pattern of the treated samples. Identification of some of the most relevant spots was also performed by mass spectrometry.

Analysis of Variance↗

PubMed2006

Multisensory processing and oscillatory activity: analyzing non-linear electrophysiological measures in humans and simians.

Stimulus-related oscillations are known to be closely linked to integrative processing in the brain. One research domain within which there has been tremendous interest in oscillatory mechanisms is in the integration of inputs across the widely separated sensory systems. Under the standard approach of assessing multisensory interactions in electrophysiological datasets, the event-related response to a multisensory stimulus is directly compared with the sum of the responses to its unisensory constituents when presented alone. When using methods like wavelet transformation or fast Fourier transformation to derive induced oscillatory signals, however, such linear operations are not appropriate. Here we introduce a simple bootstrapping procedure wherein the linear summation of single unisensory trials forms a distribution against which multisensory trials may be statistically compared, an approach that circumvents the issue of non-linearity when combining unisensory oscillatory responses. To test this approach we applied it to datasets from intracranial recordings in non-human primates and human scalp-recorded EEG, both derived from a simple audio-visual integration paradigm. Significant multisensory interactions were revealed in oscillatory activity centered at 15 and 20 Hz (the so-called beta band). Simulations of different levels of background noise further validated the results obtained by this method. By demonstrating super- and sub-additive effects, our analyses showed that this approach is a valuable metric for studying multisensory interactions reflected in induced oscillatory responses.

Adult↗

PubMed1999

Development of a general method of limited sampling for the determination of AUC for a drug that displays two-compartment pharmacokinetics.

OBJECTIVES: To develop a method of limited sampling that would enable accurate estimation of the area under the concentration time curve (AUC) when using the log trapezoidal method. METHODS: A series of datasets were simulated. Each dataset comprised 1000 subjects. Each subject was "administered" an intravenous bolus dose of a drug that displays two compartment pharmacokinetics. In the first series of simulations, a variety of combinations of the number of sampling times (K) and number of replicate measurements (R) at each of these times were tested, where K x R = 12 (i.e. N = 12). The times that each of the K samples were taken were chosen to be those that divided the AUC into K - 1 trapezoids of equal area. The concentration-time curves were estimated based on a priori estimates of the population parameters. The best combination of K and R was tested under various conditions of parameter variability and assay variability. The combinations were compared with a conventional sampling strategy, where N = 12, K = 12 (R = 1). RESULTS: The combination K = 4 and R = 3 proved to be the "best". It had similar accuracy to the conventional method. The best limited sampling combination was superior to the conventional method when assay variability was high (CV= 30%), was similar when assay variability was 15%, but the conventional method became statistically superior when assay variability was 7.5% or less. The accuracy of the best limited sampling combination was inversely related to the parameter variability. If K was set to 4 and R allowed to increase to 6 (i.e. N is not equal to 12), there was no further gain in accuracy. CONCLUSION: The proposed method of limited sampling is at least as accurate as the conventional intensive sampling technique, but more efficient in terms of sampling.

Area Under Curve↗

PubMed2005

3D roadmap in neuroangiography: technique and clinical interest.

We present the first clinical results obtained with a novel technique: the three-dimensional [3D] roadmap. The major difference from the standard 2D digital roadmap technique is that the newly developed 3D roadmap is based on a rotational angiography acquisition technique with the two-dimensional [2D] fluoroscopic image as an overlay. Data required for an accurate superimposition of the previously acquired 3D reconstructed image on the interactively made 2D fluoroscopy image, in real time, are stored in the 3D workstation and constitute the calibration dataset. Both datasets are spatially aligned in real time; thus, the 3D image is accurately superimposed on the 2D fluoroscopic image regardless of any change in C-arm position or magnification. The principal advantage of the described roadmap method is that one contrast injection allows the C-arm to be positioned anywhere in the space and allows alterations in the distance between the x-ray tube and the image intensifier as well as changes in image magnification. In the clinical setting, the 3D roadmap facilitated intravascular neuronavigation with concurrent reduction of procedure time and use of contrast medium.

Cerebral Angiography↗

PubMed2026

Integrated analysis of amide proton transfer weighted MRI and proteomics uncovers altered protein dynamics in glioblastoma.

PURPOSE: Elevated amide proton transfer-weighted (APTw) MRI signals in glioblastoma (GBM) are often linked to increased intracellular mobile proteins, but the associated molecular patterns in human tissue remain unclear. We examined the relationship between regional APTw features and cellular protein composition and profiled proteomic differences between tumor and peritumoral tissue. METHODS: In this single-center prospective study, preoperative MRI data were integrated with intraoperative neuronavigation for 12 image-guided tissue samples (8 tumor and 4 peritumoral). Total, cytoplasmic, and nuclear proteins were quantified using bicinchoninic acid (BCA) assay. Data-independent acquisition (DIA) proteomics identified exploratory differentially expressed proteins (DEPs), followed by functional enrichment and protein-protein interaction (PPI) network analyses. Transcript-level expression patterns and survival associations were queried in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets to provide indirect external clinical context. RESULTS: Tumor regions showed higher APTw signals than peritumoral regions (p < 0.001) and increased cytoplasmic protein concentration (p < 0.05), without a corresponding increase in total or nuclear protein levels. DIA identified 654 DEPs. Further analysis highlighted 36 higher-significance DEPs, and prioritized 12 hub proteins in the PPI network. In public transcriptomic datasets, ERBB2, RUNX1, and SHC1 showed higher expression in GBM and were associated with poorer overall survival. CONCLUSION: These findings suggest that elevated APTw signal in GBM may be associated with increased cytoplasmic protein content and distinct proteomic alterations. This imaging-proteomic framework provides exploratory regional context for future mechanistic and follow-up studies, but larger, spatially matched and independently validated cohorts are required to confirm the molecular contributors to APTw contrast.

Humans↗

PubMed2002

rtREV: an amino acid substitution matrix for inference of retrovirus and reverse transcriptase phylogeny.

Retroviral and other reverse transcriptase (RT)-containing sequences may be subject to unique evolutionary pressures, and models of molecular sequence evolution developed using other kinds of sequences may not be optimal. Here we develop and present a new substitution matrix for maximum likelihood (ML) phylogenetic analysis which has been optimized on a dataset of 33 amino acid sequences from the retroviral Pol proteins. When compared to other matrices, this model (rtREV) yields higher log-likelihood values on a range of datasets including lentiviruses, spumaviruses, betaretroviruses, gammaretroviruses, and other elements containing reverse transcriptase. We provide evidence that rtREV is a more realistic evolutionary model for analyses of the pol gene, although it is inapplicable to analyses involving the gag gene.

Amino Acid Substitution↗

PubMed2025

Triage and workflow optimization with artificial intelligence in pediatric imaging.

Artificial intelligence (AI) is being increasingly utilized in various aspects by the radiology department. With an ever-increasing burden on the healthcare system, particularly in emergency units, the need to incorporate AI in patient triage and workflow optimization cannot be overstated. Machine learning (ML)-based algorithms form the core of AI-based software, aiding healthcare professionals at nearly every step in delivering appropriate patient care. Regarding the radiology section of the hospital, AI-based algorithms have proven exceptionally useful in assisting radiologists and technicians with image acquisition. From accurate clinical referrals to scheduling computed tomography/magnetic resonance imaging scan appointments, from ensuring the lowest radiation exposure to offering timely follow-up reminders, ML-based software has indeed revolutionized the concept of modern image acquisition, especially in the pediatric radiology section. Although the implementation of these algorithms is swift, several technical challenges and the limited availability of pediatric datasets preclude their widespread use. The utility of multimodal pediatric datasets, which combine imaging, genomics, and clinical data, for comprehensive AI triage models can help AI systems evolve toward greater adaptability and integration, resulting in enhanced efficiency, reduced turnaround times, and improved patient outcomes in pediatric radiology departments in the future. In this article, we highlight and review the utility of AI and machine learning-based algorithms in efficiently aiding triage and streamlining the workflow in the pediatric radiology section, thereby ensuring an overall improvement in the departmental workflow.

Triage↗

PubMed2025

The protective role of γδ T cells in endometrial cancer.

Γδ T cells are non-conventional T cells that are not MHC restricted and have T cell receptors (TCRs) that are stimulated by phosphoantigens, stress-induced proteins, lipids, and other antigens. These cells are prognostic across cancer types in The Cancer Genome Atlas (TCGA) but have not been well studied in endometrial cancer, which has a rising incidence and mortality rate. Endometrial cancer patients have variable responses to checkpoint inhibitors which are related to the molecular subtype of their cancer. As such, there is a pressing need to understand the immune microenvironment in endometrial cancer. This study addresses this gap in knowledge by investigating γδ T cell repertoires and transcriptomes in this disease site. γδ T cell repertoires were obtained for 543 endometrial cancer patients within the TCGA and from 5 endometrial cancer patients in the single cell dataset SRP349751 using TRUST4. GLIPH2 was used to identify TCRs predicted to bind the same antigen. Transcriptomes were investigated in the single cell dataset. DNA Polymerase Epsilon Exonuclease (POLE) and Microsatellite Instability High (MSI-H) endometrial cancer subtypes had the most γδ T cell infiltration. Vδ1 and Vδ3 γδ T cell infiltration was prognostic independent of stage and molecular subtype. GLIPH2 analysis revealed TCRδ motifs for TDK, YTD, and GEL were public across all four molecular subtypes and were present in the single cell data set. Vδ1 γδ T cell transcriptomes were associated with cytotoxicity and recent TCR stimulation. These data support further investigation of immunotherapies targeting γδ T cells in endometrial cancer.

Humans↗

PubMed2005

A quantitative tool for assessing the integrity of southern coastal California streams.

We developed a benthic macro-invertebrate index of biological integrity (B-IBI) for the semi-arid and populous southern California coastal region. Potential reference sites were screened from a pool of 275 sites, first with quantitative GIS landscape analysis at several spatial scales and then with local condition assessments (in-stream and riparian) that quantified stressors acting on study reaches. We screened 61 candidate metrics for inclusion in the B-IBI based on three criteria: sufficient range for scoring, responsiveness to watershed and reach-scale disturbance gradients, and minimal correlation with other responsive metrics. Final metrics included: percent collector-gatherer + collector-filterer individuals, percent non-insect taxa, percent tolerant taxa, Coleoptera richness, predator richness, percent intolerant individuals, and EPT richness. Three metrics had lower scores in chaparral reference sites than in mountain reference sites and were scored on separate scales in the B-IBI. Metrics were scored and assembled into a composite B-IBI, which was then divided into five roughly equal condition categories. PCA analysis was used to demonstrate that the B-IBI was sensitive to composite stressor gradients; we also confirmed that the B-IBI scores were not correlated with elevation, season, or watershed area. Application of the B-IBI to an independent validation dataset (69 sites) produced results congruent with the development dataset and a separate repeatability study at four sites in the region confirmed that the B-IBI scoring is precise. The SoCal B-IBI is an effective tool with strong performance characteristics and provides a practical means of evaluating biotic condition of streams in southern coastal California.

Animals↗

PubMed2000

ENVIRONMENTAL AUDITING: Patterns of Aquatic Species Imperilment in the Southern Appalachians: An Evaluation of Regional Databases.

/ For regional analyses of species imperilment patterns, data on species distributions are available from the U.S. Fish and Wildlife Service and from the state heritage programs. We compared these two different databases as sources of best available information for regional analyses of patterns of aquatic species imperilment for 132 counties in the southern Appalachians and examined patterns produced from the databases. The heritage program database contained information about a greater number of imperiled species because species need not be federally listed as threatened or endangered to be included in this database. In the southern Appalachians, about half of imperiled molluscs and about one-fourth of imperiled fish were listed as threatened or endangered; much smaller proportions of other taxonomic groups were federally listed. Most threatened and endangered species appeared on both lists, but for about 40% of the species inconsistencies exist, notably a lack of recent records in the heritage program dataset. Numbers of species in each county were significantly different between the two datasets for Georgia, Tennessee, and Virginia, where the largest number of threatened and endangered species reside. Nevertheless, some counties always appeared as centers of imperilment, and the general spatial patterns of imperilment were similar.

Journal Article↗

PubMedDate not supplied

Computational fluid dynamics: hemodynamic changes in abdominal aortic aneurysm after stent-graft implantation.

The aim of this study was to demonstrate quantitatively and qualitatively the hemodynamic changes in abdominal aortic aneurysms (AAA) after stent-graft placement based on multidetector CT angiography (MDCT-A) datasets using the possibilities of computational fluid dynamics (CFD). Eleven patients with AAA and one patient with left-side common iliac aneurysm undergoing MDCT-A before and after stent-graft implantation were included. Based on the CT datasets, three-dimensional grid-based models of AAA were built. The minimal size of tetrahedrons was determined for grid-independence simulation. The CFD program was validated by comparing the calculated flow with an experimentally generated flow in an identical, anatomically correct silicon model of an AAA. Based on the results, pulsatile flow was simulated. A laminar, incompressible flow-based inlet condition, zero traction-force outlet boundary, and a no-slip wall boundary condition was applied. The measured flow volume and visualized flow pattern, wall pressure, and wall shear stress before and after stent-graft implantation were compared. The experimentally and numerically generated streamlines are highly congruent. After stenting, the simulation shows a reduction of wall pressure and wall shear stress and a more equal flow through both external iliac arteries after stenting. The postimplantation flow pattern is characterized by a reduction of turbulences. New areas of high pressure and shear stress appear at the stent bifurcation and docking area. CFD is a versatile and noninvasive tool to demonstrate changes of flow rate and flow pattern caused by stent-graft implantation. The desired effect and possible complications of a stent-graft implantation can be visualized. CFD is a highly promising technique and improves our understanding of the local structural and fluid dynamic conditions for abdominal aortic stent placement.

Aortic Aneurysm, Abdominal↗

PubMed2003

Visualization of the temporal bone of the Chinese Visible Human.

Temporal bone anatomy is very difficult to understand. After dataset acquisition of the first Chinese Visible Human, we processed the two-dimensional images to build a digitized visible model of the temporal bone and explore the role of virtual endoscopy in the inner ear. On a SGI workstation three-dimensional computer reconstructions of the ear were generated from the Chinese visible human dataset, viewing the middle and inner ear imitating the traditional otoscopy. The three-dimensional data of the temporal bone were then converted to STL format, and the temporal bone replica were fabricated with rapid prototyping by laminated object manufacturing. The virtual model of the ear was successfully completed, and the virtual endoscopy improved three-dimensional visualization of the middle and inner ear. Physical replica of the temporal bone were built with paper; the accuracy was +/-0.2 mm. The reconstructed model and the replica of the temporal bone can be used to make preoperative plans in the complicated otoneurosurgical operations, allowing various surgical exercises to be carried out on the three-dimensional stereophysical model. The virtual endoscopy stands as a promising new visualization technique for elucidation of the middle and inner ear and reveals a tremendous potential in both clinical and educational settings, providing morphological data for the image diagnosis and otoneurosurgery.

Anatomy, Cross-Sectional↗

PubMed2004

CT colonography: effect of experience and training on reader performance.

The purpose of this paper was to investigate the effect of radiologist experience and increasing exposure to CT colonography on reader performance. Three radiologists of differing general experience (consultant, research fellow, trainee) independently analysed 100 CT colonographic datasets. Readers had no prior experience of CT colonography and received feedback and training after the first 50 cases from an independent experienced radiologist. Diagnostic performance and reporting times were compared for the first and second 50 datasets and compared with the results of a radiologist experienced in CT colonography. Before training only the consultant reader achieved statistical equivalence with the reference standard for detection of larger polyps. After training, detection rates ranged between 25 and 58% for larger polyps. Only the trainee significantly improved after training ( P=0.007), with performance of other readers unchanged or even worse. Reporting times following training were reduced significantly for the consultant and fellow ( P<0.001 and P=0.03, respectively), but increased for the trainee ( P<0.001). In comparison to the consultant reader, the odds of detection of larger polyps was 0.36 (CI 0.16, 0.82) for the fellow and 0.36 (CI 0.14, 0.91) for the trainee. There is considerable variation in the ability to report CT colonography. Prior experience in gastrointestinal radiology is a distinct advantage. Competence cannot be assumed even after directed training via a database of 50 cases.

Clinical Competence↗

PubMed2005

Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging.

The aim of this work was to assess magnetic resonance (MR) perfusion patterns of chronic, non-embolic pulmonary diseases of congenital and neoplastic origin and to compare the findings with results obtained with pulmonary, contrast-enhanced multislice computed tomography (CT) imaging to prove that congenital and neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion cycle to successfully and directly detect changes in lung perfusion patterns. Twenty-five patients underwent concurrent CT and MR evaluation of chronic pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary and vascular regions of interest in corresponding positions. MR perfusion calculated time-to-peak enhancement, maximal enhancement and the area under the perfusion curve. CT datasets provided pulmonary signal-to-noise ratio measurements. Vessel center-lines of bronchial arteries were determined. Underlying perfusion type, such as pulmonary arterial or systemic arterial supply, as well as regions with significant variations in perfusion were determined statistically. Analysis of the pulmonary perfusion pattern detected pulmonary arterial supply in 19 patients; six patients showed systemic arterial supply. In pulmonary arterial perfusion, MR and multislice CT imaging consistently detected the perfusion type and regions with altered perfusion patterns. In bronchial arterial supply, MR perfusion and CT imaging showed significant perfusion differences. Patients with bronchial arterial supply had bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and neoplastic pulmonary conditions allowed characterization of the pulmonary perfusion type. CT imaging suggested the presence of systemic arterial perfusion by visualizing hypertrophied bronchial arteries.

Adolescent↗