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Clinical experiences with computed radiography.

Computed radiography (CR) based on photostimulable phosphor is currently the only feasible way for a radiological department to digitize the bulk of radiological data: the lung and skeletal examinations. Regarding the quality of images for diagnostic purposes, CR imaging is never inferior to a screen/film system (SF) and for several clinical entities CR is superior. Of the many processing possibilities of the image plate (IP) image, the unsharp masking or edge enhancement should be used at a minimum. Dose reduction with CR ranges from 15% to 95%; at our institution it is 37%. Softcopy reading of CR images is advantageous due to the many postprocessing and improved display facilities. Currently there is little use for a 4000 x 4000 (4 K) pixel imaging and display. All images (including mammography) can be read in 2 K without any loss of clinically important information. To include CR in a picture archive and communication system (PACS) is demanding because of the load of data that each CR image represents. Networks for image distribution are essential if digital imaging is to have any impact on patient treatment and hospital organization.

Bone and Bones↗

[Digital slide training portal. Training slides available on the Internet from the German division of the IAP].

Alternatively to sending glass slides via mail order, the German division of the IAP established a digital slide training portal on the Internet. Following the principle of virtual microscopy, histology slides were scanned completely in high resolution, stored on a server, and can be accessed over the Internet. The slide training portal can be used with current Internet browsers without additional plugins. Working on digital slides with the virtual microscope is easy but flexible. Loading a detail image using image streaming technologies takes about 500 ms with the German research network (DFN) and about 3 s with DSL. The digital slide training portal of the German IAP provides a clear choice and is always available for every member. Despite the little experience some users had with the Internet and diagnostics at the monitor, image quality and usability were rated as good.

Germany↗

Nested co-expression network analysis identifies compact gene clusters in a black box.

MOTIVATION: Digital analysis of biological systems requires methods capable of identifying both broad and nested gene modules reflecting complex biological processes. Existing transcriptomic methods often miss compact gene sets corresponding to subprocesses in specialized cell types, limiting insights into functional heterogeneity. RESULTS: We present Nested-WGCNA, a two-stage unsupervised network analysis algorithm designed to identify coarse-grained and fine-grained gene modules. Applied to bulk RNA-Seq data, Nested-WGCNA reveals stable modules reproducible across datasets. When validated against scRNA-Seq data, these modules correspond to both major and minor immune cell subtypes. Application to immunotherapy response datasets uncovers predictive and prognostic biomarkers, highlighting its utility in treatment stratification and biomarker discovery. AVAILABILITY: The NestedWGCNA source code and analysis pipeline are available on GitHub (https://github.com/ilyada/NestedWGCNA) and archived on Zenodo (https://doi.org/10.5281/zenodo.18959244).

Algorithms↗

Measuring the facial phenotype of individuals with prenatal alcohol exposure: correlations with brain dysfunction.

The purpose of this report is to demonstrate how to measure the magnitude of expression of the fetal alcohol syndrome (FAS) facial phenotype using the new 4-Digit Diagnostic Code and the previously developed D-score and to demonstrate how these two measures of the FAS facial phenotype correlate with brain function and structure; correlations that fail to be identified by the older gestalt method of facial measurement. The D-score and the facial component of the 4-Digit Diagnostic Code quantitatively measure the magnitude of expression of the FAS facial phenotype using three facial features (palpebral fissure length, philtrum smoothness, and upper lip thinness). These facial measurement systems were developed by the Washington State FAS Diagnostic and Prevention Network (FAS DPN) of clinics and are used to screen and diagnose the facial component of FAS for all patients evaluated in the network of clinics (1500 to date). The 4-Digit Diagnostic Code is a comprehensive diagnostic system developed by the FAS DPN in 1997 to diagnose the full spectrum of outcomes among patients with prenatal alcohol exposure. The four digits reflect the magnitude of expression of the four key diagnostic features of FAS in the following order: (1) growth deficiency; (2) the FAS facial phenotype; (3) brain dysfunction; (4) gestational alcohol exposure. The 4-Digit Diagnostic Code was developed to overcome the subjective, highly variable gestalt method of diagnosis that has been used as the standard to date, worldwide. Prior to the development of the 4-Digit Diagnostic Code, the first 445 patients evaluated in the FAS DPN were diagnosed using the gestalt method. For research purposes, their gestalt diagnoses were transformed into 4-Digit Diagnostic Codes, presenting a unique opportunity to directly compare the two diagnostic methods. When the facial phenotype was measured using the 4-Digit Diagnostic Code or D-score, the magnitude of expression of the FAS facial phenotype was significantly correlated with structural, neurologic, and functional measures of brain damage, and the phenotype of those receiving a 4-Digit Diagnosis of FAS showed little variability. When the gestalt method of diagnosis was used, the magnitude of expression of the FAS facial phenotype did not correlate with structural, neurologic and functional measures of brain damage, and the facial phenotype of those receiving a gestalt diagnosis of FAS was highly variable. The 4-Digit Diagnostic Code and D-score thus provide more precise and accurate measures of the FAS facial phenotype and reveal important correlations with brain structure and function, suggesting that intermediate expressions of the FAS facial phenotype may serve as important risk factors for brain damage caused by prenatal alcohol exposure.

Adolescent↗

In situ hybridization to the Crithidia fasciculata kinetoplast reveals two antipodal sites involved in kinetoplast DNA replication.

Kinetoplast DNA is a network of interlocked minicircles and maxicircles. In situ hybridization, using probes detected by digital fluorescence microscopy, has clarified the in vivo structure and replication mechanism of the network. The probe recognizes only nicked minicircles. Hybridization reveals prereplication kinetoplasts (with closed minicircles), donut-shaped replicating kinetoplasts (with nicked minicircles on the periphery and closed minicircles in the center), and postreplication kinetoplasts (with nicked minicircles). Replicating kinetoplasts are associated with two peripheral structures containing free minicircle replication intermediates and DNA polymerase. Replication may involve release of closed minicircles from the center of the kinetoplast and their migration to the peripheral structures, replication of the free minicircles therein, and then peripheral reattachment of the progeny minicircles to the kinetoplast.

Animals↗

Quality control for digital mammography in the ACRIN DMIST trial: part I.

The Digital Mammography Imaging Screening Trial, conducted by the American College of Radiology Imaging Network, is a clinical trial designed to compare the accuracy of full-field digital mammography (FFDM) versus screen-film mammography in a screening population. Five FFDM systems from four manufacturers (Fischer, Fuji, General Electric, and Lorad) were employed in the study at 35 clinical sites. A core physics team devised and implemented tests to evaluate these systems. A detailed description of physics and quality control tests is presented, including estimates of: mean glandular dose, modulation transfer function (MTF), 2D noise power spectra, and signal-to-noise ratio (SNR). The mean glandular doses for the standard breast ranged from 0.79 to 2.98 mGy, with 1.62 mGy being the average across all units and machine types. For the five systems evaluated, the MTF dropped to 50% at markedly different percentages (22% to 87%) of the Nyquist limit, indicating that factors other than detector element (del) size have an important effect on spatial resolution. Noise power spectra and SNR were measured; however, we found that it was difficult to standardize and compare these between units. For each machine type, the performance as measured by the tests was very consistent, and no predictive benefit was seen for many of the tests during the 2-year period of the trial. It was found that, after verification of proper operation during acceptance testing, if systems failed they generally did so suddenly rather than through gradual deterioration of performance. Because of the relatively short duration of this study further, investigation of the long-term failure characteristics of these systems is advisable.

Algorithms↗

Learning in human neural networks on microelectrode arrays.

This paper describes experiments involving the growth of human neural networks of stem cells on a MEA (microelectrode array) support. The microelectrode arrays (MEAs) are constituted by a glass support in which a set of tungsten electrodes are inserted. The artificial neural network (ANN) paradigm was used by stimulating the neurons in parallel with digital patterns distributed on eight channels, then by analyzing a parallel multichannel output. In particular, the microelectrodes were connected following two different architectures, one inspired by the Kohonen's SOM, the other by the Hopfield network. The output signals have been analyzed in order to evaluate the possibility of organized reactions by the natural neurons.f The results show that the network of human neurons reacts selectively to the subministered digital signals, i.e., it produces similar output signals referred to identical or similar patterns, and clearly differentiates the outputs coming from different stimulations. Analyses performed with a special artificial neural network called ITSOM show the possibility to codify the neural responses to different patterns, thus to interpret the signals coming from the network of biological neurons, assigning a code to each output. It is straightforward to verify that identical codes are generated by the neural reactions to similar patterns. Further experiments are to be designed that improve the hybrid neural networks' capabilities and to test the possibility of utilizing the organized answers of the neurons in several ways.

Embryonic Stem Cells↗

Classification of microcalcifications in radiographs of pathologic specimens for the diagnosis of breast cancer.

RATIONALE AND OBJECTIVES: Early detection of breast cancer depends on accurate classification of microcalcifications. We have developed a computer vision system that has the potential to classify microcalcifications objectively and consistently to aid radiologists in diagnosing breast cancer. METHODS: A convolution neural network (CNN) was used to classify benign and malignant microcalcifications in radiographs of pathologic specimens. Digital images were acquired by digitizing radiographs at a high resolution of 21 microns x 21 microns. RESULTS: Eighty regions of interest selected from digitized radiographs of pathologic specimens were used for training and testing of the neural network system. The CNN achieved an Az value (area under the receiver operating characteristic curve) of 0.90 in classifying clusters of microcalcifications associated with benign and malignant processes. CONCLUSION: Classification of microcalcifications in pathologic specimens for diagnosis of breast cancer was achieved at a high level in our computer vision system, which consists of high-resolution digitization of mammograms and a CNN.

Breast Neoplasms↗

Information retrieval in digital libraries: bringing search to the net.

A digital library enables users to interact effectively with information distributed across a network. These network information systems support search and display of items from organized collections. In the historical evolution of digital libraries, the mechanisms for retrieval of scientific literature have been particularly important. Grand visions in 1960 led first to the development of text search, from bibliographic databases to full-text retrieval. Next, research prototypes catalyzed the rise of document search, from multimedia browsing across local-area networks to distributed search on the Internet. By 2010, the visions will be realized, with concept search enabling semantic retrieval across large collections.

Abstracting and Indexing↗

Potential of digital flashing tomosynthesis for angiocardiographic evaluation.

A system for digital flashing tomosynthesis (DFTS) consists of four electrocardiogram-gated and simultaneously flashed x-ray tubes, a 14" image intensifier, a unit for digital subtraction angiography (DSA), a personal computer-hosted transputer network for three-dimensional (3D) reconstruction as well as for quantitative coronary angiography and ventriculography, a display unit and an individual digital archive. DFTS-tomoangiograms may be presented in single slice mode or as multiple slices of arbitrary thickness, using rotating and stereographic presentation of 3D images. DFTS represents a configuration for standardized digital angiocardiography with digital archiving and assures optimal reproducibility and safety. This angiographic configuration is feasible for both ambulatory angiography to allow high volume cardiovascular angiographic screening and for the quantitative assessment of natural progression or potential regression of coronary artery disease resulting from interventional or pharmacological therapy.

Angiocardiography↗

An Internet-based nuclear medicine teaching file.

UNLABELLED: Teaching file cases play an important role in the training of nuclear medicine residents; however, film-based teaching files have limitations, such as difficulty in accessing cases in a department with several remote clinical sites. The goal of this project was to develop a digital teaching file with the capability for local and remote (Internet) network access, with the additional requirements that viewing existing cases and addition of new cases be easy and simple. METHODS: The teaching file software (TF-Web) utilizes applications developed for the World-Wide-Web in combination with locally developed programs for importing images, entering case information, indexing, searching, case selection and case editing. The time required to add cases to the TF-Web and to access existing cases from local and remote network sites as well as computer storage requirements were assessed. RESULTS: Cases entered in TF-Web may be viewed either with or without diagnoses and may be accessed with acceptable speed (2-14 sec) from both local and remote network sites. A relatively complex case required 1.2 megabytes of storage, with lesser storage requirements for simpler cases. CONCLUSION: A digital teaching file has been developed that allows easy access from computers located both locally and elsewhere on the Internet. Digital storage requirements are reasonable, and, because of the unique nature of TF-Web, case storage may be distributed among multiple institutions.

Computer Communication Networks↗

Nuclear medicine data communications.

Nuclear Medicine was one of the earliest imaging modalities to adopt the use of computers for acquisition, processing, storage, and display of digital images. Originally used for processing images, computer technologies were quickly adopted for image storage, display, and transmission. Modern nuclear medicine cameras produce digital images that can be transmitted over computer networks to other cameras, storage devices, workstations, and printers. In order to achieve nuclear medicine data communication, images must be successfully acquired and transmitted to the appropriate location to be displayed or printed. Standards have been developed over the years to facilitate the creation of interfaces between vendors and equipment, notably the interfile format for nuclear medicine and the DICOM standard for medical images. Studies can be transmitted over network communication links to other sites using telecommunication protocol standards where they can be stored and/or displayed on a wide variety of devices. This ability to move images in a well-understood format to general purpose devices using standard equipment enables the use of the Internet to disseminate nuclear medicine study information over a wide area for clinical use, research, and education. A number of universities have created Internet sites with nuclear medicine teaching files and information. As technology advances, it will be feasible to transmit medical images of all kinds to virtually anyone who needs them in near real-time, without regard to the distance between locations, or the types of instrumentation and computers used. The next few years should prove to be very interesting for digital medical imaging in general and nuclear medicine in particular.

Computer Communication Networks↗

Automated diagnosis of brain tumours astrocytomas using probabilistic neural network clustering and support vector machines.

A computer-aided diagnosis system was developed for assisting brain astrocytomas malignancy grading. Microscopy images from 140 astrocytic biopsies were digitized and cell nuclei were automatically segmented using a Probabilistic Neural Network pixel-based clustering algorithm. A decision tree classification scheme was constructed to discriminate low, intermediate and high-grade tumours by analyzing nuclear features extracted from segmented nuclei with a Support Vector Machine classifier. Nuclei were segmented with an average accuracy of 86.5%. Low, intermediate, and high-grade tumours were identified with 95%, 88.3%, and 91% accuracies respectively. The proposed algorithm could be used as a second opinion tool for the histopathologists.

Algorithms↗

[Statements of general practitioners on cooperation with specialists and a future health care system].

BACKGROUND AND PURPOSE: Ideas of general practitioners (GPs) could be of value for the restructuring of the German ambulant health care system. The way managed care is seen by GPs is of particular interest. The aim of this study was to record opinions of GPs, working in Berlin, in regard to several aspects of their daily work. METHODS: 14 female and 16 male GPs from Berlin participated in a qualitative survey. These 30 GPs were interviewed about their attitude toward cooperation with specialized colleagues and their opinions on a future medical care system. The interviews performed were summarized, structured and analyzed according to the qualitative content analysis by Mayring. RESULTS: From the GPs' point of view, ambulant cooperation is facilitated by knowing specialized colleagues, by staying in close contact to them via telephone and by being able to arrange short-term appointments with these specialists. A closer cooperation with specialists in a network as well as an advanced use of digital information systems for accessing patients' data were considered to be vital elements for a future health care system. CONCLUSION: An important reason for choosing the cooperation with specialists is to find quick comprehensive treatment strategies for patients. It may be concluded that ambulant managed care of patients could be optimized with the creation of medical networks.

Adult↗

Developing a medical image content repository for e-learning.

The integration of medical informatics and e-learning systems could provide many advanced applications including training, knowledge management, telemedicine, etc. Currently, both the domains of e-learning and medical image have sophisticated specifications and standards. It is a great challenge to bring about integration. In this paper, we describe the development of a Web interface for searching and viewing medical images that are stored in standard medical image servers. With the creation of a Web solution, we have reduced the overheads of integration. We have packaged Digital Imaging and Communications in Medicine (DICOM) network services as a component that can be used via a Web server. The Web server constitutes a content repository for searching, editing, and storing Web-based medical image content. This is a simple method by which the use of Picture Archiving and Communication System (PACS) can be extended. We show that the content repository can easily interact and integrate with a learning system. With the integration, the user can easily generate and assign medical image content for e-learning. A Web solution might be the simplest way for system integration. The demonstration in this paper should be useful as a method of expanding the usage of medical information. The construction of a Web-based repository and integrated with a learning system may be also applicable to other domains.

Computer Security↗

Neurovascular alignment in adult mouse skeletal muscles.

OBJECTIVE: Muscle blood flow increases with motor unit recruitment. The physical relationships between somatic motor nerves, which control muscle fiber contraction, and arterioles, which control microvascular perfusion, are unexplored. The authors tested the hypothesis that motor axons align with arterioles in adult skeletal muscle. METHODS: Transgenic mice (C57BL/6 background, n = 5; 10 months of age) expressing yellow fluorescent protein in all motor nerves underwent vascular casting (Microfil). Excised epitrochlearis, gracilis, gluteus maximus, and spinotrapezius muscles were imaged at 380x and 760x and a computer-integrated tracing system (Neurolucida) was used to acquire 3-dimensional digital renderings of entire arteriolar and neural networks within each muscle. RESULTS: Arteriolar networks were typically approximately 3-fold longer than neural networks. Nerves coursed with arterioles until terminating at motor endplates. Across muscles, proximity analyses revealed that approximately 75% of total nerve length (9.8-48.8 mm) lay within 200 microm of the nearest arteriole (diameters of 15-60 microm). CONCLUSIONS: Somatic motor nerves and arterioles align closely within adult mammalian skeletal muscle. Understanding the signals governing neurovascular alignment may hold important clues for the advancement of tissue engineering and regeneration.

Animals↗

A modeled economic analysis of a digital tele-ophthalmology system as used by three federal health care agencies for detecting proliferative diabetic retinopathy.

The objective of this study was to compare, using a 12-month time frame, the cost-effectiveness of a non-mydriatic digital tele-ophthalmology system (Joslin Vision Network) versus traditional clinic-based ophthalmoscopy examinations with pupil dilation to detect proliferative diabetic retinopathy and its consequences. Decision analysis techniques, including Monte Carlo simulation, were used to model the use of the Joslin Vision Network versus conventional clinic-based ophthalmoscopy among the entire diabetic populations served by the Indian Health Service, the Department of Veterans Affairs, and the active duty Department of Defense. The economic perspective analyzed was that of each federal agency. Data sources for costs and outcomes included the published literature, epidemiologic data, administrative data, market prices, and expert opinion. Outcome measures included the number of true positive cases of proliferative diabetic retinopathy detected, the number of patients treated with panretinal laser photocoagulation, and the number of cases of severe vision loss averted. In the base-case analyses, the Joslin Vision Network was the dominant strategy in all but two of the nine modeled scenarios, meaning that it was both less costly and more effective. In the active duty Department of Defense population, the Joslin Vision Network would be more effective but cost an extra 1,618 dollars per additional patient treated with panretinal laser photo-coagulation and an additional 13,748 dollars per severe vision loss event averted. Based on our economic model, the Joslin Vision Network has the potential to be more effective than clinic-based ophthalmoscopy for detecting proliferative diabetic retinopathy and averting cases of severe vision loss, and may do so at lower cost.

Cost-Benefit Analysis↗

SurvGRN: a multi-feature fusion framework for bladder cancer survival prediction.

Bladder cancer survival outcomes exhibit significant heterogeneity, influenced by multifaceted factors. While digital pathology-based survival models leveraging artificial intelligence show promise, they often overlook complementary data sources. Conversely, imaging lacks cellular detail, and genomics/proteomics entail complexity and cost. To integrate multidimensional data for enhanced survival prediction, we propose SurvGRN, a multi-feature fusion framework. SurvGRN synergistically combines clinical variables, transcriptomics, and digital pathology slides using a gated residual network architecture. Pathological features are extracted via multiple instance learning, while clinical and transcriptomic data are processed as static inputs. These features are dynamically fused using a long short-term memory (LSTM) network for comprehensive survival risk assessment. Evaluated on 400 bladder cancer patients, SurvGRN significantly outperformed existing methods: improving the C-index by 12.6% over DeepMISL; 20.6% and 7.1% over graph-based models (DeepGraphConv and Patch-GCN); and 5.4% and 4.0% over attention-based approaches (Surformer and HVTSurv). Ablation studies confirmed the contributions of pathology features (extracted via ResNet-50 pre-trained on bladder tissue), clinical/transcriptomic data, and the LSTM fusion. SurvGRN also enabled significant stratification of patients into distinct risk cohorts. This work demonstrates that holistic integration of multi-source data through tailored fusion architectures substantially improves bladder cancer survival prediction.

bladder cancer↗