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Dose in bone and tissue near bone-tissue interface from electron beam.

This work has quantitatively studied the variation of dose both within bone and in unit density tissue near bone-tissue interfaces. Dose upstream of a bone-tissue interface is increased because of an increase in the backscattered electrons from the bone. The magnitude of this effect was measured using a thin parallel-plate ionization chamber upstream of a polymethyl methacrylate (PMMA)-hard bone interface. The electron backscatter factor (EBF) increased rapidly with bone thickness until a full EBF was achieved. This occurred at approximately 3.5 mm at 2 MeV and 6 mm at 13.1 MeV. The full EBF at the interface ranged from approximately 1.018 at 13.1 MeV to 1.05 at 2 MeV. It was also observed that the EBF had a dependence on the energy spectrum at the interface. The penetration of the backscattered electrons in the upstream direction of PMMA was also measured. The dose penetration fell off rapidly in the upstream direction of the interface. Dose enhancement to unit density tissue in bone was measured for an electron beam by placing thermoluminescent dosimeters (TLDs) in a PMMA-bone-PMMA phantom. The maximum dose enhancement in bone was approximately 7% of the maximum dose in water. However, the pencil-beam algorithm of Hogstrom et al. predicted an increase of only 1%, primarily owing to the inverse-square correction. Film was also used to measure the dose enhancement in bone. The film plane was aligned either perpendicular or parallel to the central axis of the beam. The film data indicated that the maximum dose enhancement in bone was approximately 8% for the former film alignment (which was similarly predicted by the TLD measurements) and 13% for the latter film alignment. These results confirm that the X ray film is not suitable to be irritated "edge on" in an inhomogeneous phantom without making perturbation corrections resulting from the film acting as a long narrow inhomogeneous cavity within the bone. In addition, the results give the radiotherapist a basis for clinical judgment when electron beams are used to treat lesions behind bone or near bony structures. We feel these data enhance the ability to recognize the shortcomings of the current dose calculation algorithm used clinically.

Bone and Bones

Tracking multiple independent targets: evidence for a parallel tracking mechanism.

There is considerable evidence that visual attention is concentrated at a single locus in the visual field, and that this locus can be moved independent of eye movements. Two studies are reported which suggest that, while certain aspects of attention require that locations be scanned serially, at least one operation may be carried out in parallel across several independent loci in the visual field. That is the operation of indexing features and tracking their identity. The studies show that: (a) subjects are able to track a subset of up to 5 objects in a field of 10 identical randomly-moving objects in order to distinguish a change in a target from a change in a distractor; and (b) when the speed and distance parameters of the display are designed so that, on the basis of some very conservative assumptions about the speed of attention movement and encoding times, the predicted performance of a serial scanning and updating algorithm would not exceed about 40% accuracy, subjects still manage to do the task with 87% accuracy. These findings are discussed in relation to an earlier, and independently motivated model of feature-binding--called the FINST model--which posits a primitive identity maintenance mechanism that indexes and tracks a limited number of visual objects in parallel. These indexes are hypothesized to serve the function of binding visual features prior to subsequent pattern recognition.

Algorithms

Segmentation, modelling and reconstruction of arterial bifurcations in digital angiography.

The paper presents a method to model an arterial bifurcation from a pair of X-ray angiographic images. It is the initial step of a reconstruction process aiming at detecting and quantifying abnormal sites located on bifurcations. The method proposed consists of two steps. First, each image is independently segmented to extract the vessels in the images. The algorithm uses dynamic programming first to find the bifurcation centrelines from the original images, and secondly to extract vessel edges from the morphological gradient images, under a constraint of parallelism with the previously detected centrelines. Then, a three-dimensional bifurcation model is built by adapting cylinders around the three-dimensional bifurcation centrelines. These cylinders are obtained as a stack of binary orientable ellipses fitted to the projection densities in the corresponding cross-sections. Results obtained on simulated data, phantom and femoral bifurcations are displayed.

Angiography, Digital Subtraction

PRISM: privacy-preserving rare disease analysis using fully homomorphic encryption.

MOTIVATION: Rare diseases affect millions of people worldwide, yet their genomic foundations remain poorly understood due to limited patient data and strict privacy regulations, such as the General Data Protection Regulation (GDPR) (https://gdpr.eu/tag/gdpr/) in March 2025. These restrictions can hinder the collaborative analysis of genomic data necessary for uncovering disease-causing variants. RESULTS: We present PRISM, a novel privacy-preserving framework based on fully homomorphic encryption (FHE) that facilitates rare disease variant analysis across multiple institutions without exposing sensitive genomic information. To address the challenges of centralized trust, PRISM is built upon a Threshold FHE scheme. This approach decentralizes key management across participating institutions and ensures no single entity can unilaterally decrypt sensitive data. Our method filters disease-causing variants under recessive, dominant, and de novo inheritance models entirely on encrypted data. We propose two algorithmic variants: a multiplication-intensive (MUL-IN) approach and an addition-intensive (ADD-IN) approach. The ADD-IN algorithms minimize the number of costly multiplication operations, enabling up to a 17× improvement in runtime for recessive/dominant filtering and 22× for de novo filtering, compared to MUL-IN methods. While ADD-IN produces larger ciphertexts, efficient parallelization via SIMD and multithreading allows it to handle millions of variants in reasonable time. To the best of our knowledge, this is the first study that utilizes FHE for privacy-preserving rare disease analysis across multiple inheritance models, demonstrating its practicality and scalability in a single-cloud setting. AVAILABILITY AND IMPLEMENTATION: The source code and the data used in this work can be found in https://github.com/mdppml/PRISM.git.

Computer Security

Cone-beam transmission computed tomography for nonuniform attenuation compensation of SPECT images.

This paper develops and tests cone-beam transmission computed tomography (CB-CT) for attenuation compensation of SPECT images. CB-CT was implemented on a rotating gamma camera with a point source (1-2 mCi) of 99mTc, and a light-weight aluminum source holder. A cone-beam collimator may be used but is not required. Since the point source is either located at the collimator focal point, or the camera is uncollimated, CB-CT has excellent sensitivity (at least 150 times that of a parallel-hole, high-resolution collimator). The predicted resolution is equal to the intrinsic gamma camera resolution (3-4 mm), which is much higher than for a high-resolution, parallel-hole collimator (10-20 mm). In the present study, CB-CT provided low noise, high-resolution attenuation maps for use in a nonuniform attenuation-weighted backprojection algorithm. The attenuation compensation accuracy was tested using basic geometries of line sources and nonuniform density models. For the appropriate scaling of the attenuation map, the attenuation compensation was accurate and removed the SPECT image distortion associated with nonuniform attenuation. Attenuation maps acquired either with cone beam collimator or without any collimator were both successful. Using CB-CT, SPECT can thus be made much more accurate without adding unduly to the imaging time, complexity, or cost.

Algorithms

An automated geometric modeling framework in GATE for the design and optimization of high-sensitivity converging-beam SPECT collimators.

Objective.The trade-off between detection sensitivity and spatial resolution is a fundamental challenge in designing organ-dedicated Single-photon emission computed tomography (SPECT) collimators. While converging-hole geometries offer a solution, their optimization is often hindered by the lack of flexible computational tools capable of modeling large-scale, non-parallel hole arrays. This study aims to develop an automated geometric modeling framework to facilitate the design and evaluation of complex converging- and diverging-hole collimators within standard Monte Carlo environments.Approach.We developed a specialized modeling framework by implementing custom C++ classes and a vector-based alignment algorithm within GATE. This platform enables automated, orientation-consistent construction of large-scale converging arrays not natively supported by standard implementations. A high-sensitivity pure cone-beam collimator (CBC) was designed using this framework. The evaluation used hot-rod, disc, and Jaszczak phantoms for physical characterization, while XCAT and dedicated brain models were employed for clinical tasks, including cardiac, brain perfusion, and DaTscan SPECT simulations.Main results.The CBC achieved a nearly fourfold sensitivity increase compared to a conventional low-energy high-resolution parallel-hole collimator at a 20 cm radius of rotation, while maintaining comparable spatial resolution. Despite a 52.3% field of view reduction, the CBC yielded a 2.2-fold noise reduction (CV: 11.7% vs 25.9%) and mitigated partial volume effects via geometric magnification. XCAT and brain phantom simulations confirmed enhanced anatomical definition and contrast recovery in cardiac, perfusion, and DaTscan tasks.Significance.This work provides an efficient computational tool for rapid design space exploration of advanced collimator geometries. The results demonstrate that the proposed CBC design offers a significant sensitivity advantage, making it highly suitable for high-performance, small-volume clinical applications such as brain and cardiac molecular imaging.

Tomography, Emission-Computed, Single-Photon

Clustering a large number of compounds. 2. Using the Connection Machine.

About 230,000 compounds in the National Cancer Institute Repository are available for screening under a new protocol. This paper is the second on an project to extract a representative sample of these compounds by clustering. The clustering program was implemented on the Connection Machine, a massively parallel computer with 16K processing elements. This implementation reduced a formidable task to a relatively routine run.

Algorithms

[SPECT images using a multislice fan beam collimator].

Several methods to improve the image resolution of single photon emission computed tomography (SPECT) occur to us. It is one method to use multislice fan beam collimators which have the parallel collimation along the cephalic-caudul axis of a patient and the conversing collimation within planes parpendicular to that axis. It is impossible to obtain corrective image when we used the algorithm which is commonly used for reconstruction of SPECT images. We proposed a reconstruction algorithm for multislice fan beam collimator in this paper. An interpolation method developed for fan beam type X-ray CT was modified to reconstruct images from SPECT with multislice fan beam collimator. This algorithm was confirmed by means of computer simulation studies. Beside improving the system resolution by effectively reducing the intrinsic resolution of the cameras, this collimator also increases the system sensitivity by utilizing a large fraction of the crystal area. We have thought that to use multislice fan beam collimator is beneficial for SPECT images.

Tomography, Emission-Computed

Visual and auditory association areas of the cat's posterior ectosylvian gyrus: thalamic afferents.

The feline posterior ectosylvian gyrus contains a broad band of association cortex that is bounded anteriorly by tonotopic auditory areas and posteriorly by retinotopic visual areas. To characterize the possible functions of this cortex and to throw light on its pattern of internal divisions, we have carried out an analysis of its thalamic afferents. Deposits of differentiable retrograde tracers were placed at 17 cortical sites in nine cats. The deposit sites spanned the crown of the posterior ectosylvian gyrus and adjacent cortex in the suprasylvian sulcus. We compiled counts of retrogradely labeled neurons in 12 thalamic nuclei delineated by use of Nissl and acetylcholinesterase stains. We then employed a statistical clustering algorithm to identify groups of injections that gave rise to similar patterns of thalamic labeling. The results suggest that the posterior ectosylvian gyrus contains 3 fundamentally different cortical districts that have the form of parallel vertical bands. Very anterior cortex, overlapping previously identified tonotopic auditory areas (AI, P and VP) receives a dense projection from the laminated division of the medial geniculate body (MGl). An intermediate strip, to which we refer as the auditory belt, is innervated by axons from nontonotopic divisions of the medial geniculate body (MGds, MGvl, MGm, and MGd), from the lateral division of the posterior group (Pol), and from the posterior suprageniculate nucleus (SGp). A posterior strip, to which we refer as EPp, receives strong projections from the LM-SG complex (LM-SGa and LMp), and lighter projections from the intralaminar and lateroposterior (LPm and LPl) nuclei. On grounds of thalamic connectivity, EPp is not obviously distinguishable from adjacent retinotopic visual areas (PLLS, DLS, and VLS), and may be regarded as forming, together with these areas, a connectionally homogeneous visual belt.

Animals

A dosimetric comparison of three compensator design methods for the mantle field.

The mid-plane dose was measured in an anthropomorphic phantom for parallel opposed mantle fields as typically used in the treatment of Hodgkin's Disease. Doses were measured for four cases: no compensator, a compensator designed by a three-dimensional CT based treatment planning algorithm, a compensator designed from a port film, and a compensator designed from surface topography. The results showed all three compensators gave a significant better dose distribution than using no compensator at all. Without a compensator, doses varied from 92 percent to 131 percent, with a standard deviation of 10.9 percent for 65 measured points. The treatment planning algorithm gave the best performance with a standard deviation of 3.2 percent with all points but three within 5 percent out of the 65 points measured, and no points outside of 10 percent. The port film compensator was next best with a standard deviation of 4.4 percent, with 19 points outside of 5 percent, and doses from 88 to 106 percent. The surface topography compensator had a standard deviation of 6.1 percent with 31 points outside of 5% and doses from 89 to 114 percent.

Hodgkin Disease

A novel method for across-chromosome phasing without relative data.

MOTIVATION: Across-chromosome phasing identifies which haplotypes of different chromosomes come from the same parent. This differs from within-chromosome phasing, which uses linkage disequilibrium patterns to determine which alleles were co-inherited within each chromosome but does not match haplotypes across different chromosomes. While across-chromosome phasing can be conducted using genotypes from parents or close relatives, current methods perform poorly for samples of unrelated individuals. Here, we introduce a novel approach for across-chromosome phasing that employs a window-based SNP-similarity metric, eliminating the need for data from close relatives or detection of identical-by-descent haplotypes. RESULTS: Using UK Biobank offspring with both parents genotyped as a gold standard, we evaluated the performance of our method by phasing the offspring without using parental data. In genomic data with no within-chromosome phase errors, our algorithm achieved a mean across-chromosome phasing accuracy of 95%, with 53% of individuals phased perfectly. When data was pre-phased computationally using a standard within-chromosome phasing algorithm, mean accuracy for across-chromosome phasing dropped to 83.1%. Thus, our method is limited primarily by the accuracy of within-chromosome phasing accuracy and can approach near-perfect across-chromosome phasing accuracy as within-chromosome phasing accuracy improves. AVAILABILITY AND IMPLEMENTATION: The implementation was executed within a multi-node computational environment of University of Colorado Boulder Research Computing (Blanca Cluster: https://www.colorado.edu/rc/resources/blanca), employing parallelization techniques in the C programming language. The source code has been made publicly accessible online at https://github.com/emmanuelsapin/AcrossChromosomesPhasing, thereby facilitating reproducibility of the results for researchers with authorized access to the UK Biobank dataset.

Algorithms

Cone beam tomography of the heart using single-photon emission-computed tomography.

The authors evaluated cone beam single-photon emission-computed tomography (SPECT) of the heart. A new cone beam reconstruction algorithm was used to reconstruct data collected from "short scan" acquisitions (of slightly more than 180 degrees) of a detector anteriorally traversing a noncircular orbit. The less than 360 degrees acquisition was used to minimize the attenuation artifacts that result from reconstructing posterior projections of 201T1 emissions from the heart. The algorithm includes a new method for reconstructing truncated projections of background tissue activity that eliminates reconstruction ring artifacts. Phantom and patient results are presented which compare a high-resolution cone beam collimator (50-cm focal length; 6.0-mm full width at half maximum [FWHM] at 10 cm) to a low-energy general purpose (LEGP) parallel hole collimator (8.2-mm FWHM at 10 cm) which is 1.33 times more sensitive. The cone beam tomographic results are free of reconstruction artifacts and show improved spatial and contrast resolution over that obtained with the LEGP parallel hole collimator. The limited angular sampling restrictions and truncation problems associated with cone beam tomography do not deter from obtaining diagnostic information. However, even though these preliminary results are encouraging, a thorough clinical study is still needed to investigate the specificity and sensitivity of cone beam tomography.

Algorithms

Simultaneous multinuclear magnetic resonance imaging and spectroscopy.

A technique has been developed to perform simultaneous multinuclear magnetic resonance imaging and spatially localized spectroscopy. It is inherently superior in terms of time efficiency over current approaches which use sequential or interleaved methods. The pulse sequence uses a parallel excitation and acquisition scheme to acquire multislice proton images concurrently with phosphorus-31 spectroscopic images. Because the phosphorus signal is necessarily collected in the presence of a gradient, an essential element of the technique is an algorithm to extract pure chemical-shift information.

Algorithms

Mathematical resolution of mixed in vivo voltammetry signals. Models, equipment, assessment by simultaneous microdialysis sampling.

A microcomputer-assisted curve-fitting procedure was developed for the quantitative estimation of the components of the mixed "catechol peak" recorded with differential normal pulse voltammetry (DNPV) at electrochemically pretreated carbon fiber microelectrodes in the living brain. The contribution of each of the relevant electroactive species is fitted by a normal probability function, the parameters of which are previously determined in vitro for each electrode and substance. The voltammogram is thus modeled as a mixture of normal curves corresponding to the individual oxidizable substances plus a low order polynomial approximating the baseline. In a former approach the function was solved by linear least squares techniques. As a further improvement, we now propose a non-linear model of the voltammogram and a Gauss-Newton iterative algorithm with stepwise regression for parameter estimation. This report shows the application of the method for the resolution of the dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) components of the DNPV signal recorded from the striatum of freely moving animals in response to amphetamine and pargyline. The method was validated by the chemical assay of contralateral microdialysates collected simultaneously. The changes detected by both methodologies were closely parallel, with highly significant correlation coefficients (0.87 and 0.99 for DA and DOPAC, respectively, P less than 0.001). This study further illustrates that the in vivo voltammetry methodology can be improved substantially by incorporating a suitable mathematical treatment of the electrochemical signals.

3,4-Dihydroxyphenylacetic Acid

Scattered wave inversion by image projections.

A three-dimensional diffraction tomography algorithm based on image projections is implemented. For each view, the measured scattered field is directly backpropagated onto a single plane in the image space. The backpropagated field evaluated on the plane is defined as the image projection because it closely approximates the straight line projection of the object. The object is then reconstructed by parallel slices using conventional straight ray tomographic techniques. This approach permits practical three-dimensional reconstruction using a limited number of views. The reconstructions made with image projections are of comparable quality to ideal diffraction-limited images. By backpropagating the field prior to filtering, curved or misaligned recording surfaces can be used. The limits on the image projection technique for multiple object systems are explored. A diffuse structure is reconstructed.

Algorithms

Integrating NECTIN4 Amplification With Membranous Nectin-4 Expression to Develop a Scoring System for Predicting Enfortumab Vedotin Response in Urothelial Carcinoma.

PURPOSE: Enfortumab vedotin (EV) is standard therapy for metastatic urothelial carcinoma (mUC), yet the predictive relevance of NECTIN4 expression-especially membranous versus cytoplasmic-remains unclear. Here, we sought to extend previous findings on NECTIN4 gene amplification in parallel with a systematic subcellular evaluation of NECTIN4 expression. EXPERIMENTAL DESIGN: We retrospectively analyzed 179 EV-treated mUC patients. NECTIN4 amplification was assessed by FISH and NECTIN4 protein levels by IHC. A four-tier membranous scoring algorithm (0,1+,2+,3+) adapted from CAP HER2 gastric guidelines was benchmarked against H-score. We integrated amplification status with membranous staining to refine predictive stratification and compared associations with objective response rate (ORR) to EV-301 data. RESULTS: Combining membranous and cytoplasmic compartments resulted in a median composite H-score of 260 (78.2% &#x2265;150), closely matching NECTIN4 expression prevalence reported in EV-301 (median 250; 82.6% &#x2265; 150). A &#x2265;150 cut-off enriched for EV responders in both cohorts; in EV-301 with ORR of 45.8% vs. 20% (P = 0.001). High membranous expression based on the scoring (2+/3+) predicted response (ORR 55.1% vs. 25.5%; P < 0.001), with longer PFS (7.1 vs. 2.9 months; HR 0.45) and OS (12.3 vs. 6.9 months; HR 0.57), whereas cytoplasmic expression lacked predictive value. NECTIN4-amplified tumors showed particularly favorable outcomes (PFS 12.2 months; OS 30.1 months). An integrated three-tier model-amplified, non-amplified/high-membranous, and non-amplified/low-membranous-yielded ORRs of 77.2%, 42.9%, and 26.1% and separated survival outcomes. CONCLUSIONS: Our NECTIN4 scoring system integrating NECTIN4 amplification with membranous NECTIN4 expression accurately predicts outcomes, supporting combined genomic and membranous assessment as complementary biomarkers for optimizing EV selection.

Journal Article

Using SEEK for multichannel pattern recognition.

The author's work on computerized analysis of the 2-channel, 24-hr electrocardiogram has previously resulted in the development of multichannel signal processing systems that learn by observation. A new tool for implementing such algorithms is described: the pattern recognition language SEEK. Programs written in SEEK build a knowledge base containing treelike data structures, each of which stores acquired information about a particular multichannel waveform. Input data are interpreted by performing an efficient parallel evaluation of the structures in the knowledge base. The work is applicable to a wide variety of pattern recognition problems that arise in medical signal processing. The approach is illustrated with examples drawn from ECG analysis.

Computers

Accuracy in clinical electron beam dose planning using pencil beam algorithms.

The accuracy of two different pencil beam models for electron beam dose planning is shown by comparisons with measured dose distributions. The investigation is restricted to two-dimensional geometries. In one model the multiple scattering of the electrons is considered by the small angle Gaussian approximation of Fermi and Eyges. In the other, the generalized Gaussian model, the large angle single scattering events are also considered. The parallel slab approximation is used in both models. The comparisons have been made for two different anatomical phantoms. One phantom was constructed to simulate a transversal cross-section through the chest wall and lung in radiotherapy of breast cancer. The other phantom was made to simulate the head at the level of the nose. The measurements in these phantoms were made with thermoluminescence dosimetry, LiF rods. The accuracy of the oblique incidence case was investigated in a homogenous water phantom. The results show that for oblique incidence and geometries where the semi-infinite slab approximation is reasonably good, the generalized Gaussian model is more accurate. Within and behind low density cavities, in the phantom, the Gaussian model often gives a better agreement to experimental data. This is shown to be due to mutually balancing errors from the semi-infinite slab approximation and the Gaussian approximation.

Algorithms