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PubMed1998

Compression of the upper cervical spinal cord causing symptoms of brainstem compromise. A case report.

STUDY DESIGN: A case is reported in which a flexion-induced compression of the upper cervical spinal cord caused symptoms of brainstem compromise in the absence of radiographic evidence of osseous instability. OBJECTIVES: A 41-year-old woman developed postoperative cervical instability with flexion-induced neurologic symptoms referable to the brainstem. The instability was caused by direct compression at the third cervical vertebral body, which in turn was caused by differential movements between the neuraxis and skeletal elements in the upper cervical spine. SUMMARY OF BACKGROUND DATA: Pathologic processes at the craniocervical junction may cause brainstem compromise with neurologic symptoms. The mechanism of brainstem involvement is usually either vertebrobasilar insufficiency or direct mechanical compression. In cases where the brainstem is compressed by skeletal elements, the compressing osseous structures usually are the walls of the foramen magnum or the odontoid process, or, less frequently, the atlas or axis vertebrae. Symptoms of brainstem dysfunction caused by dynamic compression at the level of the third cervical vertebra in the absence of hindbrain herniation are unusual and, to the best of the authors' knowledge, have not been described previously. METHODS: The patient underwent initial examination, evaluation, and periodic follow-up examination with magnetic resonance imaging from the time of her first visit until 26 months after the surgical treatment. The patient experienced postsurgical instability with dynamic compression by the C3 vertebral body, which caused brainstem compromise. Surgical treatment consisted of decompressive C3 corpectomy and fusion of C2 to C6, supplemented by anterior fixation. RESULTS: After undergoing surgical decompression of C3, reconstruction, and anterior internal fixation of C2 to C6, the patient had dramatic neurologic improvement. Diplopia, paresthesia, and nystagmus disappeared immediately after surgery. Swallowing difficulties, hoarseness, and vertigo improved gradually. At follow-up examination 26 months after surgery, the patient was asymptomatic. Magnetic resonance imaging showed good position of the construct, with no evidence of compression of the spinal cord or brainstem. CONCLUSIONS: Instability of the cervical spine may result in symptoms of brainstem dysfunction, even in the absence of hindbrain herniation. This instability is explained by the differential movement between the bony structures and neuraxis in the upper cervical region. Diagnosis and adequate management of this instability alleviates the neurologic symptoms and prevents possible hazardous complications.

Adult↗
PubMed1999

Detection and statistical analysis of human cortical sulci.

Many studies dealing with the human brain use the spatial coordinate system of brain anatomy to localize functional regions. Unfortunately, brain anatomy, and especially cortical sulci, is characterized by a high interindividual variability. Specific tools called anatomical atlases must then be considered to make the interpretation of anatomical examinations easier. The work described here first aims at building a numerical atlas of the main cortical sulci. Our system is based on a database containing a collection of anatomical MRI of healthy volunteer brains. Their sulci have been manually drawn and labeled for both hemispheres. Sulci are represented as 3D superficial curves. After a nonlinear registration process, a statistical atlas of the cortical topography of a particular MRI is built from the database. It is an a priori model of cortical sulci, including three major components: an average curve represents the average shape and position of each sulcus; a search area accounts for its spatial variation domain; a set of quantitative parameters describes the variability of sulci geometry and topology. This atlas is completely individualized and adapted to the features of the brain under examination. The atlas is represented by a graph, the nodes of which represent sulci and the edges the relations between sulci. It can also be considered a statistical model that describes the cortical topography as well as its variability.

Adult↗
PubMedDate not supplied

Detection and mapping of abnormal brain structure with a probabilistic atlas of cortical surfaces.

PURPOSE: We have devised, implemented, and tested a technique for creating a comprehensive probabilistic atlas of the human cerebral cortex, based on high-dimensional fluid transformations. The goal of the atlas is to detect and quantify subtle and distributed patterns of deviation from normal cortical anatomy, in a 3D brain image from any given subject. METHOD: Given a 3D MR image of a new subject, a high-resolution surface representation of the cerebral cortex is automatically extracted. The algorithm then calculates a set of high-dimensional volumetric maps, fluidly deforming this surface into structural correspondence with other cortical surfaces, selected one by one from an anatomic image database. The family of volumetric warps so constructed encodes statistical properties of local anatomical variation across the cortical surface. Additional strategies are developed to fluidly deform the sulcal patterns of different subjects into structural correspondence. A probability space of random transformations, based on the theory of anisotropic Gaussian random fields, is then used to encode information on complex variations in gyral and sulcal topography from one individual to another. A complete system of 256(2) probability density functions is computed to reflect the observed variability in stereotaxic space of the points whose correspondences are found by the warping algorithm. Confidence limits in stereotaxic space are determined for cortical surface points in the new subject's brain. RESULTS: Color-coded probability maps are generated, which highlight and quantify regional patterns of deformity in the anatomy of new subjects. These maps indicate locally the probability of each anatomic point being as unusually situated, given the distributions of corresponding points in the scans of normal subjects. 3D MRI volumes are analyzed, from subjects with clinically determined Alzheimer disease and age-matched normal subjects. CONCLUSION: Applications of the random fluid-based probabilistic atlas include the transfer of multisubject 3D functional, vascular, and histologic maps onto a single anatomic template, the mapping of 3D atlases onto the scans of new subjects, and the rapid detection, quantification, and mapping of local shape changes in 3D medical images in disease and during normal or abnormal growth and development.

Aged↗
PubMedDate not supplied

An early hand-wrist atlas and its implications for secular change in bone age.

A little-known 'Skiagraphic Atlas' documenting radiographic changes in the bones of the hand and wrist was published by Poland in 1898. Nineteen skiagrams of British children, 1-17 years of age, were included. Tanner-Whitehouse-2 bone ages were assessed for 15 individuals in this series and differences from chronological ages were calculated. Mean differences for 20-bone, RUS and carpal bone ages are significantly larger than zero. Hence, these children were relatively advanced compared to present children. Comparisons of Poland's expected ages for onset and fusion of secondary ossification centres in the hand and wrist with more recent reference data indicated a secular increase in the rates of skeletal maturation of approximately 0.22-0.66 year/decade, with relatively greater change in expected ages of fusion.

Adolescent↗
PubMed2002

Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.

An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463-468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high-resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254-266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps.

Brain↗
PubMed2005

Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei.

In a previous study, a three-dimensional (3D) MRI atlas of the human cerebellar nuclei was introduced based on findings in one healthy human subject [Dimitrova, A., Weber, J., Redies, C., Kindsvater, K., Maschke, M., Kolb, F.P., Forsting, M., Diener, H.C., Timmann, D., 2002. MRI atlas of the human cerebellar nuclei. NeuroImage 17, 240-255]. The present MRI investigation was designed to study variability of the anatomy of the dentate/interposed nuclei in a larger group of healthy subjects. Similar to our previous study, iron-induced susceptibility artifacts were used to visualize the cerebellar nuclei as hypointensities on MR images. Data of 63 healthy subjects (27 female, 36 male; mean age 45.3+/-13.4 years, age range 22--71 years) were included. A 3D axial volume of the cerebellum was acquired using a T2*-weighted FLASH sequence on a Siemens Sonata 1.5 T MR scanner. Each volume was registered, re-sampled to 1.00 x 1.00 x 1.00 mm(3) voxel size and spatially normalized into a standard proportional stereotaxic space using SPM99. Dentate/interposed nuclei were traced on axial images and saved as regions of interest using MRIcro-software by two independent examiners. A probabilistic 3D MRI atlas of the cerebellar dentate/interposed nuclei is presented based on findings in all subjects.

Adolescent↗
PubMed1995

[Normal cerebral perfusion of 99mTc-HMPAO brain SPECT--evaluation by ananatomical standardization technique].

Single photon labeled tracer 99mTc-hexamethylpropylene amine oxime (HMPAO) has been used for rCBF studies by SPECT. However, normal perfusion pattern of this agent still remains unclear. The purpose of this study was to investigate normal 99mTc-HMPAO SPECT image voxel by voxel. Eighteen male subjects without any prior or present history of medical illness participated in this study. All SPECT images were globally normalized to 100 count/voxel. Each subject had an X-ray CT scan at the same day of SPECT measurement. All subjects had normal X-ray CT scans. The standard anatomical structures of the computerized brain atlas of Roland et al. were fitted to X-ray CT images of a subject by linear and non-linear parameters. These parameters were subsequently used to transform SPECT images of the subject. After the anatomical standardization, mean and SD images of eight standardized images were calculated voxel-by-voxel basis. In the mean image, following structures showed relatively higher radioactivity; the putamen, the cerebellum, and the frontal lobe. In addition, the occipital lobe, parietal lobe, frontal lobe, and the putamen showed large degree of SD. Anatomical standardization of SPECT images may be useful as a reference to diagnose and evaluate various brain disorders.

Adult↗
PubMed2003

Attenuation compensation in cerebral 3D PET: effect of the attenuation map on absolute and relative quantitation.

It is generally well accepted that transmission (TX)-based non-uniform attenuation correction can supply more accurate absolute quantification; however, whether it provides additional benefits in routine clinical diagnosis based on qualitative interpretation of 3D brain positron emission tomography (PET) images is still the subject of debate. The aim of this study was to compare the effect of the two major classes of method for determining the attenuation map, i.e. uniform versus non-uniform, using clinical studies based on qualitative assessment as well as absolute and relative quantitative volume of interest-based analysis. We investigated the effect of six different methods for determining the patient-specific attenuation map. The first method, referred to as the uniform fit-ellipse method (UFEM), approximates the outline of the head by an ellipse assuming a constant linear attenuation factor (mu=0.096 cm(-1)) for soft tissue. The second, referred to as the automated contour detection method (ACDM), estimates the outline of the head from the emission sinogram. Attenuation of the skull is accounted for by assuming a constant uniform skull thickness (0.45 cm) within the estimated shape and the correct micro value (0.151 cm(-1)) is used. The usual measured transmission method using caesium-137 single-photon sources was used without (MTM) and with segmentation of the TX data (STM). These techniques were finally compared with the segmented magnetic resonance imaging method (SMM) and an implementation of the inferring attenuation distributions method (IADM) based on the digital Zubal head atlas. Several image quality parameters were compared, including absolute and relative quantification indexes, and the correlation between them was checked. The qualitative evaluation showed no significant differences between the different attenuation correction techniques as assessed by expert physicians, with the exception of ACDM, which generated artefacts in the upper edges of the head. The mean squared error between the different attenuation maps was also larger when using this latter method owing to the fact that the current implementation of the method significantly overestimated the head contours on the external slices. Correlation between the mean regional cerebral glucose metabolism (rCGM) values obtained with the various attenuation correction methods and those obtained with the gold standard (MTM) was good, except in the case of ACDM (R(2)=0.54). The STM and SMM methods showed the best correlation (R(2)=0.90) and the regression lines agreed well with the line of identity. Relative differences in mean rCGM values were in general less than 8%. Nevertheless, ANOVA results showed statistically significant differences between the different methods for some regions of the brain. It is concluded that the attenuation map influences both absolute and relative quantitation in cerebral 3D PET. Transmission-less attenuation correction results in a reduced radiation dose and makes a dramatic difference in acquisition time, allowing increased patient throughput.

Algorithms↗
PubMed2005

Lagrangian frame diffeomorphic image registration: Morphometric comparison of human and chimpanzee cortex.

We develop a novel Lagrangian reference frame diffeomorphic image and landmark registration method. The algorithm uses the fixed Langrangian reference frame to define the map between coordinate systems, but also generates and stores the inverse map from the Eulerian to the Lagrangian frame. Computing both maps allows facile computation of both Eulerian and Langrangian quantities. We apply this algorithm to estimating a putative evolutionary change of coordinates between a population of chimpanzee and human cortices. Inter-species functional homologues fix the map explicitly, where they are known, while image similarities guide the alignment elsewhere. This map allows detailed study of the volumetric change between chimp and human cortex. Instead of basing the inter-species study on a single species atlas, we diffeomorphically connect the mean shape and intensity templates for each group. The human statistics then map diffeomorphically into the space of the chimpanzee cortex providing a comparison between species. The population statistics show a significant doubling of the relative prefrontal lobe size in humans, as compared to chimpanzees.

Algorithms↗
PubMed2005

Anatomical data on the craniocervical junction and their correlation with degenerative changes in 30 cadaveric specimens.

OBJECT: The goal of this project was to measure vertebral dimensions at the craniocervical junction and to investigate degenerative changes in this region and their correlations with the anatomical data. These studies will assist in an understanding of biomechanical conditions in this region, which are clinically relevant in cases of cervicogenic headaches and vertigo. METHODS: The authors examined 30 cadaveric specimens obtained from patients ranging in age from 24 to 88 years at death. Measurements of angles of the vertebrae were conducted using an imprint method. Microsections of osseous endplates and articular cartilage were graded according to their degrees of degeneration by using the Petersson classification (0, no sign of degeneration; I, superficial degeneration with several fragmentations; II, deeper degeneration with cartilaginous disintegration and penetrating ulceration; or III, complete cartilaginous degeneration with the appearance of subchondral bone in > 50% of the articular surface). The authors found Grade I changes in 100% of the occiput specimens. In the superior articular cartilage of C-1 no changes (Grade 0) were found in two specimens, whereas 6% of the specimens exhibited Grade II changes and 89% exhibited Grade I changes. In the inferior articular cartilage of C-1, 57% of the specimens displayed Grade I changes, 14% Grade II, and 20% Grade III changes. In the superior articular cartilage of C-2, 62.5% of the specimens displayed Grade I changes and 25% Grade II changes. At the occiput-C1 level the authors found a higher frequency of degeneration at the upper left articular surface of the atlas (Quadrants 1 and 3), and at the C1-2 level they found a higher frequency of degeneration at the upper left and upper right articular surfaces of the axis (Quadrants 2 and 3, respectively). Using the McNemar test, the authors investigated the frequency of affection of single quadrants in a left-right side comparison (lateral reversal). Significant differences were identified for Quadrant 2 of the upper left articular surface of C-2 and Quadrant 3 of the upper right articular surface of C-2. These results correlate with the analysis of single articular surfaces of the axis, but contradict the results for the atlas, in which no significant difference in the left-right side comparison was found. CONCLUSIONS: Severe degeneration in the atlantooccipital joints appears to be a rare condition, with no Grade II or III degeneration found in the occipital condyles and 6% Grade I, 89% Grade II, but no Grade III changes in the superior articular cartilage of the atlas. Degeneration of the inferior articular cartilage of C-1 and the superior articular cartilage of C-2 indicates that the atlantoaxial joint faces more intense mechanical exposure, which is increased at the upper joint surfaces.

Adult↗
PubMed1989

A computer based handbook and atlas of pathology.

The Diagnostic Encyclopaedia Workstation (DEW) is a computerized handbook of pathology intended for use in diagnostic practice. It consists of a combination of a personal computer (PC), a video disc player (VDP), for which a specially developed disc is used, two monitors, a mouse and software. The hard disc of the computer contains textual information on diagnoses in categories such as macroscopy, common histology, immunopathology, clinical observations and prognosis and case histories. This information is frequently illustrated by pictures on a video disc which is automatically addressed by the computer software. All pictures, at present some 3000, pertain to case histories which are included in the system. Also integrated are classification aids in two categories: diagnostic criteria and differential diagnosis. Advantages of DEW over the use of conventional manuals are 1) the extensive volume of text, 2) the large number of high quality illustrations, 3) the immediate access to cross references and 4) the potential for continuous revision.

Anatomy, Artistic↗
PubMed2004

Cingulotomy for psychiatric disease: microelectrode guidance, a callosal reference system for documenting lesion location, and clinical results.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI)- and microelectrode recording-guided cingulotomy for patients with psychiatric disorders and to develop a new method of mapping lesion location in anterior cingulate cortex that takes into account the significant interindividual variability in callosal morphometry. METHODS: MRI and microelectrode recording were used to guide placement of radiofrequency lesions in patients with obsessive-compulsive disorder (n = 21) or affective disorders (n = 5). Postoperative improvement was evaluated with the Yale-Brown Obsessive-Compulsive Scale in 15 of the 21 obsessive-compulsive disorder patients studied. From the postoperative MRI scans, we developed a coordinate system for position in the anterior cingulate cortex. The callosal line passes from the most anterior point of the corpus callosum (c = 0) to the most posterior (c = 100). We reconstructed the lesions onto a sagittal map from the Talairach and Tournoux atlas using the distance along the callosal line and the distance above the upper surface of the corpus callosum. RESULTS: The location of neuronal activity distinguished gray and white matter and was useful in delineating the upper and lower cortical banks of the cingulate gyrus, the cingulate bundle, and the corpus callosum. This information was used to place the lesions. Lesions typically were 6 to 8 mm in diameter on T2-weighted MRI scans. The inferior margins were along the corpus callosum from c = 16 to c = 38. Four of 15 patients with obsessive-compulsive disorder had a documented decrease of more than 35% on the Yale-Brown Obsessive-Compulsive Scale, but only one patient had a sustained benefit for more than 1 year. CONCLUSION: Microelectrode recording is useful for lesion placement. Our system for reporting location in anterior cingulate cortex normalizes for differences in callosal morphometry. These techniques may aid future study.

Adult↗
PubMed2003

Emerging ethical issues in instructions to authors of high-impact biomedical journals.

Public interest in issues concerning the maintenance of high ethical standards in the conduct of scientific research and its publication has been increasing. Some of the developments in these issues as reflected in the publication of the medical literature are traced here. This paper attempts to determine whether public interest is reflected in the specific requirements for authors for manuscript preparation as stated in the "Instructions to Authors" for articles being prepared for submission to 124 "high-impact" journals. The instructions to authors of these journals were read on the Web for references to ethical standards or requirements. The ethical issues that the instructions most often covered were specifically related to the individual journal's publication requirements. The results suggest that while the editors and publishers of the biomedical literature are concerned with promoting and protecting the rights of the subjects of the experiments in the articles they publish, and while these concerns are not yet paramount, they are evolving and growing.

Authorship↗
PubMed1994

C1 burst fracture.

OBJECTIVE: The presentation of a patient to a chiropractic office with an undiagnosed C1 burst fracture (Jefferson fracture) secondary to head trauma from a motor vehicle accident is introduced. CLINICAL FEATURES: A 67-yr-old real estate manager suffered from neck pain and stiffness following release from a major metropolitan medical center. Anteroposterior open mouth radiographic examination of the cervical spine revealed 10-mm displacement of the lateral masses of C1 relative to the superior articulating facets of C2, indicating the presence of a C1 burst fracture with possible disruption of the transverse ligament. INTERVENTION AND OUTCOME: The patient was transferred by ambulance to a local medical center where a CT scan of the cervical spine and neurosurgical evaluation were obtained. The patient's cervical spine was immobilized in a Philadelphia collar for 3 months. Follow-up radiographic evaluation indicated nonunion of the fracture fragments and the patient was referred for further neurosurgical consultation. CONCLUSION: The presumption of proper and competent prior medical treatment, without confirmation by radiographic examination and review of records, could have resulted in catastrophic consequences for this patient, had chiropractic manipulation been performed. A history of trauma should be a clear signal to the chiropractic practitioner that they should proceed with caution, regardless of the patient's prior history of examination and treatment.

Aged↗
PubMed2025

A pluripotent stem cell atlas of multilineage differentiation.

Human pluripotent stem cells offer a scalable platform to study genetic and signalling mechanisms governing cell lineage decisions during differentiation. Genome-wide and single-cell transcriptomics technologies likewise offer high-throughput analysis of heterogeneous cell differentiation states. While in vivo development has been extensively characterised using these technologies, there remains a need for comprehensive single-cell transcriptomic profiling of stem cell differentiation from pluripotency. Understanding gene expression changes governing differentiation in vitro is key to developing high fidelity differentiation protocols and understanding fundamental mechanisms of development. We generated a single-cell RNA sequencing time course to study the role of developmental signalling pathways on multilineage diversification from pluripotency in vitro. The combined dataset of over 60,000 cells spans cell types from a time course of differentiation across all germ layers, ranging from gastrulation cell states to progenitor and committed cell types. These data provide a diverse benchmarking reference point to compare against in vivo development and advance understanding of signalling regulation of differentiation, providing insights into protocol development, drug screening, and regenerative medicine applications.

Pluripotent Stem Cells↗
PubMed1996

Computer-assisted image-averaging strategies for the topographic analysis of in situ hybridization autoradiographs.

We report the application of a computer-based image-averaging strategy to the quantitative topographic analysis of in situ hybridization autoradiographs, based upon a disparity-analysis algorithm. We illustrate this approach for a representative antisense riboprobe-the astrocytic marker, glial fibrillary acid protein (GFAP)-in the setting of fluid-percussion brain injury in rats. Sequential coronal autoradiographs in individual animals are first digitized and aligned by disparity analysis. Next, coronal sections of all brains of a given experimental group are placed in register with one another, using a common anatomic reference level. One brain of the series serves as a template, and corresponding sections of other brains are mapped into its contour at each level. In this manner, average and standard deviation image data sets may be generated. With thresholding techniques, individual data sets can be dichotomized with respect to a chosen threshold, and frequency maps can be generated at each coronal level, displaying numbers of brains showing supra-threshold levels of mRNA at each pixel location. Pixel-by-pixel statistical comparison of data sets obtained under two different conditions (e.g., 30 min vs. 24 h following brain trauma) is then feasible. A digitized functional-anatomic brain atlas may be fitted to the images to assist analysis. Computer-based image analysis of in situ hybridization autoradiographs greatly extends the utility and applicability of this technique.

Animals↗
PubMed2025

Tumor-immune partitioning and clustering algorithm for identifying tumor-immune cell spatial interaction signatures within the tumor microenvironment.

BACKGROUND: Growing evidence supports the importance of characterizing the organizational patterns of various cellular constituents in the tumor microenvironment in precision oncology. Most existing data on immune cell infiltrates in tumors, which are based on immune cell counts or nearest neighbor-type analyses, have failed to fully capture the cellular organization and heterogeneity. METHODS: We introduce a computational algorithm, termed Tumor-Immune Partitioning and Clustering (TIPC), that jointly measures immune cell partitioning between tumor epithelial and stromal areas and immune cell clustering versus dispersion. As proof-of-principle, we applied TIPC to a prospective cohort incident tumor biobank containing 931 colorectal carcinoma cases. TIPC identified tumor subtypes with unique spatial patterns between tumor cells and T lymphocytes linked to certain molecular pathologic and prognostic features. T lymphocyte identification and phenotyping were achieved using multiplexed (multispectral) immunofluorescence. In a separate hepatocellular carcinoma cohort, we replaced the stromal component with specific immune cell types-CXCR3+CD68+ or CD8+-to profile their spatial relationships with CXCL9+CD68+ cells. RESULTS: Six unsupervised TIPC subtypes based on T lymphocyte distribution patterns were identified, comprising two cold and four hot subtypes. Three of the four hot subtypes were associated with significantly longer colorectal cancer (CRC)-specific survival compared to a reference cold subtype. Our analysis showed that variations in T-cell densities among the TIPC subtypes did not strictly correlate with prognostic benefits, underscoring the prognostic significance of immune cell spatial patterns. Additionally, TIPC revealed two spatially distinct and cell density-specific subtypes among microsatellite instability-high colorectal cancers, indicating its potential to upgrade tumor subtyping. TIPC was also applied to additional immune cell types, eosinophils and neutrophils, identified using morphology and supervised machine learning; here two tumor subtypes with similarly low densities, namely 'cold, tumor-rich' and 'cold, stroma-rich', exhibited differential prognostic associations. Lastly, we validated our methods and results using The Cancer Genome Atlas colon and rectal adenocarcinoma data (n = 570). Moreover, applying TIPC to hepatocellular carcinoma cases (n = 27) highlighted critical cell interactions like CXCL9-CXCR3 and CXCL9-CD8. CONCLUSIONS: Unsupervised discoveries of microgeometric tissue organizational patterns and novel tumor subtypes using the TIPC algorithm can deepen our understanding of the tumor immune microenvironment and likely inform precision cancer immunotherapy.

Humans↗
PubMed1999

Perceptual variation in grading hand, hip and knee radiographs: observations based on an Australian twin registry study of osteoarthritis.

OBJECTIVE: The radiographic diagnosis of osteoarthritis (OA) in the peripheral skeleton is dependent on the skilled examination of several morphological characteristics of the condition as visualised on plain radiographs. However, the process is perceptual and generally enhanced by comparison against photographic standards. This study assessed the intra-rater and inter-rater reliability of radiologists experienced in reporting hand, hip and knee films derived from a community-based sample when using the photographic atlas recently developed by Burnett et al. METHODS: This study was part of a multifaceted diagnostics protocol, evaluating methodological issues, in the conduct of genetic research in osteoarthritis. From a cohort of 118 twin pairs, registered with the Australian Twins Registry (ATR), standard clinical examinations were performed on 74 complete and 11 incomplete pairs of twins over age 50 years, followed by standard AP hand, AP pelvis and AP standing radiographs of the knees. The pairs were selected both to represent twin pairs who had previously self reported a diagnosis of OA, as well as those who had not. Radiologists read the films blind to the original self reported diagnosis and without reference to their pairing. The films were read by comparison against photographic standards and were scored according to specific features. All films were read independently by two consultant radiologists blind to one another's assessments, and selected films were thereafter assigned for rereading. Inter-rater and intra-rater agreement were different for different features, different anatomic areas, and, for the former, were different for the two radiologists. RESULTS: Inter-rater agreement was different for different anatomic areas, different radiographic features, and the two radiologists. Intra-rater agreement for the presence or absence of OA was as follows: actual observed agreement = 0.79 to 0.97 and 0.83 to 0.98; adjusted kappa statistic = 0.58 to 0.94 and 0.67 to 0.96; inter-rater agreement was as follows: actual observed agreement = 0. 77 to 0.97; adjusted kappa statistic = 0.54 to 0.94. Agreement was generally high in most of the principal target joints for OA: DIP, PIP, 1st CMC, hip and knee. CONCLUSIONS: Although assessor agreement was not perfect, it is concluded that for genetic epidemiology purposes, while duplicate assessments may be advantageous, it is possible for radiographs to be examined accurately by a single experienced assessor. However, for less experienced assessors independent examinations should be made by at least two assessors and either a consensus reached on disparate examinations or an algorithm developed to adjudicate any discrepancies.

Adult↗