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Spatial resolution of fMRI in the human parasylvian cortex: comparison of somatosensory and auditory activation.

In spite of its outstanding spatial resolution, the biological resolution of functional MRI may be worse because it depends on the vascular architecture of the brain. Here, we compared the activation patterns of the secondary somatosensory and parietal ventral cortex (SII/PV) with that of the primary auditory cortex and adjacent areas (AI/AII). These two brain regions are located immediately adjacent to each other on opposite banks of the Sylvian fissure, and are anatomically and functionally distinct. In 12 healthy subjects, SII/PV was activated by pneumatic tactile stimuli applied to the index finger (0.5 cm2 contact area, 4 bar pressure), and AI/AII by amplitude-modulated tones (800 Hz carrier frequency, modulated at 24-36 Hz). Functional images were obtained with a 1.5-T scanner and were evaluated using SPM99. Sensitivity of fMRI activation in this unselected sample was 71% for tactile and 83% for auditory stimulation. Group analysis showed activation of SII/PV by tactile and activation of three locations in AI/AII by auditory stimuli. Distributions extended to the opposite side of the fissure (19-58% after tactile and 13-14% after auditory stimulation, depending on the side of stimulation/hemisphere). Morphometry of individual sulcal anatomy revealed that the course of the Sylvian fissure varied by 5.3 mm (SD) in vertical direction. Taking this into account, SII/PV was located 5.8 +/- 2.7 mm above the Sylvian fissure, whereas AI/AII was located 6.3 +/- 1.7 mm below the Sylvian fissure. Even in individual analysis, the most significant voxel after tactile stimuli in one subject was found on the "wrong" side of the fissure; this error could be ascribed to the spatial normalization procedure. These data show that fMRI signals may overlap substantially, even if the activated regions are separated by 12 mm across a major sulcus. Spatial normalization to an atlas template can introduce additional variance. Individual sulcal anatomy should be preferred over mean atlas locations.

Acoustic Stimulation↗

Ultrasonographic, computed tomographic and magnetic resonance imaging anatomy of the normal canine stifle joint.

Ultrasonographic (US), magnetic resonance (MR) and computed tomographic (CT) images of normal canine stifle joints were obtained and compared with plastinated cross-sectional slices of cadaver specimens from the same dogs. The bony and articular structures were identified and correlated with the three diagnostic imaging modalities. These results provide an atlas of normal cross-sectional US, MR and CT anatomy of the canine stifle, which can be used for the interpretation of stifle images from any of these imaging modalities.

Anatomy, Cross-Sectional↗

A three-dimensional MRI atlas of the mouse brain with estimates of the average and variability.

Although there is growing interest in finding mouse models of human disease, no technique for quickly and quantitatively determining anatomical mutants currently exists. Magnetic resonance imaging (MRI) is ideally suited to probe fine structures in mice. This technology is three-dimensional, non-destructive and rapid compared to histopathology; hence MRI scientists have been able to create detailed three-dimensional images of 60 mum resolution or better. The data is digital which lends itself to sophisticated image processing algorithms. Here we show a variational MRI atlas constructed from nine excised brains of 8 week old 129S1/SvImJ male mice. This new type of atlas is comprised of an unbiased average brain--created from alignment of the individual brains--and the mathematical descriptors of anatomical variation across the individuals. We found that the majority of internal points in the individuals never varied more than 117 microm from equivalent points in the atlas. A three-dimensional annotation of the average image was performed and used to estimate the mean and standard deviation of volumes in a variety of structures across the individual brains; these volumes never differed by more than 5%. Our results indicate that variational atlases of inbred strains represent a well-defined basis against which mutant outliers can be readily compared.

Algorithms↗

The role of the supramammillary commissure in MR localization of the subthalamic nucleus.

PURPOSE: We have discovered a method for localization of the subthalamic nucleus (STN) utilizing the supramammillary commissure (SMC) as reference point. It is our purpose to present our experience and compare our methods with others. MATERIALS AND METHODS: Sixteen patients targeted for bilateral DBS for 32 total STN targets were studied by 1 mm MP-RAGE images with coronal T2W images. A modified red nucleus and mustache method was applied. The predicted target points were then confirmed with electronic calipers measuring the differences in methods. RESULTS: Modified red nucleus method using Surgiplan, and EBAL and BAGM electronic brain map atlas matched the target loci of 12 mm, -3 mm, -4 mm on an X-, Y-, and Z-coordinate system with zero at the mid-commissural point. From the coronal view Y is fixed at -3 mm. The mustache method was in error with values of X-axis at 14.25 (+/- 1.41 SD) (p = 0.69), and of Z-axis at -5.0 (+/- 1.60 SD) (p = 0.55). Three-fourths had moderate to marked ventricular enlargement of the III, but only 3 had enlargement of the frontal horns. CONCLUSION: The mustache method erred in the X-axis because the thalamocaudate groove was located lateral to the target point of the STN, and in the Z-axis because of varying thicknesses of the SMC. The top of the SMC is directly lateral from the STN target by 12 mm from the anterior and posterior commissures line. The SMC being a recognizable structure with constant relation to the STN should be the target structure.

Brain Mapping↗

Glucose metabolism in the human cerebellum: anatomical-functional correlations.

Functional maturation of human cerebellar structures was previously difficult to evaluate with positron emission tomography (PET) because of scanner resolution. Only vermis and cerebellar hemispheres could be reliably identified with 2-deoxy-2[18F]fluoro-D-glucose (FDG) PET. In the present study, we have used a new high resolution PET system, the Siemens EXACT-HR, to study, in depth, the patterns of glucose metabolism in various cerebellar structures. Due to the orientation of the cerebellar fissures which are important landmarks, the largest number of regions could be identified when the cerebellar regions were displayed on coronal planes. The high resolution PET images, together with magnetic resonance imaging (MRI) data and standard atlases, now allow identification of the following cerebellar structures: anterior vermis, posterior vermis, dentate nucleus, anterior lobe, posterior quadrangular lobule, superior semilunar lobule, inferior semilunar, gracile, and biventer lobules, tonsil, and cerebellar white matter. These cerebellar regions are displayed in an atlas format together with magnetic resonance images to allow easy identification. The present study is a prerequisite for detailed PET analyses of cerebellar metabolism in children with diseases of the cerebellum.

Adolescent↗

Stereotaxy-based regional brain volumetry applied to segmented MRI: validation and results in deficit and nondeficit schizophrenia.

A method for postprocessing of segmented routine brain MRI studies providing automated definition of major structures (frontal, parietal, occipital, and temporal lobes; cerebellar hemispheres; and lateral ventricles) according to the Talairach atlas is presented. The method was applied to MRI studies from 25 normal subjects (NV), 14 patients with deficit schizophrenia (DS), and 14 with nondeficit schizophrenia (NDS), to evaluate their gray matter and CSF regional volumes. The two patient groups did not differ in mean age at illness onset, duration of illness, severity of psychotic symptoms, or disorganization; DS had more severe avolition and worse social functioning than NDS. For validation purposes, brain structures were manually outlined on original MR images in 10 studies, thus obtaining reference measures. Manual and automated measures were repeated 1 month apart to measure reproducibilities of both methods. The automated method required less than 1 min/operator per study vs more than 30 min for manual assessment. Mean absolute difference per structure between the two techniques was 4.8 ml. Overall reproducibility did not significantly differ between the two methods. In subjects with schizophrenia, a significant decrease in GM and increase in CSF were found. GM loss was confined to frontal and temporal lobes. Lateral ventricles were significantly larger bilaterally in NDS compared to NV and only on the right in NDS compared to DS. The finding of greater structural brain abnormalities in NDS adds to the evidence that deficit schizophrenia does not represent just the more severe end of the schizophrenia continuum.

Adolescent↗

Advertising, patient decision making, and self-referral for computed tomographic and magnetic resonance imaging.

BACKGROUND: Self-referred imaging is one of the latest health care services to be marketed directly to consumers. Most aspects of these services are unregulated, and little is known about the messages in advertising used to attract potential consumers. We conducted a detailed analysis of print advertisements and informational brochures for self-referred imaging with respect to themes, content, accuracy, and emotional valence. METHODS: Forty print advertisements from US newspapers around the country and 20 informational brochures were analyzed by 2 independent raters according to 7 major themes: health care technology; emotion, empowerment, and assurance; incentives; limited supporting evidence; popular appeal; statistics; and images. The Fisher exact test was used to identify significant differences in information content. RESULTS: Both the advertisements and the brochures emphasized health care and technology information and provided assurances of good health and incentives to self-refer. These materials also encouraged consumers to seek further information from company resources; virtually none referred to noncomplying sources of information or to the risks of having a scan. Images of people commonly portrayed European Americans. We found statistical differences between newspaper advertisements and mailed brochures for references to "prevalence of disease" (P<.001), "death" (P<.003), and "radiation" (P<.001). Statements lacking clear scientific evidence were identified in 38% of the advertisements (n = 15) and 25% of the brochures (n = 5). CONCLUSIONS: Direct-to-consumer marketing of self-referred imaging services, in both print advertisements and informational brochures, fails to provide prospective consumers with comprehensive balanced information vital to informed autonomous decision making. Professional guidelines and oversight for advertising and promotion of these services are needed.

Advertising↗

Multiomics approaches to cardiovascular disease: technological innovations and clinical translation.

Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality, reflecting a persistent gap between clinical phenotyping and the molecular mechanisms that govern disease initiation, progression, and interindividual variability. Recent advances in emerging technologies have fundamentally reshaped cardiovascular physiology by enabling high-resolution, cross-layer profiling of the heart and vasculature across genomic, epigenomic, transcriptomic, proteomic, metabolomic, lipidomic, glycomic, and fluxomic layers, increasingly at single-cell and spatial resolution. These approaches reveal CVD as a coordinated, multilayered process driven by dynamic interactions among cell types, regulatory programs, and metabolic states, rather than isolated gene-level defects. In this review, we synthesize how emerging multiomic, computational, and functional genomic technologies are redefining the study of cardiovascular disease across molecular, cellular, and tissue levels. We highlight recent innovations in single-cell and spatial atlases, long-read sequencing, proteomics and metabolomics, integrative data modeling, and functional omics approaches, including genome-scale perturbation screens and single-cell perturbation frameworks. These platforms enable mechanistic dissection of regulatory circuits, distinguish primary disease drivers from secondary adaptations, and directly assess therapeutic reversibility, advancing the field beyond associative biomarker discovery toward mechanism-guided target prioritization. We further discuss key methodological and translational challenges accompanying high-dimensional cardiovascular data, including preanalytical variability, control selection, temporal misalignment across molecular layers, population diversity, and reference bias. By integrating technological innovation with computational rigor and functional validation, this review frames emerging omics-enabled strategies as a unified, physiologically grounded framework for translating molecular insight into clinically meaningful cardiovascular phenotypes and advancing precision cardiovascular medicine.

Humans↗

Single-cell multi-omics dissects transcript isoform and immune repertoire dynamics in human immunosenescence.

Immunosenescence, a major hallmark of systemic aging, refers to the progressive functional decline of the immune system. This decline not only compromises host defense and immunological memory but also fuels chronic inflammation and tissue degeneration (collectively known as inflammaging). While single-cell RNA sequencing (scRNA-seq) has revealed transcriptomic alterations associated with immune aging, analyses restricted to transcript abundance fail to capture deeper regulatory layers, such as transcript isoform diversity and the remodeling of immune receptor repertoires. To address this limitation, we present a human peripheral immune single-cell multi-omics atlas that integrates gene expression, transcript isoform diversity, and immune receptor repertoires. By combining single-cell full-length transcriptome sequencing (scCycloneSEQ), short-read scRNA-seq, and single-cell immune receptor sequencing (scTCR/BCR-seq), we systematically profiled peripheral blood mononuclear cells (PBMCs) from healthy donors aged 30-40 and 60-70 years. Our analyses uncovered extensive age-related remodeling of immune cell composition, functional states, and TCR/BCR diversity. Notably, we found that CD4+ effector memory T cells exhibited widespread differential isoform usage (DIU), 3'UTR length variation, and a marked reshaping of cytotoxic T lymphocyte (CTL) clonotypes-all of which were closely associated with aging-related inflammation and cellular senescence. This multi-omics atlas delineates key molecular features of immunosenescence and provides a high-resolution resource for deciphering the regulatory architecture underlying immune aging.

TCR/BCR↗

Broadsheet number 46: Internet for pathologists.

The Internet, and its most user-friendly manifestation, the World Wide Web (WWW), has undergone an exponential growth in the last few years. The volume of medical and pathology related information available has kept pace, making the Internet invaluable tool for the practising pathologist, supplementing traditional hard-copy textbooks and professional journals. E-mail, newsgroups, mailing lists, access to libraries, Medline, atlases, case studies and tutorials are only some of the additional features to which the net offers rapid access from your work-station. To make optimal use of electronic resources, a basic understanding of the hardware, software, communication protocols and information retrieval tools underlying the Internet is desirable. This paper is intended only as a brief introduction to what the Net has to offer to pathology in particular, and medicine in general, it is not meant to supplement the many excellent and more detailed reviews already available (see references). Parallel with the information explosion on the Net, concerns for the quality of posted material and possibility of misinformation have arisen. These issues will be addressed. Website addresses are given in parentheses in the text [e.g.: the website address of the Royal College of Pathologists of Australasia (RCPA) is given as (http:/(/)www.rcpa.edu.au/)] for easy retrieval on your Web browser. Because of the constantly evolving nature of the Web, I apologise in advance if some of the listed sites are no longer current.

Australia↗

Variability and asymmetry in the human precentral motor system. A cytoarchitectonic and myeloarchitectonic brain mapping study.

The morphology of the region of the primary motor cortex in the human brain is variable, and putative asymmetries between the hemispheres have been noted since the beginning of last century. Such variability may confound the results of clinical lesion or functional activation studies. We measured Brodmann area (BA) 4 and the identifiable precentral component of the pyramidal tract (PRPT) in 11 human post-mortem brains using techniques of quantitative cytoarchitectonic and myeloarchitectonic image analysis. Topography and variability in the localization of architectonic borders were analysed and mapped to a computerized spatial reference system, which consists of an individual in vivoMRI brain. All maps were superimposed to produce probabilistic maps of BA 4 and PRPT which can be co-registered with any image of brain structure or function that has also been transformed to Talairach coordinates. These maps can be readily applied to future brain mapping studies. We observed a considerable degree of variability between hemispheres (intra-individual) and between brains (inter-individual). The variation zones of BA 4 and PRPT differ from the templates of the Talairach atlas. Voxel-based morphometry shows significant side differences with larger volumes of PRPT in the left hemisphere than in the right hemisphere. This larger volume of the descending cortical motor fibres may be related to the known left-hemisphere dominance for handedness in >90% of the population. In contrast, BA 4 was symmetrically organized. The lack of a significant correlation between the size of BA 4 and the size of PRPT may relate to the fact that additional non-primary motor and sensory cortices contribute to the origins and size of the pyramidal tract proper.

Adult↗

Analysis of neuroreceptor PET-data based on cytoarchitectonic maximum probability maps: a feasibility study.

Three-dimensional maximum probability maps (MPMs) of cytoarchitectonically defined cortical regions based on postmortem histological studies have recently been made available in the stereotaxic reference space of the Montreal Neurological Institute (MNI) single subject template. This permits the use of cytoarchitectonic maps for the analysis of functional in vivo datasets, including neuroreceptor positron emission tomography (PET) studies. In this feasibility study, we used 5-hydroxytryptamine 2A (5-HT2A) receptor PET to test the applicability of maximum cytoarchitectonic probability maps for quantitative analysis. As the outcome parameter, we extracted local distribution volume ratios (DVRs) from 19 cytoarchitectonically defined volumes of interest (VOIs) per hemisphere from five healthy subjects. The experimental design included a forward ('PET to atlas' normalization) and a backward ('atlas to PET' normalization) procedure to double-check the stability of transformation and overlay. Resulting DVRs were compared with receptor densities (RDs) obtained from postmortem [3H]ketanserin autoradiography of multiple areas. Correlations between the bi-directional normalization procedures (r = 0.89; 38 VOIs) as well as between in vivo and vitro data (nine VOIs; r = 0.64 and r = 0.47 for forward and backward procedure, respectively) suggest that the implementation of cytoarchitectonic maximum probability maps is a promising method for an accurate and observer-independent analysis of neuroreceptor PET data.

Adult↗

A randomised controlled trial of intra-articular corticosteroid injection of the carpometacarpal joint of the thumb in osteoarthritis.

OBJECTIVE: To investigate the efficacy of corticosteroid injections into the carpometacarpal joint of the thumb (CMCJ) in patients with osteoarthritis. DESIGN: A double blind, randomised controlled trial using 40 hospital referred patients with CMCJ osteoarthritis who received intra-articular injections of 5 mg triamcinolone hexacetonide (0.25 ml) or sterile 0.9% saline (0.25 ml). Injections were given under imaging control. MAIN OUTCOME MEASURES: The primary outcome was improvement in a pain visual analogue score (VAS) of 20% at 24 weeks. In addition patients were assessed at 4, 12, and 24 weeks for joint stiffness, joint tenderness, and physician and patient global assessments. Hand radiographs were evaluated for the degree of CMC joint space narrowing and marginal osteophytes according to the OARSI atlas. RESULTS: Baseline clinical variables were not significantly different between the two treatment groups. There was no improvement in the VAS of pain at 24 weeks. At each assessment point there was no significant difference between the steroid and placebo groups in median values for joint stiffness, joint tenderness, or patient and physician global assessments. Non-parametric analysis of each group individually revealed statistically significant improvements in patient and physician global assessments at weeks 4, 12, and 24 in the placebo group and at weeks 4 and 12 in the steroid group. CONCLUSIONS: No clinical benefit was gained from intra-articular steroid injection to the CMCJ in moderate to severe osteoarthritis compared with placebo injection.

Adult↗

Central sulcus patterns at MRI.

Radiologists can now use Talairach's bicommissural reference system and simple T-weighted sagittal magnetic resonance imaging (MRI) sections to recognize the central sulcus of the brain with its spatial features. In this study of 50 MRI examinations performed on normal subjects with contiguous 9 mm thick sagittal sections related to a standard proportional model that takes into account variations in the size and shape of the brain, the central sulcus could be identified on each section, despite its complexity on lateral projections and its frequent changes of course. By comparisons with the co-planar stereotaxic atlas of Talairach and Tournoux, it will be possible to localize the classical functional areas of the telencephalon.

Adolescent↗

[Classification of injuries of the cervical spine].

Recent advances and the technical options that have lately become available in the surgical treatment of spinal injuries mean that clear definition of the indications is essential. Precise observation and classification of each injury to the cervical spine are of paramount importance for this purpose, to allow the comparison of proposed methods of treatment and of the results obtained with them. There are a number of classification systems for injuries to the cervical spine, none of which, however, is generally accepted. These classification systems are based on different criteria, such as nature of the accident at which the injury was sustained, neurologic deficits, morphological criteria, the concept of instability, and implications for treatment and prognosis. These criteria, however, hardly allow the classification of most of the injuries affecting the upper and those affecting the lower cervical spine in a single system. Therefore, the authors propose a system of their own, which draws on the principles of classification suggested by the ASIF for fractures of the extremities. According to this proposed new system, injuries are divided into those of the upper and those of the lower cervical spine, and each of these two main groups is further divided into three subgroups. In the case of the lower cervical spine, injuries are classed according as whether they affect the anterior or the posterior section of the spine more, or both to the same degree. Beyond this, injuries are subdivided with reference to whether they affect primarily bone, bone and ligament equally, or primarily ligament. Further subdivision by severity and implications for treatment allows more detailed differentiation. This classification system is based on the analysis of over 200 cases of injury to the cervical spine treated by the authors and of cases from the literature.

Axis, Cervical Vertebra↗

Web-based training modules in dermatology.

With the goal of using the full power of the World Wide Web for computer-based education, we developed an interactive system for training in dermatology with a database of several thousand color images. The system consists of lecture scripts, case reports with recorded sound, an online atlas, and a quiz system--all relying on the underlying image database. The images used have been reviewed and rated by a senior dermatologist. At present, they are described with a hierarchical key system that permits searching for images by their content. We have evaluated our statistics on access and the results of an open user survey based on an adaptive questionnaire. The responses to 200 questionnaires completed in a two-month study period are encouraging. The online resources are being used not only for training in dermatology but also for continuing education and reference.

Computer Communication Networks↗

GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.

BACKGROUND: Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data. METHODS: We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best. RESULTS: Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis. CONCLUSIONS: GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.

Humans↗

Imaging of childhood torticollis due to atlanto-axial rotatory fixation.

Atlanto-axial rotatory fixation is a rare cause of childhood torticollis. It may occur spontaneously or may be associated with trauma, upper respiratory tract infection or congenital abnormality of the cervical spine. Presentation is usually with persistent torticollis and "cock robin" deformity of the neck. In this paper the radiological experience in three patients is presented. Investigations included plain radiographs, plain anteroposterior tomography, CT and MRI. Displacement of the lateral mass of the atlas and the eccentric position of the odontoid peg can be seen in the plain films. CT scan can exclude fractures and confirm atlanto-axial rotation. The superimposition of CT images is demonstrated as a way of diagnosing subluxation. MRI offers better soft tissue differentiation and allows assessment of the integrity of the transverse ligament. This has an important bearing on the prognosis and may influence surgical treatment. It is important to recognise the plain film features of this uncommon condition and confirm the diagnosis with CT or MRI. The treatment options are discussed with particular reference to long term outcome.

Atlanto-Axial Joint↗