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PubMed2025

Multi-omics analysis reveals distinct spatial compartmentalization of lung repair niches in pediatric ARDS.

BACKGROUND: Pediatric acute respiratory distress syndrome (PARDS), often triggered by viral infections, is a life-threatening condition. Despite its severity, children demonstrate significantly better survival rates and superior lung repair compared to adults. However, the mechanisms underlying this age-specific advantage remain incompletely understood. PATIENTS AND METHODS: We conducted a pilot multi-omics study of influenza-associated PARDS integrating single-cell RNA sequencing (scRNA-seq) of pediatric lung tissue and bronchoalveolar lavage fluid (BALF), spatial transcriptomics, and plasma proteomics. Analyses were harmonized with the Human Lung Cell Atlas (HLCA) reference, reanalysis of public pediatric PARDS airway scRNA-seq, and contextual comparisons to adult lethal COVID-19 lung. RESULTS: Tissue scRNA-seq and spatial data indicated outcome-linked divergence in PARDS. Survivor showed spatially restricted repair with preserved alveolar type II (AT2) cells, AT2-to-alveolar type I (AT1) differentiation signatures, and higher KRT17, whereas fatal case and adults exhibited diffuse immune activation with pro-fibrotic and pro-apoptotic signaling. In BALF, KRT17-positive airway stress–repair epithelial cells (hillock-like) increased from the acute to recovery phase, and plasma proteomics showed higher circulating KRT17 in survivors. HLCA-based label transfer strengthened cell-type definitions and enabled pediatric–adult comparisons suggesting biological and developmental differences; the adult lethal COVID-19 atlas provided a benchmark with attenuated epithelial repair and prominent collagen CTHRC1-pathologic fibroblasts. Fibroblast programs were regionally compartmentalized, with injury-enriched CTHRC1+ states versus alveolar fibroblasts in preserved areas, and showed stronger injury–homeostasis anti-correlation in fatalities. Myeloid remodeling included BALF transitions from FCN1-high inflammatory states toward FABP4-positive resident-like states, consistent with public pediatric datasets showing reduced inflammatory and interferon-stimulated gene (ISG) modules and severity-linked increases in aged neutrophils. CONCLUSIONS: This pilot multi-omics case series outlines putative pediatric lung repair niches in influenza-associated PARDS. KRT17-positive transitional epithelium, preserved AT2 differentiation, and restoration of resident-like macrophages may align with recovery, whereas diffuse immune activation and CTHRC1-enriched fibroblast programs may accompany worse outcomes. HLCA-guided annotations and adult benchmarks indicate possible age-related differences, warranting validation in larger multi-center cohorts.

Humans↗
PubMed2001

Molecular Constants for the v=0, b(1)Sigma(g)(+) Excited State of O(2): Improved Values Derived from Measurements of the Oxygen A-Band Using Intracavity Laser Spectroscopy.

High-resolution intracavity laser spectroscopy (ILS) absorption measurements have been made on the b-X oxygen electronic transition (the A-band) which has bandheads occurring in the region of 13 165 cm(-1). The positions of the lines were determined to an accuracy that is based on calibration with I(2) absorption lines using the Laboratoire Aimé Cotton (Orsay) Atlas as reference. Based on the ILS measurements and the more accurately determined positions given by L. R. Brown and C. Plymate (J. Mol. Spectrosc. 199, 166-179 (2000)) and with the (3)Sigma(g)(-) ground state molecular constants fixed at the values determined by G. Rouillé et al. (J. Mol. Spectrosc. 154, 372-382 (1992)), the following values (in cm(-1)) were found for the molecular constants: T(0)=13122.2524(1); B(0)=1.391244(2); D(0)=5.352(4)x10(-6); and H(0)=-1.2(2)x10(-11). These results are compared with values derived from fits of the line positions listed in several other studies of this transition. Copyright 2001 Academic Press.

Journal Article↗
PubMed2005

Geometric modeling of the human normal cerebral arterial system.

We propose an anatomy-based approach for an efficient construction of a three-dimensional human normal cerebral arterial model from segmented and skeletonized angiographic data. The centerline-based model is used for an accurate angiographic data representation. A vascular tree is represented by tubular segments and bifurcations whose construction takes into account vascular anatomy. A bifurcation is defined quantitatively and the algorithm calculating it is given. The centerline is smoothed by means of a sliding average filter. As the vessel radius is sensitive to quality of data as well as accuracy of segmentation and skeletonization, radius outlier removal and radius regression algorithms are formulated and applied. In this way, the approach compensates for some inaccuracies introduced during segmentation and skeletonization. To create the frame of vasculature, we use two different topologies: tubular and B-subdivision based. We also propose a technique to prevent vessel twisting. The analysis of the vascular model is done on a variety of data containing 258 vascular segments and 131 bifurcations. Our approach gives acceptable results from anatomical, topological and geometrical standpoints as well as provides fast visualization and manipulation of the model. The approach is applicable for building a reference cerebrovascular atlas, developing applications for simulation and planning of interventional radiology procedures and vascular surgery, and in education.

Cerebral Arteries↗
PubMed2002

Optimal location of thalamotomy lesions for tremor associated with Parkinson disease: a probabilistic analysis based on postoperative magnetic resonance imaging and an integrated digital atlas.

OBJECT: Renewed interest in stereotactic neurosurgery for movement disorders has led to numerous reports of clinical outcomes associated with different treatment strategies. Nevertheless, there is a paucity of autopsy and imaging data that can be used to describe the optimal size and location of lesions or the location of implantable stimulators. In this study the authors correlated the clinical efficacy of stereotactic thalamotomy for tremor with precise anatomical localization by using postoperative magnetic resonance (MR) imaging and an integrated deformable digital atlas of subcortical structures. METHODS: Thirty-one lesions were created by stereotactic thalamotomy in 25 patients with tremor-dominant Parkinson disease. Lesion volume and configuration were evaluated by reviewing early postoperative MR images and were correlated with excellent, good, or fair tremor outcome categories. To allow valid comparisons of configurations of lesions with respect to cytoarchitectonic thalamic boundaries, the MR image obtained in each patient was nonlinearly deformed into a standardized MR imaging space, which included an integrated atlas of the basal ganglia and thalamus. The volume and precise location of lesions associated with different clinical outcomes were compared using nonparametric statistical methods. Probabilistic maps of lesions in each tremor outcome category were generated and compared. Statistically significant differences in lesion location between excellent and good. and excellent and fair outcome categories were demonstrated. On average, lesions associated with excellent outcomes involved thalamic areas located more posteriorly than sites affected by lesions in the other two outcome groups. Subtraction analysis revealed that lesions correlated with excellent outcomes necessarily involved the interface of the nucleus ventralis intermedius (Vim; also known as the ventral lateral posterior nucleus [VLp]) and the nucleus ventrocaudalis (Vc; also known as the ventral posterior [VP] nucleus). Differences in lesion volume among outcome groups did not achieve statistical significance. CONCLUSIONS: Anatomical evaluation of lesions within a standardized MR image-atlas integrated reference space is a useful method for determining optimal lesion localization. The results of an analysis of probabilistic maps indicates that optimal relief of tremor is associated with lesions involving the Vim (VLp) and the anterior Vc (VP).

Aged↗
PubMed2001

Brain mapping: its use in patients with neurological disorders.

Using imaging to study disorders of the brain is a process that is now almost a century old. The most rapid advances and the greatest number of new techniques have been developed in the last thirty years. These methods provide previously unavailable insights into the mechanism of disease, diagnostic information for patients as well as an objective and noninvasive way of planning and monitoring therapy. The overall strategy for using these methods is discussed in this review along with illustrative highlights of three techniques: diffusion and perfusion magnetic resonance imaging, helical X-ray computed tomography and optical intrinsic signal imaging. While new techniques provide different perspectives about brain physiology and pathophysiology, advanced analytic methods for all techniques, new and old, have demonstrated their ability to extract more information from these methods than simple qualitative analysis can provide. Strategies for developing large population, probabilistically-based references and atlases are discussed along with disease-specific atlases of use in studying the natural history of a disorders, therapeutic interventions and strategies for monitoring clinical trials of new therapeutic agents. The integration of information across modalities, spatial and temporal scales, subjects and clinical trials should provide an effective way of providing more comprehensive insights into the mechanisms of disorders that effect the human nervous system, both improving diagnostics and the planning and monitoring of therapeutics.

Brain↗
PubMed1995

Updated osteoarthritis reference standard.

The Kellgren and Lawrence atlas has been the reference standard for radiographic classification of osteoarthritis (OA) for nearly 40 years. Limitations include employment of a global grade, over-emphasis of the osteophyte, and submergence of other features so measurement of disease progression is difficult. Observer bias, drift, and variability cause concern. To address deficiencies and optimize observer accuracy, precision, and agreement, an updated atlas was created. From a photographic set of clinical radiographs, 4 readers selected a subset by consensus. Major radiographic features of hand, hip, and knee OA are graded on a 4-point scale. Using this atlas, it should be possible to individually score each relevant feature in a given joint. It is hoped the atlas will be adopted for population studies, assessment of disease progression, and protocols that evaluate new agents capable of modifying disease.

Hand↗
PubMed2005

Automatic selection of DBS target points using multiple electrophysiological atlases.

In this paper we study and evaluate the influence of the choice of a particular reference volume as the electrophysiological atlas on the accuracy of the automatic predictions of optimal points for deep brain stimulator (DBS) implants. We refer to an electrophysiological atlas as a spatial map of electrophysiological information such as micro electrode recordings (MER), stimulation parameters, final implants positions, etc., which are acquired for each patient and then mapped onto a single reference volume using registration algorithms. An atlas-based prediction of the optimal point for a DBS surgery is made by registering a patient's image volume to that reference volume, that is, by computing a correct coordinate mapping between the two; and then by projecting the optimal point from the atlas to the patient using the transformation from the registration algorithm. Different atlases, as well as different parameterizations of the registration algorithm, lead to different and somewhat independent atlas-based predictions. We show how the use of multiple reference volumes can improve the accuracy of prediction by combining the predictions from the multiple reference volumes weighted by the accuracy of the non-rigid registration between each of the corresponding atlases and the patient volume.

Brain Mapping↗
PubMed2001

Exhibits facilitate histology laboratory instruction: student evaluation of learning resources.

Some professional schools have replaced microscopes for histology laboratory instruction with printed and electronic media. It is recognized that these media cannot replace experience with the microscope and that there is a cognitive dissonance of completely replacing microscope study. In addition, students believe that their time is not optimally used in the traditional histology laboratory. Therefore, at Loma Linda University, nine weekly microscope exhibits consisting of 10-15 slides each were prepared. For each exhibited slide, a one page "atlas" is provided, consisting of labeled low- and high-power color micrographs taken from that slide and an informative legend. By referring to the atlas, the student can easily identify the exact field and the labeled features with little help from an instructor. A live or taped video demonstration of the microscope exhibit is available on the first day of the exhibit. During the eighth week of the quarter, students were asked to evaluate the various learning resources available to them. No resource was valued significantly more than the microscope exhibits, but the video demonstrations were valued significantly more than the printed black and white atlas or the color atlas on CD. These exhibits have been used for 2 years to instruct a class of 90 dental students. Advantages are (1) students' time is used efficiently, (2) only one slide set and a fourth as many microscopes need be maintained compared with a traditional laboratory, and (3) one-of-a-kind slides derived from research activities provide for high impact learning.

Computer-Assisted Instruction↗
PubMed2026

SCMO: a deep learning model integrating the single-cell resolution TME ecosystem and multi-omics for survival prediction in CRC patients.

BACKGROUND: Colorectal cancer (CRC) remains a leading cause of global cancer mortality, highlighting the need for precise survival prediction to guide clinical decisions. Although tissue-level multi-omics is widely utilized for survival prediction, its limited resolution cannot capture tumor heterogeneity. Single-cell RNA sequencing (scRNA-seq) enables dissection of the tumor microenvironment (TME) at cellular resolution, supporting personalized prognostic assessment. METHODS: We collected 213 CRC scRNA-seq samples and established a CRC-specific TME atlas comprising 339,060 cells. Using this atlas as a reference, we deconvolved bulk RNA-seq data from TCGA-CRC cohort with the EcoTyper algorithm to reconstruct TME features. Clinical, genomic, and transcriptomic data were obtained from the Xena platform; microbial data were sourced from the BIC database. We integrated TME and multi-omics features through a self-normalizing neural network to construct a deep learning model (single-cell resolution TME ecosystem with multi-omics data [SCMO]) for survival prediction. To enhance interpretability, we utilized the Integrated Gradients algorithm and spatial transcriptomic data to analyze multi-omics and TME features. We performed anticancer drug screening with tumor necrosis factor receptor-associated protein 1 (TRAP1), a critical feature according to the Integrated Gradients algorithm, as a potential target. RESULTS: We identified 13 survival-related TME features from the CRC-specific atlas: 12 cell states and one multi-cellular ecosystem. SCMO, which combined TME and multi-omics features, improved survival prediction and outperformed existing methods, achieving a concordance index of 0.762. The SCMO demonstrated robust performance for long-term predictions, achieving areas under the curve (AUCs) of 0.752, 0.772, and 0.869 for 1-, 3-, and 5-year predictions in the training set, with corresponding test set AUCs of 0.639, 0.756, and 0.772. TME features from the SCMO model revealed that ecosystem density increased with CRC malignancy. Multi-omics features included TRAP1 as a potential drug target. Drug screening identified saikosaponin A as a novel TRAP1 inhibitor, and its anticancer activity was validated in vitro. We developed SCMO-Lite, a simplified model incorporating 12 high-attribution-weight multi-omics features, which demonstrated robust risk stratification. CONCLUSIONS: SCMO combines analytical precision with biological interpretability, offering novel insights for oncology survival prediction.

Humans↗
PubMed1997

Construction of a standard reference for PET studies of methionine accumulation using a computerised brain atlas.

Positron emission tomography (PET) is valuable for assessing the biochemistry and physiology of the human brain. A computerised brain atlas has been developed which allows demonstration of anatomical regions of PET images and manipulation of these images into a standardised anatomical space. Once the images are in this standardised three-dimensional space it is possible to make comparisons between individuals and groups of individuals. We describe the use of this atlas in the generation of a set of mean reference images using methionine PET images of normal volunteers.

Adult↗
PubMed1998

Degeneration of the dendritic arbor as an index of neurotoxicity in identified catecholamine neurons in rat brain slices.

Although catecholamine neurons are vulnerable targets for neurotoxins and degenerative disease, few in vitro studies have investigated the mechanisms of neurodegeneration in these cells. We therefore developed a brain slice preparation for this purpose. Rats were killed by cervical dislocation and 400-microm-thick horizontal slices containing midbrain catecholamine neurons were incubated for 2 h in the presence or absence of kainic acid (KA, 50 microM). After fixation, the slices were recut by a technique that provided thin (40 microm) sections in the same plane as the parent slice. Catecholamine neurons in these coplanar sections were labeled by immunostaining for tyrosine hydroxylase (TH) coupled with diaminobenzidine. The topographical organization of the horizontal plane of the brain was retained in the coplanar sections, enabling precise identification of catecholamine neurons in the thin sections, by reference to an atlas in the horizontal plane. In this study we examined neurons in the substantia nigra (SN). A key feature of the immunostaining was that it revealed both the cell body and also the extensive dendritic projections of SN neurons in the horizontal plane. After treatment with KA, cell bodies remained intact but the dendrites were truncated or fragmented. The loss of dendrites is a sensitive and readily quantifiable indicator of damage. KA caused significant reductions in the proportion of SN neurons with intact dendrites and in the total length of the dendrites, measured using a computer program. The sensitive index of damage and the facility to clearly distinguish catecholamine groups that are topographically close yet functionally distinct are the principal features of the experimental approach that we have developed. The preparation offers major advantages for investigating the selective vulnerability or resistance of particular types of catecholamine neurons to damage.

Animals↗
PubMed2000

Differential vulnerabilities of substantia nigra catecholamine neurons to excitatory amino acid-induced degeneration in rat midbrain slices.

Although differential vulnerability in different regions of the central nervous system is a characteristic feature of neurodegenerative disorders in vivo, its cellular basis is not well understood. In the present study we investigated whether catecholamine neurons in different regions of the substantia nigra (SN) are differentially vulnerable to excitatory amino acid-induced damage in a midbrain slice preparation. Rats were anesthetized by halothane inhalation and killed, the brain was rapidly removed, and 300-microm-thick midbrain slices were cut horizontally on a vibratome. The slices were incubated at 35 degrees C for 2 h in saline buffer containing either kainic acid (KA) or N-methyl-d-aspartate (NMDA) (10-50 microM). They were then fixed and cut into 30-microm sections that were coplanar with the horizontal slice. Individual catecholamine neurons were identified in these thin sections using an antibody to tyrosine hydroxylase coupled to diaminobenzidine. Catecholaminergic neurons in the dorsal and ventral tiers of the SN were readily identified by reference to an atlas of the distribution of catecholamine neurons in the horizontal plane. Using dendritic degeneration as a sensitive index of damage, and submaximal concentrations of KA and NMDA, we found that catecholamine neurons in the dorsal tier were more vulnerable than those in the ventral tier. For example, KA (10 microM) caused a significant reduction in the proportion of neurons with dendrites in the dorsal tier (from 60 to 34%) without altering the dendritic arbor of ventral tier neurons. After treatment with 50 microM KA, only 11% of dorsal tier neurons retained any dendrites while 45% of ventral tier neurons retained their dendrites. These differences were statistically significant (P<0.001). A similar differential vulnerability was apparent in slices treated with NMDA; neurons in the dorsal tier lost dendrites before detectable damage in the ventral tier. An understanding of the comparative anatomical, neurochemical, and physiological properties of vulnerable (dorsal tier) and resistant (ventral tier) catecholamine neurons in rat SN may provide significant insights into the mechanisms and treatment of neurodegenerative disorders involving catecholamine neurons.

Animals↗
PubMed2005

Functional MRI BOLD response to Tower of London performance of first-episode schizophrenia patients using cortical pattern matching.

Due to its three-dimensional folding pattern, the human neocortex poses a challenge for accurate co-registration of grouped functional brain imaging data. The present study addressed this problem by employing three-dimensional continuum-mechanical image-warping techniques to derive average anatomical representations for co-registration of functional magnetic resonance brain imaging data obtained from 10 male first-episode schizophrenia patients and 10 age-matched male healthy volunteers while they performed a version of the Tower of London task. This novel technique produced an equivalent representation of blood oxygenation level dependent (BOLD) response across hemispheres, cortical regions, and groups, respectively, when compared to intensity average co-registration, using a deformable Brodmann area atlas as anatomical reference. Somewhat closer association of Brodmann area boundaries with primary visual and auditory areas was evident using the gyral pattern average model. Statistically-thresholded BOLD cluster data confirmed predominantly bilateral prefrontal and parietal, right frontal and dorsolateral prefrontal, and left occipital activation in healthy subjects, while patients' hemispheric dominance pattern was diminished or reversed, particularly decreasing cortical BOLD response with increasing task difficulty in the right superior temporal gyrus. Reduced regional gray matter thickness correlated with reduced left-hemispheric prefrontal/frontal and bilateral parietal BOLD activation in patients. This is the first study demonstrating that reduction of regional gray matter in first-episode schizophrenia patients is associated with impaired brain function when performing the Tower of London task, and supports previous findings of impaired executive attention and working memory in schizophrenia.

Adolescent↗
PubMed2006

Phenomenological model of diffuse global and regional atrophy using finite-element methods.

The main goal of this work is the generation of ground-truth data for the validation of atrophy measurement techniques, commonly used in the study of neurodegenerative diseases such as dementia. Several techniques have been used to measure atrophy in cross-sectional and longitudinal studies, but it is extremely difficult to compare their performance since they have been applied to different patient populations. Furthermore, assessment of performance based on phantom measurements or simple scaled images overestimates these techniques' ability to capture the complexity of neurodegeneration of the human brain. We propose a method for atrophy simulation in structural magnetic resonance (MR) images based on finite-element methods. The method produces cohorts of brain images with known change that is physically and clinically plausible, providing data for objective evaluation of atrophy measurement techniques. Atrophy is simulated in different tissue compartments or in different neuroanatomical structures with a phenomenological model. This model of diffuse global and regional atrophy is based on volumetric measurements such as the brain or the hippocampus, from patients with known disease and guided by clinical knowledge of the relative pathological involvement of regions and tissues. The consequent biomechanical readjustment of structures is modelled using conventional physics-based techniques based on biomechanical tissue properties and simulating plausible tissue deformations with finite-element methods. A thermoelastic model of tissue deformation is employed, controlling the rate of progression of atrophy by means of a set of thermal coefficients, each one corresponding to a different type of tissue. Tissue characterization is performed by means of the meshing of a labelled brain atlas, creating a reference volumetric mesh that will be introduced to a finite-element solver to create the simulated deformations. Preliminary work on the simulation of acquisition artefacts is also presented. Cross-sectional and longitudinal sets of simulated data are shown and a visual classification protocol has been used by experts to rate real and simulated scans according to their degree of atrophy. Results confirm the potential of the proposed methodology.

Alzheimer Disease↗
PubMed2006

Three-dimensional models of individual cardiac histoanatomy: tools and challenges.

There is a need for, and utility in, the acquisition of data sets of cardiac histoanatomy, with the vision of reconstructing individual hearts on the basis of noninvasive imaging, such as MRI, enriched by reference to detailed atlases of serial histology obtained from representative samples. These data sets would be useful not only as a repository of knowledge regarding the specifics of cardiac histoanatomy, but could form the basis for generation of individualized high-resolution cardiac structure-function models. The current article presents a step in this general direction: it illustrates how whole-heart noninvasive imaging can be combined with whole-heart histology in an approach to achieve automated construction of histoanatomically detailed models of cardiac 3D structure and function at hitherto unprecedented resolution and accuracy (based on 26.4 x 26.4 x 24.4 microm MRI voxel size, and enriched by histological detail). It provides an overview of the tools used in this quest and outlines challenges posed by the approach in the light of applications that may benefit from the availability of such data and tools.

Animals↗
PubMed2004

Operative surgical education: results of a society of surgical oncology fellowship survey and proposal for an operative database.

BACKGROUND: Preparation of surgical trainees for oncological operative procedures is challenging. The purpose of this survey was to focus on identifying methods and resources used by trainees to prepare for procedures and to ascess the need for additional educational tools. METHODS: A 34-item survey was mailed electronically to 97 surgical oncology fellows at 14 Society of Surgical Oncology-approved training programs. General surgery residents at an affiliate training program (n = 65) and residents attending an American Board of Surgery In-Training Examination review course (n = 129) were polled via hard-copy mailings. The survey was distributed with the Dillman method. Self-education practices, factors influencing operative education, and strengths/weaknesses of available resources were identified. RESULTS: Response rates were 56% and 78% for fellows and residents, respectively. Trainees prepare for more than 50% of cases they perform (82%; 169 of 205), devoting up to 1 hour (87%; 178 of 205) in review the evening before a procedure (64%; 131 of 205). Time availability and attending of record were dominant factors influencing resident preparation, whereas case complexity was the most important variable motivating fellows. Surgical atlases, texts, anatomical references, and case discussion with attending staff were the most useful and available resources rated by trainees. Skills stations were recognized as the least valuable. Critical assessment of six educational resources identified no one particular area for improvement. CONCLUSIONS: There is a need for contemporary operative educational tools, incorporating time-sensitive and procedure-specific needs of surgical trainees preparing for oncological operative procedures.

Computer-Assisted Instruction↗