SEARCH · PubMed Health

Results for “spatial sequencing”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,513 records · Page 84Linked to original sources

PubMed2004

[Cardio-MRT. The multimodal functional analysis of the future].

Since initial reports in the early 1990s cardiac magnetic resonance imaging (CMR) has matured and is likely to become an established method for routine cardiac diagnostics. The development of faster gradient-echo sequences and stronger magnetic fields has led to improved temporal and spatial resolution. Myocardial viability can be examined by morphological and functional analysis. Contrast enhanced MRI (ceMRI), perfusion measurements and regional wall motion analysis are the major diagnostic tools. The ability to image in arbitrary double oblique planes provides comprehensive visualization of the heart. The introduction of the MR navigator technique allowed for free-breathing motion corrected 3D coronary MR angiography with improved spatial resolution. Using this approach proximal and mid parts of the coronary arteries have been visualized. Subsequently, sensitivity and specificity for the detection of significant coronary stenoses has been evaluated in a multicenter trial demonstrating good sensitivity and specificity for the detection of significant left main and three vessel disease. However, specificity for the detection of single vessel disease was relatively low. Improved motion compensation techniques and novel imaging sequences (SSFP) are currently under investigation to further refine this technique. Despite these promising results coronary MR-angiography is not likely to replace conventional coronary angiography especially with regard to in-plane spatial resolution, coronary collateralization and in-stent restenosis. In contrast, coronary MR-angiography can provide useful morphological informations including functional analysis of the coronary vascular bed. The combination of a conventional cathlab with CMR may provide CMR-guided myocardial interventions. With further improvements in the catheter technology, CMR interventions using real-time imaging guidance will allow to take advantage of the excellent soft tissue contrast of CMR and the simultaneous visualization of the pulmonary, aortic and coronary vessels. CMR is advantageous for screening and follow-up examinations, and it offers comprehensive assessment of cardiac morphology and function in one single examination.

Cardiomyopathies↗

PubMedDate not supplied

Lipid-suppressed single- and multisection proton spectroscopic imaging of the human brain.

Spectroscopic images of the brain have great potential in disease diagnosis and treatment monitoring. Unfortunately, interfering lipid signals from subcutaneous fat and poor water suppression due to magnetic field inhomogeneities can make such images difficult to obtain. A pulse sequence that uses inversion recovery for lipid suppression and a spectral-spatial refocusing pulse for water suppression is introduced. In contrast to methods that eliminate fat signal by restricting the excited volume to lie completely within the brain, inversion-recovery techniques allow imaging of an entire section without such restrictions. In addition, the spectral-spatial pulse was designed to provide water suppression insensitive to a reasonable range of B0 and B1 inhomogeneities. Several data processing algorithms have also been developed and used in conjunction with the new pulse sequence to produce metabolite maps covering large volumes of the human brain. Images from single- and multisection studies demonstrate the performance of these techniques.

Brain↗

PubMed2005

[Evaluation of the extent of ductal carcinoma in situ: comparison of MDCT and high-spatial-resolution MR imaging].

PURPOSE: To compare dual-phase contrast-enhanced multidetector-row CT (MDCT) with high-spatial-resolution MRI using a three-dimensional volumetric interpolated breath-hold examination (VIBE) sequence for evaluation of the extent of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: A retrospective review was conducted in 17 consecutive patients with DCIS in which both MDCT and MRI had been performed. The early phase of MDCT and MRI was started 60 sec after commencing contrast injection. The late phase was started 4 min after the injection. The size of the lesion on MDCT and MRI was measured in coronal images obtained during the early and late phases. Histological evaluation of the size was considered the gold standard, and the deviation in tumor size as measured in the early- and late-phase images from the histologically determined tumor size was calculated. RESULTS: The sensitivity rates of MDCT and MRI for the detection of DCIS were 88.2% (15/17)and 100%, respectively, and no lesions were detected in the late-phase images alone. The accuracy of detection of tumor diameters with a deviation of less than 2 cm was 76.5% (13/17) with MDCT and 94.1% (16/17) with MRI. The tumor diameter was overestimated by more than 2 cm in 2 lesions (11.8%) on MDCT and one lesion (5.9%)on MRI, in both early- and late-phase scans. Tumor diameter was underestimated in early- as compared to late-phase scans in 3 cases on MDCT and one case on MRI. CONCLUSION: High-spatial-resolution MRI using the VIBE sequence is more accurate for the detection and evaluation of the extent of DCIS than MDCT. In dynamic studies, more accurate evaluation of the extent of DCIS is possible in late-phase images.

Adult↗

PubMed2026

Multiregion profiling of genomic and transcriptional heterogeneity in head and neck squamous-cell carcinoma.

BACKGROUND: Intratumoral heterogeneity (ITH) is thought to contribute to tumour evolution and treatment resistance but its biological and clinical significance in localised head and neck squamous-cell carcinoma (HNSCC) remains incompletely understood. PATIENTS AND METHODS: In the prospective SCANDARE study, we analysed 87 patients with resectable HNSCC treated with upfront surgery. Two to five spatially distinct tumour regions per patient underwent pathological evaluation, targeted DNA sequencing, and bulk RNA sequencing. Genomic ITH (gITH) was quantified using clonal deconvolution and Shannon diversity indices, whereas transcriptional heterogeneity (tITH) was assessed using the intratumour expression distance metric. Associations between ITH, molecular features, tumour microenvironment composition, and clinical outcomes were explored using multivariable statistical models. RESULTS: Pathology-based spatial heterogeneity showed limited prognostic value. gITH was common, with 37% of tumours displaying regionally heterogeneous pathogenic variants, including spatially actionable alterations in 10% of patients. In an initial multivariable Cox model, higher gITH was associated with shorter disease-free survival. However, after Ridge-penalised modelling and bootstrap internal validation, the effect size was attenuated [corrected hazard ratio 1.42, 95% confidence interval (CI) 0.91-2.75]. The overall model retained moderate discriminative performance (optimism-corrected C-index 0.69, 95% CI 0.59-0.79). gITH was associated with tumour cellularity, reduced estimated endothelial cell infiltration, and alterations in KMT2C and PIK3CA. tITH differed according to human papillomavirus (HPV) status, with lower tITH in HPV-positive tumours, and was associated with distinct biological pathways and genomic alterations. Genomic and tITH were not correlated. CONCLUSIONS: This prospective multiregion study provides a comprehensive characterisation of genomic and tITH in localised HNSCC. Our findings highlight substantial spatial molecular diversity within primary tumours and suggest potential associations between heterogeneity, tumour biology, and clinical outcome that warrant validation in independent cohorts.

head and neck squamous-cell carcinoma (HNSCC)↗

PubMed1997

Molecular evolution of a portion of the mitochondrial 16S ribosomal gene region in scleractinian corals.

Relationships among families and suborders of scleractinian corals are poorly understood because of difficulties 1) in making inferences about the evolution of the morphological characters used in coral taxonomy and 2) in interpreting their 240-million-year fossil record. Here we describe patterns of molecular evolution in a segment of the mitochondrial (mt) 16S ribosomal gene from taxa of 14 families of corals and the use of this gene segment in a phylogenetic analysis of relationships within the order. We show that sequences obtained from scleractinians are homologous to other metazoan 16S ribosomal sequences and fall into-two distinct clades defined by size of the amplified gene product. Comparisons of sequences from the two clades demonstrate that both sets of sequences are evolving under similar evolutionary constraints: they do not differ in nucleotide composition, numbers of transition and transversion substitutions, spatial patterns of substitutions, or in rates of divergence. The characteristics and patterns observed in these sequences as well as the secondary structures, are similar to those observed in mt 16S ribosomal DNA sequences from other taxa. Phylogenetic analysis of these sequences shows that they are useful for evaluating relationships within the order. The hypothesis generated from this analysis differs from traditional hypotheses for evolutionary relationships among the Scleractinia and suggests that a reevaluation of evolutionary affinities in the order is needed.

Animals↗

PubMed1992

Perturbing highly conserved spatial relationships in the regulatory domain that controls inducible cat translation.

Chloramphenicol activates translation of cat-86 mRNA by stalling a ribosome in the leader of individual transcripts. Stalling triggers two sequential events: the destabilization of a region of secondary structure that sequesters the cat ribosome-binding site (RBS-C), and the initiation of cat translation. The site of drug-dependent ribosome stalling is dictated by the leader sequence, crb; crb causes a ribosome to stall with its aminoacyl site at leader codon 6. We demonstrate that induction requires the maintenance of a precise spatial relationship between crb and sequences within the left inverted repeat of the secondary structure. Therefore, destabilization of the secondary structure during chloramphenicol induction may result from the interaction of a stalled ribosome with a specific sequence in the secondary structure rather than from non-specific masking of RNA sequences. cat-86 regulation also depends on the distance that separates crb from RBS-C. This interval of 33 nucleotides was incrementally increased and decreased by mutations within a loop in the secondary structure. Shortening the distance between crb and RBS-C by three nucleotides reduced induction by half and a deletion of nine nucleotides abolished induction. Insertion mutations were without effect on induced expression but elevated basal expression. The results indicate that when the A site of a ribosome occupies leader codon 6 the secondary structure is destabilized and there is no interference with entry of a second ribosome at RBS-C. The data further demonstrate that when the A site of a ribosome in the leader is within 30 nucleotides of RBS-C, cat expression decreases. This decrease probably results from competition of the leader ribosome with the ribosome initiating cat translation. Our observations demonstrate that in wild-type cat-86 the distances between crb and the secondary structure, and between crb and RBS-C provide the precise spacing necessary to achieve three interdependent effects: the destabilization of the RNA secondary structure by a ribosome stalled at crb; a lack of competition between a ribosome stalled at crb and the initiating ribosome; and maintenance of a low, but measurable, basal level of cat expression. The spatial relationships identified as necessary for the regulation of cat-86 are conserved in the regulatory regions for five other inducible cat genes.

Base Sequence↗

PubMed2003

Resolution enhancement in lung 1H imaging using parallel imaging methods.

Resolution in (1)H lung imaging is limited mainly by the acquisition time. Today, half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences, with short echo time (TE) and short interecho spacing (T(inter)) have found increased use in lung imaging. In this study, a HASTE sequence was used in combination with a partially parallel acquisition (PPA) strategy to increase the spatial resolution in single-shot (1)H lung imaging. To investigate the benefits of using a combination of single-shot sequences and PPA, five healthy volunteers were examined. Compared to conventional imaging methods, substantially increased resolution is obtained using the PPA approach. Representative in vivo (1)H lung images acquired with a HASTE sequence in combination with the generalized autocalibrating partially parallel acquisition (GRAPPA) method, up to an acceleration factor of three, are presented.

Humans↗

PubMed1998

Spatial and temporal dynamics of DNA replication sites in mammalian cells.

Fluorescence microscopic analysis of newly replicated DNA has revealed discrete granular sites of replication (RS). The average size and number of replication sites from early to mid S-phase suggest that each RS contains numerous replicons clustered together. We are using fluorescence laser scanning confocal microscopy in conjunction with multidimensional image analysis to gain more precise information about RS and their spatial-temporal dynamics. Using a newly improved imaging segmentation program, we report an average of approximately 1,100 RS after a 5-min pulse labeling of 3T3 mouse fibroblast cells in early S-phase. Pulse-chase-pulse double labeling experiments reveal that RS take approximately 45 min to complete replication. Appropriate calculations suggest that each RS contains an average of 1 mbp of DNA or approximately 6 average-sized replicons. Double pulse-double chase experiments demonstrate that the DNA sequences replicated at individual RS are precisely maintained temporally and spatially as the cell progresses through the cell cycle and into subsequent generations. By labeling replicated DNA at the G1/S borders for two consecutive cell generations, we show that the DNA synthesized at early S-phase is replicated at the same time and sites in the next round of replication.

3T3 Cells↗

PubMed1999

Functional MR microscopy of the lung using hyperpolarized 3He.

A new strategy designed to provide functional magnetic resonance images of the lung in small animals at microscopic resolution using hyperpolarized 3He is described. The pulse sequence is based on a combination of radial acquisition (RA) and CINE techniques, referred to as RA-CINE, and is designed for use with hyperpolarized 3He to explore lung ventilation with high temporal and spatial resolution in small animal models. Ventilation of the live guinea pig is demonstrated with effective temporal resolution of 50 msec and in-plane spatial resolution of <100 microm using hyperpolarized 3He. The RA-CINE sequence allows one to follow gas inflow and outflow in the airways as well as in the distal part of the lungs. Regional analysis of signal intensity variations can be performed and can help assess functional lung parameters such as residual gas volume and lung compliance to gas inflow.

Animals↗

PubMed2000

The restoration of fertility in male sterile tobacco demonstrates that transgene silencing can be mediated by T-DNA that has no DNA homology to the silenced transgene.

Male sterile tobacco plants expressing a pathogenesis-related (PR) beta-1,3-glucanase gene driven by the Arabidopsis thaliana A3 or A9 tapetum-specific promoter, were partially restored to fertility by retransformation with a range of pA9-driven sense and antisense PR glucanase fragments. The restored plants exhibited improved seed set. PR glucanase protein was undetectable in the anthers of these plants and there was an associated increase in microsporocyte callose, the structural target of the A3 and A9-driven PR glucanase. This phenotype was not solely dependent on interactions between sense and antisense PR glucanase transcripts since a pA9-driven restorer was also capable of down regulating a pA3-GUS construct in the absence of extensive promoter, coding region, or terminator sequence homology. Since the A3 and A9 promoters have similar temporal and spatial expression patterns, it is possible that trans-acting factors common to both promoters become limiting in the PR glucanase double transformants resulting in improved levels of fertility. An alternative hypothesis is that additional sequences present in both the silencing and target T-DNAs can mediate the silencing of adjacent non-homologous transgenes.

Arabidopsis↗

PubMed1996

A polynomial-time algorithm for a class of protein threading problems.

This paper presents an algorithm for constructing an optimal alignment between a three-dimensional protein structure template and an amino acid sequence. A protein structure template is given as a sequence of amino acid residue positions in three-dimensional space, along with an array of physical properties attached to each position; these residue positions are sequentially grouped into a series of core secondary structures (central helices and beta sheets). In addition to match scores and gap penalties, as in a traditional sequence-sequence alignment problem, the quality of a structure-sequence alignment is also determined by interaction preferences among amino acids aligned with structure positions that are spatially close (we call these 'long-range interactions'). Although it is known that constructing such a structure-sequence alignment in the most general form is NP-hard, our algorithm runs in polynomial time when restricted to structures with a 'modest' number of long-range amino acid interactions. In the current work, long-range interactions are limited to interactions between amino acids from different core secondary structures. Dividing the series of core secondary structures into two subseries creates a cut set of long-range interactions. If we use N, M and C to represent the size of an amino acid sequence, the size of a structure template, and the maximum cut size of long-range interactions, respectively, the algorithm finds an optimal structure-sequence alignment in O(21C NM) time, a polynomial function of N and M when C = O(log(N + M)). When running on structure-sequence alignment problems without long-range intersections, i.e. C = 0, the algorithm achieves the same asymptotic computational complexity of the Smith-Waterman sequence-sequence alignment algorithm.

Algorithms↗

PubMed2026

A Molecularly Anchored Spatial Transcriptomic Framework for Precise CA1-Subiculum Parcellation and Region-Resolved Analysis in Alzheimer's Disease.

BACKGROUND: The precise molecular delineation of the interface between the Subiculum (Sub) and cornu ammonis 1 (CA1) is a challenge in hippocampal research, as conventional cytoarchitectural boundaries are often ambiguous and limit reproducible regional annotation. Here, we developed a molecularly anchored spatial transcriptomic framework to define CA1-Sub regional identities using high-definition spatial transcriptomics (Stereo-seq) and single-nucleus RNA sequencing (snRNA-seq) references. FINDINGS: Using a human hippocampal Stereo-seq dataset from 12 donors, we established a data-driven parcellation framework that defines reproducible molecular features distinguishing CA1 and Sub while capturing the transition between these regions. FN1 was identified as a Sub-enriched marker in a subset of EX_Sub and, together with ETV1 and additional regional markers, enabled molecular assignment of CA1 and Sub identities across datasets. The Sub association of FN1 and ETV1 was further supported by human 10X Genomics spatial transcriptomics, mouse in situ hybridization data, and a mouse spatial transcriptomic dataset. Applying this framework to Alzheimer's disease (AD) tissues revealed region-specific transcriptional alterations across CA1 and Sub, including enrichment of mitochondrial energy metabolism-related transcripts in the Sub, suggesting exploratory transcriptional associations of altered metabolic function. CONCLUSIONS: This study provides a molecularly anchored framework for human CA1-Sub parcellation that complements conventional annotation. By defining regional molecular states while preserving the biological continuum across CA1-Sub interface, this approach enables more consistent regional analysis of human hippocampus tissue across donors, datasets, and disease conditions.

Journal Article↗

PubMed1990

The Xenopus XIHbox 6 homeo protein, a marker of posterior neural induction, is expressed in proliferating neurons.

XIHbox 6 is an early spatially restricted marker for molecular studies of neural induction. The sequence of the full-length XIHbox 6 protein is reported. An antibody raised against a beta-galactosidase/XIHbox 6 fusion protein was used to analyze the expression of XIHbox 6 proteins during frog embryogenesis. The anterior border of XIHbox 6 expression lies just posterior of the hindbrain/spinal cord junction. Immunostaining extends the entire length of the spinal cord. A much weaker transient expression with a similar anterior border is observed in mesoderm. Almost all nuclei in the newly closed spinal cord contain XIHbox 6. The number of positive nuclei decreases over the next stages of development, until in later embryos XIHbox 6 is restricted to nuclei of the dividing neuroepithelium, and not the mantle or marginal zones of the spinal cord. When the limb buds begin to grow, there is a second burst of XIHbox 6 expression in proliferating neurons of the cervical and lumbar enlargements, where nerves arise that supply the limbs. The data suggest that XIHbox 6 expression is spatially and temporally restricted to immature neurons of the spinal cord, before their differentiation into mature neurons.

Amino Acid Sequence↗

PubMed1999

Unaliasing by fourier-encoding the overlaps using the temporal dimension (UNFOLD), applied to cardiac imaging and fMRI.

In several applications, MRI is used to monitor the time behavior of the signal in an organ of interest; e.g., signal evolution because of physiological motion, activation, or contrast-agent accumulation. Dynamic applications involve acquiring data in a k-t space, which contains both temporal and spatial information. It is shown here that in some dynamic applications, the t axis of k-t space is not densely filled with information. A method is introduced that can transfer information from the k axes to the t axis, allowing a denser, smaller k-t space to be acquired, and leading to significant reductions in the acquisition time of the temporal frames. Results are presented for cardiac-triggered imaging and functional MRI (fMRI), and are compared with data obtained in a conventional way. The temporal resolution was increased by nearly a factor of two in the cardiac-triggered study, and by as much as a factor of eight in the fMRI study. This increase allowed the acquisition of fMRI activation maps, even when the acquisition time for a single full time frame was actually longer than the paradigm cycle period itself. The new method can be used to significantly reduce the acquisition time of the individual temporal frames in certain dynamic studies. This can be used, for example, to increase the temporal or spatial resolution, increase the spatial coverage, decrease the total imaging time, or alter sequence parameters e.g., repetition time (TR) and echo time (TE) and thereby alter contrast. Magn Reson Med 42:813-828, 1999.

Algorithms↗

PubMed2005

Keratin 19 gene drives Cre recombinase expression throughout the early postimplantation mouse embryo.

The development of Cre-lox technology has created new opportunities for studying the tissue-specific functions of genes in vivo during development and disease. We analyzed the spatial and temporal activity of Cre recombinase whose coding sequence was inserted into the endogenous locus for keratin 19. Rather than providing epithelial-specific recombination during organogenesis, this K19cre allele allows unexpected recombination in early embryonic development, resulting in recombination of a loxP-flanked allele throughout all tissues of the mouse, but with sparing of the extraembryonic endoderm, including the anterior visceral endoderm.

Animals↗

PubMedDate not supplied

Ex vivo evaluation of ferromagnetism, heating, and artifacts produced by heart valve prostheses exposed to a 1.5-T MR system.

Ex vivo testing techniques were used to determine the ferromagnetic qualities of, presence of heating in, and artifacts produced by 13 different heart valve prostheses exposed to a 1.5-T (64-MHz) magnetic resonance (MR) system. None of the heart valve prostheses showed a measurable deflection in the 1.5-T static magnetic field. Only minimal artifacts were produced during MR imaging with a fast spoiled GRASS (gradient-recalled acquisition in the steady state) pulse sequence. The largest temperature changes measured during a "worst case" MR imaging sequence (estimated average specific absorption rate, 2.5 W/kg; estimated spatial peak specific absorption rate, 7.6 W/kg) were +0.2 degree C with the implant imaged "in air" and +0.3 degrees C with the implant imaged in normal saline. Therefore, MR procedures performed with a 1.5-T (64-MHz) MR system may be performed safely in patients with any of the 13 different heart valve prostheses evaluated in this study.

Absorption↗

PubMedDate not supplied

Registration of images from sequential MR studies of the brain.

For sequential studies of patients with brain tumors, the authors have designed an automated registration procedure for intra- and interexamination alignment of magnetic resonance images. This was evaluated with artificially misregistered data and data from repeat studies of six healthy volunteers and six brain tumor patients. In a subset of cases, a manual procedure based on matching of neuroanatomic landmarks was also applied for comparison. The results showed that the technique is robust and reproducible, giving an accuracy in the range of 1-2 mm, which corresponded to the spatial resolution of the images. Subject motion between imaging sequences within the same study was negligible, although adjustments (one to two section thicknesses) were required in the z direction to correlate multisection and volume images and to allow accurate image segmentation. For alignment between sequential volunteer and patient examinations, translations of up to 22 mm and rotations in the x, y, and z axes of up to 9 degrees were required. This alignment procedure may be valuable in numerous aspects of treatment planning and patient follow-up.

Adult↗

PubMedDate not supplied

Dual dynamic contrast-enhanced MR imaging.

A method was devised for obtaining dynamic contrast-enhanced T1-weighted and relaxation rate (delta R2*) images simultaneously to evaluate regional hemodynamics of the brain tumors. On a 1.5-T MR system, dual dynamic contrast-enhanced images were obtained using a gradient echo (dual echo fast field echo) pulse sequence with the keyhole technique to improve temporal and spatial resolution during a rapid bolus injection of gadopentetate dimeglumine. The dynamic T1 contrast images were obtained from the first echo: moreover. integral delta R2*dt values were calculated from the first and the second echo images. The dynamic T1 contrast images provided information about characteristic enhancement pattern (vascularization and disruption of blood-brain barrier), and the integral delta R2*dt values provided a map of regional blood pool in tumor site, peritumoral edema, and other surrounding regions of the brain. The ability to obtain dynamic contrast-enhanced T1 contrast and delta R2* imaging at the same time allows optimization of the advantages of each and thereby more information about the microvascular circulation of the brain lesions.

Brain↗