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Results for “spatial sequencing”

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PubMed2005

No sequence dependent modulation of the Simon effect in Parkinson's disease.

This study sought to evaluate impaired response tendencies and modulation of automatic processes in Parkinson's disease (PD), utilising a saccadic Simon task with stimulus-response (S-R) compatibility determined on the basis of cue shape. The appearance of either a circle or a square in one of two boxes presented peripherally required the generation of a leftward or rightward horizontal saccade, respectively. These goal-directed responses were considered behaviourally relevant to an examination of visuospatial performance. Although response times are typically faster when stimulus and response are spatially compatible than when they are not, sequence-dependent modulation of this effect results in large differences between S-R compatible and S-R incompatible trials when stimulus and response are spatially compatible in the preceding trial, and reduced or absent differences when stimulus and response are spatially incompatible in the preceding trial. Unlike control subjects, PD patients demonstrated significantly shorter saccadic latencies overall, compared to a baseline condition involving endogenously-driven saccades. Patients also responded erroneously to cue stimuli with greater frequency. Analyses of both saccadic latency and errors to cue demonstrated a Simon effect (relatively faster response for S-R compatible trials), irrespective of the preceding trial. This suggests impaired modulation of the Simon effect in PD, consistent with predictions of inhibitory dysfunction, or impaired episodic memory. These results demonstrate the pivotal role of the basal ganglia in the regulation of context-dependent neural activity.

Adult↗

PubMed2005

Location and function of vesicle clusters, active zones and Ca2+ channels in the lamprey presynaptic terminal.

Synaptic transmission requires spatial and temporal coordination of a specific sequence of events. The trigger for synaptic vesicle exocytosis is Ca(2)(+) entry into presynaptic terminals, leading to neurotransmitter release at highly specialized sites known as active zones. Ca(2)(+) channel proximity to exocytotic proteins and vesicle clusters at active zones have been inferred from biochemical, histological and ultrastructural data, but direct evidence about functional relationships between these elements in central synapses is absent. We have utilized the lamprey giant reticulospinal synapse to characterize functional colocalization of known synaptic markers in the presynaptic terminal, as well as their reliability during repeated activation. Recycling vesicle clusters, surrounding actin filaments, and physiologically relevant Ca(2)(+) influx all show identical morphological distribution. Ca(2)(+) influx is mediated by clusters of Ca(2)(+) channels that colocalize with the vesicle clusters, defined by imaged sites of vesicle recycling and actin localization. Synaptic transmission is inhibited by block of actin depolymerization, but Ca(2)(+) signalling is unaffected. Functional Ca(2)(+) channels are localized to presynaptic clusters, and Ca(2)(+) transients at these sites account for neurotransmitter release based on their spatial and temporal profiles. Ca(2)(+) transients evoked by single axonal action potentials are mediated solely by voltage-operated Ca(2)(+) channel activation, and slower Ca(2)(+) rises observed throughout the axon result from Ca(2)(+) diffusion from the synaptic regions. We conclude that at lamprey giant reticulospinal synapses, Ca(2)(+) channels and release sites colocalize, creating a close spatial relationship between active zones and Ca(2)(+) entry sites, which is necessary for site-specific, Ca(2)(+)-dependent secretion.

Animals↗

PubMed2026

RNF43 Mutations Are Associated With the Classical Molecular Subtype, Vigorous Antitumor Immune Responses, and Prolonged Survival in Pancreatic Adenocarcinoma.

RNF43 mutations were correlated with microsatellite status in colorectal cancer and with fewer and later recurrences in pancreatic ductal adenocarcinoma (PDAC). Here, we undertake a detailed assessment of RNF43 mutations in PDAC. A total of 313 PDACs (308 microsatellite stable [MSS] and 5 microsatellite-instable [MSI] cases) underwent next-generation sequencing (Oncomine Tumor Mutation Load assay; Thermo Fisher). Spatial analyses (NanoString) classified PDACs according to their transcriptomic and proteomic immune signaling. Fluorescent imaging was used to define spatial compartments (tumor: pancytokeratin+/CD45- and leukocytes: pancytokeratin-/CD45+). Each of 20 PDACs with RNF43 mutations (RNF43mut) and without RNF43 mutations (RNF43wt) underwent multiplex immunofluorescence analysis to determine immune status. A total of 153 PDACs (22 RNF43mut and 131 RNF43wt cases) underwent bulk RNA sequencing to assign into molecular subtypes. Overall, 24 RNF43 mutations were identified (22 MSS PDACs and 2 MSI PDACs). The incidence of RNF43 mutations in MSS PDACs (7.1%) was consistent with The Cancer Genome Atlas (6.7%). However, RNF43 mutations were more frequent among MSI PDACs (40%). Additionally, RNF43mut had differential frequencies of other mutations (including Wnt pathway genes), higher tumor mutational burden values (5.5 mut/mb vs 1.67 mut/mb; P < .01), and significantly longer overall survival (47 vs 18 months; P < .0001) than RNF43wt. Moreover, RNF43mut exhibited significantly higher densities of CD8+ T lymphocytes, dendritic cells, and B lymphocytes (P < .001) and an upregulation of ITGAX, CD11c, CD8, and HLA-DR compared with RNF43wt. Patients with RNF43mut PDACs were more often of the classical molecular subtype (20/22, 90.9%). RNF43mut PDACs showed high tumor mutational burden values, suggesting increased neoantigen load coupled with an abundance of antigen-presenting immune cells and an upregulation of immune determinants promoting antigen presentation. All this contributes to stronger antitumor immune responses and improved clinical outcomes.

Humans↗

PubMed1989

Temporal and spatial control of the mother-cell regulatory gene spoIIID of Bacillus subtilis.

Gene expression during endospore formation in Bacillus subtilis is compartmentalized between the mother-cell and forespore chambers of the sporangium, which follow separate pathways of cellular differentiation. The earliest acting regulatory gene so far identified in the mother-cell line of gene expression is spoIIID, whose product is required for the transcription of the composite gene (sigK) encoding the mother-cell RNA polymerase sigma-factor sigma K and for the chromosomal rearrangement that gives rise to the composite gene. Here we report the nucleotide sequence of spoIIID and studies on the temporal, spatial, and genetic control of its expression during sporulation. We show that the deduced spoIIID gene product, a 93-residue-long polypeptide, is a previously identified transcription factor that is known to activate the promoter for the sigK gene in vitro. Expression of spoIIID is largely confined to the mother-cell chamber of the sporangium and is turned on at, or shortly before, the time (hour 3 of sporulation) that the mother-cell chromosome is rearranged and transcription of the sigK gene commences. This gene expression depends strongly on the sporulation sigma-factor sigma E and partially on the spoIIID gene product, itself. We conclude that the timing and compartmentalization of the rearrangement and transcription of the sigK gene and, hence, of subsequent gene activation in the mother cell, are, in part, direct consequences of the temporal and spatial control of spoIIID gene expression.

Amino Acid Sequence↗

PubMed1996

GenomeInspector: a new approach to detect correlation patterns of elements on genomic sequences.

MOTIVATION: Most of the sequences determined in current genome sequencing projects remain at least partially unannotated. The available software for DNA sequence analysis is usually limited to the prediction of individual elements (level 1 methods), but does not assess the context of different motifs. However, the functionality of biological units like promoters depends on the correct spatial organization of multiple individual elements. RESULTS: Here, we present a second-level software package called GenomeInspector [[http:@www.gsf.de/biodv/genomeinspector.html ]], for further analysis of results obtained with level 1 methods (e.g. MatInspector [[http:@www.gsf.de/biodv/matinspector.html ]] or ConsInspector [[http:@www.gsf.de/biodv/consinspector.html++ +]]). One of the main features of this modular program is its ability to assess distance correlations between large sets of sequence elements which can be used for the identification and definition of basic patterns of functional units. The program provides an easy-to-use graphical user interface with direct comprehensive display of all results for megabase sequences. Sequence elements showing spatial correlations can be easily extracted and traced back to the nucleotide sequence with the program. GenomeInspector identified promoters of glycolytic enzymes in yeast [[http:@www.mips.biochem.mpg.de/mips/yeast/]] as members of a subgroup with unusual location of an ABF1 site. Solely on the basis of distance correlation analysis, the program correctly selected those transcription factors within these promoters already known to be involved in the regulation of glycolytic enzymes, demonstrating the power of this method.

Algorithms↗

PubMed2003

Cyclic summation versus m-sequence technique in the multifocal ERG.

BACKGROUND: The m-sequence technique is a typical tool for the multifocal ERG. The use of LEDs instead of a computer monitor enables a new technique that merits closer investigation: The cyclic summation technique. The aim of this study was to compare the two methods. METHODS: Six normal right eyes were examined with the RETIscan system using DTL electrodes. With an LED array (display diameter 52 degrees, 103 segments, 1 foveal + 102 arranged in six concentric rings) we studied: (1). first order kernels (m-sequence); (2). 30-Hz flicker responses (m-sequence); (3). 30-Hz flicker responses (cyclic summation). The three methods were tested with a pattern of concentric rings generated by selective deactivation of LEDs (the central LED and rings 2, 4 and 6; rings 1, 3 and 5 remained active). In each case six cumulative measurements (40 s each) were made and stored separately. To determine the signal-to-noise ratio, the average mf ERG response to all active LEDs was divided by the average response to the inactive ones. RESULTS: 1. Using cyclic summation the signal-to-noise ratio exceeds the signal-to-noise ratio of both m-sequence-controlled stimuli about twofold. This implies also better spatial resolution with the cyclic summation technique 2. Since the signal-to-noise ratio increases faster with the cyclic summation technique than with the m-sequence technique, the gain of time in mf ERG can reach 80%. CONCLUSION: As far as the signal-to-noise ratio and measuring time is concerned, the cyclic summation technique outmatches the m-sequence technique in mf ERG.

Adult↗

PubMed2005

Beta-amyloid peptide binds equivalently to binary and ternary alpha2-macroglobulin-protease complexes.

alpha2-Macroglobulin (alpha2M) is a protease inhibitor that has separate binding sites for transforming growth factor-beta (TGF-beta) and beta-amyloid peptide (Abeta), both of which have been identified in the beta2M sequence. In the 3D-structure of alpha2M, TGF-beta occupies the alpha2M central cavity, overlapping with the space that can accommodate up to two molecules of protease. As a result, ternary alpha2M-protease complexes (2 mol protease/mol alpha2M) have been reported to not bind TGF-beta. The goal of the present study was to test whether binding of Abeta to alpha2M is controlled by steric constraints imposed by associated proteases, similarly to TGF-beta. We confirmed that binary alpha2M-trypsin complex (1 mol trypsin/mol alpha2M) binds increased amounts of TGF-beta1, compared with native alpha2M, while ternary alpha2M-trypsin complex binds substantially decreased amounts of TGF-beta1. By contrast, Abeta-binding to binary and ternary alpha2M trypsin complex was equivalent. In both cases, binding was substantially increased compared with the negligible level observed with native alpha2M. Plasmin is a large protease (Mr approximately 82,000) that substantially occupies the alpha2M central cavity; however, alpha2M-plasmin complex also bound increased amounts of Abeta, compared with native alpha2M. We conclude that Abeta accesses its binding site, in alpha2M, from outside the alpha2M central cavity. The TGF-beta- and Abeta-binding sites are spatially separated not only in the primary sequence of alpha2M, but also in the 3D-structure.

Amyloid beta-Peptides↗

PubMed1997

High-resolution MRI of pancreatic masses with a new circularly polarized body phased-array coil.

A total of 18 patients with clinical suspicion of a pancreatic tumor underwent dynamic contrast-enhanced CT and MRI examinations. A fat-suppressed T1-weighted 2D fast-low-angle-shot (FLASH) sequence and a T2-weighted spin-echo (SE) sequence were applied in a transverse orientation using a circularly polarized (CP) body phased-array coil. The FLASH sequence was repeated after Gd-DTPA administration. The highest spatial resolution was 1.37 x 1.37 x 3.00 mm3. In two cases a half Fourier single-shot turbo-SE sequence (HASTE) was additionally applied. In a comparison between CT and MRI, pancreatic masses could be demonstrated and characterized with excellent image quality. The fat-saturated 2D FLASH sequence yielded the highest contrast-to-noise ratios after Gd-DTPA administration between pancreas and inflammatory or neoplastic lesion. One non-contour deforming carcinoma could be detected only with MRI and was only retrospectively visible on CT with an element of uncertainty. Magnetic resonance imaging using a CP body phased-array coil and fat-suppressed T1- and T2-weighted FLASH, SE, and turbo-SE sequences offers diagnostic possibilities in improved imaging of the pancreas.

Aged↗

PubMed2005

Cloning of Smad2, Smad3, Smad4, and Smad7 from the goldfish pituitary and evidence for their involvement in activin regulation of goldfish FSHbeta promoter activity.

Follicle-stimulating hormone (FSH), a glycoprotein consisting of an alpha subunit and a unique beta subunit, is essential for gonadal development and function in vertebrates including teleosts. FSH is regulated by a variety of neuroendocrine and endocrine factors, and its biosynthesis is primarily determined by the expression of the beta subunit. Although the regulation of FSH biosynthesis has been well documented in mammals, the molecular mechanisms underlying the regulation are poorly understood. Our previous studies demonstrated that activin stimulated goldfish FSHbeta expression in the primary pituitary cell culture and enhanced its promoter activity in the mouse gonadotrope cell line LbetaT-2 cells. However, little is known about the signal transduction pathway involved in the transcriptional activation of this gene by activin. To assess the involvement of intracellular signaling protein Smads in regulating goldfish FSHbeta promoter, we first cloned full-length cDNAs for goldfish Smad2, Smad3, Smad4, and Smad7 from the pituitary. All Smads cloned show high sequence conservation with their mammalian counterparts. The spatial expression of these Smads overlapped with that of activin subunits and its receptors in various tissues examined. In addition, we demonstrated that activin induced Smad3 and Smad7 expression, but not Smad2 and Smad4. Co-transfection of Smad2 or Smad3 cDNA into the LbetaT-2 cells with the reporter construct of goldfish FSHbeta promoter significantly enhanced basal and activin-stimulated reporter (SEAP, secreted alkaline phosphatase) expression, while Smad7 completely blocked basal and Smad2/3-stimulated FSHbeta activity. Interestingly, the effect of Smad3 was much higher than that of Smad2, suggesting that Smad3 is likely the principal signal transducing molecule involved in activin stimulation of FSHbeta expression in the goldfish. This work lays a foundation for further analysis of goldfish FSHbeta promoter for the cis-regulatory elements involved in activin signaling.

Activins↗

PubMed1981

Linkage and evolutionary diversification of developmentally regulated multigene families: tandem arrays of the 401/18 chorion gene pair in silkmoths.

The coordinately expressed silkmoth chorion genes, 401 and 18, are closely linked as a pair, in divergent orientation. Analysis of overlapping clones (chromosomal "walk") demonstrated that each of the multiple copies of this gene pair is embedded within a larger deoxyribonucleic acid unit, which is tandemly repeated in a few arrays or possibly a single array. Southern analysis and examination of clones from a single individual moth demonstrated that the repeat units are extensively polymorphic in restriction sites, length, and possibly number, no differential amplification was evident during choriogenesis. Intron and 5'-flanking sequences were shown to be specific for the 401/18 gene pair and not to be present elsewhere in the genome. The spatial distribution of variations in the genes and their flanking sequences were examined.

Animals↗

PubMed1998

Identification of an evolutionarily conserved 110 base-pair cis-acting regulatory sequence that governs Wnt-1 expression in the murine neural plate.

The generation of anterior-posterior polarity in the vertebrate brain requires the establishment of regional domains of gene expression at early somite stages. Wnt-1 encodes a signal that is expressed in the developing midbrain and is essential for midbrain and anterior hindbrain development. Previous work identified a 5.5 kilobase region located downstream of the Wnt-1 coding sequence which is necessary and sufficient for Wnt-1 expression in vivo. Using a transgenic mouse reporter assay, we have now identified a 110 base pair regulatory sequence within the 5.5 kilobase enhancer, which is sufficient for expression of a lacZ reporter in the approximate Wnt-1 pattern at neural plate stages. Multimers of this element driving Wnt-1 expression can partially rescue the midbrain-hindbrain phenotype of Wnt-1(-/-) embryos. The possibility that this region represents an evolutionarily conserved regulatory module is suggested by the identification of a highly homologous region located downstream of the wnt-1 gene in the pufferfish (Fugu rubripes). These sequences are capable of appropriate temporal and spatial activation of a reporter gene in the embryonic mouse midbrain; although, later aspects of the Wnt-1 expression pattern are absent. Genetic evidence has implicated Pax transcription factors in the regulation of Wnt-1. Although Pax-2 binds to the 110 base pair murine regulatory element in vitro, the location of the binding sites could not be precisely established and mutation of two putative low affinity sites did not abolish activation of a Wnt-1 reporter transgene in vivo. Thus, it is unlikely that Pax proteins regulate Wnt-1 by direct interactions with this cis-acting regulatory region. Our analysis of the 110 base pair minimal regulatory element suggests that Wnt-1 regulation is complex, involving different regulatory interactions for activation and the later maintenance of transgene expression in the dorsal midbrain and ventral diencephalon, and at the midbrain-hindbrain junction.

Animals↗

PubMed2025

Multi-omics analyses reveal DjTcf4 critical for proper timing of differentiation in planarian regeneration.

The blastema is key to forming complete tissues in regenerating Dugesia japonica (D. japonica). However, the dynamic changes in cellular compositions and transcription landscapes in blastema during regeneration are understudied. Here, through genome reannotation, 3D spatial transcriptome construction, single-cell RNA sequencing (scRNA-seq), and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analyses of changes in gene expression and chromatin structures, we delineate key transcription factors regulating the developmental trajectories of major cell clusters in the regenerating head. Importantly, we find that the T cell factor 4 (DjTcf4)-positive cells highly accumulate at wound areas, and its gene network is critical for the proper timing of development during regeneration in multiple progenitor cells. Depletion of DjTcf4 and its target genes leads to singular eye and/or dull tail phenotypes and delays regeneration. Taken together, we build multi-omics atlases in D. japonica and reveal the noncanonical function of the DjTcf4 network in developmental pattern formation, laying a foundation for studies of regeneration in D. japonica.

Animals↗

PubMed1984

Neuromagnetic evidence of spatially distributed sources underlying epileptiform spikes in the human brain.

Neuromagnetic measurements were performed on 17 subjects with focal seizure disorders. In all of the subjects, the interictal spike in the scalp electroencephalogram was associated with an orderly extracranial magnetic field pattern. In eight of these subjects, multiple current sources underlay the magnetic spike complex. The multiple sources within a given subject displayed a fixed chronological sequence of discharge, demonstrating a high degree of spatial and temporal organization within the interictal focus.

Brain↗

PubMed1999

Insect immunity: molecular cloning, expression, and characterization of cDNAs and genomic DNA encoding three isoforms of insect defensin in Aedes aegypti.

Aedes aegypti were immune activated by injection with bacteria, and the expression of insect defensins was measured over time. Northern analyses indicated that defensin transcriptional activity continued for at least 21 days after bacterial injection, and up to 10 days after saline inoculation. Mature defensin levels in the haemolymph reached approximately 45 microM at 24 h post inoculation. cDNAs encoding the preprodefensins of three previously described mature Ae. aegypti defensins were amplified by PCR, cloned and sequenced. Genomic clones were amplified using primers designed against the cDNA sequence. Sequence comparison indicates that there is significant inter- and intra-isoform variability in the signal peptide and prodefensin sequences of defensin genes. Preprodefensin sequences of isoforms A and B are very similar, consisting of a signal peptide region of twenty amino acids, a prodefensin region of thirty-eight amino acids and a forty amino acid mature peptide domain. The sequence encoding isoform C is significantly different, comprising a signal peptide region of twenty-three amino acids, a prodefensin region of thirty-six amino acids, and the mature protein domain of forty amino acids. Analysis of the genomic clones of each isoform revealed one intron spatially conserved in the prodefensin region of all sequences. The intron in isoforms A and B is 64 nt long, and except for a 4 nt substitution in one clone, these intron sequences are identical. The intron in isoform C is 76 nt long and does not share significant identity with the intron sequences of isoforms A or B. The defensin gene mapped to chromosome 3, between two known loci, blt and LF168.

Aedes↗

PubMed1998

Evolving reaction-diffusion ecosystems with self-assembling structures in thin films.

Recently, new types of coupled isothermal polynucleotide amplification reactions for the investigation of in vitro evolution have been established that are based on the multi-enzyme 3SR reaction. Microstructured thin-film open bioreactors have been constructed in our laboratory to run these reactions spatially resolved in flow experiments. Artificial DNA/RNA chemistries close to the in vitro biochemistry of these systems have been developed, which we have studied in computer simulations in configurable hardware (NGEN). These artificial chemistries are described on the level of individual polynucleotide molecules, each with a defined sequence, and their complexes. The key feature of spatial pattern formation provides a weak stabilization of cooperative catalytic properties of the evolving molecules. Of great interest is the step to include extended self-assembly processes of flexible structures-allowing the additional stabilization of cooperation through semipermeable, flexible, self-organizing membrane boundaries. We show how programmable matter simulations of experimentally relevant molecular in vitro evolution can be extended to include the influence of self-assembling flexible membranes.

Bioreactors↗

PubMed2006

The transcriptional regulator CBP has defined spatial associations within interphase nuclei.

It is becoming increasingly clear that nuclear macromolecules and macromolecular complexes are compartmentalized through binding interactions into an apparent three-dimensionally ordered structure. This ordering, however, does not appear to be deterministic to the extent that chromatin and nonchromatin structures maintain a strict 3-D arrangement. Rather, spatial ordering within the cell nucleus appears to conform to stochastic rather than deterministic spatial relationships. The stochastic nature of organization becomes particularly problematic when any attempt is made to describe the spatial relationship between proteins involved in the regulation of the genome. The CREB-binding protein (CBP) is one such transcriptional regulator that, when visualised by confocal microscopy, reveals a highly punctate staining pattern comprising several hundred individual foci distributed within the nuclear volume. Markers for euchromatic sequences have similar patterns. Surprisingly, in most cases, the predicted one-to-one relationship between transcription factor and chromatin sequence is not observed. Consequently, to understand whether spatial relationships that are not coincident are nonrandom and potentially biologically important, it is necessary to develop statistical approaches. In this study, we report on the development of such an approach and apply it to understanding the role of CBP in mediating chromatin modification and transcriptional regulation. We have used nearest-neighbor distance measurements and probability analyses to study the spatial relationship between CBP and other nuclear subcompartments enriched in transcription factors, chromatin, and splicing factors. Our results demonstrate that CBP has an order of spatial association with other nuclear subcompartments. We observe closer associations between CBP and RNA polymerase II-enriched foci and SC35 speckles than nascent RNA or specific acetylated histones. Furthermore, we find that CBP has a significantly higher probability of being close to its known in vivo substrate histone H4 lysine 5 compared with the closely related H4 lysine 12. This study demonstrates that complex relationships not described by colocalization exist in the interphase nucleus and can be characterized and quantified. The subnuclear distribution of CBP is difficult to reconcile with a model where chromatin organization is the sole determinant of the nuclear organization of proteins that regulate transcription but is consistent with a close link between spatial associations and nuclear functions.

Acetylation↗

PubMed1999

Echoplanar chemical shift imaging.

A novel method of chemical shift imaging utilizing echoplanar imaging (EPI) has been developed for the purpose of improving the spatial resolution of metabolite images for the specific goal of high spatial resolution mapping of neuronal content. An EPI sequence was modified to allow temporal offsets of the 180 degree refocusing pulse that encode the chemical shift information into the phase of the signal. Implementation of this method on 1.5 and 3 T human imagers has resulted in images of N-acetyl aspartate in humans with spatial resolution of 360 microl and signal-to-noise ratio approximately 7:1 in less than 13 min.

Aspartic Acid↗

PubMed2005

Prostate MR imaging at high-field strength: evolution or revolution?

As 3 T MR scanners become more available, body imaging at high field strength is becoming the subject of intensive research. However, little has been published on prostate imaging at 3 T. Will high-field imaging dramatically increase our ability to depict and stage prostate cancer? This paper will address this question by reviewing the advantages and drawbacks of body imaging at 3 T and the current limitations of prostate imaging at 1.5 T, and by detailing the preliminary results of prostate 3 T MRI. Even if slight adjustments of imaging protocols are necessary for taking into account the changes in T1 and T2 relaxation times at 3 T, tissue contrast in T2-weighted (T2w) imaging seems similar at 1.5 T and 3 T. Therefore, significant improvement in cancer depiction in T2w imaging is not expected. However, increased spatial resolution due to increased signal-to-noise ratio (SNR) may improve the detection of minimal capsular invasion. Higher field strength should provide increased spectral and spatial resolution for spectroscopic imaging, but new pulse sequences will have to be designed for overcoming field inhomogeneities and citrate J-modulation issues. Finally, dynamic contrast-enhanced MRI is the method of imaging that is the most likely to benefit from the increased SNR, with a significantly better trade-off between temporal and spatial resolution.

Artifacts↗