scholarly journals Simultaneous Recording of the Uptake and Conversion of Glucose and Choline in Tumors by Deuterium Metabolic Imaging

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4034
Author(s):  
Andor Veltien ◽  
Jack van Asten ◽  
Niveditha Ravichandran ◽  
Robin A. de Graaf ◽  
Henk M. De Feyter ◽  
...  
Keyword(s):  
High Resolution ◽  
Simultaneous Detection ◽  
Simultaneous Recording ◽  
Metabolic Imaging ◽  
Choline Uptake ◽  
Deuterated Water ◽  
Post Infusion ◽  
Repetition Time ◽  
Tumor Accumulation ◽  
Clinical Potential

Increased glucose and choline uptake are hallmarks of cancer. We investigated whether the uptake and conversion of [2H9]choline alone and together with that of [6,6′-2H2]glucose can be assessed in tumors via deuterium metabolic imaging (DMI) after administering these compounds. Therefore, tumors with human renal carcinoma cells were grown subcutaneously in mice. Isoflurane anesthetized mice were IV infused in the MR magnet for ~20 s with ~0.2 mL solutions containing either [2H9]choline (0.05 g/kg) alone or together with [6,6′-2H2]glucose (1.3 g/kg). 2H MR was performed on a 11.7T MR system with a home-built 2H/1H coil using a 90° excitation pulse and 400 ms repetition time. 3D DMI was recorded at high resolution (2 × 2 × 2 mm) in 37 min or at low resolution (3.7 × 3.7 × 3.7 mm) in 2:24 min. Absolute tissue concentrations were calculated assuming natural deuterated water [HOD] = 13.7 mM. Within 5 min after [2H9]choline infusion, its signal appeared in tumor spectra representing a concentration increase to 0.3–1.2 mM, which then slowly decreased or remained constant over 100 min. In plasma, [2H9]choline disappeared within 15 min post-infusion, implying that its signal arises from tumor tissue and not from blood. After infusing a mixture of [2H9]choline and [6,6′-2H2]glucose, their signals were observed separately in tumor 2H spectra. Over time, the [2H9]choline signal broadened, possibly due to conversion to other choline compounds, [[6,6′-2H2]glucose] declined, [HOD] increased and a lactate signal appeared, reflecting glycolysis. Metabolic maps of 2H compounds, reconstructed from high resolution DMIs, showed their spatial tumor accumulation. As choline infusion and glucose DMI is feasible in patients, their simultaneous detection has clinical potential for tumor characterization.

scholarly journals Simultaneous Recording of the Uptake and Conversion of Glucose and Choline in Tumors by Deuterium Metabolic Imaging (DMI)

2021 ◽  
Author(s):  
Andor Veltien ◽  
Jack van Asten ◽  
Niveditha Ravichandran ◽  
Robin De Graaf ◽  
Henk De Feyter ◽  
...  
Keyword(s):  
High Resolution ◽  
Simultaneous Detection ◽  
Simultaneous Recording ◽  
Carcinoma Cells ◽  
Metabolic Imaging ◽  
Choline Uptake ◽  
Bolus Administration ◽  
Post Infusion ◽  
Repetition Time ◽  
Clinical Potential

: Increased glucose and choline uptake are hallmarks of cancer. We investigated if the uptake and conversion of [2H9]choline alone and together with that of [6,6’ 2H2]glucose can be assessed in subcutaneous tumors by deuterium metabolic imaging (DMI) after bolus administration of these compounds. Therefore tumors with human renal carcinoma cells were grown subcutaneously in mice up to ~0.5 cm3. Mice were anesthetized with isoflurane and IV infused in the MR magnet for ~20 sec with ~0.2 ml solutions containing either [2H9]choline (0.05g/kg) alone or together with [6,6’ 2H2]glucose (1.3g/kg). 2H MR was performed on a 11.7T MR system with a home-built 2H/1H coil using a 900 excitation pulse and 400ms repetition time. 3D DMI was recorded at high resolution (2x2x2mm) in 37 min or at low resolution (3.7x3.7x3.7mm) in 2:24 min. Absolute tissue concentrations were calculate assuming initial [HOD]=13.7mM. Within 5 minutes after [2H9]choline infusion its signal appeared in tumor spectra representing concentration increasing up to 0.3–1.2 mM and then slowly decreased or remained constant over 100 minutes. In plasma [2H9]choline disappeared within 15 minutes post-infusion implying that its tumor signal arises from tissue and not blood. After infusing a mixture of [2H9]choline and [6,6’ 2H2]glucose their signals were observed separately in tumor 2H spectra. Over time the [2H9]choline signal broadened, possibly due to conversion to other choline compounds, [[6,6’ 2H2]glucose] declined, [HOD] increased and a lactate signal appeared, reflecting glycolysis. Metabolic maps of all 2H compounds were reconstructed from high resolution DMIs. As choline infusion and glucose DMI is feasible in patients, their simultaneous detection has clinical potential for tumor characterization.

scholarly journals BIMG-04. MAPPING HETEROGENEITY OF HIGH-GRADE GLIOMA METABOLISM USING HIGH RESOLUTION 7T MRSI

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i1-i1
Author(s):  
Gilbert Hangel ◽  
Cornelius Cadrien ◽  
Philipp Lazen ◽  
Sukrit Sharma ◽  
Julia Furtner ◽  
...  
Keyword(s):  
High Resolution ◽  
Imaging Techniques ◽  
Basis Set ◽  
Metabolic Imaging ◽  
Tumor Segmentation ◽  
Low Grade ◽  
High Grade ◽  
Isotropic Resolution ◽  
Contrast Enhanced ◽  
Definition Of

Abstract OBJECTIVES Neurosurgical resection in gliomas depends on the precise preoperative definition of the tumor and its margins to realize a safe maximum resection that translates into a better patient outcome. New metabolic imaging techniques could improve this delineation as well as designate targets for biopsies. We validated the performance of our fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in high-grade gliomas (HGGs) as first step to this regard. METHODS We measured 23 patients with HGGs at 7T with MRSI covering the whole cerebrum with 3.4mm isotropic resolution in 15 min. Quantification used a basis-set of 17 neurochemical components. They were evaluated for their reliability/quality and compared to neuroradiologically segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast-enhanced+edema, peritumoral) and histopathology (e.g., grade, IDH-status). RESULTS We found 18/23 measurements to be usable and ten neurochemicals quantified with acceptable quality. The most common denominators were increases of glutamine, glycine, and total choline as well as decreases of N-acetyl-aspartate and total creatine over most tumor regions. Other metabolites like taurine and serine showed mixed behavior. We further found that heterogeneity in the metabolic images often continued into the peritumoral region. While 2-hydroxy-glutarate could not be satisfyingly quantified, we found a tendency for a decrease of glutamate in IDH1-mutant HGGs. DISCUSSION Our findings corresponded well to clinical tumor segmentation but were more heterogeneous and often extended into the peritumoral region. Our results corresponded to previous knowledge, but with previously not feasible resolution. Apart from glycine/glutamine and their role in glioma progression, more research on the connection of glutamate and others to specific mutations is necessary. The addition of low-grade gliomas and statistical ROI analysis in a larger cohort will be the next important steps to define the benefits of our 7T MRSI approach for the definition of spatial metabolic tumor profiles.

scholarly journals Ultrastructural visualization of cytoskeletal mRNAs and their associated proteins using double-label in situ hybridization.

1989 ◽  
Vol 108 (6) ◽  
pp. 2343-2353 ◽  
Author(s):  
R H Singer ◽  
G L Langevin ◽  
J B Lawrence
Keyword(s):  
In Situ Hybridization ◽  
High Resolution ◽  
Colloidal Gold ◽  
Messenger Rna ◽  
Signal To Noise Ratio ◽  
Simultaneous Detection ◽  
Gold Particles ◽  
Rna Molecules ◽  
Nucleic Acid Molecule

We have been able to visualize cytoskeletal messenger RNA molecules at high resolution using nonisotopic in situ hybridization followed by whole-mount electron microscopy. Biotinated cDNA probes for actin, tubulin, or vimentin mRNAs were hybridized to Triton-extracted chicken embryo fibroblasts and myoblasts. The cells were then exposed to antibodies against biotin followed by colloidal gold-conjugated antibodies and then critical-point dried. Identification of mRNA was possible using a probe fragmented to small sizes such that hybridization of several probe fragments along the mRNA was detected as a string of colloidal gold particles qualitatively and quantitatively distinguishable from nonspecific background. Extensive analysis showed that when eight gold particles were seen in this iterated array, the signal to noise ratio was greater than 30:1. Furthermore, these gold particles were colinear, often spiral, or circular suggesting detection of a single nucleic acid molecule. Antibodies against actin, vimentin, or tubulin proteins were used after in situ hybridization, allowing simultaneous detection of the protein and its cognate message on the same sample. This revealed that cytoskeletal mRNAs are likely to be extremely close to actin protein (5 nm or less) and unlikely to be within 20 nm of vimentin or tubulin filaments. Actin mRNA was found to be more predominant in lamellipodia of motile cells, confirming previous results. These results indicate that this high resolution in situ hybridization approach is a powerful tool by which to investigate the association of mRNA with the cytoskeleton.

scholarly journals Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis

2020 ◽  
Vol 1 (2) ◽  
pp. 100017
Author(s):  
Dimitra Pouli ◽  
Hong-Thao Thieu ◽  
Elizabeth M. Genega ◽  
Laura Baecher-Lind ◽  
Michael House ◽  
...  
Keyword(s):  
High Resolution ◽  
Intraepithelial Neoplasia ◽  
Metabolic Imaging ◽  
Label Free

scholarly journals A high-resolution system for metabolic imaging of cancer

2013 ◽  
Vol 7 (S2) ◽  
Author(s):  
Eduardo H Moriyama ◽  
Eric Leung ◽  
Naz Chaudary ◽  
Tuula Kalliomaki ◽  
Richard P Hill ◽  
...  
Keyword(s):  
High Resolution ◽  
Metabolic Imaging ◽  
Resolution System

Development of High Resolution DNA Melting Analysis for Simultaneous Detection of Potato Mop-Top Virus and Its Vector, Spongospora subterranea, in Soil

Plant Disease ◽  
2020 ◽  
Author(s):  
Xianzhou Nie ◽  
Mathuresh Singh ◽  
Dahu Chen ◽  
Cassandra Gilchrist ◽  
Yasmine Soqrat ◽  
...  
Keyword(s):  
High Resolution ◽  
Simultaneous Detection ◽  
Soil Samples ◽  
Dna Melting ◽  
Spongospora Subterranea ◽  
Rt Pcr ◽  
Efficient Detection ◽  
Melting Analysis ◽  
Potato Mop Top Virus ◽  
Negative Detection

In this study, a set of duplex reverse transcription (RT)-PCR-mediated high resolution DNA melting (HRM) analyses for simultaneous detection of potato mop-virus (PMTV) and its protist vector, Spongospora subterranea f.sp. subterranea (Sss), was developed. The infestation of soil by PMTV was detected by using a tobacco-based baiting system. Total RNA extracted from the soil led to successful RT-PCR gel-electrophoresis detection of both PMTV and Sss. To facilitate more efficient detection, newly designed primer pairs for PMTV RNA species (i.e., RNA-Rep, -CP, and -TGB) were analyzed together with the existing Sss primers using real-time RT-PCR. The resulting amplicons exhibited melting profiles that could be readily differentiated. Under duplex RT-PCR format, all PMTV and Sss primer combinations led to successful detection of respective PMTV RNA species and Sss in the samples by high resolution DNA melting (HRM) analyses. When the duplex HRM assay was applied to soil samples collected from six fields at four different sites in New Brunswick, Canada, positive detection of PMTV and/or Sss was found in 63-100% samples collected from fields in which PMTV-infected tubers had been observed. In contrast, the samples from fields where neither PMTV- nor Sss-infected tubers had been observed resulted in negative detection by the assay. Bait tobacco bioassay for PMTV and Sss produced similar results. Between 63%-83% and 100% of the soil samples collected from PMTV-infested fields led to PMTV and Sss infections in the bait tobacco plants, respectively; whereas no PMTV or Sss infected plants were obtained from soil samples collected from PMTV/Sss-free fields.

A Rapid Multiplex Real-Time PCR High-Resolution Melt Curve Assay for the Simultaneous Detection of Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus in Food

2016 ◽  
Vol 79 (5) ◽  
pp. 810-815 ◽  
Author(s):  
FEREIDOUN FORGHANI ◽  
SHUAI WEI ◽  
DEOG-HWAN OH
Keyword(s):  
Staphylococcus Aureus ◽  
Listeria Monocytogenes ◽  
High Resolution ◽  
Bacillus Cereus ◽  
Real Time ◽  
Real Time Pcr ◽  
Simultaneous Detection ◽  
Cost Savings ◽  
High Resolution Melt ◽  
And Staphylococcus Aureus

ABSTRACTThree important foodborne pathogens, Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus, are of great concern for food safety. They may also coexist in food matrices and, in the case of B. cereus and S. aureus, the resulting illnesses can resemble each other owing to similar symptoms. Therefore, their simultaneous detection may have advantages in terms of cost savings and rapidity. Given this context, a rapid multiplex real-time PCR high-resolution melt curve assay for the simultaneous detection of these three pathogens in food was developed. The assay successfully detected B. cereus (gyrB), L. monocytogenes (hly), and S. aureus (nuc) in a single reaction, and the average melting temperatures were 76.23, 80.19, and 74.01°C, respectively. The application of SYTO9 dye and a slow melt curve analysis ramp rate (0.1°C/s) enabled the production of sharp, high-resolution melt curve peaks that were easily distinguishable from each other. The detection limit in food (milk, rice, and lettuce) was 3.7 × 103 CFU/g without an enrichment step and 3.7 × 101 CFU/g following the 10-h enrichment. Hence, the assay developed here is specific and sensitive, providing an efficient tool for implementation in food for the simultaneous detection of B. cereus, L. monocytogenes, and S. aureus.

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