bioRxiv Science⌕ Search

Biology subjects

Kodibagkar, V. D.

Publications and source records attributed to Kodibagkar, V. D..

5 recordsLinked to original sources

Comparison of HDO production from Glucose as a marker of Glucose metabolism

PURPOSEGlycolytic production of HDO from the metabolism of perdeuterated glucose provides a means for metabolic imaging with 2H MRI. The present study compared HDO production from a cost-efficient [2,3,4,6,6-2H5]glucose with [2H7]glucose in vitro and in vivo. METHODS2H NMR spectroscopy was performed to measure glucose consumption, lactate, and HDO production in the SFxL glioblastoma cell line. In vivo studies in healthy mice using 2H magnetic resonance spectroscopy were performed at 11.1 T after administering a bolus of either metabolic contrast agent. In vivo metabolite levels were quantified using unlocalized and slice-selective localized spectra. RESULTSOur in vitro results demonstrated similar glucose consumption and HDO production kinetics, although significant differences in lactate labeling were observed. The in vivo study showed comparable glucose consumption and HDO production kinetics following tail-vein bolus administration of either metabolic contrast agent, while lactate was not detected in the brain. CONCLUSION[2,3,4,6,6-2H5]glucose shows comparable HDO production to [2H7]glucose, while offering lower cost and reduced spectral complexity. These findings place [2,3,4,6,6-2H5]glucose as an alternative to [2H7]glucose for HDO-based DMI studies.

neuroscience↗

Tissue-Adhesive Endoscopic Tattoo Inks for Precise Marking and Surveillance of Gastrointestinal Lesions

Accurate marking of lesions and polyps is essential for effective management of gastrointestinal (GI) diseases, including colorectal cancer. Existing FDA-approved endoscopic carbon suspensions diffuse extensively within tissue and can extravasate intraperitoneally, compromising lesion localization, increasing fibrosis risk, and triggering inflammatory responses. These limitations reduce surgical precision and adversely affect patient outcomes. Here, we developed Tissue Adhesive Tattoos, generation 2 (TAT2) inks, composed of iron oxide nanoparticles encapsulated in bioadhesive polymers to improve spatial accuracy while maintaining high endoscopic contrast. TAT2 inks exhibit easy injectability, long-term stability, low macrophage inflammation, and strong spatial localization in ex vivo porcine intestinal tissue. Compared to clinical carbon ink, which spreads widely, TAT2 inks remained sharply localized with excellent contrast after submucosal injection in live mice and pigs. TAT2 also enabled visualization from both luminal and serosal surfaces and supported precise quadrant marking. Additionally, TAT2 inks were MR-compatible, expanding multimodality. Overall, TAT2 inks are biocompatible, non-inflammatory, precisely localized, and improve endoscopic marking for GI disease. TeaserEngineered bioadhesive tattoo inks deliver precise, durable GI marking with minimal spread and compatibility across imaging modalities.

bioengineering↗

2H MRI-based quantification of leucine uptake in glioblastoma multiforme

Glioblastoma (GBM) brain tumors are among the most lethal of all human cancers, with a median survival time of [~]15 months. Treatment planning requires radiologic demarcation of tumor boundaries with contrast-enhanced magnetic resonance imaging (CE MRI); however, significant tumor burden extends beyond the contrast-enhancing margins of the tumor. GBM tumors have an increased expression of amino acid (AA) transporters, including the Alanine, Serine, Cysteine Transporter 2 (ASCT2) and the L-Type Amino Acid Transporter 1 (LAT1). This upregulation has been leveraged in positron emission tomography (PET) studies to detect tumor burden beyond the contrast-enhancing margins identified by standard-of-care CE MRI. Here we leverage recent approaches in deuterium metabolic magnetic resonance with this known upregulation of AA transporters in GBM to demonstrate that 2H MR can detect glioma based on enhanced branched- chain amino acid (BCAA) uptake. To the best of our knowledge, these data represent the first non- invasive quantification of AA concentrations in brain tumor and raises the potential to (i) detect tumor burden beyond contrast-enhancing margins and (ii) quantify AA metabolism using 2H MR spectroscopy.

cancer biology↗

GdDO3NI allows imaging of hypoxia after brain injury

PurposeIn this study, we use the hypoxia targeting agent (GdDO3NI, a nitroimidazole-based T1 MRI contrast agent) for imaging hypoxia in the injured brain after experimental traumatic brain injury (TBI) using magnetic resonance imaging (MRI), and validate the results with immunohistochemistry (IHC) using pimonidazole. MethodsTBI induced mice (controlled cortical impact model) were imaged at 7T using a T2 weighted fast spin-echo sequence to estimate the extent of the injury. The mice were then were intravenously injected with either conventional T1 agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n=5 for each cohort) along with pimonidazole (60 mg/kg). Mice were imaged pre- and post-contrast using a T1-weighted spin-echo sequence for three hours. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post imaging for immunohistochemical analysis. ResultsGdDO3NI is retained in the injury region for up to 3 hours post-injection (p< 0.05 compared to gadoteridol) while it rapidly clears out of the muscle region. On the other hand, conventional MRI contrast agent gadoteridol clears out of both the injury region and muscle rapidly, although with a relatively more delayed wash out in the injury region. Minimal contrast enhancement was seen for both agents in the contralateral hemisphere. Pimonidazole staining confirms the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort shows good agreement with MRI contrast enhancement. ConclusionGdDO3NI was successfully shown to visualize hypoxia in the brain post-TBI using T1-wt MRI.

bioengineering↗

Sex-dependent macromolecule and nanoparticle delivery in experimental brain injury

Development of effective therapeutics for brain disorders is challenging, in particular, the blood-brain barrier (BBB) severely limits access of the therapeutics into the brain parenchyma. Traumatic brain injury (TBI) may lead to transient BBB permeability that affords a unique opportunity for therapeutic delivery via intravenous administration ranging from macromolecules to nanoparticles (NP) for developing precision therapeutics. In this regard, we address critical gaps in understanding the range/size of therapeutics, delivery window(s), and moreover the potential impact of biological factors for optimal delivery parameters. Here we show, for the first time, to the best of our knowledge, that 24 h post-focal TBI female mice exhibit a heightened macromolecular tracer and NP accumulation compared to male mice, indicating sex-dependent differences in BBB permeability. Furthermore, we report for the first time the potential to deliver NP-based therapeutics within 3 d after focal injury in both female and male mice. The delineation of injury-induced BBB permeability with respect to sex and temporal profile is essential to more accurately tailor time-dependent precision and personalized nanotherapeutics.

bioengineering↗