Biology subjects

Mallett, C. L.

Publications and source records attributed to Mallett, C. L..

5 recordsLinked to original sources

bioRxiv2025

Myelin Decompaction in Mice Given Anesthetics during Magnetic Resonance Imaging

AbstractThe objective of this secondary analysis of a prior investigation was to determine if prolonged exposure to the anesthetics isoflurane and dexmedetomidine during MRI was associated with a higher proportion of axons with myelin decompaction. 16 mice underwent an MRI protocol in which they had prolonged exposure to isoflurane and dexmedetomidine, while 10 mice did not undergo this protocol. All mice were sacrificed and electron microscope images were taken of various brain regions including the right prefrontal cortex (anterior cingulate and prelimbic area), the nucleus accumbens, the amygdala, and the ventral hippocampus.. Proportion of decompacted axons was calculated for each mouse, and an inter-rater reliability score of 80% was achieved. Welchs t-tests were used to test the hypothesis that mice undergoing MRI with prolonged anesthesia had greater levels of myelin decompaction than mice that did not experience prolonged anesthesia. Mice with prolonged anesthetic exposure during MRI had significantly higher proportions of decompacted axons than mice that did not experience prolonged anesthesia (p-value of 0.00003642). Prolonged exposure to anesthetics, particularly isoflurane, may be associated with myelin decompaction. These findings, if replicated, have potential to impact future anesthesia use in clinical work and scientific research. Significance StatementProlonged exposure to the anesthetics isoflurane and dexmedetomidine during brain imaging may lead to myelin decompaction in adult rodents. Myelin is a protective sheath around nerve fibers that ensures efficient transmission of electrical signals in the nervous system. Decompaction of myelin can disrupt these signals, potentially leading to neurological issues. This discovery is significant because it highlights potential risks associated with these anesthetics, which are commonly used in fMRI studies of rodents and in veterinary and medical procedures.

neuroscience↗

bioRxiv2023

MRI of OATP-expressing transplanted cells using clinical doses of gadolinium contrast agent

Hepatic organic anion transporting polypeptides (OATPs) transport off-the-shelf, FDA-approved, hepatospecific Gd-based MRI contrast agents into cells that express the transporters enhancing signal on clinical T1-weighted MRI. Studies have used MRI to identify OATP-overexpressing tumors and metastases in mice following the delivery of Gd-EOB-DTPA at 27-67-fold higher than clinical doses. With safety and regulatory concern over Gd-based contrast agents, translation of this imaging paradigm to humans for regenerative medicine cell therapy will require substantially lower doses of agent. Here we complemented static T1-weighted MRI and/or T1-mapping with dynamic contrast enhanced (DCE)-MRI and show that even low intracellular accumulation of contrast agent results in a sustained signal enhancement in OATP-overexpressing tumors while control, non-expressing tumors have rapid wash-in and wash-out dynamics which could be distinguished by performing area-under-the-curve (AUC) analyses.

bioengineering↗

bioRxiv2023

MRI-based cell tracking of OATP-expressing cell transplants by pre-labeling with Gd-EOB-DTPA

PurposeTo detect cell transplants labeled with a clinical gadolinium-based contrast agent as hyperintense signals using a clinically familiar T1-weighted MRI protocol. MethodsHEK293 cells were stably transduced to express human OATP1B3, a hepatic transporter that transport Gd-EOB-DTPA into cells that express the transporters, the intracellular accumulation of which cells causes signal enhancement on T1-weighted MRI. Cells were labeled in media containing Gd-EOB-DTPA for MRI evaluation and indocyanine green for cryofluorescence tomography validation. Labeled cells were injected into chicken hearts, in vitro, after which MRI and cryofluorescence tomography were performed in tandem. ResultsOATP1B3-expressing cells had substantially reduced T1 following labeling with Gd-EOB-DTPA in culture. Following their implantation into chicken heart, these cells were easily identified in T1-weighted MRI. Cryofluorescence tomography validated that the areas of signal enhancement in MRI overlapped with areas of indocyanine green signal, indicating that signal enhancement was due to the transplanted cells. ConclusionOATP1B3-expressing cells can be pre-labeled with Gd-EOB-DTPA prior to injection into tissue, affording the use of clinically familiar T1-weighted MRI to robustly detect cell transplants.

bioengineering↗

bioRxiv2020

Dynamic contrast enhanced MRI with clinical hepatospecific MRI contrast agents in pigs: initial experience

Pigs are an important translational research model for biomedical imaging studies, and especially for modeling diseases of the liver. Dynamic contrast enhanced (DCE)-MRI is experimentally used to measure liver function in humans, but has never been characterized in pig liver. Here we performed DCE-MRI of pig liver following the delivery of two FDA approved hepato-specific MRI contrast agents, Gd-EOB-DTPA (Eovist) and Gd-BOPTA (Multihance), and the non-hepatospecific agent Magnevist, and optimized the anesthesia and animal handling protocol to acquire robust data. A single pig underwent 5 scanning sessions over six weeks, each time injected at clinical dosing either with Eovist (twice), Multihance (twice) or Magnevist (once). DCE-MRI was performed at 1.5T for 60 minutes. DCE-MRI showed rapid hepatic MRI signal enhancement following IV injection of Eovist or Multihance. Efflux of contrast agent from liver exhibited kinetics similar to that in humans, except for one hyperthermic animal where efflux was very fast. As expected, Magnevist was non-enhancing in the liver. The hepatic signal enhancement from Eovist matched that seen in humans and primates, while the hepatic signal enhancement from Multihance was different, similar to rodents and dogs, likely the result of differential hepatic organic anion transport polypeptides. This first experience with these agents in pigs provides valuable information on contrast agent dynamics in normal pig liver. Given the disparity in contrast agent uptake kinetics with humans for Multihance, Eovist should be used in porcine models for biomedical imaging. Proper animal health maintenance, especially temperature, seems essential for accurate and reproducible results.

physiology↗

bioRxiv2018

Age-dependent visualization of neural progenitor cells within the rostral migratory stream via MRI and endogenously labeled micron-sized iron oxide particles

The subventricular zone (SVZ) is one of the primary sources for rodent neural progenitor cells (NPC), however, aging greatly impacts the substructure of the region and rate of new cell birth. To determine if age impacts the rate of in vivo migration within animals, we examined the rostral migratory stream (RMS) of animals across 12 days using an established MRI technique. To visualize NPCs, we injected micron sized particles of iron oxide (MPIO) into the lateral ventricle to endogenously label cells within the SVZ, which then appeared as hypo-intensive spots within MR images. Our in vivo MRI data showed that the rate of migration was significantly different between all ages examined, with decreases in the distance traveled as age progressed. The total number of iron oxide labeled cells within the olfactory bulb on day 12, decrease significantly when compared across ages in ex vivo high-resolution scans. We also, for the first time, demonstrated the endogenous labeling of cells within the dentate gyrus (DG) of hippocampus. Here too, there was a significant decrease in the number of labeled cells within the structure across age. Histology of the NPCs verified the decrease in labeling of cells with doublecortin (DCX) as age progressed for both regions. The dramatic reduction of labeling in NPCs within the SVZ and DG observed with MRI, demonstrates the importance of understanding the impact of age on the relationship of NPC and disease.

neuroscience↗