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Simultaneous MR imaging for tissue engineering in a rat model of stroke.

Nicholls FJ, Ling W, Ferrauto G, Aime S, Modo M - Sci Rep (2015)

Bottom Line: Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging.The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment.The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Pittsburgh, PA.

ABSTRACT
In situ tissue engineering within a stroke cavity is gradually emerging as a novel therapeutic paradigm. Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging. The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment. The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents. The development of sophisticated imaging methods is essential to guide delivery of the building blocks for in situ tissue engineering, but will also be essential to understand the dynamics of cellular interactions leading to the formation of de novo tissue.

No MeSH data available.


Related in: MedlinePlus

Magnetization Transfer (MT) effect simulation.(A) Numerical calculation of Bloch-McConnell equation shows similar z spectra to experimentally acquired data of agent in solution (1.5 s, 15 μT presaturation pulse for Eu, and 800 ms, 23 μT pulse for Yb). (B) When the pulses are altered (to 800 ms, 28 μT for Eu and 600 ms, 56 μT for Yb) to provide improved contrast in vivo, the water peak becomes wider, but contrast achieved for Yb is significantly increased. (C) MT effects in brain tissue further widen the water peak, (D) resulting in decreased agent contrast.
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f4: Magnetization Transfer (MT) effect simulation.(A) Numerical calculation of Bloch-McConnell equation shows similar z spectra to experimentally acquired data of agent in solution (1.5 s, 15 μT presaturation pulse for Eu, and 800 ms, 23 μT pulse for Yb). (B) When the pulses are altered (to 800 ms, 28 μT for Eu and 600 ms, 56 μT for Yb) to provide improved contrast in vivo, the water peak becomes wider, but contrast achieved for Yb is significantly increased. (C) MT effects in brain tissue further widen the water peak, (D) resulting in decreased agent contrast.

Mentions: Spectra acquired in solution typically have a narrow water peak at 0 ppm with clearly defined peaks associated with each agent, whereas in cells the water peak becomes much wider due to MT effects. To investigate these effects and optimize detection, a Bloch simulation modeling these effects was calculated using parameters estimated based on z spectra measured for Eu-HPDO3A and Yb-HPDO3A in solution (Suppl Table 1). Solution spectra reflect the asymmetries observed experimentally for concentrations equivalent to those in cell pellets (Fig. 4A). These notably demonstrate a narrow water peak with specific exchange sites. When RF conditions are altered to those used in vivo, the water peak marginally widens due to the increased power, but a significant increase in agent contrast is visible for Yb (Fig. 4B). The same RF conditions on brain tissue reveals a much broader water peak (Fig. 4C). As Yb-HPDO3A requires a higher RF power, the water peak is broader than for Eu-HPDO3A, even in the absence of any paraCEST agent. Once the paraCEST agents are added to the simulations, the widened water peak due to brain tissue causes additional significant loss of signal (Fig. 4D). Specifically, the simulation revealed that MT effects account for the signal loss seen experimentally in Eu-HPDO3A from 31% to 1.1% at 6.8 mM concentration and from 21% to 10% for a 9.5 mM of intracellular Yb-HPDO3A. This shows that MT effects have a much more significant impact on Eu than Yb, due to the closer proximity to the water peak. This makes Yb more sensitive in cells, whereas Eu is more sensitive in solution. A simultaneous in vivo detection therefore will depend on the detection of low levels of asymmetry of high concentrations of paraCEST agent.


Simultaneous MR imaging for tissue engineering in a rat model of stroke.

Nicholls FJ, Ling W, Ferrauto G, Aime S, Modo M - Sci Rep (2015)

Magnetization Transfer (MT) effect simulation.(A) Numerical calculation of Bloch-McConnell equation shows similar z spectra to experimentally acquired data of agent in solution (1.5 s, 15 μT presaturation pulse for Eu, and 800 ms, 23 μT pulse for Yb). (B) When the pulses are altered (to 800 ms, 28 μT for Eu and 600 ms, 56 μT for Yb) to provide improved contrast in vivo, the water peak becomes wider, but contrast achieved for Yb is significantly increased. (C) MT effects in brain tissue further widen the water peak, (D) resulting in decreased agent contrast.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588587&req=5

f4: Magnetization Transfer (MT) effect simulation.(A) Numerical calculation of Bloch-McConnell equation shows similar z spectra to experimentally acquired data of agent in solution (1.5 s, 15 μT presaturation pulse for Eu, and 800 ms, 23 μT pulse for Yb). (B) When the pulses are altered (to 800 ms, 28 μT for Eu and 600 ms, 56 μT for Yb) to provide improved contrast in vivo, the water peak becomes wider, but contrast achieved for Yb is significantly increased. (C) MT effects in brain tissue further widen the water peak, (D) resulting in decreased agent contrast.
Mentions: Spectra acquired in solution typically have a narrow water peak at 0 ppm with clearly defined peaks associated with each agent, whereas in cells the water peak becomes much wider due to MT effects. To investigate these effects and optimize detection, a Bloch simulation modeling these effects was calculated using parameters estimated based on z spectra measured for Eu-HPDO3A and Yb-HPDO3A in solution (Suppl Table 1). Solution spectra reflect the asymmetries observed experimentally for concentrations equivalent to those in cell pellets (Fig. 4A). These notably demonstrate a narrow water peak with specific exchange sites. When RF conditions are altered to those used in vivo, the water peak marginally widens due to the increased power, but a significant increase in agent contrast is visible for Yb (Fig. 4B). The same RF conditions on brain tissue reveals a much broader water peak (Fig. 4C). As Yb-HPDO3A requires a higher RF power, the water peak is broader than for Eu-HPDO3A, even in the absence of any paraCEST agent. Once the paraCEST agents are added to the simulations, the widened water peak due to brain tissue causes additional significant loss of signal (Fig. 4D). Specifically, the simulation revealed that MT effects account for the signal loss seen experimentally in Eu-HPDO3A from 31% to 1.1% at 6.8 mM concentration and from 21% to 10% for a 9.5 mM of intracellular Yb-HPDO3A. This shows that MT effects have a much more significant impact on Eu than Yb, due to the closer proximity to the water peak. This makes Yb more sensitive in cells, whereas Eu is more sensitive in solution. A simultaneous in vivo detection therefore will depend on the detection of low levels of asymmetry of high concentrations of paraCEST agent.

Bottom Line: Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging.The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment.The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Pittsburgh, PA.

ABSTRACT
In situ tissue engineering within a stroke cavity is gradually emerging as a novel therapeutic paradigm. Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging. The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment. The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents. The development of sophisticated imaging methods is essential to guide delivery of the building blocks for in situ tissue engineering, but will also be essential to understand the dynamics of cellular interactions leading to the formation of de novo tissue.

No MeSH data available.


Related in: MedlinePlus