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Using magnetic resonance microscopy to study the growth dynamics of a glioma spheroid in collagen I: A case study.

Huang S, Vader D, Wang Z, Stemmer-Rachamimov A, Weitz DA, Dai G, Rosen BR, Deisboeck TS - BMC Med Imaging (2008)

Bottom Line: Our MRM data successfully documented the volumetric growth dynamics of an MTS in a collagen I gel over the 12-hour period.The histopathology results confirmed cell viability in the MRM sample, yet displayed distinct patterns of cell proliferation and invasion as compared to control.We argue that MRM can be employed as a complementary non-invasive tool to characterize microscopic MTS expansion, and thus, together with integrative computational modeling, may allow bridging of the experimental and clinical scales more readily.

View Article: PubMed Central - HTML - PubMed

Affiliation: Harvard-MIT (HST) Athinoula A, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA. shuning@mit.edu

ABSTRACT

Background: Highly malignant gliomas are characterized by rapid growth, extensive local tissue infiltration and the resulting overall dismal clinical outcome. Gaining any additional insights into the complex interaction between this aggressive brain tumor and its microenvironment is therefore critical. Currently, the standard imaging modalities to investigate the crucial interface between tumor growth and invasion in vitro are light and confocal laser scanning microscopy. While immensely useful in cell culture, integrating these modalities with this cancer's clinical imaging method of choice, i.e. MRI, is a non-trivial endeavour. However, this integration is necessary, should advanced computational modeling be able to utilize these in vitro data to eventually predict growth behaviour in vivo. We therefore argue that employing the same imaging modality for both the experimental setting and the clinical situation it represents should have significant value from a data integration perspective. In this case study, we have investigated the feasibility of using a specific form of MRI, i.e. magnetic resonance microscopy or MRM, to study the expansion dynamics of a multicellular tumor spheroid in a collagen type I gel.

Methods: An U87mEGFR human giloblastoma multicellular spheroid (MTS) containing approximately 4.103 cells was generated and pipetted into a collagen I gel. The sample was then imaged using a T2-weighted 3D spoiled gradient echo pulse sequence on a 14T MRI scanner over a period of 12 hours with a temporal resolution of 3 hours at room temperature. Standard histopathology was performed on the MRM sample, as well as on control samples.

Results: We were able to acquire three-dimensional MR images with a spatial resolution of 24 x 24 x 24 microm3. Our MRM data successfully documented the volumetric growth dynamics of an MTS in a collagen I gel over the 12-hour period. The histopathology results confirmed cell viability in the MRM sample, yet displayed distinct patterns of cell proliferation and invasion as compared to control.

Conclusion: In this study, we demonstrate that a specific form of MRI, i.e. magnetic resonance microscopy or MRM, can be used to study the dynamic growth of a multicellular tumor spheroid (MTS) with a single cell scale spatial resolution that approaches the level of light microscopy. We argue that MRM can be employed as a complementary non-invasive tool to characterize microscopic MTS expansion, and thus, together with integrative computational modeling, may allow bridging of the experimental and clinical scales more readily.

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Related in: MedlinePlus

Volumetric rendering and growth dynamics of the MTS in the collagen I matrix at four consecutive time points. (A) The segmented MTS is reconstructed in 3D and the color-coding indicates the growth increase at each time point. The MTS appears to grow anistropic, which may indicate regional heterogeneities in composition of either MTS or microenvironment, or both, and/or point towards a heterogeneous local interaction between cells and gel. (B) MTS volume and surface area are calculated and plotted over time.
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Figure 2: Volumetric rendering and growth dynamics of the MTS in the collagen I matrix at four consecutive time points. (A) The segmented MTS is reconstructed in 3D and the color-coding indicates the growth increase at each time point. The MTS appears to grow anistropic, which may indicate regional heterogeneities in composition of either MTS or microenvironment, or both, and/or point towards a heterogeneous local interaction between cells and gel. (B) MTS volume and surface area are calculated and plotted over time.

Mentions: The 3D reconstruction shows rather heterogeneous expansion patterns with rough surface growth areas throughout over the course of the observation period (Figure 2(A)). Intriguingly, once started (orange droplets at the MTS' proximal apex at time point '3 hours') glioma cell expansion into the gel seems to give rise to an 'imprinting' process which confirms the 'trailblazer' concept that has been described previously in [2,4]. Finally, corresponding to the MTS' preserved structural viability (compare with Fig. 3) Figure 2(B) also confirms its functionality in that both MTS volume and surface area increase throughout the observation period.


Using magnetic resonance microscopy to study the growth dynamics of a glioma spheroid in collagen I: A case study.

Huang S, Vader D, Wang Z, Stemmer-Rachamimov A, Weitz DA, Dai G, Rosen BR, Deisboeck TS - BMC Med Imaging (2008)

Volumetric rendering and growth dynamics of the MTS in the collagen I matrix at four consecutive time points. (A) The segmented MTS is reconstructed in 3D and the color-coding indicates the growth increase at each time point. The MTS appears to grow anistropic, which may indicate regional heterogeneities in composition of either MTS or microenvironment, or both, and/or point towards a heterogeneous local interaction between cells and gel. (B) MTS volume and surface area are calculated and plotted over time.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2270258&req=5

Figure 2: Volumetric rendering and growth dynamics of the MTS in the collagen I matrix at four consecutive time points. (A) The segmented MTS is reconstructed in 3D and the color-coding indicates the growth increase at each time point. The MTS appears to grow anistropic, which may indicate regional heterogeneities in composition of either MTS or microenvironment, or both, and/or point towards a heterogeneous local interaction between cells and gel. (B) MTS volume and surface area are calculated and plotted over time.
Mentions: The 3D reconstruction shows rather heterogeneous expansion patterns with rough surface growth areas throughout over the course of the observation period (Figure 2(A)). Intriguingly, once started (orange droplets at the MTS' proximal apex at time point '3 hours') glioma cell expansion into the gel seems to give rise to an 'imprinting' process which confirms the 'trailblazer' concept that has been described previously in [2,4]. Finally, corresponding to the MTS' preserved structural viability (compare with Fig. 3) Figure 2(B) also confirms its functionality in that both MTS volume and surface area increase throughout the observation period.

Bottom Line: Our MRM data successfully documented the volumetric growth dynamics of an MTS in a collagen I gel over the 12-hour period.The histopathology results confirmed cell viability in the MRM sample, yet displayed distinct patterns of cell proliferation and invasion as compared to control.We argue that MRM can be employed as a complementary non-invasive tool to characterize microscopic MTS expansion, and thus, together with integrative computational modeling, may allow bridging of the experimental and clinical scales more readily.

View Article: PubMed Central - HTML - PubMed

Affiliation: Harvard-MIT (HST) Athinoula A, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA. shuning@mit.edu

ABSTRACT

Background: Highly malignant gliomas are characterized by rapid growth, extensive local tissue infiltration and the resulting overall dismal clinical outcome. Gaining any additional insights into the complex interaction between this aggressive brain tumor and its microenvironment is therefore critical. Currently, the standard imaging modalities to investigate the crucial interface between tumor growth and invasion in vitro are light and confocal laser scanning microscopy. While immensely useful in cell culture, integrating these modalities with this cancer's clinical imaging method of choice, i.e. MRI, is a non-trivial endeavour. However, this integration is necessary, should advanced computational modeling be able to utilize these in vitro data to eventually predict growth behaviour in vivo. We therefore argue that employing the same imaging modality for both the experimental setting and the clinical situation it represents should have significant value from a data integration perspective. In this case study, we have investigated the feasibility of using a specific form of MRI, i.e. magnetic resonance microscopy or MRM, to study the expansion dynamics of a multicellular tumor spheroid in a collagen type I gel.

Methods: An U87mEGFR human giloblastoma multicellular spheroid (MTS) containing approximately 4.103 cells was generated and pipetted into a collagen I gel. The sample was then imaged using a T2-weighted 3D spoiled gradient echo pulse sequence on a 14T MRI scanner over a period of 12 hours with a temporal resolution of 3 hours at room temperature. Standard histopathology was performed on the MRM sample, as well as on control samples.

Results: We were able to acquire three-dimensional MR images with a spatial resolution of 24 x 24 x 24 microm3. Our MRM data successfully documented the volumetric growth dynamics of an MTS in a collagen I gel over the 12-hour period. The histopathology results confirmed cell viability in the MRM sample, yet displayed distinct patterns of cell proliferation and invasion as compared to control.

Conclusion: In this study, we demonstrate that a specific form of MRI, i.e. magnetic resonance microscopy or MRM, can be used to study the dynamic growth of a multicellular tumor spheroid (MTS) with a single cell scale spatial resolution that approaches the level of light microscopy. We argue that MRM can be employed as a complementary non-invasive tool to characterize microscopic MTS expansion, and thus, together with integrative computational modeling, may allow bridging of the experimental and clinical scales more readily.

Show MeSH
Related in: MedlinePlus