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Noninvasive In-Vivo Quantification of Mechanical Heterogeneity of Invasive Breast Carcinomas.

Liu T, Babaniyi OA, Hall TJ, Barbone PE, Oberai AA - PLoS ONE (2015)

Bottom Line: In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging.By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors.Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous.

View Article: PubMed Central - PubMed

Affiliation: Scientific Computation Research Center, Rensselaer Polytechnic Institute, Troy, NY, USA.

ABSTRACT
Heterogeneity is a hallmark of cancer whether one considers the genotype of cancerous cells, the composition of their microenvironment, the distribution of blood and lymphatic microvasculature, or the spatial distribution of the desmoplastic reaction. It is logical to expect that this heterogeneity in tumor microenvironment will lead to spatial heterogeneity in its mechanical properties. In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging. By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors. Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of tumorigenesis in breast cancer (adapted from [7, 8]).(a) Healthy milk duct. (b) Proliferation of tumor cells within the duct is accompanied by desmoplasia in the extra-cellular matrix. (c) Changes in the morphology collagen fiber bundles from a wavy and tortuous state to a straight and taut state, and the emergence of a site where the fiber orientation is predominantly radial with respect to the tumor boundary. (d) Invasion of cancer cells to surrounding glandular tissue from this site. (e) Invasion of the cancer cells to nearby ducts. (f) A fully invasive tumor state. The dashed red curve represents the envelope of the tumor components that would appear as a region with elevated Young’s modulus.
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pone.0130258.g001: Schematic diagram of tumorigenesis in breast cancer (adapted from [7, 8]).(a) Healthy milk duct. (b) Proliferation of tumor cells within the duct is accompanied by desmoplasia in the extra-cellular matrix. (c) Changes in the morphology collagen fiber bundles from a wavy and tortuous state to a straight and taut state, and the emergence of a site where the fiber orientation is predominantly radial with respect to the tumor boundary. (d) Invasion of cancer cells to surrounding glandular tissue from this site. (e) Invasion of the cancer cells to nearby ducts. (f) A fully invasive tumor state. The dashed red curve represents the envelope of the tumor components that would appear as a region with elevated Young’s modulus.

Mentions: Cancerous tumors in the breast often present as stiff lumps or lesions. One of the leading causes for the increased stiffness of these tumors is stromal desmoplasia, a process that leads to the proliferation of activated fibroblasts and myofibroblasts and the formation of a dense, collagen-rich stroma around the tumor [1, 2]. The increased collagen in turn leads to a stiffer mechanical response of the stroma. Desmoplasia is also thought to mechanically confine the tumor causing it to grow along very specific directions (see Fig 1). In particular, it has been observed that cancerous cells tend to migrate from a milk duct into the surrounding glandular tissue at locations where the collagen fiber alignment departs from a circumferential orientation to a radial orientation [3]. As a result the tumor invades the surrounding tissue and grows around these specific locations. This pattern of growth leads to the characteristic “stellate” or “spiculated” appearance of cancerous tumors [4]. It also leads to a spatially heterogeneous distribution of the stroma and, by extension, a heterogeneous distribution of tissue modulus. Other factors that contribute to the mechanical heterogeneity of the cancerous tumors include, functional heterogeneity in cancer-associated fibroblasts (CAFs) [5], which leads to heterogeneity in the degree of desmoplasia, and heterogeneity in the mechanical properties of tumor-associated vasculature and epithelium [6].


Noninvasive In-Vivo Quantification of Mechanical Heterogeneity of Invasive Breast Carcinomas.

Liu T, Babaniyi OA, Hall TJ, Barbone PE, Oberai AA - PLoS ONE (2015)

Schematic diagram of tumorigenesis in breast cancer (adapted from [7, 8]).(a) Healthy milk duct. (b) Proliferation of tumor cells within the duct is accompanied by desmoplasia in the extra-cellular matrix. (c) Changes in the morphology collagen fiber bundles from a wavy and tortuous state to a straight and taut state, and the emergence of a site where the fiber orientation is predominantly radial with respect to the tumor boundary. (d) Invasion of cancer cells to surrounding glandular tissue from this site. (e) Invasion of the cancer cells to nearby ducts. (f) A fully invasive tumor state. The dashed red curve represents the envelope of the tumor components that would appear as a region with elevated Young’s modulus.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4496079&req=5

pone.0130258.g001: Schematic diagram of tumorigenesis in breast cancer (adapted from [7, 8]).(a) Healthy milk duct. (b) Proliferation of tumor cells within the duct is accompanied by desmoplasia in the extra-cellular matrix. (c) Changes in the morphology collagen fiber bundles from a wavy and tortuous state to a straight and taut state, and the emergence of a site where the fiber orientation is predominantly radial with respect to the tumor boundary. (d) Invasion of cancer cells to surrounding glandular tissue from this site. (e) Invasion of the cancer cells to nearby ducts. (f) A fully invasive tumor state. The dashed red curve represents the envelope of the tumor components that would appear as a region with elevated Young’s modulus.
Mentions: Cancerous tumors in the breast often present as stiff lumps or lesions. One of the leading causes for the increased stiffness of these tumors is stromal desmoplasia, a process that leads to the proliferation of activated fibroblasts and myofibroblasts and the formation of a dense, collagen-rich stroma around the tumor [1, 2]. The increased collagen in turn leads to a stiffer mechanical response of the stroma. Desmoplasia is also thought to mechanically confine the tumor causing it to grow along very specific directions (see Fig 1). In particular, it has been observed that cancerous cells tend to migrate from a milk duct into the surrounding glandular tissue at locations where the collagen fiber alignment departs from a circumferential orientation to a radial orientation [3]. As a result the tumor invades the surrounding tissue and grows around these specific locations. This pattern of growth leads to the characteristic “stellate” or “spiculated” appearance of cancerous tumors [4]. It also leads to a spatially heterogeneous distribution of the stroma and, by extension, a heterogeneous distribution of tissue modulus. Other factors that contribute to the mechanical heterogeneity of the cancerous tumors include, functional heterogeneity in cancer-associated fibroblasts (CAFs) [5], which leads to heterogeneity in the degree of desmoplasia, and heterogeneity in the mechanical properties of tumor-associated vasculature and epithelium [6].

Bottom Line: In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging.By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors.Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous.

View Article: PubMed Central - PubMed

Affiliation: Scientific Computation Research Center, Rensselaer Polytechnic Institute, Troy, NY, USA.

ABSTRACT
Heterogeneity is a hallmark of cancer whether one considers the genotype of cancerous cells, the composition of their microenvironment, the distribution of blood and lymphatic microvasculature, or the spatial distribution of the desmoplastic reaction. It is logical to expect that this heterogeneity in tumor microenvironment will lead to spatial heterogeneity in its mechanical properties. In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging. By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors. Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous.

No MeSH data available.


Related in: MedlinePlus