TY - JOUR
T1 - Magnetic resonance angiography shows increased arterial blood supply associated with murine mammary cancer
AU - Mustafi, Devkumar
AU - Leinroth, Abby
AU - Fan, Xiaobing
AU - Markiewicz, Erica
AU - Zamora, Marta
AU - Mueller, Jeffrey
AU - Conzen, Suzanne D.
AU - Karczmar, Gregory S.
N1 - Funding Information:
The authors acknowledge support from Florsheim foundation, Segal foundation, and VPH prism grant from the European Union. The Lynn S. Florsheim Magnetic Resonance Laboratory subcore of the Integrated Small Animal Imaging Research Resource is partially supported by funds from the University of Chicago Comprehensive Cancer Center from the National Cancer Institute Cancer Center Support Grant P30CA014599. This research is supported by grants from the National Institutes of Health (R01-CA133490 and R01-CA167785).
Publisher Copyright:
© 2019 Devkumar Mustafi et al.
PY - 2019
Y1 - 2019
N2 - Breast cancer is a major cause of morbidity and mortality in Western women. Tumor neoangiogenesis, the formation of new blood vessels from pre-existing ones, may be used as a prognostic marker for cancer progression. Clinical practice uses dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to detect cancers based on increased blood flow and capillary permeability. However, DCE-MRI requires repeated injections of contrast media. Therefore we explored the use of noninvasive time-of-flight (TOF) MR angiography for serial studies of mouse mammary glands to measure the number and size of arteries feeding mammary glands with and without cancer. Virgin female C3(1) SV40 TAg mice (n=9), aged 18-20 weeks, were imaged on a 9.4 Tesla small animal scanner. Multislice T 2 -weighted (T2W) images and TOF-MRI angiograms were acquired over inguinal mouse mammary glands. The data were analyzed to determine tumor burden in each mammary gland and the volume of arteries feeding each mammary gland. After in vivo MRI, inguinal mammary glands were excised and fixed in formalin for histology. TOF angiography detected arteries with a diameter as small as 0.1 mm feeding the mammary glands. A significant correlation (r=0.79; p< 0.0001) was found between tumor volume and the arterial blood volume measured in mammary glands. Mammary arterial blood volumes ranging from 0.08 mm 3 to 3.81 mm 3 were measured. Tumors and blood vessels found on in vivo T2W and TOF images, respectively, were confirmed with ex vivo histological images. These results demonstrate increased recruitment of arteries to mammary glands with cancer, likely associated with neoangiogenesis. Neoangiogenesis may be detected by TOF angiography without injection of contrast agents. This would be very useful in mouse models where repeat placement of I.V. lines is challenging. In addition, analogous methods could be tested in humans to evaluate the vasculature of suspicious lesions without using contrast agents.
AB - Breast cancer is a major cause of morbidity and mortality in Western women. Tumor neoangiogenesis, the formation of new blood vessels from pre-existing ones, may be used as a prognostic marker for cancer progression. Clinical practice uses dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to detect cancers based on increased blood flow and capillary permeability. However, DCE-MRI requires repeated injections of contrast media. Therefore we explored the use of noninvasive time-of-flight (TOF) MR angiography for serial studies of mouse mammary glands to measure the number and size of arteries feeding mammary glands with and without cancer. Virgin female C3(1) SV40 TAg mice (n=9), aged 18-20 weeks, were imaged on a 9.4 Tesla small animal scanner. Multislice T 2 -weighted (T2W) images and TOF-MRI angiograms were acquired over inguinal mouse mammary glands. The data were analyzed to determine tumor burden in each mammary gland and the volume of arteries feeding each mammary gland. After in vivo MRI, inguinal mammary glands were excised and fixed in formalin for histology. TOF angiography detected arteries with a diameter as small as 0.1 mm feeding the mammary glands. A significant correlation (r=0.79; p< 0.0001) was found between tumor volume and the arterial blood volume measured in mammary glands. Mammary arterial blood volumes ranging from 0.08 mm 3 to 3.81 mm 3 were measured. Tumors and blood vessels found on in vivo T2W and TOF images, respectively, were confirmed with ex vivo histological images. These results demonstrate increased recruitment of arteries to mammary glands with cancer, likely associated with neoangiogenesis. Neoangiogenesis may be detected by TOF angiography without injection of contrast agents. This would be very useful in mouse models where repeat placement of I.V. lines is challenging. In addition, analogous methods could be tested in humans to evaluate the vasculature of suspicious lesions without using contrast agents.
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U2 - 10.1155/2019/5987425
DO - 10.1155/2019/5987425
M3 - Article
C2 - 30792738
AN - SCOPUS:85060792376
SN - 1687-4188
VL - 2019
JO - International Journal of Biomedical Imaging
JF - International Journal of Biomedical Imaging
M1 - 5987425
ER -