MRI accurately identifies early murine mammary cancers and reliably differentiates between <i>in situ</i> and invasive cancer: correlation of MRI with histology

Mustafi, Devkumar; Zamora, Marta; Fan, Xiaobing; Markiewicz, Erica; Mueller, Jeffrey; Conzen, Suzanne D.

doi:10.1002/nbm.3348

Cited by 9 publications

(23 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, MRI provides excellent soft tissue contrast, can detect early cancer in vivo much more reliably than other imaging modalities, allows evaluation of the surrounding parenchyma, and allows accurate tumor volume measurements over time. Previous work from our laboratory demonstrated that in vivo T 2 ‐weighted MRI reliably detects very early in situ mammary tumors in SV40TAg mice with high sensitivity and specificity, and differentiates in situ from invasive cancer . Precise correlations between in vivo MR and histology images have also been demonstrated .…”

Section: Introductionmentioning

confidence: 75%

“…The right inguinal gland from each mouse was chosen for ex vivo MRI and histology. The selected gland was then excised from the skin and placed between two layers of pathology foam, mimicking the exact position of the ex vivo mammary gland on the skin, and the exact position of the mammary gland in hematoxylin and eosin (H&E)‐stained slices, as previously described . Since the ex vivo gland was scanned by MRI in the same orientation as the H&E‐stained tissue, the ex vivo MR images served as a ‘bridge’ between in vivo MRI and histology to facilitate accurate correlation.…”

Section: Methodsmentioning

confidence: 99%

“…Typical tissue dimensions were 15 mm in length, 10 mm in width, and about 1.5 mm in thickness. About 20 H&E slices were sectioned from the 1.5 mm thick slice of tissue, as described previously . Histological slides were then evaluated by an experienced breast pathologist (J.M.)…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple‐negative breast cancer

et al. 2017

Self Cite

View full text Add to dashboard Cite

High animal fat consumption is associated with an increase in triple-negative breast cancer (TNBC) risk. Based on previous MRI studies demonstrating the feasibility of detecting very early non-palpable mammary cancers in simian virus 40 large T antigen (SV40TAg) mice, we examined the effect of dietary fat fed from weaning to young adulthood in this model of TNBC. Virgin female C3(1)SV40TAg mice (n = 16) were weaned at 3–4 weeks of age and then fed either a low fat diet (LFD) (n = 8, 3.7 kcal/g; 17.2% kcal from vegetable oil) or a high animal fat diet (HAFD) (n = 8, 5.3 kcal/g; 60% kcal from lard). After 8 weeks on the diet (12 weeks of age), fast spin echo MR images of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed and inguinal mammary glands were excised and formalin fixed for ex vivo MRI. 3D volume-rendered MR images were then correlated with mammary gland histology to assess the glandular parenchyma and tumor burden. Using in vivo MRI, an average of 3.88 ± 1.03 tumors were detected per HAFD-fed mouse compared with an average of 1.25 ± 1.16 per LFD-fed mouse (p < 0.007). Additionally, the average tumor volume was significantly higher following HAFD feeding (0.53 ± 0.45 mm3) compared with LFD feeding (0.20 ± 0.08 mm3, p < 0.02). Analysis of ex vivo MR and histology images demonstrated that HAFD mouse mammary glands had denser parenchyma, irregular and enlarged ducts, dilated blood vessels, increased white adipose tissue, and increased tumor invasion. MRI and histological studies of the SV40TAg mice demonstrated that HAFD feeding also resulted in higher cancer incidence and larger mammary tumors. Unlike other imaging methods for assessing environmental effects on mammary cancer growth, MRI allows routine serial measurements and reliable detection of small cancers as well as accurate tumor volume measurements and assessment of the three-dimensional distribution of tumors over time.

show abstract

Section: Introductionmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple‐negative breast cancer

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Based on size criteria defined for in situ and invasive cancers as previously published [16], we identified a total of 31 in situ cancers and 10 invasive tumors (Table 1) in the inguinal mammary glands of eight SV40 mice by examining all MRI slices through the glands. No cancers were found in the FVB/N mice.…”

Section: Resultsmentioning

confidence: 99%

“…As a result, all FVB/N mice were injected on the right side, four SV40 mice were injected on right side, and four were injected on the left side. A cancer was classified as in situ when its size was between 150 – 400 microns, and classified as invasive if its size was >400 microns in largest diameter, based on previous work from this group that correlated cancers on MRI with histology [16]. …”

Section: Methodsmentioning

confidence: 99%

MRI ductography of contrast agent distribution and leakage in normal mouse mammary ducts and ducts with in situ cancer

Markiewicz

Fan

Mustafi

et al. 2017

Magnetic Resonance Imaging

Self Cite

View full text Add to dashboard Cite

High resolution 3D MRI was used to study contrast agent distribution and leakage in normal mouse mammary glands and glands containing in situ cancer after intra-ductal injection. Five female FVB/N mice (~19 weeks old) with no detectable mammary cancer and eight C3(1) SV40 Tag virgin female mice (~15 weeks old) with extensive in situ cancer were studied. A 34G, 45° tip Hamilton needle with a 25uL Hamilton syringe was inserted into the tip of the nipple and approximately 15uL of a Gadodiamide was injected slowly over one minute into the nipple and throughout the duct on one side of the inguinal gland. Following injection, the mouse was placed in a 9.4 T MRI scanner, and a series of high resolution 3D T1-weighted images was acquired with a temporal resolution of 9.1 minutes to follow contrast agent leakage from the ducts. The first image was acquired at about 12 minutes after injection. Ductal enhancement regions detected in images acquired between 12 and 21 minutes after contrast injection was five times smaller in SV40 mouse mammary ducts (p < 0.001) than in non-cancerous FVB/N mouse mammary ducts, perhaps due to rapid washout of contrast agent from the SV40 ducts. The contrast agent washout rate measured between 12 minutes and 90 minutes after injection was ~20% faster (p < 0.004) in SV40 mammary ducts than in FVB/N mammary ducts. These results may be due to higher permeability of the SV40 ducts, likely due to the presence of in situ cancers. Therefore, increased permeability of ducts may indicate early stage breast cancers.

show abstract

Magnetic resonance angiography reveals increased arterial blood supply and tumorigenesis following high fat feeding in a mouse model of triple‐negative breast cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

Breast cancer is the second most commonly diagnosed malignancy among women globally. Past MRI studies have linked a high animal fat diet (HAFD) to increased mammary cancer risk in the SV40Tag mouse model of triple‐negative breast cancer. Here, serial MRI examines tumor progression and measures the arterial blood volume feeding mammary glands in low fat diet (LFD) or HAFD fed mice. Virgin female C3(1)SV40Tag mice (n = 8), weaned at 3 weeks old, were assigned to an LFD (n = 4, 3.7 kcal/g, 17.2% kcal from vegetable oil) or an HAFD (n = 4, 5.3 kcal/g, 60% kcal from lard) group. From ages 8 to 12 weeks, weekly fast spin echo MR images and time‐of‐flight (TOF) MR angiography of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed. Inguinal mammary glands were excised and fixed for ex vivo MRI and histology. Tumor, blood, and mammary gland volumes for each time point were measured from manually traced regions of interest; tumors were classified as invasive by histopathology‐blinded observers. Our analysis confirmed a strong correlation between total tumor volume and blood volume in the mammary gland. Tumor growth rates from weeks 8‐12 were twice as high in HAFD‐fed mice (0.42 ± 0.14/week) as in LFD‐fed mice (0.21 ± 0.03/week), p < 0.004. Mammary gland blood volume growth rate was 2.2 times higher in HAFD mice (0.29 ± 0.11/week) compared with LFD mice (0.13 ± 0.06/week), p < 0.02. The mammary gland growth rate of HAFD‐fed mice (0.071 ± 0.011/week) was 2.7 times larger than that of LFD‐fed mice (0.026 ± 0.009/week), p < 0.01. This is the first non‐invasive, in vivo MRI study to demonstrate a strong correlation between an HAFD and increased cancer burden and blood volume in mammary cancer without using contrast agents, strengthening the evidence supporting the adverse effects of an HAFD on mammary cancer. These results support the potential future use of TOF angiography to evaluate vasculature of suspicious lesions.

show abstract

MRI accurately identifies early murine mammary cancers and reliably differentiates between in situ and invasive cancer: correlation of MRI with histology

Cited by 9 publications

References 22 publications

MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple‐negative breast cancer

MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple‐negative breast cancer

MRI ductography of contrast agent distribution and leakage in normal mouse mammary ducts and ducts with in situ cancer

Magnetic resonance angiography reveals increased arterial blood supply and tumorigenesis following high fat feeding in a mouse model of triple‐negative breast cancer

Contact Info

Product

Resources

About