| ObjectiveEstablish animal model of rat breast cancer and study the induced rat breast cancer CT scan, CT enhancement and CT perfusion imaging (CTPI) performance, investigate the correlation of CTPI with tumor grade, histological type microvascular vessel density (MVD), and further identify the diagnostic value of CTPI on breast cancer.MethodsThirty-five female Wistar rats were arranged, with the age of 40 days and the weight of 100~140 g. 100 ml sesame oil was heated in 60℃thermostatic waterbath for 10 mins. Added 1 g 7, 12-dimethylben(a)anthracene (DMBA) into the heated sesame oil and stired to dissolve. Thirty-five rats were divided into 3 groups by the induced time of breast cancer, included A (10~15 weeks), B (15~20 weeks), and C (20~25 weeks). Each rat was administrated intragastrically with 10 mg/ml DMBA.The induced rats were anesthetized by intraperitoneal injection of 6 ml/kg chloral hydrate, fixed on the fixing plate. Inguinal skin was slitted to paracentesis the femoral vein by 24 G intravenous catheter needle. Fixing plate was put in CT scanner table and localized appropriately. Each rat was performed 64-slice spiral CT routine scan, enhanced scan and CTPI. Scanning data was delivered to CT exclusive image post-processing workstation of AW 4.3, and post-processed by body tumor software installed in CT perfusion 3 to obtain CTPI parameters of blood flow (BF), blood volume (BV), mean transit time (MTT), permeability surface (PS), as well as time density curve (TDC).After CT examination and perfusion-fixation procedure, tissues of breast tumor were performed HE stain and FactorⅧrelated antigen immunohistochemisty (SABC method) and immunofluorescence to observe the pathological type of tumors. Initially, 3 hyperdense vascular area (hotspot) were chosen under low power lens (×100), and then calculated under high power lens (×200). The average data was obtained to evaluate MVD. ResultsThirty breast tumors were successfully induced in 35 rats, 8 were benign and 22 were malignant. The total achievement ratio of induced breast lump was 85.7%, and the achievement ratio of induced breast cancer was 62.9%. All lumps of breast proliferative disease were solitary, 5 in 22 of breast cancer were induced two lesion of malignant lump. The size of tumor between 0.2×0.3 cm and 3.6×2.7 cm, the mean size of breast proliferative lump was (1.19±0.28)×(1.39±0.28) cm, and the mean size of breast cancer was (2.27±0.17)×(1.56±0.12) cm. When the size of lump small than 2 cm, the malignant ratio was 50 %; between 2 and 3 cm, the ratio was 60 %; large than 3 cm, the ratio was 100 %. There was significant difference between each other (P<0.05). The pathological type of breast cancer included infiltrating ductal breast cancer (n=6), infiltrating lobular carcinoma (n=6), and other types of adenocarcinoma (n=10). The differentiation of breast cancer included well differentiated (n=1), moderately differentiated (n=15) and poorly differentiated (n=6). The mean CT value of breast cancer was 62.53±4.42 Hu, showed as soft tissue. The morphology of tumor was irregular or lobulated. The density of some tumor was asymmetrical, and showed central necrosis in 5 comparatively large tumors. The high degree malignant tumor showed invasive growth, obscure boundary,few spicule sign and none calcification. The mean CT value of breast cancer was 101.31±5.33 Hu in CT enhanced scanning, 38.77±1.79 Hu higher than CT routine scanning. It showed that well-distributed enhancement or circularity uneven enhancement, and some showed dispersed spots or small patches enhanced lesions, accorded with"quick-in-quick-out"feature.Both outflow-type (5 rats) and platform-type (4 rats) TDC were malignant, flat-type (2 rats) TDC were benign. 19 rats showed inflow-type TDC, included 68.4% (13 rats) malignant and 31.6% (6 rats) benign. The type of TDC had significant differences (P<0.05) between benign and malignant.The BF,BV,MTT and PS of breast cancer central region and marginal region were 20.00±44.45 ml/min/100g,151.72±93.43 ml/min/100g;0.80±1.09 ml/100g,9.55±7.88 ml/100g;9.67±10.48 sec,2.43±1.64 sec;6.55±9.64 ml/min/100g,15.70±12.19 ml/min/100g. Breast cancer showed marginal hypertransfusion, BF, BV and PS were higher than centre area, MTT lower than centre area, and it had significant difference (P<0.05). The BF,BV,MTT and PS of moderately differentiated and poorly differentiated breast cancer were 115.30±15.46 ml/min/100g, 256.52±132.19 ml/min/100g; 9.76±9.00 ml/100g, 10.35±4.56 ml/100g; 2.49±1.90 sec, 2.42±1.00 sec; 13.86±8.91 ml/min/100g, 22.68±17.12 ml/min/100g. And The BF,BV,MTT and PS of breast proliferative disease were 42.96±32.42 ml/min/100g, 2.17±1.36 ml/100g, 4.89±5.78 sec, 8.45±6.23 ml/min/100g. BF and BV of malignant were higher than benign (P<0.05), and varied by the tissue differentiation (P<0.05). MTT of malignant was lower than benign (P<0.05), but showed no significant differences by malignant differentiation (P>0.05). There was no significant difference of PS between malignant and benign (P>0.05). The positive correlation of MVD with BF, BV and PS heightened while the differentiation decreased (P<0.05). The positive correlation of MVD with BF, BV and PS heightened while the differentiation decreased (P<0.05).Conclusion⑴Induced rat breast cancer is a suitable model for CT perfusion study.⑵CT routine scanning of rat breast cancer showed the same feature of human breast cancer, included character of irregular morphology, lobulated, soft tissue liked density, obvious enhancement and"quick-in-quick-out".⑶Breast cancer TDC always showed outflow-type and platform-type, it can help to different the benign and malignant breast tumor.⑷BF and BV of breast cancer are higher than benign and skeletal muscles. It can be used as reference index for diagnosis and differential diagnosis of breast cancer.⑸CTPI is conducive to reflect tumor differentiation, and closely associated with microvascular vessel density of tumor.
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