I.INTRODUCTION
18F-FDG PET/CT is a useful test for detecting cancer by assessing the abnormal uptake of FDG by cancer cells due to the glucose metabolism1-3). Generally, the high uptake of FDG by cancer cells and inflammatory diseases was observed4). Nonetheless, normal cells may show abnormal uptake depending on the physiological characteristic of patients. In particular, the structural changes that occur in the uterine wall according to the menstrual cycle influence the pelvic ultrasonography results5,6). Moreover, the endometrium shows abnormal FDG uptake and influences the PET/CT test due to the change i n female h ormones. In fertile w omen, the menstrual cycle is generally 28 days7). The menstrual cycle is divided to the Menstrual Flow Phase, Proliferative Phase, Ovulatory Phase, and Secretory Phase according to the changes in the uterus and follicle8). The uterus undergoes changes as a regular cycle. During each menstrual cycle, the ovary undergoes changes in two stages, Follicular Phase and Luteal Phase. During this process, the representative female hormones estrogen and progesterone are secreted9-11). After menstruation, the endometrium becomes thick due to the influence of estrogen released from the follicle, and the uterine glands and blood vessels developed simultaneously12-14). The progesterone released from the corpus luteum stimulates the proliferation of endometrium and blood flow in the breast resulting in an increase in the elasticity of breast connective tissues and fat deposition, which induces the development of the lactiferous duct and mammary glands15,16). Therefore, its influence on the result of mammography and PET/CT should not be ruled out.
In Korean women, breast cancer is the second highest cancer next to thyroid cancer, and the importance of PET-CT for determining the stage of breast cancer and assessing the prognosis after the treatments has been emphasized. On the other hand, the abnormal FDG uptake by the breast of women according to the menstrual cycle may be a factor that impairs an accurate diagnosis of breast micro-lesions. Therefore, this study assessed the optimal time for a PET-CT test by comparing the uptake of FDG by the breast according to the menstrual cycle to improve the ability to diagnose micro-lesions in the breast.
II.MATERIALS & METHODS
A.Patients information
The subjects were 160 female patients (mean age, 34 ± 3.5 years) without a disease history of gynecological disease, and with a regular menstrual cycle for longer than 6 months(Figure 1). The subjects were divided into the following phases by history taking and the application of Pregnancy Calculator Ver.0.14: the menstrual flow phase, proliferative phase, ovulatory phase and secretory phase. Information of 40 patients in each phase was collected.
B.Equipment and test methods
The Discovery STE scanner (Milwaukee, Wi, GE Healthcare, Co., USA) was used for PET/CT. BGO was used a s the crystal. A 6 .0 mm f ull width at h alf maximum (FWHM) was used as the intrinsic resolution. The display field of view (DFOV) was 70.0 mm, and the Overlap per 1 bed was 9 mm. CT consisted of 8 slices with a 2 mm slice thickness. As the reconstruction method, “subset” was performed 28 times and “iterative” was performed 2 times using the iterative method. As the pretreatment test, the patients were fasted for a minimum of 8 hours, and excessive exercise was prohibited on the day before the test and on the day of the test. The patients took sufficient liquid, more than 100 ~ 500 ml. The blood glucose levels prior to the test were <6.69 mmol/l (120 mg/dl). For the administration of 18F-FDG, after the patients were allowed to rest for approximately 15 minutes, approximately 5.6 MBq/kg (0.15 mCi) was injected intravenously. Movements were restrained to prevent uptake by the muscles, and a full-body scan was performed after 60 ~ 90 minutes. In a full-body scan, the test range was from the base of the brain to the proximal femoral area in the supine position. Non contrast computed tomography (NCCT) without contrast was performed under the condition of 140 kVp and 30 mAs. Subsequently, an emission scan for 3 minutes per bed was performed (Figure 2). After the emission scan, contrast enhanced computed tomography (CECT) was performed. OMNIPAQ UE (300 mg iodine/ml, GE Healthcare Co., Ireland) was used as the contrast. At that time, it was injected at a dose of 2 cc per kg of the patient’s body weight and a speed of 2 ml per s econd. A d ual shot i njector optivantage (Mallinchrodt, LIEBEL FLARSHEIM Co., USA) was used as the automatic injector.
C.Image analysis
Using Pregnancy Calculator Ver. 0. 14 and history taking prior to the test, the women were classified according to their menstrual cycle, and in each phase, the changes in SUV in the liver, lung and breast were compared and analyzed (Figure 3).
In addition, a macroscopic evaluation was performed by 3 radiologists as a Blind Tests. The level of FDG uptake by the lung, liver and breast was measured in each menstrual phase. Cases in whom the FDG uptake by the breast was comparable to the lung were classified as Grade I. Cases in whom the FDG uptake of the breast was between the lung and liver were Grade II. Cases in whom the FDG uptake of the breast was comparable to the liver or higher than the liver were Grade III (Figure 4).
III.RESULTS
The SUVmax of the menstrual, proliferative, ovulatory and secretory phases was 1.64 ± 0.25 g/ml, 0.93 ± 0.28 g/ml, 1.66 ± 0.26 g/ml and 1.77 ± 0.28 g/ml, respectively(Table 1 ). The SUV was h ighest in the secretory phase followed in order by the menstrual flow phase and the ovulatory phase (p < 0.05).
In addition, the change in SUV in each menstrual phase was drawn as a Box Plot, which revealed an increased in the secretory phase, menstrual flow phase and ovulatory phase. The SUV was lower in the proliferative phase(Fig. 5). On the other hand, the SUV in the lung and the liver showed no change according to the menstrual cycle(Fig. 6).Table 2
Three radiologists evaluated the uptake of the 160 patients by macroscopic analysis as a blind test. The results revealed, Grade I in 34 patients (21.2 %). Among them, 2 and 32 cases were in the menstrual flow and proliferative phases, respectively. No cases were observed in the ovulatory and secretory phases. Most of the patients who underwent the test during the proliferative phase corresponded to Grade I. Forty six (28.8 %) patients were in Grade II; 13 and 16 cases were in the menstrual flow and ovulatory phase, respectively. Eighty cases (50 %) were Grade III, of which the FDG uptake was highest. Thirty one patients were in the secretory phase, and their ratio was highest. In particular, all images of the secretory phase corresponded to Grades II or III, and the FDG uptake by the breast was noticeably higher than the proliferative phase(Figure 7).
IV.DISCUSSION
In a PET/CT full-body scan, hormonal changes according to the menstrual cycle increase the FDG uptake by the breast. The change in FDG uptake was largest in the secretory phase, and its effect was lowest in the proliferative phase. Based on this study, the SUV changes in the breast according to the menstrual cycle and the macroscopic changes in uptake by the breast could be detected by a full-body PET/CT scan. If a PET/CT test is performed during the proliferative phase in collaboration with the diagnosis department, it can provide an accurate test that could detect even micro lesions in the breast. Nonetheless, in the present study, the subjects were patients with a regular menstrual cycle. Patients with an irregular menstrual cycle were excluded. Accordingly, many studies will be needed before this can be applied to patients with an irregular menstrual cycle.
V.CONCLUSION
The level of the FDG uptake by the breast in fertile women varies according to the menstrual cycle. In particular, information on the menstrual cycle can be applied widely for a diagnosis of breast micro-lesions. Through this study, the uptake of FDG by the breast in each phase was compared. In fertile women, the FDG uptake by the breast was highest during the secretory phase and lowest in the proliferative phase. Therefore, it is believed that false negative results of micro breast lesions may be reduced by assessing the accurate menstrual cycle through history taking before the test and by performing the test at the appropriate phase.
