Investigation of imaging features in contrast-enhanced magnetic resonance imaging of benign and malignant breast lesions.

PURPOSE: This study aimed to enhance the diagnostic accuracy of contrast-enhanced breast magnetic resonance imaging (MRI) using gadobutrol for differentiating benign breast lesions from malignant ones. Moreover, this study sought to address the limitations of current imaging techniques and criteria based on the Breast Imaging Reporting and Data System (BI-RADS). MATERIALS AND METHODS: In a multicenter retrospective study conducted in Japan, 200 women were included, comprising 100 with benign lesions and 100 with malignant lesions, all classified under BI-RADS categories 3 and 4. The MRI protocol included 3D fast gradient echo T1- weighted images with fat suppression, with gadobutrol as the contrast agent. The analysis involved evaluating patient and lesion characteristics, including age, size, location, fibroglandular tissue, background parenchymal enhancement (BPE), signal intensity, and the findings of mass and non-mass enhancement. In this study, univariate and multivariate logistic regression analyses were performed, along with decision tree analysis, to identify significant predictors for the classification of lesions. RESULTS: Differences in lesion characteristics were identified, which may influence malignancy risk. The multivariate logistic regression model revealed age, lesion location, shape, and signal intensity as significant predictors of malignancy. Decision tree analysis identified additional diagnostic factors, including lesion margin and BPE level. The decision tree models demonstrated high diagnostic accuracy, with the logistic regression model showing an area under the curve of 0.925 for masses and 0.829 for non-mass enhancements. CONCLUSION: This study underscores the importance of integrating patient age, lesion location, and BPE level into the BI-RADS criteria to improve the differentiation between benign and malignant breast lesions. This approach could minimize unnecessary biopsies and enhance clinical decision-making in breast cancer diagnostics, highlighting the effectiveness of gadobutrol in breast MRI evaluations.

Effects of gadobutrol on background parenchymal enhancement and differential diagnosis between benign and malignant lesions in dynamic magnetic resonance imaging of the breast.

BACKGROUND: The high concentration of gadolinium in gadobutrol, which is widely used in Japan, helps visualize signal enhancement of neoplastic lesions, however, there was concern that high T1 relaxivity could decrease the contrast between the lesion and the background mammary gland. We evaluate the effect of gadobutrol on background parenchymal enhancement (BPE) and differential diagnosis between benign and malignant lesions in dynamic MRI of the breast. METHODS: Ninety-nine patients were enrolled prospectively. Measurements of the following signal intensities (SIs) were obtained: breast tissue on a pre-contrast image (SIpre) and an early-phase image (SIearly); and the SIs of breast cancer on a pre-contrast image (SIpre-cancer) and an early-phase image (SIearly-cancer). We calculated the BPE ratio, i.e., (SIearly - SIpre)/SIpre and the cancer/BPE ratio, i.e., (SIearly-cancer - SIpre-cancer)/(SIearly on the affected side - SIpre on the affected side). These quantitative assessments were compared with the data from the recently published multicenter study (reference study without use of gadobutrol). In addition, two radiologists reinterpreted each of the MR images, and a third radiologist set the ROIs in the lesions and performed kinetic analysis as a Reader 3. RESULTS: While there was no significant difference in the SI of breast cancer in the premenopausal patients between the two studies, that in postmenopausal patients was significantly higher in the present study than in the reference study (p = 0.002). Although there was no significant difference in the cancer/BPE ratio in the postmenopausal patients between the two studies, the cancer/BPE ratio in the premenopausal patients was significantly higher in the reference study than in the present study (p = 0.028). For differentiation between benign and malignant masses, the mass margin was found to be the most important term (p < 0.001). According to the data of Reader 3, visual washout was observed in all 18 patients in whom the interpretation was changed from "plateau" to "washout". CONCLUSIONS: Gadobutrol may decrease the contrast between breast cancer and background parenchyma in premenopausal patients, and it may have a characteristic that "washout" does not easily occur, leading to "plateau" in patients with breast cancer.

Overlapping MERS and mild AESD caused by HHV-6 infection.

We report the case of an overlapping encephalopathy syndrome consisting of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and a mild form of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) caused by human herpesvirus-6. A previously healthy 17-month-old girl was admitted to our hospital as a precaution because of seizures that had developed more than 25 hours (h) after fever. Brain diffusion-weighted images (DWI) showed high signal intensity in the central splenial region on Day 2. She regained consciousness 16 h after the second seizure. On Day 6, she had a secondary cluster of partial seizures. DWI showed resolution of the splenial lesion and revealed reduced diffusion in the fronto-subcortical white matter. She regained consciousness 36 h after the secondary cluster of seizures without any sequelae. A third DWI performed on Day 15 showed that the fronto-subcortical white matter lesions had completely disappeared. Based on the clinicoradiological findings, we diagnosed the patient with overlapping MERS and mild AESD. Our case, together with previous reports, suggests that patients can develop combined encephalopathy syndromes as a phenotype. Many encephalopathy syndromes have been established and classified; however, some may not present as independent syndromes.

Influence of human serum albumin on the bile acid-mediated inhibition of liver microsomal type 1 11ß-hydroxysteroid dehydrogenase.

The influence of human serum albumin (HSA) on the bile acid-mediated inhibition of liver microsomal type 1 11ß-hydroxysteroid dehydrogenase (11ß-HSD1) was studied in vitro. A rat liver microsomal fraction was prepared, and the 11ß-HSD1 enzyme activity in the presence of various concentrations of bile acids and HSA was determined using hydrocortisone as the substrate. The products of the reaction were extracted and analyzed using high-performance liquid chromatography. The magnitude of the inhibition decreased with the addition of HSA in a dose-dependent manner. Four percent human albumin decreased the inhibitory effects of 100 µM chenodeoxycholic acid and lithocholic acid from 89.9 ± 5.6 to 54.5 ± 6.1% and from 83.8 ± 4.8 to 20.8 ± 4.2%, respectively. In contrast, ursodeoxycholic acid and deoxycholic acid showed no inhibitory effect on the enzyme activity in the presence of 4% human serum albumin, and the addition of 1% γ-globulin to the assay mixture in the presence of bile acids did not affect the enzyme activity. Our in vitro study showed that the addition of HSA ameliorated the inhibition of 11ß-HSD1 and that the magnitude of the change is dependent on the species of bile acid, presumably based on the numbers of hydroxyl groups. These results suggest that HSA seems to protect the bile acid-mediated inhibition of 11ß-HSD1 in the healthy subject. On the other hand, in the patients with obstructive biliary diseases, not only elevated serum bile acid but also the accompanying hypoalbuminemia is important to evaluate the pathophysiology of the bile acid-mediated inhibition of 11ß-HSD1 of the disease.

Total synthesis of 10-isocyano-4-cadinene and its stereoisomers and evaluations of antifouling activities.

The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae, and determination of its absolute stereochemistry were achieved. 10-Isocyano-4-cadinene is expected to be a novel nontoxic antifouling agent. In the synthesis, intermolecular Diels-Alder reaction and samarium diiodide induced Barbier-type cyclization were employed as key steps. The absolute configuration of 10-isocyano-4-cadinene was determined as (1S,6S,7R,10S) by comparison of the optical rotations between natural and synthetic samples. In addition, the authors successfully synthesized 10-epi- and di-1,6-epi-10-isocyano-4-cadinene through the same synthetic pathway. Antifouling activities against Balanus amphitrite with the cadinenes were also evaluated.

MR and US imaging for breast cancer patients who underwent conservation surgery after neoadjuvant chemotherapy: comparison of triple negative breast cancer and other intrinsic subtypes.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is commonly utilized to treat operable breast cancer. The purpose of this study was to review the findings of ultrasonography (US) and magnetic resonance (MR) imaging in patients treated with breast conservation surgery (BCS) after NAC with a focus on intrinsic subtypes. METHODS: Eighty-six patients underwent BCS after NAC. The tumors were classified into four subgroups by receptor status. US and MR were performed before and after NAC. The tumor diameters in US and MR after NAC were examined for correlations with pathological tumor distances in the specimens from BCS after NAC. RESULTS: The correlation coefficient (r) of US to pathological tumor size was 0.3 in all tumors, 0.6 in HER2-type tumors, and 0.7 in triple negative breast cancers (TNBC). The correlation coefficient of tumor size in MR to pathological tumor size was 0.9 in TNBC, and other correlations were not statistically significant. CONCLUSIONS: The correlation between tumor size in MR and pathological tumor size in triple negative breast cancers corresponded best. This information is one of the clues to selecting patients for BCS after NAC.

Total synthesis of 10-isocyano-4-cadinene and determination of its absolute configuration.

The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae, was achieved. The cadinene is expected to be a novel nontoxic antifouling agent. In the synthesis, an intermolecular Diels-Alder reaction and a SmI(2)-induced Barbier-type reaction were employed as key steps. The absolute configuration of 10-isocyano-4-cadinene was determined to be (1S, 6S, 7R, 10S) on the basis of the total synthesis. Antifouling activities against Balanus amphitrite with both enantiomers of 10-isocyano-4-cadinene were also evaluated.

Clinicopathological study of invasive ductal carcinoma with large central acellular zone: special reference to magnetic resonance imaging findings.

Invasive ductal carcinoma (IDC) with central acellular zone is sometimes encountered, but its clinicopathological features have not yet been fully investigated. The clinicopathological features of 10 resected cases of IDC with a large central acellular zone were investigated. The tumor size ranged from 6 to 28 mm with a mean of 14.3 +/- 6.9 mm. Contrast-enhanced magnetic resonance imaging (MRI) showed a ring-like appearance in the tumor. Sagittal fat-suppressed T2-weighted MRI had very high to intermediate signal intensity in a central area. Histologically, cancer tissue was located in the periphery of the tumor with a ring-like pattern and a large central area was occupied by acellular amorphous tissue that was strongly stained by alcian blue. Lymph vessel permeation was seen in eight cases. Among the tumors with focal enhancement in the central areas >1 cm in diameter on contrast MRI, marked increase of microvessel was observed in the enhanced spot. The mean of p53 and Ki-67 labeling indices was 56.2% and 36.3%, respectively. IDC with a large central acellular zone presenting with characteristic MRI should be noted as a new morphological entity.

The evolving non-surgical ablation of breast cancer: MR guided focused ultrasound (MRgFUS).

MRgFUS (MR guided Focused Ultrasound) being one of the non-surgical ablation techniques. We have already achieved favorable results in the past clinical study of MRgFUS to local treatment. New twenty one cases of invasive/noninvasive ductal carcinoma of the breast were treated by MRgFUS. Core needle biopsy led to the definitive diagnosis. All the patients were positioned prone in the treatment, using the therapeutic apparatus such as Signa Excite 1.5 T for MRI and ExAblate 2000 version 2.6/4.1 for FUS. Irradiation was not applied to all the 21 cases after MRgFUS. Axillary lymph node metastases were examined by dissection or sentinel lymph node biopsy. Recurrence or abnormal area of residual cancer was treated with Re-MRgFUS or ablated by usual surgery. All the 21 cases were from women patients. Median age is 54 years (range: 34-72). Median diameter of tumor is 15 mm (range: 5-50). As for the numbers of treatment, 17 patients were treated once, and 4 patients twice. Median period of observation is 14 months (range: 3-26). One case of recurrence of pure mucinous carcinoma was experienced. No evidences of recurrence were obtained through MRI for the rest of 20 cases. Skin burns were found in 2 cases. The patient had dimple on the skin immediately above tumor. In conclusion, MRgFUS is a good mean as local control of breast cancer, but the indicated case must be selected strictly. And it needs to observe longer the patients who ware treated by MRgFUS alone.

A case of alpha-thalassemia-2 associated with pulmonary infarction.

Pulmonary infarction is an entity of medical significance that develops concurrently in beta-thalassemia but not in alpha-thalassemia. The reason for this difference is yet to be elucidated. We have evaluated a 21-year-old male alpha-thalassemia-2 patient who had profound microcytic anemia and pulmonary infarction. Analysis of the alpha-globin gene revealed -alpha3.7/alpha alpha genotype. His mother also had the same heterozygous gene deletion, though she had neither anemia nor pulmonary infarction. Since the patient had no other predisposition to pulmonary infarction, it is suggested that there is a close etiologic relationship between morphologic abnormality of the erythrocytes caused by alpha-thalassemia-2 and development of pulmonary infarction.

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness.

BACKGROUND: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive technique that has been shown to coagulate benign and malignant tumors. The purpose of this study was to evaluate MRgFUS safety and effectiveness for the ablation of breast carcinomas. STUDY DESIGN: Thirty women with biopsy-proved breast cancer underwent MRgFUS treatment. Gadolinium-enhanced MR images were used for treatment planning and posttreatment radiologic assessment of treated tissue, and temperature-sensitive MR images provided real-time treatment monitoring. After MRgFUS, all 30 women underwent wide excision or mastectomy. The extent of thermal ablation was assessed with tumor histology. RESULTS: Treatment was well tolerated, with a minimum of adverse effects, especially when performed under local anesthesia. On pathologic examination, mean (+/-SD) necrosis of the targeted breast tumors was 96.9 +/- 4% (median 100%, range 78% to 100%) of tumor volume. Fifteen (53.5%) of 28 evaluable patients had 100% necrosis of the ablated tumor; only 3 patients (10.7%) had less than 95% necrosis. In 28 (93.3%) patients, 100% of the malignancy was within the treatment field, and 98% and 95% of tumor lay within the treatment field in 2 remaining patients. Retrospective analysis in two patients with residual tumor showed treatment was not delivered to the full recommended area, reaffirming the need for precise localization and the value of contrast-enhanced images for treatment planning. CONCLUSIONS: MRgFUS has great potential to become a viable noninvasive replacement for lumpectomy. Additional studies focusing on posttreatment image-based evaluation are needed.

A comparison of MR imaging, galactography and ultrasonography in patients with nipple discharge.

BACKGROUND: The aim of this study is to assess the usefulness of three-dimensional contrast-enhanced magnetic resonance (MR) imaging, compared with galactography and ultrasonography(US). METHODS: Fifty-five patients with bloody nipple discharge were investigated retrospectively. All patients were examined by galactography, ultrasonography and MR imaging. These three sets of findings were compared with the histopathological results from 16 intraductal biopsies, 3 excisional biopsies, 24 microdochectomies and 12 mastectomies. RESULTS: Contrast enhanced MR imaging demonstrated all malignant lesions including ductal carcinoma in situ (DCIS). Four cases of DCIS were not visualized by ultrasonography and three malignant lesions were missed by galactography. In the MR study, segmental clumped enhancement (positive predictive value =100 %), and focal mass with smooth border (negative predictive value =87.5 %) were the statistically significant predictive factors. CONCLUSIONS: Among the three modalities, contrast-enhanced three-dimensional MR imaging demonstrated the location and distribution of the lesions most clearly, especially in cases of ductal carcinoma in situ. It has the potential to be a useful diagnostic tool for patients with nipple discharge.

Accumulation of 4- and 5-ene steroid sulfates in human breast cyst fluids.

Gross cystic disease of the breast is one of the most common diseases of adult females. Breast cyst fluid contains various steroid hormones. In order to obtain more information about the concentrations of 4- and 5-ene steroids in human breast cyst fluids, levels of pregnenolone sulfate (PREGS), pregnenolone (PREG), dehydroepiandrosterone sulfate (DHEAS) and dehydroepiandrosterone (DHEA) were determined by high-performance liquid chromatography (HPLC). A total of 35 human breast cyst fluid samples, obtained from 35 patients (28-54 years old) were analyzed. Cyst fluid electrolytes were simultaneously determined. Levels of PREGS (mean+/-S.D.) were 26.9+/-20.0 micromol/l (N=35) and of PREG were <0.1 micromol/l. Levels of DHEAS and DHEA were 89.1+/-111.7 micromol/l (N=35) and 0.3+/-0.2 micromol/l (N=35), respectively. Cyst fluids were divided into two groups (types I and II) according to their electrolyte ratio (K(+)/Na(+)). The cysts of the type I group (K(+)/Na(+) >1.5) contained significantly higher levels of PREGS (39.9+/-21.1 micromol/l) and DHEAS (133.2+/-87.9 micromol/l) than those of the type II group (K(+)/Na(+) <1.5), the mean levels of which were 19.8+/-16.2 micromol/dl for PREGS, and 36.3+/-29.0 micromol/dl for DHEAS (P<0.05). PREGS and DHEAS levels in the cysts were significantly correlated (r=0.49; P<0.01). Human breast cyst fluids contain high concentration of DHEAS and PREGS, especially in the cyst fluids containing high K(+)/Na(+) ratios.

Extension of breast cancer: comparison of CT and MRI.

PURPOSE: To compare three-dimensional (3D) helical CT with 3D MRI in the evaluation of intraductal spread of breast cancer. METHODS: Fifty patients with breast cancer were examined. Tumor size ranged from Tis to T2. The whole breast was scanned by both breath-holding helical CT and MRI with contrast media. Linear or segmental enhancement, and spotty enhancement around the main tumor were considered to indicate ductal carcinoma in situ (DCIS) or ductal spread. These findings were compared with thin section histopathologic data. RESULTS: Seventeen of 35 patients had intraductal spread with invasive cancer and 15 patients had DCIS. The sensitivity, specificity, and accuracy of 3D CT in detecting intraductal spread or DCIS were 71.9%, 83.3%, and 76.0%, respectively, and those of 3D MRI were 87.5%, 61.1%, and 78.0%. Overestimations numbered three (6.0%) on CT and seven (14.0%) on MRI, and underestimations numbered nine (18.0%) on CT and four (8.0%) on MRI. CONCLUSION: 3D helical CT can provide good information about the spread of breast cancer and could be an alternative to 3D MRI for preoperative examination of breast cancer.