Prognostic Value of "Prepectoral Edema" in MR-mammography.

BACKGROUND/AIM: Previous studies have indicated a highly significant correlation between invasive tumors and accompanying prepectoral edema (PE) in MR-mammography (MRM). The aim of the present study was to identify prognostic factors associated with PE as a diagnostic sign. MATERIALS AND METHODS: A total of 1,109 consecutive MRM exams were included in this study. Exclusion criteria were previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy (HRT) or previous mastitis. One hundred and sixty-two patients with 180 lesions were evaluated and histologically correlated. Diagnostic evaluations were performed by four experienced radiologists in consensus. RESULTS: One hundred and eighty lesions included 104 malignant lesions (93 invasive and 11 non-invasive) and 76 benign lesions. PE was detected significantly more frequently in presence of lymphangiosis carcinomatosa ((53.8%; 14/26) vs. (9.8%; 4/41)) (p<0,000). PE significantly correlates with positive axillary nodal status ((19.4% (12/62) vs. 44.4% (12/27)) (p=0.020), as well as pathologic enhancement of the pectoral muscle (5.4% (5/93) vs. 22.7% (20/88)) (p=0,015). PE significantly correlates with higher tumor grading (G3) (33.9% vs. 13.9%) (p<0.05). There was no significant difference in a positive vs. negative estrogen (p=0.681) and progesterone (p=0.751) and/or human epidermal growth factor receptor-2 (HER-2) (p=0.726) receptor status accompanied by PE. CONCLUSION: The presence of PE may be a strong prognostic indicator for lymphatic spread and the cancerous infiltration of lymph nodes. It is also associated with the infiltration of the pectoral muscle, as well as high tumor grading. There is no correlation between prepectoral edema and positive tumor receptor status.

The value of "constant sharpness" as a diagnostic sign in MR-Mammography.

PURPOSE: To examine "constant lesion sharpness" as a morphological diagnostic sign in the differential diagnosis between benign and malignant lesions. MATERIAL AND METHODS: This prospective study had institutional review board approval and was HIPAA compliant. In total 1014 consecutive patients were examined (mean age 55 years ± 13 years) and evaluated in our University hospital towards the morphological shape of the lesion borders. The "Constant sharpness Sign" was defined as a lesion remaining continuously sharp for the duration of the dynamic scan. Inclusion criteria were unclear findings (e.g. BIRADS III/IV), Preoperative staging (BRIDAS IV/V), and referred patients from local clinic of gynecology. Exclusion criteria were MRM-examination ≤1 year before, status after surgery and/or biopsy, chemotherapy and/or radiation therapy. Reference Standard was histological verification. Images were diagnosed by two experienced radiologists in consensus, blinded to the standard of reference. RESULTS: 1014 patients with 1084 lesions (436 benign, 648 malignant lesions) were included into the study. 41.5% of benign lesions and 6.8% (181/436) of malignant lesions displayed a constant sharpness as an accompanying morphological sign (P < 0.001). This resulted in a sensitivity of 41.5%, specificity of 93.2%, a positive likelihood ratio of 6.1%, a negative likelihood ratio of 0.63 and an odd's ratio of 9,7%. SUMMARY AND CONCLUSION: The constant sharpness sign seems to be an accurate predictor of benign breast lesions, which may help to increase the accuracy of MRM as a morphological sign.

Focal transitional mastitis in MR-Mammography: Preliminary findings.

PURPOSE: During clinical routine, we retrospectively discovered diagnostic criteria for "focal mastitis" in MR-Mammography (MRM). The aim of this study was to prospectively evaluate these criteria. METHODS: 1975 consecutive patients were examined between 01/2010 and 12/2011. 29 patients fit the diagnostic criteria of focal mastitis. RESULTS: In follow-up scans, 28 patients showed a complete remission of the previous findings. One patient was followed-up with persisting findings, which could histologically be correlated to an area of DCIS after biopsy. CONCLUSION: The morphologic, kinetic and follow-up criteria we discovered seem to be a reliable diagnostic indicator for focal mastitis.

Perirenal Edema as a potential hint towards primary hypertension-Preliminary findings in MRI breast cancer staging.

PURPOSE: To demonstrate our primary findings, indicating perirenal edema as a first imaging sign towards primary hypertension. METHODS: Out of 3190 consecutive MR-Mammography (MRM) examinations, 777 were performed with an additional body array coil. Incidentally, "perirenal edema" could be linked to a patient history of hypertension. We Therefore specifically further observed the correlation. RESULTS: Of 777 patients 86 (11%) patients showed the perirenal edema sign (PES). Upon inquiry all of these cases (100%) confirmed a past or present history of hypertensive disease (i.e. blood pressure above 140/90 and/or anti-hypertensive treatment). CONCLUSION: Our preliminary results strongly indicate a strong correlation between perirenal edema and primary hypertension.

Is "prepectoral edema" a morphologic sign for malignant breast tumors?

RATIONALE AND OBJECTIVES: A variety of morphologic and kinetic signs of benign or malignant breast lesions contribute to a final diagnosis and differential diagnosis in magnetic resonance (MR) mammography (MRM). As a new sign, prepectoral edema (PE) in patients without any history of previous biopsy, operation, radiation, or chemotherapy was detected during routine breast MR examinations. The purpose of this study was to retrospectively evaluate the role of this morphologic sign in the differential diagnosis of breast lesions. MATERIALS AND METHODS: Between January 2005 and October 2006, a total of 1109 consecutive MRM examinations have been performed in our institution. In this study, only patients who would later be biopsied or operated in our own hospital were included. They had no previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy, or previous mastitis. In total, 162 patients with 180 lesions were included, histologically correlated later-on by open biopsy (124 patients and 136 lesions) or core biopsy (38 patients and 44 lesions). The evaluations were performed by four experienced radiologists in consensus. RESULTS: One hundred eighty evaluated lesions included 104 malignant lesions (93 invasive and 11 noninvasive cancers) and 76 benign lesions. PE was detected in 2.6% of benign lesions (2 of 76), in none of the Ductal cacinoma in situ (DCIS) cases (0 of 11), and in 25.8% of malignant lesions (24 of 93; P < .000). PE was found significantly more frequently in presence of malignant tumors >2 cm in diameter (48.5%, 17 of 35 vs. 13.8%, 8 of 58; P < .001). PE was not statistically associated to malignant tumor type, presence or absence of additional DCIS, and number of lesions. This resulted in the following diagnostic parameters for PE as an indicator for malignancy: sensitivity of 19.3%, specificity of 97.3%, positive predictive value (PPV) of 92.3%, negative predictive value of 48%, and accuracy of 57.7%. CONCLUSIONS: In case of occurrence, the "PE sign" seems to be a specific indicator for malignant tumors with a high PPV, independent from its entity.

4D co-registration of X-ray and MR-mammograms: initial clinical results and potential incremental diagnostic value.

PURPOSE: 4D co-registration of X-ray- and MR-mammograms (XM and MM) is a new method of image fusion. The present study aims to evaluate its clinical feasibility, radiological accuracy, and potential clinical value. METHODS: XM and MM of 25 patients were co-registered. Results were evaluated by a blinded reader. RESULTS: Precision of the 4D co-registration was "very good" (mean-score [ms]=7), and lesions were "easier to delineate" (ms=5). In 88.8%, "relevant additional diagnostic information" was present, accounting for a more "confident diagnosis" in 76% (ms=5). CONCLUSION: 4D co-registration is feasible, accurate, and of potential clinical value.

Breast pathology after cryotherapy. Histological regression of breast cancer after cryotherapy.

A breast saving treatment is contemporary the preferred method of treatment with comparable results in comparing with mastectomy. In this study were evaluated the effects of cryotherapy by histological verification of changes in post treatment resection specimens. Fifty-three patients in age of 38-81 year with histologically confirmed breast cancer in needle biopsies were managed by cryotherapy between 1999 and 2007. The patients were operated between day 1 and 35 after cryotherapy. The histologic examination of operation materials showed in all cases at least partial tumor destruction. In general in 54.7% of all handled cases (29 patient) there was no residual tumor. In 6 cases (22.2%) from group 1 and in 23 cases (88.5%) of group 2 no tumor rest was found. Cryotherapy can lead to complete destruction of tumoral tissue. In our study all 29 (54.7%) of tumor-free cases after cryotherapy were those with cT1 stage. The experience of operator and the correct selection of appropriate patients (primarily taking the tumor size into account) play the most important role for achieving the best results.

Liposomal encapsulation of a near-infrared fluorophore enhances fluorescence quenching and reliable whole body optical imaging upon activation in vivo.

In the past decade, there has been significant progress in the development of water soluble near-infrared fluorochromes for use in a wide range of imaging applications. Fluorochromes with high photo and thermal stability, sensitivity, adequate pharmacological properties and absorption/emission maxima within the near infrared window (650-900 nm) are highly desired for in vivo imaging, since biological tissues show very low absorption and auto-fluorescence at this spectrum window. Taking these properties into consideration, a myriad of promising near infrared fluorescent probes has been developed recently. However, a hallmark of most of these probes is a rapid clearance in vivo, which hampers their application. It is hypothesized that encapsulation of the near infrared fluorescent dye DY-676-COOH, which undergoes fluorescence quenching at high concentrations, in the aqueous interior of liposomes will result in protection and fluorescence quenching, which upon degradation by phagocytes in vivo will lead to fluorescence activation and enable imaging of inflammation. Liposomes prepared with high concentrations of DY-676-COOH reveal strong fluorescence quenching. It is demonstrated that the non-targeted PEGylated fluorescence-activatable liposomes are taken up predominantly by phagocytosis and degraded in lysosomes. Furthermore, in zymosan-induced edema models in mice, the liposomes are taken up by monocytes and macrophages which migrate to the sites of inflammation. Opposed to free DY-676-COOH, prolonged stability and retention of liposomal-DY-676-COOH is reflected in a significant increase in fluorescence intensity of edema. Thus, protected delivery and fluorescence quenching make the DY-676-COOH-loaded liposomes a highly promising contrast agent for in vivo optical imaging of inflammatory diseases.

A simple and robust classification tree for differentiation between benign and malignant lesions in MR-mammography.

OBJECTIVES: In the face of multiple available diagnostic criteria in MR-mammography (MRM), a practical algorithm for lesion classification is needed. Such an algorithm should be as simple as possible and include only important independent lesion features to differentiate benign from malignant lesions. This investigation aimed to develop a simple classification tree for differential diagnosis in MRM. METHODS: A total of 1,084 lesions in standardised MRM with subsequent histological verification (648 malignant, 436 benign) were investigated. Seventeen lesion criteria were assessed by 2 readers in consensus. Classification analysis was performed using the chi-squared automatic interaction detection (CHAID) method. Results include the probability for malignancy for every descriptor combination in the classification tree. RESULTS: A classification tree incorporating 5 lesion descriptors with a depth of 3 ramifications (1, root sign; 2, delayed enhancement pattern; 3, border, internal enhancement and oedema) was calculated. Of all 1,084 lesions, 262 (40.4 %) and 106 (24.3 %) could be classified as malignant and benign with an accuracy above 95 %, respectively. Overall diagnostic accuracy was 88.4 %. CONCLUSIONS: The classification algorithm reduced the number of categorical descriptors from 17 to 5 (29.4 %), resulting in a high classification accuracy. More than one third of all lesions could be classified with accuracy above 95 %. KEY POINTS: • A practical algorithm has been developed to classify lesions found in MR-mammography. • A simple decision tree consisting of five criteria reaches high accuracy of 88.4 %. • Unique to this approach, each classification is associated with a diagnostic certainty. • Diagnostic certainty of greater than 95 % is achieved in 34 % of all cases.

Multifactorial diagnostic NIR imaging of CCK2R expressing tumors.

Optical imaging-based diagnostics identify malignancies based on molecular changes instead of morphological criteria in a non-invasive, irradiation free process. The aim of this study was to improve imaging efficiency by the development of a new Cholecystokinin-2-receptor targeted fluorescent peptide that matches the clinical needs regarding biodistribution and pharmacokinetics while displaying superior target specificity. Furthermore we performed multifactorial imaging of Cholecystokinin-2-receptor and tumor metabolism, since simultaneous targeting of various tumor biomarkers could intensely increase tumor identification and characterization. Affinity and specificity of the fluorescent Cholecystokinin-2-receptor targeted minigastrin (dQ-MG-754) were tested in vitro. We conducted in vivo imaging of the dQ-MG-754 probe alone and in a multifactorial approach with a GLUT-1 targeted probe (IR800 2-DG) on subcutaneous xenograft bearing athymic nude mice up to 24 h after intravenous injection (n = 5/group), followed by ex vivo biodistribution analysis and histological examination. We found specific, high affinity binding (Kd = 1.77 nM ± 0.6 nM) of dQ-MG-754 to Cholecystokinin-2-receptor expressing cells and xenografts as well as favorable pharmacokinetics for fluorescence-guided endoscopy. We successfully performed multifactorial imaging for the simultaneous detection of the Cholecystokinin-2-receptor and GLUT-1 targeted probe. Prominent differences in uptake patterns of the two contrast agents could be detected. The results were validated by histological examinations. The multifactorial imaging approach presented in this study could facilitate cancer detection in diagnostic imaging and intraoperative and endoscopic applications. Especially the dQ-MG-754 probe bears great potential for translation to clinical endoscopy imaging, because it combines specific high affinity binding with renal elimination and a favorable biodistribution.

The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels.

PURPOSE: The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. METHODS: BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 µg Fe/cm(2)) or mitomycin C (up to 1.5 µg/cm(2), 24 hours) in the presence or absence of hyperthermia (43°C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. RESULTS: When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. DISCUSSION: The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our results could be used to develop new treatment strategies by repressing mechanisms that actively export drugs from the target cell, thereby improving the therapeutic outcome in oncology.

Diagnosis of focal liver lesions suspected of metastases by diffusion-weighted imaging (DWI): systematic comparison favors free-breathing technique.

Two echo planar imaging diffusion-weighted imaging (DWI) techniques [one breath hold (DWI(bh)), repetition time/echo time (TR/TE) 2100/62 ms; one at free breathing (DWI(fb)), TR/TE 2000/65 ms] were compared regarding diagnosis of focal liver lesions (FLLs) in 45 patients with suspected liver metastasis without prior treatment. Apparent diffusion coefficient values of 46 benign and 67 malignant FLLs were analyzed by receiver operating characteristics (ROC) analysis. DWI(fb) detected more malignant lesions than DWI(bh) (P=.002). Lesion size ≤10 mm was associated with FLLs missed by DWI(bh) (P=.018). Area under the ROC curve of DWI(fb) (0.801) was higher compared to that of DWI(bh) (0.669, P<.0113), demonstrating the diagnostic superiority of DWI(fb).

Association between survival in patients with primary invasive breast cancer and computer aided MRI.

PURPOSE: To identify the potential of semi-quantitative enhancement-analysis in breast MRI to predict disease-related death in primary breast cancer patients. MATERIALS AND METHODS: The present study was planned and conducted according to international recommendations. All patients referred for pretherapeutic staging of primary breast cancer during 24 consecutive months were included into the study collective. They were followed-up by our multidisciplinary breast center. For semi-quantitative MRI-analysis dedicated CAD-software (computer assisted diagnosis) was used. Association between enhancement parameters and disease-related survival was investigated using Cox proportional-hazards -regression (CR). RESULTS: A total of 115 patients were eligible for CR analysis. Median follow-up time was 52 months. In 15 patients, disease-related death occurred. CR analysis identified four enhancement parameters as independent and significant (P < 0.001) predictors of the endpoint. Coefficients were "Initial enhancement" (B = 0.0166), "Time to peak-enhancement" (B = 1.0573), "Tumor volume" (B = 0.0175), and proportion of "tumor volume" showing "slow initial enhancement" followed by a "persistent" curve-type (B = -0.0586). CONCLUSION: This study demonstrates the significant relationship between semi-quantitative enhancement analysis in breast MRI and disease-related death of breast cancer patients. As results were extracted from a routine staging examination, MRI noninvasively provides not only diagnostic information but also outcome data at one step. Future studies should address the impact of these findings on patient management and therapeutic approach.