Microwave Imaging in Breast Cancer - Results from the First-In-Human Clinical Investigation of the Wavelia System.

RATIONALE AND OBJECTIVES: Microwave Breast Imaging (MBI) is an emerging non-ionising technology with the potential to detect breast pathology. The investigational device considered in this article is a low-power electromagnetic wave MBI prototype that demonstrated the ability to detect dielectric contrast between tumour phantoms and synthetic fibroglandular tissue in preclinical studies. Herein, we evaluate the MBI system in the clinical setting. The capacity of the MBI system to detect and localise breast tumours in addition to benign breast pathology is assessed. Secondly, the safety profile and patient experience of this device is established. MATERIALS AND METHODS: Female patients were recruited from the symptomatic unit to 1 of 3 groups: Biopsy-proven breast cancers (Group-1), unaspirated cysts (Group-2) and biopsy-proven benign breast lesions (Group-3). Breast Density was determined by Volpara VDM (Volumetric Density Measurement) Software. MBI, radiological, pathological and histological findings were reviewed. Subjects were surveyed to assess patient experience. RESULTS: A total of 25 patients underwent MBI. 24 of these were included in final data analysis (11 Group-1, 8 Group-2 and 5 Group-3). The MBI system detected and localised 12 of 13 benign breast lesions, and 9 out of the 11 breast cancers. This included 1 case of a radiographically occult invasive lobular cancer. No device related adverse events were recorded. 92% (n = 23) of women reported that they would recommend MBI imaging to other women. CONCLUSION: The MBI system detected and localized the majority of breast lesions. This modality may have the potential to offer a non-invasive, non-ionizing and painless adjunct to breast cancer diagnosis. Further larger studies are required to validate the findings of this study.

The Wavelia Microwave Breast Imaging system-tumour discriminating features and their clinical usefulness.

OBJECTIVE: The Wavelia Microwave Breast Imaging (MBI) system, based on non-ionising imaging technology, has demonstrated exciting potential in the detection and localisation of breast pathology in symptomatic patients. In this study, the ability of the system to accurately estimate the size and likelihood of malignancy of breast lesions is detailed, and its clinical usefulness determined. METHODS: Institutional review board and Health Products Regulatory Authority (HPRA) approval were obtained. Patients were recruited from the symptomatic unit to three groups; breast cancer (Group-1), unaspirated cysts (Group-2) and biopsied benign lesions (Group-3). MBI, radiological and histopathological findings were reviewed. MBI size estimations were compared with the sizes determined by conventional imaging and histopathology. A Quadratic Discriminant Analysis (QDA) classifier was trained in a 3D feature space to discriminate malignant from benign lesions. An independent review was performed by two independent breast radiologists. RESULTS: 24 patients (11 Group-1, 8 Group-2 and 5 Group-3) underwent MBI. The Wavelia system was more accurate than conventional imaging in size estimation of breast cancers. The QDA accurately separated benign from malignant breast lesions in 88.5% of cases. The addition of MBI and the Wavelia malignancy risk calculation was deemed useful by the two radiologists in 70.6% of cases. CONCLUSION: The results from this MBI investigation demonstrate the potential of this novel system in estimating size and malignancy risk of breast lesions. This system holds significant promise as a potential non-invasive, comfortable, and harmless adjunct for breast cancer diagnosis. Further larger studies are under preparation to validate the findings of this study. ADVANCES IN KNOWLEDGE: This study details the potential of the Wavelia MBI system in delineating size and malignancy risk of benign and malignant breast lesions in a symptomatic cohort. The usefulness of the Wavelia system is assessed in the clinical setting.

The Impact of Preoperative Breast Magnetic Resonance Imaging on Surgical Management in Symptomatic Patients With Invasive Lobular Carcinoma.

OBJECTIVE: Due to an insidious proliferative pattern, invasive lobular breast cancer (ILC) often fails to form a defined radiological or palpable lesion and accurate diagnosis remains challenging. This study aimed to determine the value of preoperative magnetic resonance imaging (MRI) for ILC and its impact on surgical outcomes. METHODS: Consecutive symptomatic patients diagnosed with ILC in a tertiary centre over a 9-year period were reviewed. The time from diagnosis until surgery, initial type of surgery/index operation (breast-conserving surgery [BCS]/mastectomy) and the rates of reoperation (re-excision/completion mastectomy) were recorded. Patients were grouped into those who received conventional imaging and preoperative MRI (MR+) and those who received conventional imaging alone (MR-). RESULTS: There were 218 cases of ILC, and 32.1% (n = 70) had preoperative MRI. Time from diagnosis to surgery was longer in the MR+ than the MR- group (32.5 vs 21.1 days, P < .001) even when adjusting for age and breast density. Initial BCS was performed on 71.4% (n = 50) of MR+ patients and 72.3% (n = 107) of the MR- group. While the rate of completion mastectomy following initial BCS was higher in the MR+ group (30.0%, n = 15 vs 14.0%, n = 15; χ2 = 5.63; P = .018), this association was not maintained in multivariable analysis. No difference was recorded in overall (initial and completion) mastectomy rate between the MR+ and MR- group (50.0%, n = 35 vs 37.8%, n = 56; χ2 = 2.89; P = .089). Margin re-excision following BCS was comparable between groups (8.0%, n =4, vs 9.3%, n = 10; χ2 = 0.076, P = .783) despite the selection bias for borderline conservable cases in the MR+ group. The rate of usage of MRI for ILC cases declined over the study period. CONCLUSION: While MRI was associated with minor delays in treatment and did not reduce overall rates of margin re-excision or completion mastectomy, it altered the choice of surgical procedure in almost a quarter of MR+ cases. The benefit of preoperative breast MRI appears to be confined to select (younger, dense breast, borderline conservable) cases in symptomatic ILC.

Effect of transition to digital mammography on clinical outcomes.

PURPOSE: To determine the effect of transition to digital screening mammography on clinical outcome measures, including recall rate, cancer detection rate, and positive predictive value (PPV). MATERIALS AND METHODS: Institutional review board approval and the need for informed consent were waived for this HIPAA-complaint study. Practice audit data were obtained for three breast imaging radiologists from 2004 to 2009. These data were sorted by time period into the following groups: baseline (2004-2005), digital year 1 (2007), digital year 2 (2008), and digital year 3 (2009). The χ(2) and Fisher exact tests were used to assess differences in proportions among and between years. Clinical outcomes based on lesion type from 2004 to 2008 were also compared. Computer-aided detection was used. RESULTS: The three radiologists interpreted 32 600 screen-film mammograms and 33 879 digital mammograms. Recall rates increased from 6.0% at baseline to 7.1% in digital year 1 (P < .0001) and continued to increase in subsequent years to 8.5%. The cancer detection rate increased from 3.3 at baseline to 5.3 in digital year 1 (P = .0061), and it remained higher than that at baseline in subsequent years. PPV after screening mammogaphy (PPV(1)) increased from 5.6% at baseline to 7.5% in digital year 1 and returned to baseline levels in digital year 3. In contrast, PPV after biopsy (PPV(3)) decreased from 44.5% at baseline to 30.3% in digital year 3 (P = .0021). From 2004 to 2008, 3444 patients with 3493 lesions were recalled. The percentage of recalls for calcifications increased from 13.8% at baseline to a peak of 23.9% in digital year 1 and 17.9% in digital year 2. Both PPV(1) and PPV(3) decreased for calcifications after the digital transition. CONCLUSION: Recall rate and cancer detection rate increase for at least 2 years after the transition to digital screening mammography. PPV(3) is significantly reduced after digital transition, primarily in patients with microcalcifications.

Are there imaging characteristics associated with epidermal growth factor receptor and KRAS mutations in patients with adenocarcinoma of the lung with bronchioloalveolar features?

PURPOSE: To identify any particular imaging features on computed tomography (CT) in patients with confirmed adenocarcinoma with bronchioloalveolar (ABAC) features and known epidermal growth factor receptor (EGFR) and KRAS mutations. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study. Seventy-seven pulmonary nodules in 64 patients with a histologic diagnosis of ABAC and known EGFR or KRAS mutation status were assessed. Of these, 23 patients who were negative for both EGFR and KRAS mutations were used as a control group. Lesion size, margins, and density (ground glass versus solid) were assessed. Statistical analysis using the two-tailed Fisher's exact test t test was performed with multiple different variables. RESULTS: Twenty-one (33%) of 64 patients had EGFR mutations, 20 (31%) of 64 patients had a KRAS mutation, and 23 (36%) had neither. In nine patients with an EGFR mutation, there were 10 nodules with some ground glass opacity (GGO) and in nine patients with a KRAS mutation, there were nine nodules with some GGO. Twenty-six (34%) of the 77 nodules had some GGO, and 12 (46%) of these 26 nodules were entirely GGO. Sixty-two (81%) of the 77 nodules had some solid component, which also included some that were mixed with GGO. Thirty-five (45%) of 77 nodules had air bronchograms. All five nodules (100%) with a high percentage of bronchioloalveolar carcinoma (>75%) had the appearance of GGO only. The presence of GGO on CT was not significantly associated with the presence of an EGFR mutation (p = 0.44) or with the presence of a KRAS mutation (p = 0.77). CONCLUSIONS: In our sample of patients with ABAC, there was no specific CT appearance, which would correlate with either an EGFR mutation or a KRAS mutation, when compared with a control group of patients who did not have these mutations.

Insulin-like growth factor-2 regulates early neural and cardiovascular system development in zebrafish embryos.

The insulin-like growth factor (IGF) family is essential for normal embryonic growth and development and it is highly conserved through vertebrate evolution. However, the roles that the individual members of the IGF family play in embryonic development have not been fully elucidated. This study focuses on the role of IGF-2 in zebrafish embryonic development. Two igf-2 genes, igf-2a and igf-2b, are present in the zebrafish genome. Antisense morpholinos were designed to knock down both igf-2 genes. The neural and cardiovascular defects in IGF-2 morphant embryos were then examined further using wholemount in situ hybridisation, TUNEL analysis and O-dianisidine staining. Knockdown of igf-2a or igf-2b resulted in ventralised embryos with reduced growth, reduced eyes, disrupted brain structures and a disrupted cardiovascular system, with igf-2b playing a more significant role in development. During gastrulation, igf-2a and igf-2b are required for development of anterior neural structures and for regulation of genes critical to dorsal-ventral patterning. As development proceeds, igf-2a and igf-2b play anti-apoptotic roles. Gene expression analysis demonstrates that igf-2a and igf-2b play overlapping roles in angiogenesis and cardiac outflow tract development. Igf-2b is specifically required for cardiac valve development and cardiac looping. Injection of a dominant negative IGF-1 receptor led to similar defects in angiogenesis and cardiac valve development, indicating IGF-2 signals through this receptor to regulate cardiovascular development. This is the first study describing two functional igf-2 genes in zebrafish. This work demonstrates that igf-2a and igf-2b are critical to neural and cardiovascular development in zebrafish embryos. The finding that igf-2a and igf-2b do not act exclusively in a redundant manner may explain why both genes have been stably maintained in the genome.

Factors predicting outcome in a cohort of patients with atherosclerotic renal artery disease diagnosed by magnetic resonance angiography.

BACKGROUND: Atherosclerotic renal artery disease increasingly is recognized as a cause of chronic kidney disease and associated with high morbidity and mortality. We investigated factors predicting patient and renal survival in a cohort of patients with atherosclerotic renal artery disease diagnosed by means of magnetic resonance angiography (MRA). METHODS: We retrospectively analyzed a cohort of patients attending our unit in whom atherosclerotic renal artery disease was identified by means of MRA from 1998 to 2001. One hundred nine patients were followed up for a median of 2.3 years. Baseline clinical and laboratory data were assessed as predictors of outcome by using multivariate Cox proportional hazards analysis. RESULTS: Seventeen patients (16%) required dialysis and 37 patients (34%) died during a median follow-up of 841 days (interquartile range, 326 to 1,206). On multivariate Cox proportional hazards analysis, increased peripheral-blood eosinophil count (hazard ratio, 3.39; 95% confidence interval [CI], 1.45 to 7.88; P = 0.0097), creatinine clearance (hazard ratio, 0.97; 95% CI, 0.94 to 0.99; P = 0.0128), and peripheral arterial disease (hazard ratio, 2.09; 95% CI, 1.04 to 4.18; P = 0.0371) were associated with subsequent death. Only creatinine clearance (hazard ratio, 0.91; 95% CI, 0.87 to 0.96; P = 0.0004) was associated with the need for dialysis. There was no association between eosinophil count and other markers of inflammation. Severity of atherosclerotic renal artery disease was not associated independently with either the need for dialysis or death. CONCLUSION: An increased peripheral-blood eosinophil count predicts patient survival in those with atherosclerotic renal artery disease at the time of diagnosis. This novel risk factor may help identify a group of patients who could benefit from intensive medical therapy by using an assay readily available to most clinicians worldwide.

Insulin-like growth factor (IGF) signalling is required for early dorso-anterior development of the zebrafish embryo.

The insulin-like growth factor (IGF) signalling pathway has been highly conserved in animal evolution and, in mammals and Xenopus, plays a key role in embryonic growth and development, with the IGF-1 receptor (IGF-1R) being a crucial regulator of the signalling cascade. Here we report the first functional role for the IGF pathway in zebrafish. Expression of mRNA coding for a dominant negative IGF-1R resulted in embryos that were small in size compared to controls and had disrupted head and CNS development. At its most extreme, this phenotype was characterized by a complete loss of head and eye structures, an absence of notochord and the presence of abnormal somites. In contrast, up-regulation of IGF signalling following injection of IGF-1 mRNA, resulted in a greatly expanded development of anterior structures at the expense of trunk and tail. IGF-1R knockdown caused a significant decrease in the expression of Otx2, Rx3, FGF8, Pax6.2 and Ntl, while excess IGF signalling expanded Otx2 expression in presumptive forebrain tissue and widened the Ntl expression domain in the developing notochord. The observation that IGF-1R knockdown reduced expression of two key organizer genes (chordin and goosecoid) suggests that IGF signalling plays a role in regulating zebrafish organizer activity. This is supported by the expression of IGF-1, IGF-2 and IGF-1R in shield-stage zebrafish embryos and the demonstration that IGF signalling influences expression of BMP2b, a gene that plays an important role in zebrafish pattern formation. Our data is consistent with a common pathway for integration of IGF, FGF8 and anti-BMPs in early vertebrate development.