Mammography

In this volume, the topics are constructed from a variety of contents: the bases of mammography systems, optimization of screening mammography with reference to evidence-based research, new technologies of image acquisition and its surrounding systems, and case reports with reference to up-to-date multimodality images of breast cancer. Mammography has been lagged in the transition to digital imaging systems because of the necessity of high resolution for diagnosis. However, in the past ten years, technical improvement has resolved the difficulties and boosted new diagnostic systems. We hope that the reader will learn the essentials of mammography and will be forward-looking for the new technologies. We want to express our sincere gratitude and appreciation?to all the co-authors who have contributed their work to this volume

PET-MR Imaging of Hypoxia and Vascularity in Breast Cancer

Breast cancer is the most common cancer in the UK and in women globally. Imaging methods like mammography, ultrasound (US) and magnetic resonance imaging (MRI) play an important role in the diagnosis and management of breast cancer; they are generally utilised to provide anatomical or structural description of tumours in the clinical setting. It is widely accepted that the tumour microenvironment influences the phenotype, progression and treatment of breast cancer. This gave the impetus to move beyond tumour visualization in images to radiomics in order to provide additional disease characterisation and early biomarkers of tumour response. Due to their ability to assess physiological processes in vivo, positron emission tomography (PET) and MRI can provide non-invasive characterisation of the tumour microenvironment, including perfusion, vascular permeability, cellularity and hypoxia, which is associated with poor clinical outcome and metastasis. Clinical imaging studies in breast tumours have hitherto assessed tumour physiological parameters separately, with only few directly comparing data from these modalities. To this end, hybrid PET-MRI represents an attractive option as it can allow examination of functional processes and features of tumours simultaneously, while also conferring methodological advantages to the way imaging information is combined. The main aim of this thesis is to provide a better understanding of breast cancer pathophysiology using simultaneous PET and multi-parametric MRI. In particular, this work aims to explore relationships between imaging biomarkers of tumour vascularity measured by dynamic contrast-enhanced (DCE) MRI, cellularity using diffusion-weighted imaging (DWI) and hypoxic status using 18F-fluoromisonidazole (18F-FMISO) PET. Correlations between functional PET-MRI parameters and immunohistochemical (IHC) biomarkers of hypoxia and vascularity as well as MRI morphological tumour descriptors are also presented. The thesis concludes with an investigation of the utility of MRI markers of perfusion and surrogate markers of hypoxia to quantitatively monitor and predict pathological response in patients undergoing neoadjuvant chemotherapy (NACT) and provides projections for future work

Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling

BACKGROUND: Current pathways recommend positron emission tomography-computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach. OBJECTIVES: To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography-computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies. DESIGN: Multicentre comparative accuracy trial. SETTING: Secondary or tertiary outpatient settings at 16 hospitals in the UK. PARTICIPANTS: Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included. INTERVENTIONS: Baseline positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography with 2 years' follow-up. MAIN OUTCOME MEASURES: Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography. RESULTS: A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography-computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography-computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography-computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51). LIMITATIONS: The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening. CONCLUSIONS: Findings from this research indicate that positron emission tomography-computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography-dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a 'watch and wait' policy may be an approach to consider. FUTURE WORK: Integration of the dynamic contrast-enhanced component into the positron emission tomography-computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol

Evaluation of the vascular response to neoadjuvant chemotherapy in primary breast cancer.

Neoadjuvant chemotherapy (NAC) is being increasingly used in the treatment of primary breast cancer (PBC). With the primary tumour in situ, the neoadjuvant treatment setting allows an in vivo assessment of tumour chemo-responsiveness and permits an evaluation of the possible underlying biological mechanisms of response. Angiogenesis is critical for the growth and metastases of breast cancer and with the development of novel agents targeting this process, an understanding of the vascular effects of conventional chemotherapy will enable the rational design of future drug combinations. Functional magnetic resonance imaging (MRI) provides a non-invasive method for assessing tumour microvasculature. Using this technique, pre-treatment tumour vascularity and changes following two cycles of anthracycline-based NAC were measured in a series of patients with PBC. This demonstrated a significant reduction in the permeability and perfusion-related MRI parameters in tumours responding to treatment. The degree of change in K* was able to predict for pathological non-response with a positive predictive value of 84%. Further, an evaluation of the pathophysiological correlates of functional MRI demonstrated an association between the permability/perfusion-related parameters and aggressive tumour features. An evaluation of the effect of anthracycline-based NAC on immunohistochemically-derived measures of tumour angiogenesis was performed on a series of patients treated for PBC. A quantitative and a qualitative measure of tumour angiogenesis was performed (microvessel density MVD and pericyte coverage index PCI respectively), together with an assessment of VEGF expression. This demonstrated no change in MVD following treatment but a significant increase in PCI reflecting a reduction in the proportion of immature proliferating blood vessels. This was accompanied by a reduction in VEGF expression, which may be mediating this effect. These observations may have clinical importance as they may help identify patients who could benefit from alternative therapies early in their treatment course and they may assist in the rational design of combination cytotoxic and antiangiogenic treatment regimens

Interstitial diagnosis and treatment of breast tumours

This thesis exploits the interaction of light with breast tissue for diagnosis and therapy. Optical biopsy is an experimental technique, based on Elastic Scattering Spectroscopy (ESS), being developed for characterising breast tissue. An optical probe interrogates tissue with a white light pulse, with spectral analysis of the reflected light. 264 spectral measurements (50 patients) were obtained from a range of breast tissues and axillary lymph nodes and correlated with conventional histology of biopsies from the same sites. Algorithms for spectral analysis were developed using ANN (Artificial Neural Network), HCA (Hierarchical Cluster Analysis) and MBA (Model Based Analysis). The sensitivity and specificity for cancer detection in breast and lymph nodes were: [diagram]. Interstitial Laser Photocoagulation (ILP) involves image guided, thermal coagulation of lesions within the breast using laser energy delivered via optical fibres positioned percutaneously under local anaesthetic. Two groups were studied: 1) Nineteen patients with benign fibroadenomas underwent ILP and the results compared with 11 treated conservatively. Thirteen ILP patients (14 fibroadenomas) and 6 controls (11 fibroadenomas) have reached their one-year review: [diagram]. These differences are statistically significant (P<0.001). 2)Six patients with primary breast cancers underwent ILP (with pre- and post-ILP contrast enhanced MRI) within 3 weeks of diagnosis and were then treated with Tamoxifen. Four underwent surgery at 3 months, two showing complete tumour ablation. MRI was reasonably accurate at detecting residual tumour. In conclusion: a) optical biopsy is a promising 'real time' diagnostic tool for breast disease. b) ILP could provide a simple and safe alternative to surgery for fibroadenomas. c) ILP with MRI monitoring may be an alternative to surgery in the management of some patients with localised primary breast cance