Quantitative background parenchymal enhancement and fibro-glandular density at breast MRI: Association with BRCA status.

OBJECTIVES: To investigate whether MRI-based measurements of fibro-glandular tissue volume, breast density (MRBD), and background parenchymal enhancement (BPE) could be used to stratify two cohorts of healthy women: BRCA carriers and women at population risk of breast cancer. METHODS: Pre-menopausal women aged 40-50 years old were scanned at 3 T, employing a standard breast protocol including a DCE-MRI (35 and 30 participants in high- and low-risk groups, respectively). The dynamic range of the DCE protocol was characterised and both breasts were masked and segmented with minimal user input to produce measurements of fibro-glandular tissue volume, MRBD, and voxelwise BPE. Statistical tests were performed to determine inter- and intra-user repeatability, evaluate the symmetry between metrics derived from left and right breasts, and investigate MRBD and BPE differences between the high- and low-risk cohorts. RESULTS: Intra- and inter-user reproducibility in estimates of fibro-glandular tissue volume, MRBD, and median BPE estimations were good, with coefficients of variation < 15%. Coefficients of variation between left and right breasts were also low (< 25%). There were no significant correlations between fibro-glandular tissue volume, MRBD, and BPE for either risk group. However, the high-risk group had higher BPE kurtosis, although linear regression analysis did not reveal significant associations between BPE kurtosis and breast cancer risk. CONCLUSIONS: This study found no significant differences or correlations in fibro-glandular tissue volume, MRBD, or BPE metrics between the two groups of women with different levels of breast cancer risk. However, the results support further investigation into the heterogeneity of parenchymal enhancement. KEY POINTS: • A semi-automated method enabled quantitative measurements of fibro-glandular tissue volume, breast density, and background parenchymal enhancement with minimal user intervention. • Background parenchymal enhancement was quantified over the entire parenchyma, segmented in pre-contrast images, thus avoiding region selection. • No significant differences and correlations in fibro-glandular tissue volume, breast density, and breast background parenchymal enhancement were found between two cohorts of women at high and low levels of breast cancer risk.

Imaging in clinical trials: a patient-led questionnaire study to assess impact of imaging regimes on patient participation.

BACKGROUND: Cancer trials often incorporate intensive imaging with Magnetic Resonance Imaging (MRI) and Positron Emission Tomography with Computerised Tomography (PET/CT), which can be physically and mentally exhausting for patients. This questionnaire study aimed to determine the aspects of imaging that affect a patient's decision to participate in clinical trials in order to inform the design of future trials that utilise imaging. This should achieve greater patient compliance and improve the patient experience. METHOD: A detailed questionnaire assessing patient expectation and acceptability of imaging within clinical trials was developed in collaboration with two patient representatives. The questionnaire addressed the influence of scan type, length, frequency, scheduling, invasiveness and staff support on acceptability of imaging. It was applied to three patient groups. Group 1 consisted of patients newly recruited to studies with imaging, Group 2 consisted of previous participants in studies with imaging and Group 3 consisted of patients having imaging for clinical care. RESULTS: One hundred ninety six patients completed the questionnaires (Group 1:47; Group 2: 50 and Group 3: 99). The use of ionising radiation and number of scans required were identified as negative influences on decision to participate by 25% of Group 3 but only by 6% of Groups 1 and 2. Scan duration >30mins was perceived as a negative factor for decision to participate by all Groups (12-22%). Good communication provided by researchers in terms of discussing the study before and after reading study materials was a key factor in influencing decision to participate (> 50% in Groups 1 and 2 and > 20% in Group 3). CONCLUSION: Factors relating to imaging procedures within clinical trials that affect participation have been identified with communication around study materials as the key determinant. These data will be used to influence the development of future research protocols. Modification of imaging requirements within clinical trials will improve patient tolerance and acceptability and is likely to raise recruitment.

An automated approach for the optimised estimation of breast density with Dixon methods.

OBJECTIVE: To present and evaluate an automated method to correct scaling between Dixon water/fat images used in breast density (BD) assessments. METHODS: Dixon images were acquired in 14 subjects with different T1 weightings (flip angles, FA, 4°/16°). Our method corrects intensity differences between water (W) and fat (F) images via the application of a uniform scaling factor (SF), determined subject-by-subject. Based on the postulation that optimal SFs yield relatively featureless summed fat/scaled-water (F+WSF) images, each SF was chosen as that which generated the lowest 95th-percentile in the absolute spatial-gradient image-volume of F+WSF . Water-fraction maps were calculated for data acquired with low/high FAs, and BD (%) was the total percentage water within each breast volume. RESULTS: Corrected/uncorrected BD ranged from, respectively, 10.9-71.8%/8.9-66.7% for low-FA data to 8.1-74.3%/5.6-54.3% for high-FA data. Corrected metrics had an average absolute increase in BD of 6.4% for low-FA data and 18.4% for high-FA data. BD values estimated from low- and high-FA data were closer following SF-correction. CONCLUSION: Our results demonstrate need for scaling in such BD assessments, where our method brought high-FA and low-FA data into closer agreement. ADVANCES IN KNOWLEDGE: We demonstrated a feasible method to address a main source of inaccuracy in Dixon-based BD measurements.

Monitoring Tumor Volume in Patients With Prostate Cancer Undergoing Active Surveillance: Is MRI Apparent Diffusion Coefficient Indicative of Tumor Growth?

OBJECTIVE: The purpose of this study was to measure longitudinal change in tumor volume of the dominant intraprostatic lesion and determine whether baseline apparent diffusion coefficient (ADC) and change in ADC are indicative of tumor growth in patients with prostate cancer undergoing active surveillance. SUBJECTS AND METHODS: The study group included 151 men (mean age, 68.1 ± 7.4 [SD] years; range, 50-83 years) undergoing active surveillance with 3D whole prostate, zonal, and tumor volumetric findings documented at endorectal MRI examinations performed at two time points (median interval, 1.9 years). Tumor (location confirmed at transrectal ultrasound or template biopsy) ADC was measured on the slice with the largest lesion. Twenty randomly selected patients had the measurements repeated by the same observer after a greater than 4-month interval, and the limits of agreement of measurements were calculated. Tumor volume increases greater than the upper limit of agreement were designated measurable growth, and their baseline ADCs and change in ADC were compared with those of tumors without measurable growth (independent-samples t test). RESULTS: Fifty-two (34.4%) tumors increased measurably in volume. Baseline ADC and tumor volume were negatively correlated (r = -0.42, p = 0.001). Baseline ADC values did not differ between those with and those without measurable growth (p = 0.06), but change in ADC was significantly different (-6.8% ± 12.3% for those with measurable growth vs 0.23% ± 10.1% for those without, p = 0.0005). Percentage change in tumor volume and percentage change in ADC were negatively correlated (r = -0.31, p = 0.0001). A 5.8% reduction in ADC indicated a measurable increase in tumor volume with 54.9% sensitivity and 77.0% specificity (AUC, 0.67). CONCLUSION: Tumor volume increased measurably in 34.4% of men after 2 years of active surveillance. Change in ADC may be used to identify tumors with measurable growth.

Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study.

Purpose To determine the usefulness of whole-body diffusion-weighted imaging (DWI) to assess the response of bone metastases to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods A phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose) polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance (MR) imaging substudy; the study was approved by the institutional research board, and written informed consent was obtained. Whole-body DWI was performed at baseline and after 12 weeks of olaparib administration by using 1.5-T MR imaging. Areas of abnormal signal intensity on DWI images in keeping with bone metastases were delineated to derive total diffusion volume (tDV); five target lesions were also evaluated. Associations of changes in volume of bone metastases and median apparent diffusion coefficient (ADC) with response to treatment were assessed by using the Mann-Whitney test and logistic regression; correlation with prostate-specific antigen level and circulating tumor cell count were assessed by using Spearman correlation (r). Results Twenty-one patients were included. All six responders to olaparib showed a decrease in tDV, while no decrease was observed in all nonresponders; this difference between responders and nonresponders was significant (P = .001). Increases in median ADC were associated with increased odds of response (odds ratio, 1.08; 95% confidence interval [CI]: 1.00, 1.15; P = .04). A positive association was detected between changes in tDV and best percentage change in prostate-specific antigen level and circulating tumor cell count (r = 0.63 [95% CI: 0.27, 0.83] and r = 0.77 [95% CI: 0.51, 0.90], respectively). When assessing five target lesions, decreases in volume were associated with response (odds ratio for volume increase, 0.89; 95% CI: 0.80, 0.99; P = .037). Conclusion This pilot study showed that decreases in volume and increases in median ADC of bone metastases assessed with whole-body DWI can potentially be used as indicators of response to olaparib in mCRPC. Online supplemental material is available for this article.

Comparison of Dixon Sequences for Estimation of Percent Breast Fibroglandular Tissue.

OBJECTIVES: To evaluate sources of error in the Magnetic Resonance Imaging (MRI) measurement of percent fibroglandular tissue (%FGT) using two-point Dixon sequences for fat-water separation. METHODS: Ten female volunteers (median age: 31 yrs, range: 23-50 yrs) gave informed consent following Research Ethics Committee approval. Each volunteer was scanned twice following repositioning to enable an estimation of measurement repeatability from high-resolution gradient-echo (GRE) proton-density (PD)-weighted Dixon sequences. Differences in measures of %FGT attributable to resolution, T1 weighting and sequence type were assessed by comparison of this Dixon sequence with low-resolution GRE PD-weighted Dixon data, and against gradient-echo (GRE) or spin-echo (SE) based T1-weighted Dixon datasets, respectively. RESULTS: %FGT measurement from high-resolution PD-weighted Dixon sequences had a coefficient of repeatability of ±4.3%. There was no significant difference in %FGT between high-resolution and low-resolution PD-weighted data. Values of %FGT from GRE and SE T1-weighted data were strongly correlated with that derived from PD-weighted data (r = 0.995 and 0.96, respectively). However, both sequences exhibited higher mean %FGT by 2.9% (p < 0.0001) and 12.6% (p < 0.0001), respectively, in comparison with PD-weighted data; the increase in %FGT from the SE T1-weighted sequence was significantly larger at lower breast densities. CONCLUSION: Although measurement of %FGT at low resolution is feasible, T1 weighting and sequence type impact on the accuracy of Dixon-based %FGT measurements; Dixon MRI protocols for %FGT measurement should be carefully considered, particularly for longitudinal or multi-centre studies.

Delivering breast cancer care in urban India: Heterotopia, hospital ethnography and voluntarism.

Despite substantial strides to improve cancer control in India, challenges to deliver oncology services persist. One major challenge is the provision and accessibility of adequate infrastructure. This paper offers ethnographic insight on the conceptual and material conditions that are currently shaping the delivery of oncology in Mumbai, focusing specifically on the way India's socio-economic context necessitates non-biomedical acts of voluntarism or 'seva' (selfless service). Developing the premise that hospitals are not identical clones of a biomedical model, detailed attention is paid to the way 'care' emerges through 'praxis of place' (Casey, 2003) within the cancer hospital as a multi-scalar 'heterotopic' (Street and Coleman, 2012) site. Such a perspective enables global/local tensions to come into view, together with the heterogeneous confluence of juxtaposing materialities, imaginations, social practices and values that both propels and constrains the everyday delivery of care. The paper reflects on the theoretical implications of hospital seva in Mumbai in light of social science studies of hospital ethnography and health activism and contributes important ethnographic insight into the current global health debates regarding effective implementation of cancer services in India.

The secretory clear cell of the eccrine sweat gland as the probable source of excess sweat production in hyperhidrosis.

Primary hyperhidrosis is characterized by excessive sweating in palmar, plantar and axillary body regions. Gland hypertrophy and the existence of a third type of sweat gland, the apoeccrine gland, with high fluid transporting capabilities have been suggested as possible causes. This study investigated whether sweat glands were hypertrophied in axillary hyperhidrotic patients and if mechanisms associated with fluid transport were found in all types of axillary sweat glands. The occurrence of apoeccrine sweat glands was also investigated. Axillary skin biopsies from control and hyperhidrosis patients were examined using immunohistochemistry, image analysis and immunofluorescence microscopy. Results showed that glands were not hypertrophied and that only the clear cells in the eccrine glands expressed proteins associated with fluid transport. There was no evidence of the presence of apoeccrine glands in the tissues investigated. Preliminary findings suggest the eccrine gland secretory clear cell as the main source of fluid transport in hyperhidrosis.

Can we evaluate population screening strategies in UK general practice? A pilot randomised controlled trial comparing postal and opportunistic screening for genital chlamydial infection.

STUDY OBJECTIVE: To assess whether opportunistic and postal screening strategies for Chlamydia trachomatis can be compared with usual care in a randomised trial in general practice. DESIGN: Feasibility study for a randomised controlled trial. SETTING: Three West of Scotland general medical practices: one rural, one urban/deprived, and one urban/affluent. PARTICIPANTS: 600 women aged 16-30 years, 200 from each of three participating practices selected at random from a sample of West of Scotland practices that had expressed interest in the study. The women could opt out of the study. Those who did not were randomly assigned to one of three groups: postal screening, opportunistic screening, or usual care. RESULTS: 38% (85 of 221) of the approached practices expressed interest in the study. Data were collected successfully from the three participating practices. There were considerable workload implications for staff. Altogether 124 of the 600 women opted out of the study. During the four month study period, 55% (81 of 146) of the control group attended their practice but none was offered screening. Some 59% (80 of 136) women in the opportunistic group attended their practice of whom 55% (44 of 80) were offered screening. Of those, 64% (28 of 44) accepted, representing 21% of the opportunistic group. Forty eight per cent (59 of 124) of the postal group returned samples. CONCLUSION: A randomised controlled trial comparing postal and opportunistic screening for chlamydial infection in general practice is feasible, although resource intensive. There may be problems with generalizing from screening trials in which patients may opt out from the offer of screening.